Cirrhosis and Its Complications¶
Chapter 355 | Part 10: Disorders of the Gastrointestinal System
KEY CLINICAL POINTS¶
- Cirrhosis is a histopathological condition characterized by fibrosis and regenerative nodules, with complications varying by etiology.
- Key causes include alcohol, viral hepatitis (B/C), metabolic disorders, autoimmune diseases, and biliary causes (Table 355-1).
- Management prioritizes abstinence, treatment of complications (e.g., variceal bleeding, ascites), and liver transplantation for decompensated cases.
- Portal hypertension drives complications like ascites, varices, and hepatic encephalopathy, with SAAG guiding ascites etiology.
- Early diagnosis and intervention improve prognosis, particularly in alcoholic hepatitis and viral hepatitis.
1. DEFINITION & OVERVIEW¶
Cirrhosis is a chronic liver disease characterized by fibrosis and regenerative nodules, leading to impaired liver function. It results from prolonged injury (e.g., alcohol, viral hepatitis, metabolic disorders) and can be reversed if the underlying cause is removed. Complications include portal hypertension, ascites, variceal bleeding, and hepatic encephalopathy.
Table 355-1 Causes of Cirrhosis¶
| Cause | Description |
|---|---|
| Alcohol | Chronic heavy drinking leads to fibrosis and nodular regeneration. |
| Chronic Viral Hepatitis | Hepatitis B/C causes immune-mediated liver damage. |
| Inherited Metabolic Liver Disease | e.g., Hemochromatosis, Wilson’s disease, a1-antitrypsin deficiency. |
| Biliary Cirrhosis | Primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC). |
| Cryptogenic Cirrhosis | No identifiable cause, often associated with metabolic dysfunction. |
1.1 Pathologic Features¶
Fibrosis disrupts liver architecture, replacing normal tissue with regenerative nodules. Micronodular (alcohol) or macronodular (viral) patterns may develop. Fibrosis progresses to cirrhosis with portal hypertension and systemic complications.
1.2 Reversibility¶
Fibrosis may reverse with removal of the causative agent (e.g., antiviral therapy for hepatitis C, abstinence from alcohol). However, advanced cirrhosis is irreversible and leads to decompensation.
2. EPIDEMIOLOGY¶
Cirrhosis affects ~1.5% of the global population. Alcohol (48% of cirrhosis deaths), viral hepatitis (B/C), and metabolic disorders (e.g., NAFLD) are leading causes. Risk factors include heavy alcohol use (>2 drinks/day in women, >3 in men), viral infections, obesity, and genetic predispositions.
2.1 Global Prevalence¶
Hepatitis C affects ~170 million globally, with ~20–30% progressing to cirrhosis. Hepatitis B affects ~257 million, with ~5–10% developing cirrhosis. Obesity and NAFLD contribute to ~25% of cirrhosis cases.
2.2 Demographics¶
Men are more commonly affected than women. Alcohol-related cirrhosis peaks in middle age; PBC is more common in women (median age 50).
3. ETIOLOGY & PATHOPHYSIOLOGY¶
Cirrhosis arises from chronic injury (e.g., alcohol, viral hepatitis, autoimmune diseases) leading to fibrosis and nodular regeneration. Alcohol metabolism produces reactive oxygen species, while viral hepatitis triggers immune-mediated damage. Genetic disorders (e.g., hemochromatosis) cause iron overload and fibrosis.
Table 355-2 Complications of Cirrhosis¶
| Complication | Description |
|---|---|
| Portal Hypertension | Elevated hepatic venous pressure gradient (>5 mmHg) causing varices, ascites, and splenomegaly. |
| Hepatic Encephalopathy | Neurological dysfunction due to ammonia accumulation and systemic inflammation. |
| Spontaneous Bacterial Peritonitis (SBP) | Infection of ascitic fluid, common in cirrhotic patients with ascites. |
| Hepatorenal Syndrome (HRS) | Functional renal failure in advanced cirrhosis, classified as acute (HRS-AKI) or chronic (HRS-CKD). |
| Hepatocellular Carcinoma | Risk increases with cirrhosis, particularly in viral hepatitis or NAFLD. |
3.1 Alcohol-Induced Pathogenesis¶
Ethanol metabolism via ADH and ALDH generates acetaldehyde, causing oxidative stress and fibrosis. Stellate cell activation leads to collagen deposition and portal hypertension.
4. CLINICAL FEATURES¶
Symptoms include fatigue, jaundice, ascites, and hepatic encephalopathy. Physical findings may include palmar erythema, spider angiomas, and splenomegaly. Compensated cirrhosis is asymptomatic, while decompensated cirrhosis presents with ascites, variceal bleeding, or encephalopathy.
4.1 Compensated vs. Decompensated Cirrhosis¶
Compensated cirrhosis is asymptomatic with minimal functional impairment. Decompensated cirrhosis presents with ascites, variceal bleeding, encephalopathy, or spontaneous bacterial peritonitis (SBP).
4.2 Specific Syndromes¶
PBC presents with fatigue, pruritus, and cholestasis. PSC causes biliary cirrhosis with cholangitis and cholangiocarcinoma risk. Hemochromatosis leads to iron overload and cirrhosis.
5. DIFFERENTIAL DIAGNOSIS¶
Differentiate cirrhosis from Budd-Chiari syndrome (obstructive hepatic vein thrombosis), cardiac cirrhosis (right-sided heart failure), and metabolic disorders. Autoimmune diseases (e.g., AIH) and infections (e.g., schistosomiasis) must be ruled out.
5.1 Imaging and Biomarkers¶
MRI/MRCP for biliary causes, ultrasound for ascites, and liver biopsy for histopathology. AMA testing aids in PBC diagnosis.
6. INVESTIGATIONS & DIAGNOSIS¶
Diagnostic tests include liver function tests (ALT/AST, ALP, bilirubin), coagulation profiles (PT/INR), and imaging (ultrasound, MRI). SAAG (serum ascites-to-albumin gradient) differentiates portal hypertension from other causes of ascites.
Table 355-3 Classification of Portal Hypertension¶
| Type | Causes |
|---|---|
| Prehepatic | Portal vein thrombosis, splenic vein thrombosis |
| Intrahepatic | Cirrhosis, schistosomiasis, congenital hepatic fibrosis |
| Posthepatic | Budd-Chiari syndrome, cardiac cirrhosis |
6.1 Ascites Evaluation¶
SAAG >1.1 g/dL suggests portal hypertension; <1.1 g/dL indicates non-portal causes (e.g., SBP, malignancy). Ascitic fluid analysis (neutrophils >250/ µ L) confirms SBP.
6.2 Liver Biopsy¶
Histopathology confirms cirrhosis and identifies etiology (e.g., AIH, PBC). Fibrosis staging (METAVIR or IHS) guides prognosis.
7. MANAGEMENT & TREATMENT¶
Management includes abstinence, antiviral therapy (HBV/HCV), and treatment of complications. Variceal bleeding is managed with beta-blockers, endoscopic therapy (EVL), and TIPS. Ascites is treated with diuretics (spironolactone, furosemide) and paracentesis.
Table 355-2 Complications of Cirrhosis¶
| Complication | Description |
|---|---|
| Portal Hypertension | Elevated hepatic venous pressure gradient (>5 mmHg) causing varices, ascites, and splenomegaly. |
| Hepatic Encephalopathy | Neurological dysfunction due to ammonia accumulation and systemic inflammation. |
| Spontaneous Bacterial Peritonitis (SBP) | Infection of ascitic fluid, common in cirrhotic patients with ascites. |
| Hepatorenal Syndrome (HRS) | Functional renal failure in advanced cirrhosis, classified as acute (HRS-AKI) or chronic (HRS-CKD). |
| Hepatocellular Carcinoma | Risk increases with cirrhosis, particularly in viral hepatitis or NAFLD. |
7.1 Variceal Hemorrhage¶
First-line: beta-blockers (propranolol, carvedilol) or endoscopic band ligation. Recurrent bleeding requires TIPS or liver transplantation. Prophylaxis in high-risk patients (Child-Pugh B/C).
7.2 Ascites Management¶
Dietary sodium restriction (<2 g/day), diuretics (spironolactone 100 mg + furosemide 40 mg). Refractory ascites requires TIPS or large-volume paracentesis with albumin replacement.
8. PROGNOSIS & COMPLICATIONS¶
Decompensated cirrhosis has a poor prognosis, with <50% 5-year survival. Complications include portal hypertension, ascites, variceal bleeding, hepatic encephalopathy, and hepatocellular carcinoma. Malnutrition and bone disease (osteoporosis) are common in advanced stages.
8.1 Survival and Transplantation¶
Liver transplantation is the only curative option for decompensated cirrhosis. Survival improves with early intervention and abstinence.
8.2 Complication Management¶
Hepatic encephalopathy is treated with lactulose and rifaximin. SBP requires antibiotics (ceftriaxone) and albumin. HRS is managed with liver transplantation.
9. SPECIAL CONSIDERATIONS¶
Pregnancy: Cholestasis of pregnancy may mimic PBC. Pediatrics: NAFLD is increasingly common in children. Elderly: Higher risk of complications (e.g., SBP, HRS).
9.1 Pregnancy¶
Cholestasis of pregnancy may mimic PBC; monitor for pruritus and elevated LFTs. Avoid NSAIDs due to hepatotoxicity.
9.2 Pediatrics¶
NAFLD is rising in children due to obesity. Monitor for hepatic steatosis and progression to NASH/cirrhosis.
10. KEY POINTS & CLINICAL PEARLS¶
- Abstinence is critical for alcohol-related cirrhosis. 2. Early antiviral therapy (HBV/HCV) prevents cirrhosis progression. 3. TIPS is effective for refractory ascites but increases hepatic encephalopathy risk. 4. Lactulose and rifaximin manage hepatic encephalopathy. 5. Liver transplantation is the definitive treatment for decompensated cirrhosis.