Chronic Liver Diseases

Overview

• Bailey and Love's Short Practice of Surgery, 28th Ed.

Aetiology (Common Causes)

Pathophysiology

Hepatic Fibrosis

Cirrhosis

• Compensated - patient may be asymptomatic or minimally symptomatic
• Decompensated - onset of complications (ascites, variceal bleeding, hepatic encephalopathy, jaundice)

Clinical Features

Symptoms

• Early: Lethargy, weakness, malaise (often precede jaundice)
• Late: Jaundice, abdominal distension (ascites), confusion (encephalopathy)

Signs - a systematic summary:

• Bailey and Love's Short Practice of Surgery, 28th Ed.

Complications of Chronic Liver Disease / Cirrhosis

1. Portal Hypertension

• Presinusoidal: Portal vein thrombosis, schistosomiasis (most common cause worldwide)
• Sinusoidal: Cirrhosis (most common cause in Western countries)
• Postsinusoidal: Budd-Chiari syndrome, hepatic vein occlusion, cardiac

2. Oesophageal/Gastric Varices

• Portal pressure drives formation of portosystemic collaterals
• Variceal rupture follows Laplace's law: as vessel radius increases, wall tension exceeds tissue strength
• Mortality from acute variceal bleeding: 10-15%
• Management: octreotide/terlipressin (vasoconstriction), endoscopic band ligation, TIPSS (transjugular intrahepatic portosystemic shunt), beta-blockers (propranolol/carvedilol) for prophylaxis
• Rosen's Emergency Medicine; Current Surgical Therapy 14e

3. Ascites

• Results from portal hypertension + hypoalbuminaemia + sodium/water retention (activated RAAS)
• Large volume paracentesis: Administer albumin 8 g per litre of ascitic fluid removed when >5 L drained to prevent post-paracentesis circulatory dysfunction
• Diuretics: Spironolactone ± furosemide
• Note: ACE inhibitors and ARBs should be avoided in decompensated cirrhosis/ascites (markedly decreased renal clearance, risk of AKI)

4. Spontaneous Bacterial Peritonitis (SBP)

• Acute infection of ascitic fluid - consider in any patient with ascites + abdominal pain, fever, or unexplained deterioration
• Most common organisms: E. coli and Klebsiella
• Diagnosis: Ascitic fluid polymorphonuclear (PMN) count > 250 cells/mm³ is the threshold for treatment
• Treatment: Cefotaxime 2 g IV every 8 hours x 5 days

5. Hepatic Encephalopathy (HE)

• Cerebral and neuromuscular dysfunction secondary to hyperammonaemia and its effects on cerebral metabolism
• Note: severity of HE does not directly correlate with serum ammonia level

• Lactulose 30-60 g/day (reduces ammonia production/absorption)
• Rifaximin 400 mg PO every 8 hours (reduces gut ammonia-producing bacteria)
• Branched-chain amino acids (shown benefit without increased mortality)
• Correct underlying precipitants

6. Hepatorenal Syndrome (HRS)

• Functional renal failure in the setting of advanced liver disease - heralded by rising creatinine
• Associated with high mortality
• Types: HRS-AKI (Type 1 - rapid, acute) and HRS-CKD (Type 2 - progressive, gradual)
• Treatment: Terlipressin + albumin; liver transplantation is definitive

7. Coagulopathy

• Impaired synthesis of clotting factors (I, II, V, VII, IX, X, XI) and anticoagulant proteins (protein C and S, antithrombin)
• Thrombocytopenia from hypersplenism
• Target platelet count > 50,000/mm³ before invasive procedures
• For active bleeding: Cryoprecipitate (1 unit/10 kg) preferred over FFP
• Elevated INR or thrombocytopenia is not a contraindication to paracentesis

8. Hepatocellular Carcinoma (HCC)

• Major complication especially with viral hepatitis B/C and NASH cirrhosis
• Surveillance: Ultrasound every 6 months ± alpha-fetoprotein (AFP)

Assessment & Prognostic Scoring

Child-Turcotte-Pugh (CTP) Classification

• CTP-A (5-6 pts): 10% operative mortality
• CTP-B (7-9 pts): 30% operative mortality
• CTP-C (10-15 pts): 75-80% operative mortality

MELD Score

• Calculated from INR, serum bilirubin, and creatinine
• Originally developed to predict short-term prognosis after TIPSS
• Now used to prioritise patients on liver transplant waiting lists
• MELD score correlates with operative mortality
• Bailey and Love's Short Practice of Surgery, 28th Ed.

Important Specific Chronic Liver Diseases

Primary Biliary Cholangitis (PBC)

• Chronic autoimmune cholestatic disease mainly affecting middle-aged women
• Features: Malaise, lethargy, pruritus, abnormal LFTs
• Hallmark: Antimitochondrial antibody (AMA) positive (> 95%)
• Treatment: Ursodeoxycholic acid (UDCA); obeticholic acid for refractory cases

Primary Sclerosing Cholangitis (PSC)

• Chronic cholestatic disease causing diffuse progressive inflammation and fibrosis of intrahepatic and extrahepatic bile ducts
• Mainly affects young men in their 30s
• Strongly associated with ulcerative colitis
• Imaging: "Beaded" appearance of intrahepatic ducts with diffuse strictures on cholangiography (MRCP/ERCP)
• High risk of cholangiocarcinoma and gallbladder cancer
• No specific treatment; progressive - usually requires liver transplantation
• Bailey and Love's Short Practice of Surgery, 28th Ed.

Autoimmune Hepatitis (AIH)

• Chronic inflammatory liver disease; predominantly affects women
• Features: Raised transaminases, hypergammaglobulinaemia, positive ANA/anti-smooth muscle antibodies
• Treatment: Prednisolone ± azathioprine

Hereditary Haemochromatosis (HH)

• Autosomal recessive; most common in Northern European populations
• HFE gene mutations: C282Y homozygosity (85-90%), H63D
• Causes iron overload in liver (cirrhosis), pancreas (diabetes), heart (cardiomyopathy), pituitary, joints
• Treatment: Regular phlebotomy; chelation therapy

Wilson's Disease

• Autosomal recessive copper metabolism disorder (ATP7B gene)
• Features: Liver disease, neuropsychiatric symptoms, Kayser-Fleischer rings in cornea
• Diagnosis: Low ceruloplasmin, high urinary copper, liver biopsy
• Treatment: D-penicillamine, trientine, zinc

Non-Alcoholic Fatty Liver Disease (NAFLD) / MASLD

• Now termed Metabolic dysfunction-Associated Steatotic Liver Disease (MASLD)
• Spectrum: Simple steatosis → NASH → fibrosis → cirrhosis → HCC
• Strongly associated with obesity, T2DM, hypertension, dyslipidaemia
• A 2025 meta-analysis (PMID: 40204206) found high global prevalence of steatotic liver disease

Investigations

Treatment Principles

General

• Treat the underlying cause (antivirals for HBV/HCV, alcohol abstinence, immunosuppression for AIH)
• Nutritional support (protein-calorie malnutrition is common)
• Vaccinations (Hepatitis A and B, influenza, pneumococcal)
• Avoid hepatotoxic drugs (NSAIDs, aminoglycosides, nephrotoxins)

HBV Cirrhosis

• Preferred agents: Tenofovir disoproxil fumarate (TDF), Tenofovir alafenamide (TAF), or Entecavir - indefinite treatment
• Long-term antiviral therapy leads to cirrhosis regression in ~75% at year 5 with TDF
• Peginterferon may be considered in well-compensated cirrhosis only
• Decompensated cirrhosis: prompt antiviral initiation regardless of HBV DNA level
• Sleisenger and Fordtran's GI and Liver Disease

HCV

• Direct-acting antiviral agents (DAAs) - curative in > 95% even with cirrhosis

Liver Transplantation

• Definitive treatment for end-stage liver disease
• Indications: CTP-C disease, MELD > 15, HCC within Milan criteria, refractory complications
• King's College Criteria used for timing in acute liver failure

Key Points Summary

• CLD is progressive hepatic injury > 6 months, leading to fibrosis and cirrhosis
• The major complications - portal hypertension, varices, ascites, SBP, HE, HRS, and HCC - are the primary causes of morbidity and mortality
• CTP and MELD scoring are the cornerstone prognostic tools
• Long-term antiviral therapy in HBV cirrhosis can reverse fibrosis in a majority of patients
• Liver transplantation remains the definitive treatment for end-stage disease