Summary: Hepatology

Table of Contents
1. Important Scoring Patterns in Liver Disease
2. Acuteness of Liver Failure
3. MELD and PELD Scores
4. Liver Test Patterns
5. Liver Transplantation: Indications and Issues
6. Viral Hepatitis: Overview
7. Hepatitis B (HBV)
8. Fulminant Hepatic Failure from HBV
9. Hepatitis C (HCV)
10. Hepatitis D (HDV)
11. Fibrosis Test
12. Autoimmune Hepatitis
13. Alcoholic Liver Disease (ALD)
14. Non-Alcoholic Fatty Liver Disease (NAFLD)
15. Cirrhosis and Complications
16. Budd-Chiari Syndrome
17. Portosystemic Collaterals (7 sites)
18. Esophageal Variceal Bleed: Emergency Points
19. Ascites
20. Hepatorenal Syndrome
21. Hepatopulmonary Syndrome
22. Choledocholithiasis & Obstructive Jaundice
23. Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis
24. Dubin-Johnson and Rotor Syndromes
25. Wilson's Disease
26. Hemochromatosis
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Important Scoring Patterns in Liver Disease

• MELD-Na: Incorporates serum sodium with bilirubin, creatinine and INR to better predict mortality in end-stage liver disease.
• Child-Pugh: Score >7 is a criterion to list for liver transplantation.

Acuteness of Liver Failure

• Fulminant hepatic failure: Coagulopathy (INR ≥1.5) + encephalopathy in a previously healthy person within 8 weeks; toxins cause ~50% of cases.
• Subfulminant hepatic failure: Same features occurring between 8 and 26 weeks.

MELD and PELD Scores

• MELD: Used to determine need for liver transplantation; MELD >17 eligible for listing. Formula uses log bilirubin, log INR, log creatinine with constant adjustments.
• PELD: Pediatric score using log bilirubin, log INR, log albumin plus age and growth failure factors.

Liver Test Patterns

• All clotting factors are liver-made except factor VIII (endothelial cells).
• SGPT (ALT) is the most specific liver enzyme.
• Alkaline phosphatase and 5'-nucleotidase localize near bile canaliculi; GGT in ER and bile duct epithelium.
• SGOT/SGPT ratio >2 is specific for alcoholic hepatitis (not GGT).

Liver Transplantation: Indications and Issues

• Common indications: chronic hepatitis C and alcoholic liver disease; also Wilson's disease, haemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, hepatorenal and hepatopulmonary syndromes, autoimmune hepatitis.
• Typical thresholds: MELD >17 and Child-Pugh score ≈7 for consideration.
• Relative contraindications: age >70, portal vein thrombosis, severe obesity, HIV with CD4 <100, malnutrition, severe hypoxia from intrapulmonary shunt, pulmonary artery hypertension.
• Absolute contraindications: AIDS, uncontrolled hepatobiliary infection, sepsis, active alcohol abuse, metastatic disease or cholangiocarcinoma.
• Diseases that can recur post-transplant: autoimmune hepatitis, primary sclerosing cholangitis, cholangiocarcinoma, fulminant hepatitis A.

Viral Hepatitis: Overview

• Transmission patterns: Hepatitis A/E - feco-oral; Hepatitis B - sexual/parenteral/vertical; Hepatitis C - parenteral (blood, IV drugs), low/no transmission by breast milk; Hepatitis D - parenteral and depends on HBV for replication.
• HEV is a leading cause of acute viral hepatitis worldwide and in India; HCV is the leading cause of chronic hepatitis; HBV is the commonest carrier state; HDV superinfection commonly causes fulminant hepatitis; HEV commonly causes fulminant hepatitis in pregnancy.

Hepatitis B (HBV)

• Virus: Partially double-stranded circular DNA ~3.2 kb.
• Transmission: Sexual contact common in Asia; vertical transmission up to 90% if mother is HBsAg and HBeAg positive; give HB immunoglobulin within 24 hours and recombinant vaccine for newborns.
• Needlestick risk: ~30% for HBV (HB-Ig within 6 hours); HIV needlestick ~0.3% (PEP: raltegravir + emtricitabine + tenofovir).
• Antigens/markers: HBsAg (infection), HBeAg (high infectivity), HBxAg, HBV-DNA; treatment considered when viral load high with SGPT rise; first-line drug: Tenofovir (also entecavir).
• Antibodies: Anti-HBs (recovery/immunity), anti-HBc IgM (acute/window), IgG (chronic), anti-HBe (decreased replication).
• Clinical features of acute HBV: nausea, vomiting, mild weight loss, fever, jaundice, tender hepatomegaly; splenomegaly and cervical LAD in ~20%.
• Investigations: LFT-raised SGPT; ultrasound starry-sky; HB antigen profile shows HBsAg, HBeAg, IgM anti-HBc in acute infection; sequence: HBsAg → HBeAg → anti-HBc → anti-HBe → anti-HBs.
• Treatment: Acute-supportive care; diet, antiemetics (itopride/mosapride), cholestyramine for pruritus. Chronic active-tenofovir, entecavir, or alpha-interferon; successful treatment → viral load <300 copies/ml.

Fulminant Hepatic Failure from HBV

• Incidence after acute HBV: 0.1-1%.
• Features: worsening jaundice, reduced liver size, bleeding from lack of clotting factors, hepatic encephalopathy from ammonia.
• Investigations: raised serum ammonia, EEG triphasic waves in advanced encephalopathy.
• Treatment: mannitol, NG lactulose, rifaximin, L-ornithine + L-arginine infusion, dextrose, FFP for PT, consider orthotopic liver transplantation.

Hepatitis C (HCV)

• Genotype 1 most common worldwide. Acute HCV commonly progresses to chronic disease and is a leading cause of liver transplantation.
• Transmission: blood transfusion, IV drugs, sexual contact; vertical transmission ~5%.
• Diagnosis: EIA for anti-HCV antibody; if negative, test HCV RNA by PCR; treat if HCV-RNA positive regardless of transaminases.
• Treatment: Genotype 1 - ledipasvir + sofosbuvir (12-24 weeks); Genotype 2 - sofosbuvir + ribavirin; Genotype 3 - limited effective options; NS5A inhibitors end in 'asvir'.
• Acute cryoglobulinemia flares: rituximab, cyclophosphamide, methylprednisolone; pegylated interferon + ribavirin used in absence of newer drugs.

Hepatitis D (HDV)

• HDV is defective and requires HBV for replication; co-infection or superinfection worsens disease and can cause fulminant failure; HDV incidence falls with full HBV vaccination coverage.

Fibrosis Test

• Noninvasive test for fibrosis in chronic HCV using five serum markers: α-2-macroglobulin, apolipoprotein A1, haptoglobin, γ-glutamyl transpeptidase, and bilirubin; comparable to liver biopsy.

Autoimmune Hepatitis

• Types: Type I (ANA, p-ANCA), Type II/III (anti-LKM antibodies; Type II often with chronic HCV).
• Treatment of choice: prednisolone.
• Anti-LKM2 → drug-induced hepatitis; anti-LKM3 → linked to HDV.

Alcoholic Liver Disease (ALD)

• Most sensitive test: SGOT; SGOT/SGPT ratio >1 is significant. Most specific test: carbohydrate-deficient transferrin. GGT is non-specific.
• Prognosis: Maddrey's Discriminant Function uses bilirubin and INR; DF ≥32 or MELD >21 (without comorbidities) → treat with prednisolone 32 mg PO for 4 weeks then taper; pentoxifylline is an alternative.

Non-Alcoholic Fatty Liver Disease (NAFLD)

• Associated with obesity and metabolic syndrome.
• Causes include HCV, Reye syndrome, kwashiorkor, drugs, acute fatty pregnancy, HELLP, inborn errors.
• Features: macrovesicular steatosis, often asymptomatic or mild RUQ discomfort; elevated ferritin may suggest autoantibodies.
• Biopsy usually avoided; BARD score has 96% NPV to exclude significant disease. Vitamin E can help; other drugs have notable side effects. Selected cases may need liver transplantation.

Cirrhosis and Complications

• Most common cause: alcoholic (micronodular) cirrhosis.
• Compensated features: spider nevi, palmar erythema, Dupuytren's contracture, clubbing, gynecomastia, testicular atrophy/hypogonadism.
• Cardiac cirrhosis (nutmeg liver) from venous congestion; investigation by USG-guided biopsy; treatment may include transplantation.
• Ultrasound elastography: noninvasive early detection of cirrhosis by measuring liver stiffness.
• Most frequent complication: portal hypertension; common clinical features-splenomegaly (most reliable), ascites, haematemesis from oesophageal varices.

Budd-Chiari Syndrome

• Hepatic venous outflow obstruction causing hepatic vein thrombosis, sudden congestion, tender hepatomegaly with enlarged caudate lobe, ascites and RUQ pain.
• Common causes: polycythaemia vera, paroxysmal nocturnal haemoglobinuria, OCP use, hepatic vein valve abnormalities.
• Diagnosis: abdominal USG, Doppler, hepatic venography (investigation of choice).
• Treatment may include heparin and interventions to restore flow.

Portosystemic Collaterals (7 sites)

• Oesophageal varices, rectal hemorrhoids, caput medusae (umbilical veins), bare area of liver, retroperitoneal veins, lumbar veins, omental veins.

Esophageal Variceal Bleed: Emergency Points

• Concurrent falling systolic BP and active bleeding; repeated hematemesis definitive treatment: TIPS.

Ascites

• Detection thresholds: puddle sign >100 mL, shifting dullness ≥500 mL, fluid thrill in massive/tense ascites.
• Tense ascites can cause intra-abdominal hypertension; >12 mmHg = intra-abdominal HTN; >25 mmHg may cause abdominal compartment syndrome.
• SAAG = serum albumin - ascitic albumin; SAAG >1.1 indicates portal hypertension (most common cause); SAAG <1.1 exceptions include nephrotic syndrome.
• Investigation of choice: abdominal USG.
• Treatment for SAAG >1.1: salt restriction, spironolactone; large/tense ascites-paracentesis with IV salt-free albumin; recurrent ascites-TIPS.

Hepatorenal Syndrome

• Type 1: rapid doubling of creatinine or halving of creatinine clearance within 2 weeks. Type 2: slower, chronic course.
• Features: oliguria/anuria, uremia, volume overload; treatment: midodrine + octreotide + IV albumin, and dialysis as needed.

Hepatopulmonary Syndrome

• Key features: platypnea (dyspnea on sitting), orthodeoxia (positional oxygen drop); diagnosis may use ABG and lung perfusion scan; definitive treatment: orthotopic liver transplant.

Choledocholithiasis & Obstructive Jaundice

• Causes of obstruction: CBD strictures, pancreatic cancer, Klatskin tumour, Caroli disease, choledochal cyst, biliary atresia, primary biliary cirrhosis, Dubin-Johnson, Rotor syndrome.
• Clinical features: pruritus, dark (mustard) urine, clay-coloured stools, yellow sclera.
• Investigations: LFTs show conjugated hyperbilirubinaemia, normal/near-normal transaminases, markedly raised alkaline phosphatase and 5'-nucleotidase; abdominal USG initial test; MRCP for biliary/pancreatic evaluation; bromsulphalein test to differentiate Dubin-Johnson.

Primary Biliary Cirrhosis and Primary Sclerosing Cholangitis

• Primary biliary cirrhosis: intra/extrahepatic biliary dysfunction causing obstructive picture; IOC: anti-mitochondrial antibodies; definitive treatment: liver transplantation.
• Primary sclerosing cholangitis: intrahepatic biliary fibrosis with p-ANCA positivity; tests: AMA/p-ANCA, MRCP showing multiple strictures; gold standard: liver biopsy; treatments include stenting and orthotopic liver transplantation.

Dubin-Johnson and Rotor Syndromes

• Dubin-Johnson: autosomal recessive MRP2 (ABCC2) defect → accumulation of conjugated bilirubin and dark pigmented liver; diagnosed with bromsulphalein (BSP) test.
• Rotor: milder variant, normal liver color, absence of OATP1B1 and OATP1B3 transporters causing conjugated hyperbilirubinaemia.

Wilson's Disease

• Autosomal recessive copper accumulation due to ATP7B mutation on chromosome 13; presents before age 40.
• Clinical: hemolytic anemia, neurological involvement (basal ganglia → chorea), Kayser-Fleischer rings, Fanconi syndrome from proximal tubule damage.
• Diagnosis: 24-hour urine copper (screen), low serum copper, liver biopsy with hepatic copper estimation (IOC), MRI brain (characteristic changes).
• Treatment: zinc acetate for presymptomatic, children, pregnancy or hepatitis without decompensation; trientine for mild-moderate hepatic decompensation; tetrathiomolybdate for CNS features. Nazer score used for prognosis.

Hemochromatosis

• Autosomal recessive iron overload often from HFE gene (chromosome 6) mutation (primary) or from repeated transfusions (secondary).
• Clinical triad: bronze skin, diabetes mellitus, hepatomegaly; arthropathy (2nd-3rd MCP), restrictive cardiomyopathy, hypogonadism.
• Diagnosis: elevated serum ferritin, high transferrin saturation; gold standard: liver biopsy.
• Treatment: primary - phlebotomy; secondary - iron chelators (desferrioxamine, deferiprone preferred).