Cirrhosis

End-stage result of chronic liver injury characterized by diffuse hepatic fibrosis and regenerative nodule formation, causing distortion of normal hepatic architecture and vasculature, leading to portal hypertension and progressive loss of synthetic/metabolic liver function. Represents the final common pathway of most chronic liver diseases.

Major etiologies:

• Alcohol-related liver disease

• Metabolic dysfunction-associated steatotic liver disease (MASLD, formerly NAFLD/NASH), increasingly common cause globally

• Chronic viral hepatitis (HBV, HCV)

• Autoimmune hepatitis

• Cholestatic: primary biliary cholangitis (PBC), primary sclerosing cholangitis (PSC)

• Metabolic/genetic: hemochromatosis, Wilson's disease, alpha-1 antitrypsin deficiency

• Vascular: Budd-Chiari syndrome, chronic right heart failure (cardiac cirrhosis)

• Drug-induced (methotrexate, amiodarone)

Classified by:

• Compensated: asymptomatic or mild non-specific symptoms, no major complications

• Decompensated: development of ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice, marks major prognostic transition, median survival drops from ~12 years (compensated) to ~2 years (decompensated)

• Severity/prognostic scoring: Child-Pugh (A/B/C) and MELD/MELD-Na scores, guide transplant listing and prognosis

Compensated (may be asymptomatic, found incidentally):

• Fatigue, anorexia, weight loss, nausea

• Signs of chronic liver disease: spider angiomata, palmar erythema, gynecomastia, testicular atrophy, Dupuytren's contracture, caput medusae, leukonychia, clubbing

• Hepatomegaly (may become small/shrunken in advanced disease) ± splenomegaly (portal hypertension)

Decompensated:

• Ascites: abdominal distension, shifting dullness, fluid thrill, most common decompensation event

• Variceal hemorrhage: hematemesis, melena, from esophageal/gastric varices due to portal hypertension

• Hepatic encephalopathy: confusion, asterixis (flapping tremor), altered sleep-wake cycle, progressing to stupor/coma (West Haven grading I–IV)

• Jaundice: scleral icterus, generalized jaundice, reflects impaired bilirubin conjugation/excretion

• Coagulopathy: easy bruising, bleeding (reduced synthesis of clotting factors)

• Peripheral edema (hypoalbuminemia)

• Muscle wasting/sarcopenia

• Fetor hepaticus (sweet, musty breath odor)

Complications to actively screen for: hepatocellular carcinoma (HCC), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, hepatopulmonary syndrome, portal vein thrombosis.

• Labs:

• LFTs: may be normal in burnt-out cirrhosis; AST/ALT ratio >1 suggestive of alcohol-related disease

• Synthetic function: low albumin, prolonged PT/INR

• FBC: thrombocytopenia (earliest lab clue, portal hypertension/hypersplenism), anemia

• U&E/creatinine: baseline renal function (hepatorenal syndrome risk)

• Non-invasive fibrosis assessment (first-line, replacing biopsy in most cases):

• Transient elastography (FibroScan): liver stiffness measurement in kPa, values vary by etiology, generally >12–15 kPa suggestive of cirrhosis

• Serum fibrosis markers/scores: FIB-4 index, APRI score, screening tools, especially in MASLD

• MR elastography: more accurate, less available

• Liver biopsy: gold standard but reserved for diagnostic uncertainty or when etiology unclear despite non-invasive workup

• Imaging: ultrasound, nodular liver contour, coarse echotexture, splenomegaly, ascites; also used for HCC surveillance

• Etiology workup: viral hepatitis serology (HBsAg, anti-HCV), autoimmune markers (ANA, ASMA, anti-LKM, immunoglobulins), ferritin/transferrin saturation (hemochromatosis), ceruloplasmin (Wilson's, if young), alpha-1 antitrypsin level, lipid profile/HbA1c (MASLD risk factors)

• Endoscopy (OGD): screening for esophageal/gastric varices at diagnosis of cirrhosis, repeated per surveillance interval based on findings

• HCC surveillance: ultrasound ± AFP every 6 months in all cirrhotic patients

Differentials for decompensation presentations: other causes of ascites (malignancy, TB peritonitis, cardiac), other causes of encephalopathy (sepsis, uremia, drugs, intracranial pathology), other causes of UGIB (peptic ulcer).

General/etiology-specific:

• Treat underlying cause: antiviral therapy (HBV, tenofovir/entecavir; HCV, direct-acting antivirals, near-100% cure rates), alcohol cessation (+ addiction support), weight loss/metabolic control for MASLD, immunosuppression for autoimmune hepatitis, venesection for hemochromatosis

• Avoid hepatotoxic drugs, NSAIDs (renal risk in cirrhosis), sedatives (precipitate encephalopathy)

• Vaccination: hepatitis A/B (if not immune), pneumococcal, influenza, COVID-19

• Nutrition: adequate protein intake (1.2–1.5g/kg/day, do NOT protein-restrict, worsens sarcopenia), avoid prolonged fasting, late-evening snack recommended (reduces overnight catabolism)

Ascites management:

• Sodium restriction (<2g/day)

• Diuretics: spironolactone 100mg od (up titrate to max 400mg/day) ± furosemide 40mg od (up titrate to max 160mg/day), typical ratio 100:40, monitor renal function/electrolytes closely

• Large-volume paracentesis for tense/refractory ascites: albumin replacement 6–8g per liter removed if >5L drained (prevents post-paracentesis circulatory dysfunction)

• Refractory ascites: consider TIPS (transjugular intrahepatic portosystemic shunt) or liver transplant referral

Variceal hemorrhage:

• Primary prophylaxis (known varices, not yet bled): non-selective beta-blocker (propranolol, carvedilol) or endoscopic variceal band ligation

• Acute bleed: resuscitation, restrictive transfusion strategy (target Hb ~7–8g/dL), IV terlipressin or octreotide (splanchnic vasoconstriction), prophylactic antibiotics (ceftriaxone 1g IV od, reduces mortality, prevents SBP/rebleeding), urgent endoscopy within 12 hours for band ligation/sclerotherapy

• Secondary prophylaxis: combination beta-blocker + band ligation program

Hepatic encephalopathy:

• Identify/correct precipitant (infection, GI bleed, constipation, electrolyte imbalance, sedatives, dehydration)

• Lactulose 30mL PO tds-qds, titrate to 2–3 soft stools/day (traps ammonia as ammonium, laxative effect)

• Rifaximin 550mg PO bd: add-on for recurrent episodes despite lactulose (reduces ammonia-producing gut flora)

Spontaneous bacterial peritonitis (SBP): diagnostic paracentesis if new/worsening ascites, fever, abdominal pain, or encephalopathy, ascitic fluid neutrophil count >250 cells/mm³ diagnostic; treat with IV cefotaxime/ceftriaxone + IV albumin (1.5g/kg day 1, 1g/kg day 3, reduces hepatorenal syndrome risk); secondary prophylaxis with norfloxacin/ciprofloxacin after first episode

HCC: surveillance ultrasound ± AFP 6-monthly; management per BCLC staging (resection, ablation, TACE, systemic therapy, or transplant depending on stage)

Liver transplant referral: decompensated cirrhosis, MELD-Na ≥15, refractory complications (ascites, encephalopathy, recurrent variceal bleeding), HCC within transplant criteria (Milan criteria), or synthetic dysfunction (Child-Pugh C).