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MEDICIN

2023
E
HEPATOLOGY

Rasheed Mohammed
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ABNORMAL LFT'S

Liver Tests
• Aminotransferases:
1. Aspartate Aminotransferase (AST)
- Located in mitochondria
- Alcohol is mitochondrial toxin, ↑ AST > ↑ ALT in alcoholic hepatitis
- AST is also found in skeletal and cardiac muscle
- Normal level is < 50 U/L

2. Alanine Aminotransferase (ALT)

- Located in cytoplasm
- ALT is specific for the liver
- ↑ ALT > ↑ AST in most types of hepatitis with cellular damage
- ALT has a longer 1/2 life, and thus lags behind AST when liver function improves
- Normal level is < 50 U/L

• Alkaline phosphatase:
- Located in hepatocyte membrane bordering bile canaliculi
- Also found in bone, GI tract and placenta
- Levels rise in many non-liver conditions; Pregnancy (placenta), Thyroid disease, Bone disease
- If you have high ALP and you want to know, is it from the liver or not measure GGT enzyme or
Asked for ALP isoenzymes
- Normal level is 20 – 140 IU/L

• Gamma glutamyl transferase (GGT):

- An enzyme of intrahepatic biliary canaliculi
- Used to determine origin of ALP elevation: ↑ ALP plus ↑ GGT = hepatobiliary cause of ↑ Alk
Phos
- If GGT increased alone it is either due to enzyme inducing drug (e.g., Rifampicin) or heavy
alcohol consumption
- Normal level is < 40 U/L

• Bilirubin:
1. Direct/conjugated (water soluble):
- increased in hepatocyte dysfunction and impaired flow and may be excreted in urine
- conditions: hepatitis, cholestasis, obstruction, or any problem related to the liver
2. Indirect/unconjugated (water insoluble):
- increased in conditions with over production of bilirubin such as hemolysis or hematoma
resorption.
- Sometimes indirect bilirubin could be high due to defect in liver enzymes = conjugation
problem, but the principal is that indirect bilirubin mainly increases in cases of over
production

- Normal level is Total 0.1 – 1.2 mg/dL, Direct is < 0.3 mg/dL, indirect 0.2 – 0.8 mg/dl
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• Prothrombin & Albumin:

- Both are markers of synthetic liver function, Abnormalities indicate severe liver disease
- In case of liver cirrhosis there is normal ALT because there are no more functioning hepatocytes
to be broken down and hence enzyme release, but albumin and prothrombin synthesis will be
impaired.
- Half-life of serum albumin is 2 weeks, so it is not used to detect acute liver failure
- Prothrombin time (PT) is a measure of the activity of vitamin K dependent coagulation factors; In
patients with vitamin K deficiency such as antibiotic use, celiac disease, cholestatic liver disease:
administration of IV vitamin K will correct the PT in 48 hours.
- Normal serum albumin is 3.5 - 5.5 mg/dL
- Normal INR is < 1.1

Liver Test Abnormalities

• Hepatocellular Patterns:
- In acute hepatitis ALT / AST are usually elevated 7-10 times the upper limit of normal (very
high)> 1000 U / L (ALT > AST)
- In ischemic hepatitis / paracetamol overdose (very very high) > 5000 U / L)
- In alcoholic hepatitis AST > ALT
- In chronic hepatitis ALT / AST are usually elevated 2 – 5 times the upper limit of normal.

• Cholestatic pattern:
- This may affect microscopic ducts (primary biliary cirrhosis), Large bile ducts (obstruction such as
stones, CA pancreas) or both (primary sclerosing cholangitis)
- Usually results in elevation of ALP (3 – 5 upper normal limits of normal)

Follow-up Testing
1. Cholestatic pattern
o Best initial test: ultrasound
o Evaluates biliary ducts
▪ Dilated = extrahepatic cause of obstruction (stone, mass)
▪ Normal = intrahepatic cause of obstruction (primary biliary cholangitis, pregnancy)

2. Hepatocellular pattern
o Best initial test: blood tests
▪ Viral hepatitis
▪ Autoimmune hepatitis
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JAUNDICE
• Definition:
- Yellowing of skin, conjunctiva, mucous membranes
- Scleral icterus (eyes) often earliest sign
- Normal: total bilirubin < 1.0 mg/dL
- Visible hyperbilirubinemia when > 2.5 mg/dL

• Clinical Assessments
1. Serum bilirubin: Total (normal <1.0), Direct (normal <0.3) & Indirect (normal <0.7)
2. Urine urobilinogen (normally small amount)
3. Urine bilirubin (normally absent)

• Four General Causes of Hyperbilirubinemia

1. Hemolytic
2. Biliary obstruction (cholestasis)
3. Liver disease
4. Special causes

• Hemolytic:
- Excessive Hemolysis, Ineffective erythropoiesis, Hematoma resorption → ↑ heme metabolism →Too
much bilirubin sent to liver → overwhelms capacity
o Elevated serum unconjugated bilirubin
o No urine bilirubin detected [Unconjugated bilirubin cannot cross glomerulus]

• Biliary Obstruction:
- Cholestasis: lack of bile flow
o Extrahepatic: gallstones, pancreatic masses
o Intrahepatic: intrahepatic cholestasis of pregnancy, primary biliary cholangitis
- Conjugation occurs normally, however excretion is impaired → elevated direct bilirubin
- Cholestatic LFT pattern: ↑ Alk P more than ↑ ALT/AST
- Urine bilirubin detected, Conjugated bilirubin water soluble, Crosses glomerulus
- Absent urobilinogen; No bilirubin to intestine → Loss of formation of urobilinogen
- Important symptoms: Dark urine, Pale stools (lack of stercobilin), Steatorrhea: absence of bile salts, often
associated with pruritus (bile salts in skin)

• Primary Liver Diseases:

- Viral hepatitis, alcoholic hepatitis → Liver damage → ↑ Alk Phos/ALT/AST
- Hepatocellular pattern: ↑ ALT/AST more than ↑ Alk P
- Elevated total bilirubin; usually mixed increase of direct/indirect

Normal Hemolytic Biliary Obstruction

Total bilirubin 1.0 1.8 4
Unconjugated 0.7 (70%) 1.7 (90%) 1.6 (42%)
Conjugated 0.3 (30%) 0.1 (10%) 2.3 (58%)
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• Special Causes
1. Gilbert’s Syndrome
o Benign autosomal recessive condition disorder of bilirubin metabolism
o ↓ UDP-glucanosyltransferase function; Enzyme that conjugates bilirubin in liver
o Mild ↑ total and unconjugated bilirubin (usually < 3 mg/dl), ALP & ALT are normal, No bilirubin
in the urine
o Usually, no serious clinical consequences
o Transient jaundice that occurs with ↑ bilirubin production with Fasting, Febrile illnesses, Heavy
physical exertion, Stress, Menses
o Benign condition – no treatment required

2. Crigler-Najjar Syndrome
o reduced/absent UGT enzyme, severely impaired bilirubin conjugation
o Type I
▪ Autosomal recessive disorder. Absent glucoronyle transferase enzyme
▪ usually presents in infancy
▪ Severe disease; very high level of unconjugated bilirubin (often > 20 mg/dl)
▪ Jaundice, Kernicterus (cause of death)
▪ Treatment: phototherapy and Exchange transfusion
▪ Definitive treatment: liver transplant
o Type II:
▪ Autosomal recessive disorder. Partial deficiency of glucoronyle transferase enzyme
▪ Less severe than type I (bilirubin < 20 mg/dl)
▪ Reduced risk of neurologic consequences, Survival into adulthood possible
▪ Sometimes treated with phenobarbital or clofibrate [Both induce liver glucuronidation]

3. Dubin-Johnson Syndrome
o Conjugated hyperbilirubinemia
o Defective liver excretion of conjugated bilirubin
o Findings:
▪ ↑ conjugated bilirubin, Total bilirubin usually 2 to 5 mg/dL (~ 50% conjugated)
▪ May see bilirubin in urine
▪ Liver turns black (classically seen in abdominal surgery)
o Benign condition – no treatment required

4. Rotor’s Syndrome
o Similar to Dubin-Johnson
o Defect in conjugated bilirubin storage
o Milder conjugated hyperbilirubinemia
o No black liver (differentiates Dubin-Johnson)
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• CASE
 A fit 22-year-old medical student presents with yellow discoloration of the sclera. He is found to have
the following results on investigation:
o Total bilirubin: 3.0mg/d
o Direct bilirubin 0.5mg/d
o ALP & ALT are normal
o Abdominal ultrasound normal
o No bilirubin in the urine
 What is your differential diagnosis?
1. Gilbert syndrome
2. Hemolysis

-
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LIVER MASSES

Metastatic liver tumor

- The overall MC liver tumors worldwide
- Sources: Colorectal (MC), Lungs (2nd MC), Breast (3rd MC), Stomach, Uterus, Pancreas,
Hematological, Carcinoid tumors.
- Manifestations: Hepatomegaly, weight loss +/- Jaundice, ascites. ↑ALP (MC) or Normal LFTs.
- Ascitic fluid: ↑protein, +/- bloody, malignant cells
- Management:
1. Manage the primary neoplasm + [Liver mass/es: Resection, TACE].
2. Palliative care (MC), Prognosis often <6 months.

Benign Liver Tumor

• Hepatic adenoma:
- Usually occurs in female who takes OCPs, androgen or anabolic steroids.
- Occurs in non-cirrhotic patients
- Asymptomatic, Often discovered incidentally on imaging
- Complication: Rupture & haemorrhage, pre-malignant.
- Diagnosed by US (CT or MRI), but biopsy is essential to confirm.
- Management Hepatic Adenoma MRI
o Conservative (Avoid estrogen-containing drugs)
o surgical resection only if symptomatic or >5cm.

• Hemangiomas:
- The MC benign liver tumor.
- Composed of vascular spaces, often filled with thrombus
- Asymptomatic, often discovered incidentally on imaging
- Occurs in non-cirrhotic patients
- Characteristic features on CT scan and MR
o US or CT (low density with delayed filling, structures identified within lesion).
o MRI: progressive centripedal enhancement of contrast (from periphery toward
center). US Hepatic Hemangioma
- Biopsy is contraindicated. (Can lead to fatal hemorrhage)
- Conservative management, Surgery only only if symptomatic or >5cm.

• Focal nodular hyperplasia:

- Benign Non-neoplastic lesion of the liver
- Hyperplastic growth of hepatocytes due to local hemodynamic instability (Problem in the liver vasculature)
- Asymptomatic, usually occurs in Female <40yrs.
- Rarely grows or bleeds, No malignant potential
- A characteristic feature on CT scan/MRI is a prominent central scar with radiating fibrous septa
- Biopsy: Nodular regeneration w/out fibrosis
- Treatment is by reassures the patient
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Malignant Liver Tumors

Hepatocellular Carcinoma (HCC)
• Incidence: MC primary liver tumour. 5th MC Cancer. 3M:1F
• Etiology:
1. Liver cirrhosis of any cause: HBV (MCC), HCV, AIH, N/AFLD, HH, PBC.
2. Chronic HBV w/out cirrhosis: the MCC & the major risk factor worldwide (esp. in Asia & Africa). ↑ risk if
high viral load, HBeAg +ve.
3. Others: Aflatoxin, Clonorchis sinensis, Anabolic steroids.
4. Etiology in Sudan: Chronic HBV infection, HCV, Aflatoxin.
• Manifestations:
1. Often asymptomatic
2. Detected by screening in high-risk patients
• May cause decompensated cirrhosis
• Obstructive jaundice, ascites
3. Fatigue, anorexia, weight loss
4. Jaundice, RUQ pain, hepatomegaly/mass/ abdominal bruit, ascites
5. Hemobilia (Late). Suspect w/ Quincke’s triad: RUQ pain + Up. GI Haemorrhage + Jaundice.
6. Recent deterioration of CLD
• Complications:
1. Hepatic encephalopathy, portal vein thrombosis, Variceal bleeding
2. Hepatic rupture → intra-abdominal bleeding.
3. Hypoglycemia: Seen with large tumors due to high metabolic rate
4. Erythrocytosis: HCC can secrete EPO
5. Budd Chiari syndrome
• Hypercoagulable state plus compression venous structures
• Occlusion of hepatic veins that drain liver
• Classic triad: abdominal pain, ascites, hepatomegaly
6. Metastases: Usually spreads via blood not lymph, Common sites: lung and bone
• Investigations: Screen with AFT and US, then: CT+MRI.
1. LFT: variable; Usually abnormal in a non-specific pattern
2. Alfa-fetoprotein (65%): ↑w/ tumour size.
- Secreted by HCC
- Low Sensitivity & Specificity, Can be elevated in chronic liver disease so
rise in level from baseline suspicious for HCC
- For screening, disease progression & treatment response.
3. Abdominal US: detects as small as 2cm. Screening.
4. 3-phase CT:
- Rapid uptake of contrast (early enhancement) in the arterial phase
- Rapid washout of contrast in the portal venous phase
5. Dynamic contrast-enhanced MRI.
6. Biopsy:
- Focal liver lesion in non-cirrhotic liver
- In cirrhotic liver if imaging is atypical
• Diagnostic Criteria:
- Non-invasive: Cirrhotic Liver + Focal lesion >/= 1cm. + Typical findings on imaging (CT/MRI).
- Non-cirrhotic or atypical imaging require biopsy.
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• Screening in Cirrhosis
- Up to 95% of HCC occurs in cirrhotic patients
- American Association for the Study of Liver Diseases 2017 screening guidelines
o Serum AFP and US every 6 months

• Management:
1. Treat complications of cirrhosis (ascites, up GI bleeding, encephalopathy, SBP, pruritus)
2. Surgical excision: If single lesion < 5cm or three lesions each < 3cm in diameter in non-cirrhotic
3. Liver Transplantation: Single nodule > 5cm OR 2-3 masses each >3cm or cirrhotic [Milan Criteria]
4. Loco-regional Therapy:
o Percutaneous ethanol injection: lesion <2cm.
o Radiofrequency ablation: lesion 2-3cm
o Trans-arterial chemo-embolization TACE: pts. w/ preserved liver function (PST 0) & Unresectable,
Multinodular HCC on imaging
5. Systemic Chemotherapy with Sorafenib: For pts. w/ preserved liver function, Portal invasion, Extrahepatic
spread
• Prognosis:
- Poor overall
- Median survival 6 to 20 months

• Prevention:
1. HBV, HCV prevention & vaccine
2. Prevent Cirrhosis/CLD (stop alcohol, safe blood transfusion, …)
3. Screening: AFP + US every 6 months for ↑risk pts: All cirrhotic pts, Chronic HBV (even in the absence of
cirrhosis)

Cholangiocarcinoma
• Etiological factors:
1. Primary sclerosing cholangitis (Most common cause in the United States)
2. Thorotrast (thorium dioxide)
3. Parasitic infections: Opisthorchis and Clonorchis sinensis
4. Fibropolycystic liver diseases: i.e., congenital hepatic fibrosis, choledochal cysts
• Manifestations:
- Typically presents as bile duct obstruction rather than a hepatic mass.
- Fever, malaise, abdominal pain, +/- Ascites
• Investigations: ↑Bilirubin ↑↑ALP
• Management: 70% inoperable at presentation. Of those that are, 76% recur.
1. Surgery: e.g., major hepatectomy + extrahepatic bile duct excision + caudate lobe resection. [Post-op
complications include liver failure, bile leak, and GI bleeding.]
2. ERCP/Percutaneous stenting of obstructed extrahepatic biliary tree (Only improves quality of life).
3. Liver transplantation: rarely possible

• Prognosis: Poor ~5months.

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Liver Cyst
Amoebic liver abscess
• Pathology:
- Amoebic trophozoites travel to the liver in a portal venule. They multiply & lyse the liver parenchyma
causing an abscess with a chocolate brown (anchovy paste-like) liquid
- The abscess is usually in the right lobe and contains acellular debris and trophozoites [usually small and not
toxic]

• Manifestations:
- Local discomfort, malaise, later high swinging temperature & sweating w/out marked systemic
manifestations.
- Tender hepatomegaly, RUQ pain/tenderness, right shoulder pain, cough, mild jaundice in some cases
- +/- associated diarrhea. [50% have no history of amoebic dysentery]

• Complications:
- Hepatobronchial fistula, pleuropulmonary abscess, Peritonitis, Pericardial abscess

• Investigations:
- CBC: neutrophilia
- LFT: normal or cholestatic (↑ALP)
- Serology: Ag & Ab detection in blood by ELISA +ve in 95%.
- Abdominal US: hypo echoic mass → confirm the diagnosis
- Abdominal CT: ring enhancing mass
- CXR: raised right hemidiaphragm.
- Diagnostic aspiration: Odorless anchovy paste, not used, differentiate it from pyogenic abscess]

• Management:
- Metronidazole/Nitazoxanide + (followed by) Luminal agent +/- Drainage.
o Anti-amoebic: Metronidazole 800mg TID for 10d OR Tinidazole OR Ornidazole 2g/d for 3d
o Luminal agents: Diloxanide Furoate OR Paromomycin 500mg PO TID for 10d after treatment to
eliminate gut cysts.
o Drainage: for 1. Large more than 10 cm. 2. Failure of medical treatment. 3. Left lobe abscess

Pyogenic liver abscess

• Causative organism:
- E. Coli & Streptococci (esp. S. milleri) are the MCC, Anaerobes (Bacteroides) from large bowel
• Routes:
1. Ascending d/t biliary obstruction.
2. Direct Contiguous spread: gallbladder empyema.
3. Hematogenous: Intra-abdominal infections, Colonic disease (cancer, diverticulitis, IBD), Suppurative
appendicitis
4. Trauma: penetrating or non-penetrating.
5. Infection of liver tumor or cyst.

• Manifestations:
- Fever (may be PUO), +/- rigors, wt. loss.
- Abdominal pain (esp. RUQ; sometimes pleuritic +/- radiation to shoulder) MC symptom.
- Tender hepatomegaly (>50%).
- Jaundice.
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• Investigations:

- CBC: Leukocytosis - Needle aspiration

- Blood culture: +ve in 50-80% - CXR: raised right diaphragm
- US: to locate the abscess - LFT: normal or cholestatic (↑ALP)

• Management:
1. IV Antibiotics: start w/combinations (Ampicillin, Gentamicin, Metronidazole) till culture & sensitivity
results.
2. Percutaneous drainage: for large or non-responding to antibiotics.
3. If biliary obstruction/cholangitis: biliary drainage.

Cystic Echinococcosis (Hydatid Disease)

• Mode of infection:
- After ingestion of E. granulosus eggs in food contaminated by animal faeces, larvae (hydatid cyst) develop
in the liver (75% Right lobe).
- It’s Common in mid. East, Africa, Australia.

• Manifestations:
- Early/slow growing cysts are asymptomatic.
- Abdominal pain, nausea, hepatomegaly, obstructive jaundice, cholangitis, PUO.
- Other infected locations: Lung, CNS (SOL), Bone.

• Investigations:
- US/CT/MRI: avascular fluid filled cysts +/- calcifications [ddx: benign cysts, TB, mycoses, abscess, neoplasm]
- Serology: CFT, ELISA: +ve in 80%

• Management:
1. Albendazole 400mg BID for 3 months. (Often combined w/ PAIR).
2. PAIR (Puncture, Aspirate, Inject, Reaspirate) w/ peri-operative praziquantel
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CASE 1
57 years. old man, known to have liver cirrhosis, was found to have a 3 cm focal liver lesion on
routine U\S

1. What is the differential diagnosis

Hepatic adenoma, Hemangioma, Focal nodular hyperplasia, HCC, Metastasis, Degenerative nodule.
[Pt was not symptomatic (routine US) so we exclude liver abscess, Not liver cyst because focal liver
lesion = solid]
2. How would you confirm your diagnosis?
Triphasic CT scan, MRI, Alfa fetoprotein, Liver biopsy Take liver biopsy (some time no need to take
biopsy)

3. How differentiate between benign and malignant liver lesion?

By triphasic CT scan
o Hepatic adenoma: solitary, well-demarcated, heterogeneous mass
o Hemangioma: low density with delayed filling
o HCC: Rapid uptake of contrast (early enhancement) in the arterial phase, Rapid washout of
contrast in the portal venous phase
4. Triphasic CT scan shows rapid uptake and rapid washout. What is the diagnosis?
Features highly suggestive of HCC.

CASE 2
34-year-old housewife on oral contraceptives presents with vague right side abdominal pain,
abdominal ultrasound reveals a 6.0 cm lesion in the right lobe of the liver. Tri-phasic CT scan is not
typical of HCC

1. What is the next step?

Liver biopsy

CASE 3
46-year-old male complains of recurrent colicky left loin pain. He undergoes an abdominal
ultrasound which shows a 4.0 cm lesion in the right lobe of the liver. § MRI shows centripedal
enhancement of contrast

1. What is the diagnosis?

Hemangioma

CASE 4
49-year-old lady presents with right hypochondrial pain radiating to the right shoulder, fever, and
vomiting. On examination she is ill, temperature 39°C with tender hepatomegaly.
Laboratory investigations reveal a TWCC of 19,000, raised alkaline phosphatase and bilirubin.
CXR shows a raised right hemi-diaphragm.
Abdominal CT scan: Reveals a round lesion 10x 7 cm in the right lobe of the liver with thick fluid
content.
1. What is the diagnosis?
Liver abscess [Amoebic or Pyogenic]
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ASCITES
- If more than 1L → abdominal Distention, Flanks fullness, Shifting dullness, Fluid thrill/wave, umbilical
eversion, hernia, abdominal striae.

• Ascetic fluid analysis:

A. Essential:
1. Cell count Total & differential
2. Albumin level or, if not available, (total) protein level.
B. Optional/Others:
1. Color (Bloody: malignant. Milky: chylous. Cloudy: SBP).
2. Gram stain and ZN stain
3. Culture & sensitivity
4. Glucose (low: TB, malignancy)
5. LDH
6. Amylase (>1000U/L: pancreatic)
7. Triglyceride (>110mg/dL: Chylous)
C. If Exudate:
1. PCR or Adenosine Deaminase level (ADA) for TB (the MCC of exudative ascites)
2. Cytology, CT then laparoscopy for malignant causes.
D. Serum-Ascitic Albumin Gradient (SAAG): Serum albumin minus Ascitic albumin.
1. Transudate: SAAG > 1.1 g/dl
o Causes: Liver cirrhosis, CHF, chronic renal failure, Protein losing enteropathy, Malnutrition,
Hepatic venous outflow obstruction (Budd-Chiari, Veno-occlusive Disease)
2. Exudate: SAAG < 1.1 g/dl
o Causes: Malignancy (Hepatic, Peritoneal), TB, Hypothyroidism, Acute Pancreatitis, Lymphatic
obstruction (Chylous), Nephrotic syndrome.

• Other Investigations:
1. US: Best test to detect ascites, particularly small amount in obese pt.
2. CXR: Hepatic Hydrothorax (Pleural effusion): 10%, often small incidental.
3. Laparoscopy: For Peritoneal disease, Malignancy.

• Management:
- Transudative: sodium and water restriction, diuretics (Not >1L/d fluid loss) +/- paracentesis.
- Exudative: paracentesis.

1. Salt (Na) restriction: ~100mmol/d.

2. Fluid (Water) restriction: ONLY if Na ≤ 120-125mmol/L
3. Diuretics
o Spironolactone 100mg/d: First-Line, SE: painful gynecomastia, Hyperkaliemia Alternative (if SE):
Amiloride 5-10mg/d)
o Furosemide 40mg/d, SE: Fluid & electrolytes imbalance, Renal dysfunction.

- Aim for a daily weight loss ~0.5 kg/day, not more than 1Kg/d. If no improvement:
1. The dose of diuretics can be increased:
o Spironolactone up to 400mg/day
o Furosemide up to 160mg/day.
2. Check pt. compliance (diuretics are annoying, making pt. urinate a lot)
3. Stop alcohol
4. Stop NSAID (may cause fluid retention)
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• Prognosis:
- only ~15% survive for 5yrs. Poor: SBP (50% mortality at 1 year).
- Better: treat underlying cause of cirrhosis, precipitating cause for ascites (e.g. ↑Na intake).

• Refractory ascites:
- Ascites not responding or Not tolerating to medications/diuretic, Either:
o Failure of diuretics, pt. not responding to diuretics (diuretic resistant).
o Pt. non tolerating diuretics SE: electrolytes, renal impairment (diuretic intractable).

• Management:
1. Serial paracentesis: First Line for refractory ascites.
o You can still remove up to 5 liters in a single session without albumin infusion
o If more than 5 liters are removed, give albumin infusion 6-8 g/ liter removed.
o You can use other colloids e.g. Dextran 70%, Hemagell.
2. TIPS (Transjugular Intrahepatic Portosystemic shunt): For pts w/ reasonable liver function OR awaiting
transplant. Can aggravate encephalopathy in poor liver function pts.
3. Liver Transplantation: Pt having decompensated chronic liver disease (ascites and encephalopathy)
with no improvement.

• Spontaneous Bacterial Peritonitis:

• Pathology:
▪ Infection of ascitic fluid by bowel bacteria.
▪ ↑Risk: Low albumin, Low ascitic albumin, high PT/INR
▪ Must be differentiated from Secondary bacterial peritonitis which is due to viscus perforation
(Multiple organisms on culture)

• Manifestations:
▪ Fever, Abdominal pain, rebound tenderness, absent bowel sounds, in cirrhotic/ascitic pt.
• Investigations:
1. Ascitic fluid: Cloudy, Cells > 250 PMN cells/mm3.
2. Gram stain/culture: MC organism: E. coli.
• Management:
▪ Broad-spectrum till culture & sensitivity results.
▪ IV Cefotaxime 2 g/ 8hourly X 10 days (If resistant give meropenem)
▪ After treatment, prophylactic Cipro or norfloxacin 400 mg/d (reduce the incidence of future/recurrent
SBP & improve survival in cirrhotic pts w/ GI bleeding)

• Prognosis:
▪ If the pt. has one episode of SBP, he is prone to have more ones in the future. w/ SBP, mortality
increases, and survival is ~2 years. (50% Mortality at 1 year)
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Hereditary Hemochromatosis
- Genetic disorder of iron metabolism due to hepcidin deficiency results in Iron overload state
- Hepcidin is a protein that is synthesized by the liver to inhibit iron absorption
- Secondary hemochromatosis: excess intake of iron or excessive RBC hemolysis
• Genetics:
- Autosomal recessive disorder (usually) Leads to unregulated absorption iron
- Abnormal HFE gene (chromosome 6) →abnormal HFE protein
- The two common mutations are
1. C282Y: About 90% of patients with HH are homozygous for C282Y mutation; Cysteine-to-tyrosine
substitution at amino acid 282
2. H63D: People with H63D mutation rarely develop iron overload disorder

• Manifestations:
- Human body stores are approximately 4g.
- Clinical manifestations of iron overload usually occur when iron deposits reach 15 – 40 g.
- This usually occurs in the 5th decade
- Women present later in the 6th decade due to loss of iron in menstruation and pregnancy
- Clinical manifestations due to deposition of excess iron in various organ
o Liver: Hepatomegaly, Abnormal LFTs, Cirrhosis, Risk of hepatocellular carcinoma
o Pancreas: Diabetes
o Skin: Iron + melanin turns skin bronze “Bronze diabetes”
o Heart: Iron infiltration of myocardium → Commonly causes dilated cardiomyopathy (Less
commonly: Restrictive Cardiomyopathy).
o Joints: Arthropathy (joint pain)
o Testes: Atrophy, Decreased libido, Impotence
o Petitory: hypopituitarism
• Laboratory Tests:
▪ Iron profile
o Normal ferritin < 300 ng/ml
o Hemochromatosis can get > 1000 ng/ml
o  Serum iron,  serum ferritin, ↑ Transferrin,  (TIBC)
o ↑Fasting Transferrin Saturation (>45%), calculated as: serum iron + total iron binding capacity
▪ Genetic testing for C282Y mutation
o C282Y/C282Y genotype confirms diagnosis
▪ Liver MRI:
o Used to measure hepatic iron concentration instead of liver biopsy
o Liver turns black from iron (“low signal”)
▪ Liver biopsy:
o Needed if HFE genotyping is negative and for disease staging
o Prussian blue staining: blue granules from iron deposition

• Diagnosis: Clinical + Lab + Genotyping + MRI/Biopsy

• Management:
- Goal of treatment: reduce serum ferritin
- Asymptomatic with ferritin < 500: monitor
- Other we do either.
1. Phlebotomy (venesection)
o Aim to remove 500mL of blood weekly
o Measure Hb and Hct weekly before venesection
o Hb should be between 11 – 12g and Hct > 32 before venesection, if not postpone venesection
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o Repeated until ferritin falls within normal limits when it becomes between 50 – 100 microgram/L (this
may take >2yrs).
2. Iron chelating agents: Deferoxamine
o Is expensive and done for certain group of people (anemic, pancytopenic, and cirrhotic) or those how
cannot tolerate venesection
o injections are given every few weeks.
3. Liver transplant: in those with ESLD
4. Monitor: LFT
5. Monitor glucose/diabetes (HbA1c levels may be falsely low as venesection ↓ the time available for Hb
glycosylation.)
6. Screen for HCC with ultrasound ± AFP every 6 months (if cirrhotic).
7. First degree relative should undergo screening for HH; preventable disease at early stages by regular
venesection

• Prognosis:
- After treatment: Liver & heart improve, DM doesn’t resolve, Arthralgia can improve or worsen.
- W/out Cirrhosis or DM, Life expectancy is normal w/ treatment.
- W/ Cirrhosis, ~30% get HCC irrespective of therapy, especially if: age >50yrs (risk↑x13), HBsAg +ve (risk
↑x5), or alcohol abuse (risk↑x2).
- Venesection reduces but doesn’t abolish the risk of HCC in the presence of cirrhosis.
- Main cause of death: HCC.

• Secondary Hemochromatosis
- Commonly due to excessive blood transfusions
- Body unable to excrete excess iron
- Common in;
o Hematologic disorders that require chronic transfusion therapy, Beta thalassemia major, Sickle
cell anemia, Refractory aplastic anemia, Myelodysplastic syndromes, Leukemia
o Chronic liver diseases e.g., NAFLD, AFLD, chronic HBV/HCV infection
- Similar features of primary haemochromatosis. But Fe+ is predominantly found in Kupffer.
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Wilson’s Disease
• Genetics:
- Autosomal recessive disorder of copper metabolism
- Liver is key organ for metabolism. Excess copper excreted mostly in bile
- Copper incorporated in ceruloplasmin (transport molecule). Ceruloplasmin secreted into serum
- ATP7B: hepatic copper transport protein
o Incorporates copper into ceruloplasmin → serum
o Excretes copper into bile
- Mutation of ATP7B gene chromosome 13 > 100 mutations. Reduced biliary excretion of copper resulting
in copper overload. Copper accumulates in liver, ↑ free radical production → tissue damage in liver
- Copper spills into plasma, Increased free serum copper. Deposits in brain, cornea, kidneys, joints
- Lack of ceruloplasmin secretion into plasma → Low ceruloplasmin level (diagnostic hallmark)

• Clinical Features:
- Mean age onset 12 to 23 years
- Clinically may present with hepatic, neurological, ophthalmic, renal manifestation.
- Major features involved liver and CNS
▪ Liver Features (commoner in childhood)
o Wide range of possible liver features, Asymptomatic LFT abnormalities, Acute hepatitis, Acute liver
failure, Chronic hepatitis, Cirrhosis, High risk of hepatocellular carcinoma
▪ CNS Features (usually in 2nd-3rd decades)
o Due to deposition in the Basal ganglia (Parkinsonian features); Dyskinesia (abnormal movements),
Dysarthria (abnormal speech), Tremor
o Dementia, Depression/mania, behavioral changes
▪ Others
o Hemolysis; Related to copper in RBCs – exact mechanism unclear, Coombs-negative hemolytic
anemia
o Eye: Kayser–Fleischer (KF) rings (Copper in iris.), Sunflower Cataracts.
* Seen in 50% patients with liver disease, Seen in > 90% patients with CNS involvement
* Early lesions detectable on slit lamp exam; Kieser Fleisher rings, Sunflower cataract
o Renal: renal tubular acidosis, nephrolithiasis
o Blood: Hemolysis +/- hemolytic anemia
o Joints: Arthritis, hypermobile joints
• Investigations:
1. ↑Urine 24h copper excretion, eg >100mcg/24h (normal <40mcg).
2. ↑Serum copper: typically, <11μmol/L.
3. ↓Serum ceruloplasmin: <20mg/dL (<14mg/dL is pathognomonic)
4. ↑LFT: not specific (but ALT >1500 is not part of the picture).
5. Molecular genetic testing can confirm the diagnosis.
6. Slit lamp exam: KF rings in iris, Sunflower cataract
7. Liver biopsy: - ↑Hepatic copper (copper >250mcg/g dry weight).
- +/- Hepatitis or Cirrhosis.
* Hepatic Cu may also ↑ in Cholestatic diseases.
8. Brain MRI: degeneration in basal ganglia, frontotemporal, cerebellar, and brainstem.
 18

• Diagnosis:
- [Ceruloplasmin < 20mg/dl.] + [KF ring OR ↑24hrs Urinary Copper]
- Hepatic Cu content (by biopsy) may be necessary to confirm the dx in some cases.
- Disease should be considered in any patients < 30 years old with chronic liver disease and extra pyramidal
manifestations or hemolysis

• Treatment:
1. Zinc: reduce copper absorption, useful in pregnancy and in asymptomatic patient
2. Copper cheating agent: Penicillamine
o Starting dose of 250-500 mg/dL, increase gradually to 1-2 g daily
o Add a small dose of Vitamin B6 as penicillamine can cause deficiency of pyridoxine
o Treatment response is determined by an increase in urinary copper levels
3. Trientine is an alternative copper chelating agent with less side effects
4. Liver transplant is curative, It is indicated in those with ALF and EDLD

• Prognosis:
- Pre-cirrhotic liver disease is reversible, CNS damage is less so.
- Fatal events: liver failure, bleeding, infection.
 19

A1AT Deficiency
• Genetics:
- An autosomal co dominant disorder.
- MC genetic cause of liver disease in children. In adults, emphysema is more likely
- A1AT is a serine protease inhibitor that inhibits neutrophil proteases and elastases. It makes 90%
of serum alpha 1 globulin.
- A1AT has 3 genetic variants according to their electrophoretic mobility: medium (M), slow (S) &
very slow (Z).

• Manifestations:
1. May be asymptomatic or an exacerbating factor for other liver diseases (e.g. Alcoholic).
2. Emphysema (premature): dyspnoea.
3. Neonatal hepatitis: cholestatic jaundice, remits in adolescence.
4. Chronic hepatitis & Cirrhosis (25%): CLD
5. HCC.

• Investigations:
1.  Serum A1AT: not useful because may increase in Inflammatory conditions.
2. A1AT Genotyping & Phenotyping (electrophoresis)
3. Liver biopsy: PAS+ve, diastase-resistant, A1AT-containing globules (Confirms but not necessary).
4. Lung function tests: ↓ FEV1, ↓ FVC, ↓ FEV1/FVC less than 70%

• Management:
1. No effective medical treatment.
2. Patient should avoid smoking & alcohol.
3. Treat/ prevent (e.g. vaccinations) lung infections.
4. Liver transplantation is the only definitive treatment
5. Lung transplantation

• Prognosis:
• Worse w/ Male, obesity, smoking.
• Cause of death: Emphysema (MC), Liver disease (5%).
 20

Autoimmune Hepatitis
• Genetics:
- Autoimmune inflammation of the liver, occurs mostly in women
- Bimodal age distribution: First Peak in 20s, Second peak 50s/60s
- Associated with interference hepatitis on liver biopsy
- These conditions should be excluded
o Chronic viral hepatitis, Alcoholic hepatitis, Wilson’s disease, A1AT Deficiency, Hereditary
Hemochromatosis, Drug induced hepatitis
- It is associated w/ other autoimmune condition such as: Autoimmune thyroiditis, Thyrotoxicosis, Sjogren
syndrome, Vitiligo, Rheumatoid arthritis, and Type 1 DM
* Interference hepatitis: disruption of the limiting plate of portal tract by mononuclear inflammatory
infiltrate that extend into the acinus

• Classification: (not important anymore)

1. AIH- I (80%): typical pt (<40 yrs. female)
- ASMA +ve (80%), ANA +ve (10%), ↑IgG (97%)
- Good response to immune suppression (80%), 25% have Cirrhosis at presentation.

2. AIH- II: MCly in Children.

- Anti-LKM1 +ve, ASMA –ve, ANA –ve.
- More resistant to treatment, more commonly progress to cirrhosis.
• Manifestations:
- Range of symptoms.
1. Asymptomatic
2. Acute Hepatitis (~35%) w/ autoimmune manifestations:
- Fever, malaise, anorexia, later jaundice.
- Resembles acute viral hepatitis, but unlike it, w/out subsequent spontaneous resolution.
- Can progress to ALF/FHF.

3. Chronic Liver Disease (>60%): either:

a. Asymptomatic/Incidental.
b. Symptomatic (signs of CLD +/- Gradual jaundice)
* The disease may attenuate during pregnancy.
• Complications:
1. Cirrhosis.
2. Medications SE (treatment for long duration).

• Investigations:
1. CBC: Cytopenias (Hypersplenism)
2. LFTs: ↑Bilirubin, AST, ALT, ALP.
3. Plasma globulins: Hypergammaglobulinaemia (esp. ↑IgG): important in diagnosis & treatment response
4. Autoimmune liver disease profile/test: ANA (antinuclear antibodies; 80%), ASMA (anti-smooth muscle
antibodies; 70%), Anti-LKM1 (Anti-liver-kidney microsomal antibodies), Anti-SLA (Anti-soluble liver
antigen antibodies), and Others: p-ANCA (~50%), AMA (15%).
5. Liver biopsy (in some cases):
a. Interface hepatitis (disruption of the limiting plate) w/ Portal & periportal mononuclear infiltrate
(extends to the acinus)
b. +/- Fibrosis.
c. Cirrhosis: worse prognosis
6. Exclusion of other liver diseases is necessary for diagnosis: Viral screening –drugs.
 21

• Diagnosis: Autoantibodies +/- IgG levels + Histology + Exclusion of other causes.

• Management:
- Combination of Prednisolone and Azathioprine is the preferred treatment in majority of patients.
- Prednisolone monotherapy is preferred in pregnancy and in patients with severe cytopenia
- Treatment should be maintained for a minimum 2 years before considering drugs withdrawal
- Liver biopsy confirming histologic resolution & excluding of active disease is essential before drug
withdrawal
- Most of pt. continues treatment for many years.
1. Prednisolone
o PO 30mg/d for 1 month, then ↓by 5mg a month to a maintenance dose of 5-10mg/d.
o SE: Infections (acute), HTN, DM, osteoporosis (long term).
2. Azathioprine 1.0–2 mg/kg/day PO:
o Steroid-sparing drug, to maintain remission.
o SE: immunosuppression, cytopenias.
3. Liver Transplantation:
o Indications: a. Decompensated cirrhosis. b. Failure to respond to medical therapy.
o Recurrence may occur.

• Prognosis:
- 10yrs survival is ~80% whether symptomatic or not at presentation.
- Poor: a. Cirrhosis at presentation. b. AIH-PBC overlap syndrome (worse than AIH-AIC overlap).
 22

Viral hepatitis

• Etiology:
- Most common cause are Hepatitis viruses (A, B, C, D, E).
- All cause acute liver inflammation. Some cause chronic infection. Can lead to cirrhosis or
hepatocellular carcinoma

• Laboratory Testing
1. Increased AST/ALT [ALT usually > AST Contrast with alcoholic hepatitis AST>ALT]
2. Increased bilirubin
3. False positive VDRL: Viral hepatitis is common cause of false positive VDRL. Don’t confuse with
syphilis

• Spectrum
1. Acute Hepatitis: Asymptomatic – Symptomatic Anicteric – Icteric.
- Presentation:
a. Early/Nonspecific (Prodromal) symptoms: Malaise, Anorexia, N&V, Arthralgia, Headache, +/-
Fever.
b. Late/Specific: Jaundice, Hepatomegaly, RUQ pain, Splenomegaly, Adenopathy, Pruritus, dark
urine
- Lab: Bilirubin < 10 mg/dL, AST/ALT 500-5000 U/L.
- Management:
a. Supportive as outpatient unless severe vomiting or anorexia requires admission and IV fluids.
b. Bed rest, No dietary restriction.
c. Avoid alcohol, unnecessary drugs.
d. Cholestyramine for pruritus.
2. Acute/Fulminant Liver Failure.
3. Cholestatic Hepatitis:
- Presentation: Prolonged deep jaundice, dark urine, pale stools, pruritus, Hepatomegaly +/-
splenomegaly.
- Lab: bilirubin >20 mg/dL, ↑ALP
- Management: Commonly seen w/ HAV. Has a good prognosis. Management includes, Cholestyramine
for pruritus, Ursodeoxycholic acid.
4. Relapsing Hepatitis:
- MC w/ HAV.
- Symptoms & LFTs recur 6-10 wks after apparent recovery from acute hepatitis.
- Good prognosis w/ complete recovery.
5. Chronic Carrier
6. Chronic Active Hepatitis: Asymptomatic/Symptomatic
7. HCC
 23

Hepatitis A
• Transmission:
- Drinking contaminated water, Consumption of raw sea food
- Personal contact (sexual, drugs)
- Common in underdeveloped countries with Poor sanitation. MC in Childhood.

• Manifestations:
- Incubation: ~30 days
- Acute Hepatitis (MC: Asymptomatic). Jaundice is rare in children. Symptomatic disease and mortality are
more in adults.
- Cholestatic hepatitis: prolonged intrahepatic cholestasis w/ Choleric Jaundice

• Complications:
1. Fulminant Hepatic Failure
2. Prolonged Cholestasis w/ Hi ALP (cholestatic hepatitis)
3. Relapsing Hepatitis (10%)
4. Others (Rare): arthritis, vasculitis, myocarditis, AKI.

• Investigations:
- CBC: Leukopenia w/ relative lymphocytosis.
- LFT: AST, ALT (>1000 U/L)
- Virology: Acute disease: Anti-HAV IgM plus symptoms. Prior disease: Anti-HAV IgG, HAV RNA in faces

• Management:
- Self-Limiting.
- Supportive as outpatient unless severe vomiting or anorexia requires admission and IV fluids.
- Bed rest, no dietary restriction, Avoid alcohol, unnecessary drugs.
- Cholestyramine for pruritus.

• Prevention:
1. Improving personal Hygiene, sanitary practices, Boiling of drinking water (not Chlorine)
2. Vaccination:
- Inactivated vaccine is available, 1 dose gives 1 year immunity, but 20 year if booster is given w/in
6- 12 months.
- Considered for vaccination: Close contact, Travellers, Chronic Liver Disease (e.g., HBV, HCV),
Elderly, +/- Pregnant.
3. Post-exposure prophylaxis (w/in 2 wks): Normal Human Immunoglobulin +/- Vaccine
 24

Hepatitis E
• Transmission:
- Faeco-oral, contaminated food (pig), Water-borne epidemics.
- MCC sporadic hepatitis in young adults in developing countries.
- MC Viral Hepatitis in Sudan.

• Manifestations:
- Incubation period: ~40 days.
- Acute Hepatitis: self-limiting.
- Acute Liver Failure in pregnancy.
- Chronic Hepatitis in immunocompromised pts (organ transplant).

• Complications:
- Hepatic failure and & High mortality (15%) in pregnant women.

• Investigations:
- LFT: AST, ALT (>1000 U/L)
- Serology: IgM antibodies to HEV, HEV RNA in serum or faces
• Management: Nothing specific, Ribavirin may be used for chronic hepatitis.
• Prevention: Vaccine (China).
 25

Hepatitis B
• Transmission:
1. Sexual contact
2. IV (drug use, transfusion, needle stick)
3. Maternal-fetal; Especially in mothers with acute disease in 3rd trimester. Perinatal is the MCC (90%) of
infection worldwide & carries the highest risk of chronicity.
▪ Risk groups: IVDU, Homosexual men, hemophiliacs, hemodialysis, babies of HBsAg +ve mothers, Health
workers and their partners/contacts.

• Clinical Features:
1. Incubation: 1-6 months.
2. Acute hepatitis:
o 70% anicteric hepatitis: MC = Asymptomatic or mild hepatitis [Arthralgia & Urticaria are common
(>HAV)]
o 30% icteric hepatitis
o <1 % progress into Fulminant hepatic failure
o Recovery from acute HBV infection occurs within 6 months and is characterized by the
appearance of antibody to viral antigens. Persistence of HBeAg beyond this time indicates
chronic infection.
3. Chronic Hepatitis B: HBsAg +ve > 6 months.
o Progression from acute → chronic depends on age
▪ 90% peri-natal
▪ 50% children
▪ < 5% adults
o Many chronic infections asymptomatic (carriers)
o Risk of progression to: Cirrhosis, Liver failure, Hepatocellular carcinoma or Reactivation (acute
hepatitis)

• Natural History:
- Following acute infection: 90% of neonates / 50% of infants / 5 % of adults develop Chronic.
- Full recovery occurs in 90–95% of adults following acute HBV infection. The remaining 5–10% develop a
chronic hepatitis B infection.
- 5–year cumulative incidence of Cirrhosis in untreated patients is 8–20%. 5–year cumulative risk of
decompensation in cirrhotic patient is 20%. Annual risk of HCC is 2 – 5%
- Chronic infection is also common w/ immunodeficiency, e.g., Down’s syndrome, HIV.

• Complications & Extrahepatic Manifestations:

1. Fulminant hepatic failure (rare) 2. Cryoglobulinaemia
3. Cirrhosis 4. Membranous nephropathy
5. HCC 6. Polyarteritis nodosa
7. Cholangiocarcinoma 8. Gianotti-Crosti Syndrome

• Investigations:
o Serology:
1. HBsAg: Active infection (acute or chronic).
2. Anti-HBs: Immunity.
3. Anti- HBc IgM: Recent/acute infection.
4. Anti- HBc IgG: Past infection (If + HBsAg= Chronic infection, If + Anti-HBs= Resolved infection)
5. HBeAg: Replication, infectivity
6. Anti-HBe: Low infectivity
 26

o LFTs: Transaminases: elevation indicates active liver disease.

o PCR: HBV DNA: monitor response to Rx.

• Management:
o Goal/Aim:
1. Clear HBsAg 2. HBeAg seroconversion
3. Reduce viral load 4. Normalise LFTs
5. Prevent Cirrhosis & HCC.
o Acute:
1. Supportive
2. Monitor for Acute Liver Failure.

o Chronic:
1. PEGylated Interferon alpha: SC
- For 12 months. Has several SE.
- Most effective in pts. w/ Low Viral load & High transaminases.
- Better response in HBeAg +ve, genotypes A & C
- Contraindicated in advanced Cirrhosis.
- Expensive
2. Nucleoside/Nucleotide analogues (Oral Direct Acting Antivirals):
- Longer term (Lifelong), Better tolerated (Few SE).
- Better response in HBeAg –ve. All genotypes (A-H) respond equally.
- Lamivudine: Resistance after ~9 months
- Entecavir, Tenofovir: Resistance in 2% after ~3 yrs.
* Monotherpay w/ Entecavir or tenofovir is contraindicated in HIV+ve pts.
3. Transplantation w/ post liver transplant prophylaxis to prevent re-infection.
4. Follow up

• Indication for treatment

- Not all patients with chronic HBV require treatment. However, all patients require close monitoring
- All 1st degree relative and sexual partner of chronic HBV infection should be tested for HBV marker, and if
negative should be vaccinated
- Indication of treatment:
1. HBeAg positive: HBV DNA > 10,000 – 100,000 IU/mL, ALT > ULN (upper limit of normal), at least
moderate necroinflammation or fibrosis.
2. HBeAg negative: HBV DNA > 2000 IU/ml, ALT > ULN (upper limit of normal), at least moderate
necroinflammation or fibrosis.
3. HBV DNA > 20,000 IU/mL and ALT 2x Upper normal limit regardless of fibrosis.
4. All compensated or decompensated cirrhotic pts w/ detectable HBV DNA regardless of ALT.
5. Pts requiring Immunosuppression (e.g. IBD) or Chemotherapy.
6. Pregnant w/ high viral load > 200,000 IU/ml. (prevent MTCT)

• Discontinuation of therapy:
▪ In HBeAg positive
1. Loss of HBsAg.
2. HBeAg Seroconversion & development of Anti-HBe.
3. Undetectable HBV DNA.
4. Complete 12 months of consolidation therapy.
▪ In HBeAg negative: Loss of HBsAg
 27

• Prevention:
1. Application of infection control measures
2. Vaccination 3 doses: at 0, 1 & 6 months.
3. Post-exposure prophylaxis: Hepatitis B Immunoglobulin (HBIg) +/- Vaccine. For: neonates to HBsAg +ve
mothers, after exposure (e.g., needle stick injury)
4. Post- Liver Transplant Prophylaxis: Direct Antivirals + HBIg.

• Note
- HBeAg reflect the replication and infectivity of HBV (could be highly replicating virus or low), however, In
Sudan 90% of pts. with HBV infection are HBeAg –ve (due to mutation), so we can know if the pt. has
ongoing liver disease by measuring liver enzymes
- If HBeAg –ve viral load above 2,000 is considered high.
- If HBeAg +ve viral load could be very high one million or 10 million or even more
 28

Hepatitis C
• Transmission:
1. Blood (transfusion, IVDU, needlestick, sharing toothbrushes)
2. Sexual
3. Vertical.

• Natural History:
- Following acute infection, ~85% develop silent chronic infection.
- Cirrhosis develops in ~25% of pts. in 20yrs w/ 4% annual risk of HCC.
- Risk factors for progression: Male, Older, Alcohol, High viral load, HIV, HBV, Immunosuppression,
prothrombotic states.

• Manifestations:
1. Incubation: 15 days – 6 months
2. Acute Hepatitis: Asymptomatic
3. Chronic Carrier State
4. Chronic Hepatitis: asymp/fatigue, mild or nonspecific symptoms
5. Cirrhosis, HCC

• Complications & Extrahepatic Manifestations:

1. Cirrhosis 2. HCC 3. Glomerulonephritis

4. Cryoglobulinemia 5. Autoimmune hepatitis 6. PAN
7. Thyroiditis 8. Polymyositis 9. Porphyria cutanea tarda

• Investigations:
1. LFT: Normal or fluctuating <200 U/L.
2. Serology: Anti-HCV: appears 6-12 wks. after infection & persists.
3. PCR: HCV RNA: appears after only 2-4 wks.
4. Fibroscan: F0-F4
5. Liver biopsy.

- All pts. w/ CLD should be screened for HCV.

- Screen w/ Anti- HCV serology (confirms exposure), Confirm by HCV RNA PCR (confirms ongoing/active
chronic infection) Then, to determine treatment plan;
1. Assess degree of liver fibrosis: Fibroscan, FIB4 score, Metavir system, Biopsy.
2. Determine Genotype (1-6): PCR. MC genotypes in Sudan are 1 & 4.
- Genotypes 1 can be 100% treated w/ DAA.
- Genotypes 2 & 3 may require Ribavirin.
- Genotypes 4, 5, or 6 are prevalent in lower-income countries.
- If genotype can’t be determined, start Pangenotypic Treatment

• Management:
1. Interferon: Long duration (~12 months), Poor tolerability (Flu-like, depression, irritability) & compliance &
Poor response (esp. w/ genotype 1).
2. Direct Acting Antivirals: superior to interferon, used in Combinations:
a. Sofusbuvir + Ledipasvir + Ribavirin: ~12wks.
b. Sofusbuvir + Velpatisir: (Pan-genotypic)
3. Ribavirin (Nucleoside analogue): Reserved for genotypes 2 & 3. SE: anemia, teratogenic.
4. Liver transplantation: 15% re-infection of the graft.
 29

• Indications for treatment:

- Treat ALL patients (Sustained detectable HCV RNA), Especially & Urgently:
o Pts w/ F2, F3, F4 fibrosis.
o Pts w/ extrahepatic manifestations (Vasculitis, Cryoglobulinemia, Nephropathy, NHL).
▪ Duration of treatment:
o Non-cirrhotic: 8-12 wks.
o Cirrhotic: 24 wks. OR 12 wks. w/ + Ribavirin
▪ Goal of treatment:
o To eradicate the infection by achieving sustained viral response (SVR).
o Prevent complications (Cirrhosis & HCC).
* SVR 12: Undetected HCV RNA 12 wks. after end of therapy.
 30

CASE 1
55-year-old man presented with a 6\12 history of fatigue and ankle swelling. On examination he has
a tinge of jaundice, clubbing, palmar erythema, Dupuytren’s contractures, spider nevi,
Gynecomastia, liver span 6cm and splenomegaly

1. What is your diagnosis?

Chronic liver disease

2. What investigation would you do?

▪ CBC:
o Normocytic normochromic anemia → recent GI Hemorrhage
o Microcytic hypochromic → chronic blood loss
o Macrocytosis → Alcohol
o Pancytopenia due to Hypersplenism, but Platelets are more depressed due to
Decreased production. (No Thrombopoietin)
▪ LFT, INR, RFT.
▪ U/S: see ascites, liver size and texture liver, tumors, portal and splenic diameter (portal HTN)
▪ Upper GI endoscopy: see varices.
▪ Specific tests: viral Ags /Abs.

3. If the investigations were as the following

Total protein 6.0g/dl, Albumin 2.9g/dl, Bilirubin 3.0g/dl, ALT 198 IU/L, INR 1.5.
US: shrunken coarse texture liver, dilated portal and splenic veins no ascites, mild esophageal
varices.
How severe is his liver disease?
We use Child-Truscott-Pugh Classification for severity of liver cirrhosis:

Parameter 1 2 3
Ascites None Slight Moderate/severe
Encephalopathy None Grade 1-2 Grade 3-4
Albumin g/dl >3.5 2.8-3.5 <2.8
Bilirubin <2.0 2-3 >3.0
PT sec 1-3 4-6 >6
INR <1.7 1.7-2.3 >2.3

o Has 5 parameters: Albumin, bilirubin, PT, ascites, encephalopathy.

o 3 classes: A: Mild. (5-6) B: Moderate. (7 - 9) C: Severe. (10 - 15)
o It gives a prognostic measure, poor prognosis with class C
▪ Child class A: survival same as normal population if get depleted, undergo
surgery, etc.
▪ Child class B: if undergo surgery survival is 33%
▪ Child class C: if undergo surgery mortality is more than 70%
So in this pt. is child class B
o No encephalopathy (1), No ascites (1), Albumin 2.9 g/dl (2), Bilirubin 3.0 mg/dl (2), INR
1.5 (1)
 31

CASE 2
HBsAg +ve HBeAg –ve HBcAg IgG +ve HBV DNA: 38,000 U/ml
In this patient score is 7 [moderate liver disease]
1. How to manage this pt.?
Nucleoside/nucleotide analogues: Tenofovir or Entecavir
Pegylated interferon (SC) expensive.

CASE 3
HCV Ab +ve ~ HCV RNA +ve ~ Genotype 4 ~ Liver biopsy – fibroscan (F4)
1. How to manage this pt.?
Interferon free therapy: Directly acting anti-viral (DAA)
Interferon based therapy: Pegylated interferon (SC)
Ribavirin PO
2. What are the Liver biopsy contraindications?
A. High INR > 1.5 (PT GIVEN fresh frozen plasma).
B. Ascites (floating liver).
C. Thrombocytopenia < 80/100.
D. BIOPSY is difficult here because the liver size is SMALL.
 32

Hepatic encephalopathy
- Occurs in patients with acute liver disease or in those with chronic liver disease (cirrhosis).
- A clinical diagnosis is made in patients with liver disease when there is:
1. Alteration in consciousness
2. Generalized movement disorders

• Alteration in consciousness
o Grade I: mild confusion, sleep disturbance
o Grade ll: drowsy, intermittent disorientation
o Grade Ill: somnolent (sleepy), gross disorientation
o Grade IV a: coma, but arousable by painful stimuli
o Grade IV b: coma, unresponsive
• Generalized movement disorders:
o Constructional apraxia (inability to do simple learned tasks; can’t draw a circle)
o Slow monotonous speech
o Flapping tremors (Astrexis)
o Hyper-reflexia
o Muscle rigidity
o Extensor plantar response (bilateral positive Babinski sign)
 33

Acute Liver Failure

• Definition:
1. Encephalopathy within 8 – 12 weeks of onset of jaundice
2. No prior evidence of liver disease (normal liver with no cirrhosis, no alcoholic liver diseases, no chronic HBV
infection)
o If there is cirrhosis and the patient develops hepatic encephalopathy = this is called
decompensated cirrhosis
o Wilson’s disease may present with acute liver failure which is an exception of the rule.

• Causes of acute liver failure

1. Viral hepatitis: Hepatitis A, hepatitis B and hepatitis E or EBV, CMV and HSV.
2. Infections: Yellow Fever, Leptospirosis, Severe Malaria.
3. Autoimmune hepatitis
4. Alcoholic hepatitis (acute on chronic)
5. induced hepatitis: Acetaminophen overdose, anti TB, antiepileptic, anti-depressants
6. Toxins: amanita phalloides, CCl4, organic solvents
7. Ischemia (“shock liver”)
8. Budd-Chiari, acute circulatory failure, heat stroke
9. Wilson disease

• NOT Causes of Acute Liver Failure

1. Non-alcoholic fatty liver disease
2. Hemochromatosis
3. Alpha-1 antitrypsin deficiency
4. Primary sclerosing cholangitis
5. Primary biliary cholangitis

• Etiology in Sudan:
1. Seronegative hepatitis (viruses which we are not screen for them routinely)
2. HBV / HEV
3. Antituberculous drugs
4. Autoimmune hepatitis
5. Severe plasmodium falciparum malaria

• Sub classification of FHF:

• Hyper – acute: onset of jaundice – encephalopathy is 0 – 7 days (better prognosis quick recovery may
occur).
• Acute: onset of jaundice – encephalopathy 8 – 28 days
• Sub – acute: onset of jaundice – encephalopathy is more than 28 days (the worst, pt. Present late with
complete damage)

• Poor prognostic features:

1. Non – A, non – B hepatitis
2. Drug Induced
3. Jaundice – encephalopathy interval more than 7 days
4. Grade lll/lV encephalopathy at presentation
5. Age < 10 years & > 40 years
6. Prolongation of prothrombin time > 25-50 sec over the control (INR > 3.5)

• Mortality of acute liver failure in Sudan is more than 90%

 34

• Clinical Features:
- Fatigue, Weakness, Lethargy, Confusion
- Jaundice, Hepatomegaly, RUQ pain
- Elevated AST/ALT, Prolonged PT/PTT
- Thrombocytopenia (loss of TPO)

• Diagnosis:
• Requires:
1. Elevated AST and ALT
2. INR ≥1.5 (prolonged prothrombin time)
3. Evidence of hepatic encephalopathy
• Supportive findings:
1. Hyperbilirubinemia
2. Low platelets
3. Ultrasound to exclude Budd Chiari
4. Blood glucose level
5. RFT
6. CBC
7. Investigation for the cause: viral screening, ICT for Malaria, etc.…

• Complications of acute liver failure:

1. Cerebral Edema (cause of death) -> first complication
2. Hypoglycemia
3. Hepatorenal syndrome/AKI
4. Bleeding (mainly variceal)
5. Metabolic Acidosis
6. Sepsis
7. Stress ulcers

• Management of acute liver failure

1. Admission to ICU
2. NG tube with 4 things through GI tract:
a. PPI: Ulcers Prophylaxis
b. Antibiotic: neomycin, metronidazole or rifaximin → decrease ammonia production from GIT bacteria
c. Bowel enema: empties the bowel from stagnant stool and meals → decreases bacterial overgrowth
and ammonia production
d. Lactulose: induces diarrhea and is converted to lactate (negatively charged) which combines with
NH3 (ammonia) to form NH4+ which doesn’t cross the membranes
3. 4 things IV:
a. 10% dextrose: to prevent Hypoglycemia
b. Mannitol 20% (+/-hyperventilation): for Cerebral Oedema
c. Empiric IV Ceftriaxone to grade against sepsis
d. Vit K. or FFP for bleeding
4. Treat the cause (e.g. N-acetylcysteine for paracetamol overdose).
5. Monitoring:
a. Vital signs + Pupil + Urine output hourly.
b. Blood sugar every 1-4 Hrs.
c. CBC, LFT, RFT, PT/INR, Weight Daily
6. Liver transplantation
7. HRS: Hemofiltration, Hemodialysis, or Transplant
 35

CASE
A 50-year-old housewife presents with a 2 Week history of vague epigastric pain, nausea, vomiting and
headache. She received anti-Malarial treatment despite having a negative BFFM without improvement. Over
the past 5 days she noticed dark discoloration of her urine.
O/E: she is ill, jaundiced, pulse 110/min, BP 100/60, liver is palpable 4 cm BCM, liver span 14 cm (normal 8-12
cm), no splenomegaly or ascites.

1. What questions would you like to ask?

- Drug history, Alcohol consumption, Blood transfusion
- History of Contact
- Vaccination status (viruses which have vaccines: B, A, E)
2. What are the investigations you would ask for?
- General investigations:
▪ LFT 's and enzymes, PT/INR
▪ RFT, CBC, RBG
▪ Ultrasound abdomen (to rule out any obstruction)
▪ Urine analysis
- Specific:
▪ HAV− IgM, HBsAg, HBcAb IgM
▪ HCV Ab, PCR
3. If the Results was as the following:
Serum bilirubin: 10 mg/dl, Direct bilirubin: 7.3 mg/dl
T protein: 6.6 g/dl − Albumin: 3.8 g/dl −
ALP: 280 IU/L (up to 217)
AST: 600 IU/L (up to 40), ALT: 900 IU/L (up to 35/19)
INR: 1:1
CBC - RFT - RBG – Ultrasound was normal
HEV IgM +ve
4. What is the diagnosis?
- Acute viral hepatitis (HEV)

5. How to manage this patient

- Admission, IV fluids, 5 - 10% dextrose, Avoid unnecessary medications
- Home when vomiting stops, bed rest, No restrictions regarding food
The Patient improves and she is discharged home 4 days later. Readmission 2 weeks later; Unwell, confused,
agitated, drowsy, deeply jaundiced, temperature 38°C (febrile), flapping tremors, brisk reflexes.
INR 4.0 (synthetic function get impaired), TWCC 12,000, creatinine 1.3 mg/dl, RBG 70 mg/dl.
6. What is the diagnosis?
- Hepatic encephalopathy
- Febrile + high total WBCs → infection (in patients with hepatic encephalopathy mortality increases
when they become infected esp. Respiratory and urinary tract infections so administration of broad-
spectrum antibiotic is important).
- RBG 70mg/dl → hypoglycaemia (patients with acute liver failure have impaired gluconeogenesis).
7. What happened to our lady?
- Despite all measures she deteriorates.Urine output drops, creatinine rises, and she becomes
unconscious. [Hepatorenal syndrome]
- She is intubated, ventilated and undergoes hemodialysis.
8. What is her prognosis?
- Very bad, terrible
- You can do liver transplant.
 36

ALCOHOLIC & NON-ALCOHOLIC LIVER DISEASE

Alcoholism
- 1 unit of alcohol contains 8 g of ethanol
- 5 units/day carry little risk on the human body, 10 units/day carries medium risk & 20 units/day
carries high risk
- In some patients it affects the liver, in others it affects the brain or/ and the muscles. These
differences may be genetically determined.
- The amount of alcohol that produces damage varies from one person to another. However,
Effect of a given alcohol intake is worse in women
• Three ways alcohol (ethanol) can damage liver
1. Alcoholic fatty liver disease (Alcoholic Steatosis)
2. Alcoholic hepatitis
3. Alcoholic Cirrhosis
* Only 20% of those with heavy alcohol consumption will develop cirrhosis

- Risk factors: Drinking pattern (continuous), Females, Genetics (PNPLA3, Adiponutrin), Obesity.
- Steatosis → Steatohepatitis → Steatofibrosis & Cirrhosis

• Alcoholic Fatty Liver Disease (Alcoholic Steatosis): (95%)

• Pathogenesis:
- Ethanol metabolism by Alcohol & Acetaldehyde dehydrogenases generates ↑NADH leading
to ↓FA oxidation and Lipid catabolism while ↑Lipogenesis.
- Ethanol impairs Lipoproteins assembly & secretion.
• Morphology:
- Accumulation of fatty acids in liver, the cells become swollen with fat (Steatosis).
- Steatosis starts centrilobular (zone 3), then spreads outward.
- No hepatocyte injury.
- Enlarged soft yellow greasy Liver.
• Manifestations:
- Usually asymptomatic, hepatomegaly maybe It discovers incidentally on examination
- Fat disappears on stopping alcohol.
- LFT: normal
- May developed ↑ALP, GGT, bilirubin (intrahepatic cholestasis).
- ↑ risk of cirrhosis

• Diagnosis:
- CT or ultrasound: fatty infiltration appears as bright area that altered darkness of liver
- Liver Biopsy for definitive diagnosis (rarely done)
 37

• Alcoholic Hepatitis (Alcoholic Steatohepatitis): (30%)

• Pathogenesis:
- Due to hepatocyte injury by alcohol & its metabolites:
o Alcohol directly affects mitochondrial function & membranes.
o Acetaldehyde → lipid peroxidation, protein adducts → disrupts cytoskeleton &
membranes.
o Ethanol oxidation (+infiltrating neutrophils) → ROS → damage proteins & membranes.
- - +/- Gut microbiome may contribute.
• Morphology:
1. fatty change, PMNL infiltration
2. Hepatocytes (esp. Centrilobular) ballooning and necrosis.
3. Eosinophilic cytoplasmic inclusions [Mallory bodies]
• Manifestations:
- Patient may be asymptomatic
- Nay be very ill with jaundice and Feature of portal HTN (Ascites).
- Acute Liver Failure.
- If alcohol consumption continues this will progress to cirrhosis. So stop alcohol for
management
- 30% of pts. Die.
• Investigations:
1. CBC: ↑MCV
2. LFT: ↑Bilirubin, ↑ALP, ↑AST & ALT (<500), AST:ALT ratio >/= 2:1.
3. ↑ INR
4. US: shows fatty infiltration appears as bright area that altered darkness of liver
5. Histopathology show Mallory bodies or frank cirrhosis
*All these are not specific for alcohol, but they occur in alcohol

• Treatment:
1. Stop alcohol
2. IV thiamine
3. Treat withdrawal symptoms with diazepam
4. Glucocorticoids can be used: Usually for patients with severe disease; Elevated PT/PTT or
very high bilirubin
 38

• Alcoholic Cirrhosis: (15-20%)

• Morphology:
- Classically micro nodular, but may be mixed
- Brown shrunken non-fatty cirrhotic liver
• Manifestations:
- Often presents w/ signs of CLD e.g., Variceal bleeding, Ascites. [Decompensated CLD]
- Hepatomegaly (although cirrhosis).
- Other systems may also be involved (like dementia, peripheral neuropathy …)
• Complications:
1. Decompensation, ESLD
2. HCC (15%)
3. Others: Alcohol can enhance the effects of the toxic metabolites of drugs (e.g. paracetamol)
on the liver.
• Investigations:
- Establish alcohol misuse + exclude alternative or coexistent causes of liver disease + assess
the severity of liver damage
1. CBC: (↑MCV supports alcohol misuse), Anemia
2. LFT: ↑GGT
3. Liver US: Steatosis.
4. Liver Biopsy: to assess extent of damage
5. Glasgow alcoholic hepatitis score, Maddrey score (Discrimination Factor): for Prognosis.
• Management:
- Life-long Alcohol abstinence: Most important treatment and prognostic factor.
- Nutrition, enteral feeding.
- IV Thiamine
- Prednisolone
- Beware/Treat Alcohol withdrawal & Wernicke’s Encephalopathy [give diazepam]
- Treatment of alcohol dependency
- Liver transplantation
 39

Non-alcoholic Fatty Liver Disease [NAFLD]

- Fatty infiltration of liver not due to alcohol.
- The MC liver disorder in Western countries (prevalence: 25%).
- It’s etiologically associated with metabolic syndrome like obesity, diabetes, HTN and
Hyperlipidemia
- Other etiologies:
o Drugs: estrogen [OCPs], steroids, chloroquine.
o Surgical alterations of GI Tract: gastric bypass, jejuno-ileal bypass.
- Steatosis → NASH →Steatofibrosis & Cirrhosis.

• [A] Steatosis:
• Pathogenesis:
- Obesity & insulin resistance mobilize FFA from adipose tissues to accumulate in hepatocytes.
(>50%)
- In addition, they ↑ FA synthesis w/in hepatocytes (the remainder <50% of fat)
• Manifestations:
- MC: Asymptomatic (Incidental abnormal LFT, sometimes even LFTs are normal)
- Fatigue, RUQ discomfort.
• Investigation:
1. LFT: Usually normal
2. Non-invasive imaging: ultrasonography, fibro-scan (it tells you the stage of steatosis and
fibrosis), CT scan, MRI.
3. Liver biopsy is not necessary.
* Always ask about diabetes maybe they don’t control, or they didn’t discover diabetes .so
check Hba1c and fasting blood glucose and you will find high glucose or frank diabetes and
the p.t is not aware
• Complications: NASH, Cirrhosis

• [B] Non-Alcoholic Steatohepatitis (NASH):

• Pathogenesis:
- ↑ Intrahepatic lipids & their metabolites → ↑ Hepatocytes sensitivity to inflammatory
cytokines which’re already ↑in Metabolic Syndrome.
- ↑ROS, oxidative stress (↑FA oxidation)
- → Cell injury, death & Inflammation → Steatohepatitis.

• Manifestations:
- MC: Asymptomatic (incidental ↑LFTs; see investigations)
- Fatigue, RUQ discomfort.
• Investigations:
1. LFT: AST and ALT < 500, however ALT > AST
2. Non-invasive imaging: ultrasonography, fibro-scan (it tells you the stage of steatosis and
fibrosis), CT scan, MRI.
3. Liver biopsy: may be necessary if liver enzymes (AST, ALT) are elevated, This may show
steatosis, Inflammation, Mallory bodies and fibrosis.

• Complications: This may progress to fibrosis and liver cirrhosis

 40

• Cirrhosis:
• Pathogenesis:
- Chronic liver injury & inflammation activates Stellate cells (TGF-B) → Steato-fibrosis &
Cirrhosis.
• Manifestations: CLD
• Complications:
1. Decompensation, ESLD
2. HCC
- Risk factors for disease progression: age >45yrs., DM/Insulin resistance, BMI >30, HTN.
• Investigations of NAFLD:
- Exclude Alcoholic & other liver diseases, then Confirm NAFLD & determine its stage and extent
(simple steatosis/ NASH/ fibrosis/ Cirrhosis).
1. LFT: AST & ALT (< 2xUNL). ↑GGT.
2. Non-invasive imaging: ultrasonography, Fibro-scan, CT scan, MRI.
3. NAFLD Fibrosis Score, FIB-4 Score.
4. Liver Biopsy: The gold standard for dx & assessment of inflammation & fibrosis.
5. ↑Ferritin
* Note: Imaging cannot differentiate steatosis from NASH.

• Management of NAFLD:
- No specific pharmacologic agents.
1. Lifestyle modification (diet & exercise) to achieve obesity reduction & reversal of insulin
resistance.
2. Insulin-sensitising agents (Glitazones).
3. Treat coexisting dyslipidaemia (e.g. Statins, Bezafibrate).
4. Treat coexisting HTN.
5. High dose vitamin E (SE: ↑Mortality, prostate CA).
6. Beware & screen for ↑Cardiovascular risk in these pts.
7. Screen for HCC.

-
 41

Drug-Induced Liver Injury

- Incidence: 2-5%. Mechanism: Direct toxicity, hepatic activation of pro-toxin or Immune
(hapten).
- There are 2 types of injurious drugs: Intrinsic hepatotoxins & Idiosyncratic-dependent
hepatotoxins.

• Type 1: Intrinsic hepatotoxins:

- Dose dependent
- Predictable action
- Experimentally reproducible in animals
- Occurs after a short & relatively consistent period.
- E.g., Paracetamol, CCl4

• Type 2: Idiosyncratic-dependent hepatotoxins:

- Not dose-dependent
- Not experimentally reproducible
- Lower incidence
- Occurs after a latent period (may be long/variable)
- Injury is either:
1. Hypersensitivity reaction (HSR) e.g., Halothane
2. Unpredictable metabolism abnormalities leading to accumulation of toxic metabolites
e.g., INH, Phenytoin, Sulphonamides, Chlorpromazine.

• Morphologic changes caused by drug-induced injury:

1. Acute/subacute injury: Produces a syndrome resembling viral hepatitis Or Cholestasis
resembling obstructive changes.
any pt. with jaundice always asks about drug history, if you suspect that a drug may be a cause
of liver damage stops it and expect regression of symptoms and you must do follow up
investigations.
2. Chronic injury: steatosis, chronic hepatitis, Cirrhosis, vascular diseases
(Venooclusive, Hepatic vein thrombosis), neoplasms.

• Clinical features:
- Some hypersensitivity related hepatotoxins such as sulphonamides may produce hepatic injury
accompanied by systemic manifestations e.g., fever, rash, arthralgia, lymphadenopathy, and
eosinophilia
- Other hypersensitivity related drugs such as chlorpromazine, erythromycin, estolate, and
halothane may or may not be accompanied by systemic features
- Drugs causing damage by production of toxic metabolites have a latent period of days-months.
They do not produce fever, rash, or eosinophilia.

• Diagnosis:
1. Exclude viral infections, alcohol use, biliary obstruction, pre-existing liver disease.
2. Symptoms are related to the onset of drug intake
3. HSR manifestations such as fever, rash, eosinophilia may produce helpful clues
4. Liver biopsy may occasionally be helpful.
 42

• Management:
1. Withdrawal of the drug.
2. Supportive management.
3. LFT return to the normal after drug withdrawal
4. Never attempt a re-challenge as this could be fatal (e.g., HSR). [Anti-tuberculous drugs are
exception. when LFT return to the normal you can re-challenge by introducing your anti-
tuberculous drugs separately (with low doses) to know which drug cause the problem]

Acute Drug-Induced Liver Injury:

Disorder Hepatotoxic Drug
Hepatitis-like Rifampicin, INH Pyrazinamide, Indomethacin, Phenytoin,
Sulfonamides.
Acute liver failure Paracetamol, ketoconazole, halothane, INH, methyldopa

Cholestasis Amitriptyline, Septrin, Carbamazepine, Ampicillin, Captopril

Chlorpromazine, Ranitidine

Budd-Chiari syndrome Oestrogen

Chronic Drug-Induced Liver Injury:

Disorder Hepatotoxic Drug
Chronic active hepatitis INH, Methyldopa, Nitrofurantoin
Fibrosis/ cirrhosis Methyldopa, INH, Methotrexate
Steatosis Tetracyclines, Sodium Valproate
Steatohepatitis Amiodarone, Total Parenteral Nutrition
Venous outflow obstruction Azathioprine, Cyclophosphamide

Oncogenic Drugs:
Disorder Hepatotoxic drug
Cholangiocarcinoma Thorotrast
FNH OCPs
Hepatic adenoma OCPs
HCC Alcohol, Anabolic steroids
Hepatoblastoma Oestrogens
 43

CHRONIC LIVER DISEASES

Causes
1. Chronic HBV\HCV infection. 2. Hemochromatosis.
3. Wilson disease 4. Alfa 1 anti-trypsin deficiency.
5. Cholestatic liver disease. 6. Budd-chiari syndrome.
7. Alcoholic liver disease. 8. Nonalcoholic steatohepatitis (NASH)
9. Autoimmune hepatitis.

HBV
• Transmission:
4. Sexual contact
5. IV (drug use, transfusion, needle stick)
6. Maternal-fetal; Especially in mothers with acute disease in 3rd trimester. Perinatal is the MCC
(90%) of infection worldwide & carries the highest risk of chronicity.
▪ Risk groups: IVDU, Homosexual men, hemophiliacs, hemodialysis, babies of HBsAg +ve mothers,
Health workers and their partners/contacts.

• Clinical Features
4. Incubation: 1-6 months.
5. Acute hepatitis:
o 70% anicteric hepatitis: MC = Asymptomatic or mild hepatitis [Arthralgia & Urticaria are
common (>HAV)]
o 30% icteric hepatitis
o <1 % progress into Fulminant hepatic failure
o Recovery from acute HBV infection occurs within 6 months and is characterized by the
appearance of antibody to viral antigens. Persistence of HBeAg beyond this time
indicates chronic infection.
6. Chronic Hepatitis B: HBsAg +ve > 6 months.
o Progression from acute → chronic depends on age
▪ 90% peri-natal
▪ 50% children
▪ < 5% adults
o Many chronic infections asymptomatic (carriers)
o Risk of progression to: Cirrhosis, Liver failure, Hepatocellular carcinoma or Reactivation
(acute hepatitis)

• Natural History:
- Following acute infection: 90% of neonates / 50% of infants / 5 % of adults develop Chronic.
- Full recovery occurs in 90–95% of adults following acute HBV infection. The remaining 5–10%
develop a chronic hepatitis B infection.
- 5–year cumulative incidence of Cirrhosis in untreated patients is 8–20 %. 5–year cumulative risk
of decompensation in cirrhotic patient is 20%. Annual risk of HCC is 2 – 5%
- Chronic infection is also common w/ immunodeficiency, e.g., Down’s syndrome, HIV.
 44

• Complications & Extrahepatic Manifestations:

9. Fulminant hepatic failure (rare) 10. Cryoglobulinaemia
11. Cirrhosis 12. Membranous nephropathy
13. HCC 14. Polyarteritis nodosa
15. Cholangiocarcinoma 16. Gianotti-Crosti Syndrome

• Investigations:
o Serology:
7. HBsAg: Active infection (acute or chronic).
8. Anti-HBs: Immunity.
9. Anti- HBc IgM: Recent/acute infection.
10. Anti- HBc IgG: Past infection (If + HBsAg= Chronic infection, If + Anti-HBs= Resolved
infection)
11. HBeAg: Replication, infectivity
12. Anti-HBe: Low infectivity
o LFTs: Transaminases: elevation indicates active liver disease.
o PCR: HBV DNA: monitor response to Rx.

• Management:
o Goal/Aim:
6. Clear HBsAg 7. HBeAg seroconversion
8. Reduce viral load 9. Normalise LFTs
10. Prevent Cirrhosis & HCC.
o Acute:
3. Supportive
4. Monitor for Acute Liver Failure.
o Chronic:
5. PEGylated Interferon alpha: SC
- For 48 weeks. Has several SE.
- Most effective in pts. w/ Lo Viral load & Hi transaminases.
- Better response in HBeAg +ve, genotypes A & C
- Contraindicated in advanced Cirrhosis.
- Expensive
6. Nucleoside/Nucleotide analogues (Oral Direct Acting Antivirals):
- Longer term (Lifelong), Better tolerated (Few SE).
- Better response in HBeAg –ve. All genotypes (A-H) respond equally.
- Lamivudine: Resistance after ~9 months
- Entecavir, Tenofovir: Resistance in 2% after ~3 yrs.
* Monotherpay w/ Entecavir or tenofovir is contraindicated in HIV+ve pts.
7. Transplantation w/ post liver transplant prophylaxis to prevent re-infection.
8. Follow up
 45

• Indication for treatment

- Not all patients with chronic HBV require treatment. However, all patients require close
monitoring
- All 1st degree relative and sexual partner of chronic HBV infection should be tested for HBV
marker, and if negative should be vaccinated
- Indication of treatment:
7. HBeAg positive: HBV DNA > 10,000 – 100,000 IU/mL, ALT > ULN (upper limit of normal),
at least moderate necroinflammation or fibrosis.
8. HBeAg negative: HBV DNA > 2000 IU/ml, ALT > ULN (upper limit of normal), at least
moderate necroinflammation or fibrosis.
9. HBV DNA > 20,000 IU/mL and ALT 2x Upper normal limit regardless of fibrosis.
10. All compensated or decompensated cirrhotic pts w/ detectable HBV DNA regardless of
ALT.
11. Pts requiring Immunosuppression (e.g. IBD) or Chemotherapy.
12. Pregnant w/ high viral load > 200,000 IU/ml. (prevent MTCT)

• Discontinuation of therapy:
▪ In HBeAg positive
5. Loss of HBsAg.
6. HBeAg Seroconversion & development of Anti-HBe.
7. Undetectable HBV DNA.
8. Complete 12 months of consolidation therapy.
▪ In HBeAg negative: Loss of HBsAg

• Prevention:
5. Vaccination 3 doses: at 0, 1 & 6 months.
6. Post-exposure prophylaxis: Hepatitis B Immunoglobulin (HBIg) +/- Vaccine. For: neonates to
HBsAg +ve mothers, after exposure (e.g., needle stick injury)
7. Post- Liver Transplant Prophylaxis: Direct Antivirals + HBIg.
8. Infection control measures

• Note
- HBeAg reflect the replication and infectivity of HBV (could be highly replicating virus or low),
however, In Sudan 90% of pts. with HBV infection are HBeAg –ve (due to mutation), so we can
know if the pt. has ongoing liver disease by measuring liver enzymes
- If HBeAg –ve viral load above 2000 is considered high.
- If HBeAg +ve viral load could be very high one million or 10 million or even more
 46

HCV
• Transmission:
4. Blood (transfusion, IVDU, needlestick, sharing toothbrushes)
5. Sexual
6. Vertical.

• Natural History:
- Following acute infection, ~85% develop silent chronic infection.
- Cirrhosis develops in ~25% of pts. in 20yrs w/ 4% annual risk of HCC.
- Risk factors for progression: Male, Older, Alcohol, High viral load, HIV, HBV, Immunosuppression,
prothrombotic states.

• Manifestations:
6. Iincubation: 0.5 – 6 months 7. Acute Hepatitis: Asymptomatic
8. Chronic Carrier State 9. Chronic Hepatitis: asymp/fatigue, mild or
nonspecific symptoms
10. Cirrhosis, HCC

• Investigations:
6. LFT: Normal or fluctuating <200 U/L.
7. Serology: Anti-HCV: appears 6-12 wks. after infection & persists.
8. PCR: HCV RNA: appears after only 2-4 wks.
9. Fibroscan: F0-F4
10. Liver biopsy.

- All pts. w/ CLD should be screened for HCV.

- Screen w/ Anti- HCV serology (confirms exposure), Confirm by HCV RNA PCR (confirms
ongoing/active chronic infection) Then, to determine treatment plan;
3. Assess degree of liver fibrosis: Fibroscan, FIB4 score, Metavir system, Biopsy.
4. Determine Genotype (1-6): PCR. MC genotypes in Sudan are 1 & 4.
- Genotypes 1 can be 100% treated w/ DAA.
- Genotypes 2 & 3 may require Ribavirin.
- Genotypes 4, 5, or 6 are prevalent in lower-income countries.
- If genotype can’t be determined, start Pangenotypic Treatment

• Management:
5. Interferon: Long duration (~12 months), Poor tolerability (Flu-like, depression, irritability) &
compliance & Poor response (esp. w/ genotype 1).
6. Direct Acting Antivirals: superior to interferon, used in Combinations:
c. Sofusbuvir + Ledipasvir + Ribavirin: ~12wks.
d. Sofusbuvir + Velpatisir: (Pan-genotypic)
7. Ribavirin (Nucleoside analogue): Reserved for genotypes 2 & 3. SE: anaemia, teratogenic.
8. Liver transplantation: 15% re-infection of the graft.
 47

• Indications for treatment:

- Treat ALL patients (Sustained detectable HCV RNA), Especially & Urgently:
o Pts w/ F2, F3, F4 fibrosis.
o Pts w/ extrahepatic manifestations (Vasculitis, Cryoglobulinaemia, Nephropathy, NHL).
▪ Duration of treatment:
o Non-cirrhotic: 8-12 wks.
o Cirrhotic: 24 wks. OR 12 wks. w/ + Ribavirin
▪ Goal of treatment:
o To eradicate the infection by achieving sustained viral response (SVR).
o Prevent complications (Cirrhosis & HCC).
* SVR 12: Undetected HCV RNA 12 wks. after end of therapy.

• Complications & Extrahepatic Manifestations:

10. Cirrhosis 11. HCC 12. Glomerulonephritis

13. Cryoglobulinaemia 14. Autoimmune hepatitis 15. PAN
16. Thyroiditis 17. Polymyositis 18. Porphyria cutanea tarda
 48

CASE 1
55-year-old man presented with a 6\12 history of fatigue and ankle swelling. On examination he has
a tinge of jaundice, clubbing, palmar erythema, Dupuytren‟s contractures, spider nevi,
Gynecomastia, liver span 6cm and splenomegaly

4. What is your diagnosis?

Chronic liver disease

5. What investigation would you do?

▪ CBC:
o Normocytic normochromic anemia → recent GI Hemorrhage
o Microcytic hypochromic → chronic blood loss
o Macrocytosis → Alcohol
o Pancytopenia due to Hypersplenism, but Platelets are more depressed due to
Decreased production. (No Thrombopoietin)
▪ LFT, INR, RFT.
▪ U/S: see ascites, tumors, portal and splenic diameter (portal HTN)
▪ Upper GI endoscopy: see varices.
▪ Specific tests: viral Ags /Abs.

6. If the investigations were as the following

Total protein 6.0g/dl, Albumin 2.9g/dl, Bilirubin 3.0g/dl, ALT 198 IU/L, INR 1.5.
US: shrunken coarse texture liver, dilated portal and splenic veins no ascites, mild esophageal
varices.
How severe is his liver disease?
We use Child-Truscott-Pugh Classification for severity of liver cirrhosis:

Parameter 1 2 3
Ascites None Slight Moderate/severe
Encephalopathy None Grade 1-2 Grade 3-4
Albumin g/dl >3.5 2.8-3.5 <2.8
Bilirubin <2.0 2-3 >3.0
PT sec 1-3 4-6 >6
INR <1.7 1.7-2.3 >2.3

o Has 5 parameters: Albumin, bilirubin, PT, ascites, encephalopathy.

o 3 classes: A: Mild. (5-6) B: Moderate. (7 - 9) C: Severe. (10 - 15)
o It gives a prognostic measure, poor prognosis with class C
▪ Child class A: survival same as normal population if get depleted, undergo
surgery, etc.
▪ Child class B: if undergo surgery survival is 33%
▪ Child class C: if undergo surgery mortality is more than 70%
So in this pt. is child class B
o No encephalopathy (1), No ascites (1), Albumin 2.9 g/dl (2), Bilirubin 3.0 mg/dl (2), INR
1.5 (1)
-
 49

CASE 2
HBsAg +ve HBeAg –ve HBcAg IgG +ve HBV DNA: 38,000 U/ml
In this patient score is 7 [moderate liver disease]
2. How to manage this pt.?
Nucleoside/nucleotide analogues: Tenofovir or Entecavir
Pegylated interferon (SC) expensive.

CASE 3
HCV Ab +ve ~ HCV RNA +ve ~ Genotype 4 ~ Liver biopsy – fibroscan (F4)
3. How to manage this pt.?
Interferon free therapy: Directly acting anti-viral (DAA)
Interferon based therapy: Pegylated interferon (SC)
Ribavirin PO
4. What are the Liver biopsy contraindications:
E. High INR (PT GIVEN fresh frozen plasma).
F. Ascites (floating liver).
G. Thrombocytopenia >80/100.
H. BIOPSY is difficult here because the liver size is SMALL.
 50

Liver Cirrhosis
• Definition:
- End-stage, irreversible liver disease characterized by distortion of the hepatic architecture and the formation of
regenerative nodules, so It's a histological diagnosis
- It is generally considered to be irreversible in its advanced stages, at which point the only treatment option may be
liver transplantation

• Pathology:
- Liver tissue replaced by fibrosis and nodules
- Smooth liver surface replaced by nodules
- In advanced cirrhosis, liver becomes shrunken

• Stages of fibrosis:
- Stage 0 (F0): Normal hepatocytes, no fibrosis
- Stage 1 (F1): Portal fibrosis without septa → ¼ the area → mild fibrosis
- Stage 2 (F2): Periportal fibrosis with few septa → ½ the area → moderate fibrosis
- Stage 3 (F3): Numerous bridges or septa → ¾ the area → severe fibrosis
- Stage 4 (F4): Bridging fibrous septa around multiple adjacent lobules → cirrhosis

• Main characteristics of cirrhosis are:

- Disruption of the architecture of the entire liver, Lack of portal triads and sinusoids
- Parenchymal nodules, varying from micronodules to macronodules
- Bridging fibrous septa around multiple adjacent lobules

• Etiology:

• Chronic viral hepatitis B & C • Celiac disease

• Alcoholic liver disease • Idiopathic adulthood ductopenia
• Nonalcoholic fatty liver disease (NASH) • Granulomatous liver disease
• Hemochromatosis • Idiopathic portal fibrosis
• Autoimmune hepatitis • Polycystic liver disease
• Primary and secondary biliary cirrhosis • Brucellosis, syphilis, echinococcosis
• Primary sclerosing cholangitis • Right-sided heart failure
• Wilson disease, Alpha-1 antitrypsin deficiency • Hereditary hemorrhagic telangiectasia
• Medications (methotrexate, INH) • Venocclusive disease

- Viral Hepatitis and alcohol = 80-90% of causes worldwide.

- In 20-30 years, fatty liver or NASH will be the leading cause because HCV is now curable & HBV has no treatment
but has vaccine.
- Females in 80-90 years present with cryptogenic cirrhosis (no cause), retrospective they have had fatty liver and NASH
led to cirrhosis after many years.
- Viral need 20 years to cause cirrhosis but in Sudan patients can present in young age because they acquired viral hep
at birth. In west word it by IV drug use and sexual activity at young so present at 50s.
- Alcohol in females take 10y, in males’ longer time to cause cirrhosis → Female have more rapid progression to
cirrhosis compared to males
- Fatty liver needs 40-50 to cause cirrhosis, it is more in females because life expectance of females is at least 10-
15years more than males by statistics

• Cirrhosis Classification:
- Macronodular (>3mm): chronic viral hepatitis
- Micronodular (<3mm) alcohol, hemochromatosis, cholestasis, hepatic venous outflow obstruction
 51

• Limitations:
- Not clinically useful: Nonspecific to etiology
- Morphologic appearance may change with disease progression
- Requires invasive procedures: Accurate assessment of liver morphology can only be achieved at surgery,
laparoscopy, or autopsy
- Serological markers more specific than morphological appearance for determining the etiology of cirrhosis.

• Clinical Features:
1. Silent/Incidental/Asymptomatic: Fluctuating abnormal LFTs, detected before surgery.
2. Silent till Decompensation (infection, surgery…) → Acute on Chronic Liver Failure.
3. Nonspecific: Fatigue, Anorexia, N&V, Wt. loss, up. abd. discomfort, muscle cramps.
4. Jaundice
▪ Loss of bilirubin metabolism
▪ Occurs late in disease course
▪ Presented as conjunctival Icterus, Pruritus (→ scratching → infections).
5. Portal Hypertension:
▪ Blood flow: portal vein → liver → hepatic vein. In Cirrhosis → obstructed flow through liver
▪ High pressure in portal vein (“hypertension”)
▪ Presented as:
a. Ascites
b. Congestive splenomegaly; Increased hydrostatic pressure in splenic vein
c. Esophageal varices → upper GI bleeding
d. Hemorrhoids → internal hemorrhoids which may bleed
e. Periumbilical venous collaterals (caput medusae)
▪ Treatment: Portacaval shunt, Mesocaval shunt, Splenorenal shunt, TIPS

6. Ascites:
▪ Due to
a. Portal hypertension: Increase in portal vein hydrostatic pressure
b. Hypoalbuminemia; Decreases oncotic pressure
c. Secondary hyperaldosteronism:
o Low CO → ↓renal blood flow activates the RAA system → retention of Na+ and water
o Liver is unable to metabolize aldosterone
▪ Increased risk for spontaneous bacterial peritonitis
▪ Treatment: diuretic therapy or with TIPS or liver transplant

7. Hyperestrogenemia:
▪ Liver cannot degrade estrogen and androstenedione → Elevated estrogen
▪ Palmar erythema, Spider Nevi, loss of body hair
▪ Gynecomastia, testicular atrophy, Impotence and erectile dysfunction in males
▪ Amenorrhea in females
8. Hypotension:
▪ Cirrhosis → decreased mean arterial pressure due to → Low systemic vascular resistance
▪ Various vasodilators such as NO, prostacyclin and TNF are secreted from the damaged hepatocyte
▪ This is caused by arterial vasodilation, primarily in the splanchnic circulation.
▪ Previous hypertension may resolve
▪ The increased splanchnic arterial blood flow in turn leads to increased venous efflux into the portal venous
system → Hyper-dynamic circulation
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▪ May lead to renal failure (hepatorenal syndrome)

9. Hepatorenal Syndrome
▪ Renal failure with pre-renal features occurring in individuals with cirrhosis
▪ There is decreased renal perfusion pressure due to systemic vasodilation → activation RAAS causing
vasoconstriction that further decreases glomerular filtration.
▪ The syndrome’s onset begins with a decrease in urine output and rising
▪ blood urea nitrogen and creatinine levels, low urinary sodium, Normal/bland urinalysis, No protein, No/few red
or white cells
▪ Does not respond to fluid administration
▪ Treatment: Supportive care including dialysis, Vasopressin analogues (terlipressin) or norepinephrine, Albumin
for volume expansion, Liver transplantation only curative treatment. Mortality rate is >80%

10. Loss of hepatic synthetic function

▪ Hypoalbuminemia
o May cause low oncotic pressure
o Contributes to ascites
o May lead to pitting edema
▪ Coagulopathy
o Loss of clotting factors
o Elevated PT/PTT
11. Hypersplenism:
▪ Engorgement of the spleen in portal HTN leads to low platelets

• On examination:
1. Hand: Leukonychia (Hypoalbuminemia), Clubbing, Palmar Erythema, Dupuytren Contracture, asterixis
2. Jaundice, Conjunctival Icterus
3. Parotid Enlargement (Alcohol).
4. Spider Nevi, gynecomastia, loss of body hair, scratching marks, bruising, caput medusa
5. Liver: early hepatomegaly later on irregular, hard, nontender, shrunken liver
6. Splenomegaly, Ascites

• Complication:
1. Coagulopathy: bleeding tendency, purpura, ecchymosis, epistaxis.
2. Hepatic encephalopathy.
3. Hypoglycemia.
4. HRS → AKI, Oedema.
5. Hypoalbuminemia → Oedema.
6. Hypotension.
7. Portal HTN (MCC of Portal HTN is Cirrhosis) -> Ascites, Splenomegaly, Varices, haemorrhoids, Caput medusa.
8. GI bleeding: d/t: Coagulopathy + Portal HTN
9. Ascites: d/t: Portal HTN + Hypoalbuminemia + decreased Aldosterone elimination. ↑SBP risk.
10. Infections (fever): Pneumonia, sepsis, SBP.
11. Hepatopulmonary syndrome: Pleural effusion.

• Compensated vs. Decompensated Cirrhosis:

- Most patients with cirrhosis are asymptomatic → Compensated cirrhosis
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- Decompensated cirrhosis: develops when the metabolic capacity of the liver is exceeded, it’s characterized by one or
more of the following symptoms: Ascites, Variceal bleeding, Jaundice, Hepatic Encephalopathy

• Diagnosis:
1. History
▪ Ask about history of jaundice? At birth or through life
▪ Systemic Review: Associated complications
▪ Past Medical History: Blood transfusion? Vomiting blood? Ascites?
▪ Social History: IV drug use? Alcohol?
▪ Family History: genetic diseases? Hemochromatosis? Wilson disease? Viral hepatitis?
▪ Medication History: hepatotoxic drugs

2. Physical Examination: as mentioned before

3. Laboratory investigations
▪ Investigations to assess the condition
a. CBC: thrombocytopenia, pancytopenia (Hypersplenism), anemia (blood loss)
b. LFT: differ w/ etiology, but generally: ↔/↓transaminases (hepatocyte loss), ↔ GGT, ALP (↑in cholestatic
causes), ↓Albumin, ↑Unconjugated bilirubin, ↑PT/INR.
c. RFT: ↑Cr (HRS), Serum Na may ↓but w/ normal total Na (fluid shift), is important: Healthy kidney is
crucial in treatment because you will give diuretic for ascites.
▪ Investigations to identify the etiology

a. Viral screening: HBsAg, Anti-HCV, HCV RNA

b. Autoantibodies: ANA, ASMA, LKA, AMA

c. Iron profile: Serum iron, serum ferritin, T ransferrin, (TIBC)

d. Caeruloplasmin, serum Cu (young pt.), A1AT

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▪ investigation for cirrhosis:

a. Liver U/S & Duplex: Small, shrunken liver with nodules and irregular edges. Low Sensitivity, High
Specificity, if small shrunken liver → cirrhosis if normal this is not mean no cirrhosis

b. CT (Contrast may worsen kidney functions): small, shrunken, irregular +/- fluid (ascites) around the liver

c. Liver MRI: used for vascular assessment before transplant, HCC screen

d. Elastography/Fibroscan: Noninvasive test for fibrosis (alternative to biopsy). F0-F4.

e. Liver Biopsy (Percutaneous vs. Trans-Jugular): is not preferred because it's invasive and increase risk of
complications and bleeding.Only required in certain cases e.g. PSC, Haemochromatosis.

▪ Investigations to screen for Complications.

a. Ascitic Tap: Analysis, Neutrophils > 250/mm3 suggests SBP

b. Upper GI Endoscopy (Varices screen).

c. Alpha Fetoprotein (HCC screen)

▪ Note:
a. Isolated thrombocytopenia (<160,000/mm3) is the earliest biochemical sign of decompensated liver
cirrhosis
b. The most sensitive marker for liver cirrhosis is prolonged PT/INR.

• Management of cirrhosis:
A. The Goal is to:
a. Identify the cause to reverse or slow the progression
b. Prevent further damage (avoid hepatotoxic drugs)
c. Treat current complications
d. Regular screen and management and prevention of other or further complications

B. Method:
a. Medications: Review & adjust/discontinue. Avoid NSAIDs, Sedatives, and Opiates.
b. Cholestyramine PO for Pruritus.
c. Ascites: Fluid restriction, Low salt diet, Wt. Loss, Diuretics (Spironolactone +/- Furosemide), Paracentesis, TIPS.
d. SBP prophylaxis (for Hi risk pts. = ↓Albumin, ↓Ascitic albumin, ↑PT/INR): Ciprofloxacin PO.
e. SBP (common= E. coli, Klebsiella, Streptococci): IV Piperacillin + tazobactam till sensitivity results + IV Albumin.
f. Encephalopathy: Lactulose, Rifaximin/Neomycin, Phosphate Enema, Mannitol, Ceftriaxone, 10% dextrose, Vit K.
or FFP
g. HRS 1: Terlipressin, norepinephrine, Albumin, Hemodialysis.
h. HRS 2: TIPS, Liver-Kidney Transplant.
i. Varices: Screen, Beta Blockers (prevention) +/- Acute management.
j. HCC screening: US + AFP.
k. Underlying Cause (Alcohol Abstinence, Ursodeoxycholic, Penicillamine, antivirals).
l. Liver Transplantation is the only definitive treatment.
m. Follow up: U/S + Alpha Fetoprotein every 6 months (HCC). Endoscopy every 2 yrs.

• Prognosis and severity:

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- The median survival of patients with compensated cirrhosis is 12 years.

- The median survival in patients with decompensated cirrhosis is </= s6 months
- Poor prognostic feature:
1. Encephalopathy
2. HRS
3. High INR
4. Low Albumin < 2.5g/dL
5. Hyponatremia < 110 mmol/L
- 2 systems for assessment of prognosis & severity:
1. Child-Pugh system: may be subjective
2. MELD Score (Model For End-Stage Liver Disease): accurate, cornerstone for transplantation timing & listing.
- Importance of classification models is they become common language between doctors and prioritize patients to
transplant.

• Child-Pugh Classification
▪ Five variables to predict risk/survival: Albumin, Bilirubin, Clotting PT, Distension (ascites), Encephalopathy
▪ Assessment of Severity: Score (5-6): Mild (Class A) Score (7-9): Moderate (Class B) Score (10-15): Severe (Class
C)
▪ Surgical Mortality: Child A: 10%, Child C: 60-80%

• MELD Score
▪ Scoring system for chronic liver disease or cirrhosis
▪ Estimates 3-month mortality from liver disease
▪ Point system using: Bilirubin level, Creatinine level, INR
▪ Normal MELD is score 6. Between 6 and 40 is leaner relationship so you can predict very accurately
▪ > 40 = 71% – 100% mortality in 90 days
▪ < 9 = 2% mortality in 90 days

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