Cirrhosis and portal hypertension (PHT)

Cirrhosis is an irreversible, end-stage liver disease characterized by progressive fibrosis, formation of regenerative nodules and loss of normal architecture of the liver. Fibrotic bands link portal tracts to one another. The space of Disse is filled with scar tissue and the endothelial fenestrations are lost (capillarization of sinusoids) from fibrosis. Kupffer cells, inflammatory cells and bile duct epithelial cells secrete cytokines and growth factors like transforming growth factor beta which drives fibrosis. Activated myofibroblasts that derive from perisinusoidal hepatic stellate cells and portal or central vein fibroblasts proliferate and produce excess extracellular matrix. Blood is shunted from the portal veins and arteries to central veins. Intrahepatic resistance rises causing portal hypertension with splanchnic vasodilation, hypoperfusion of the kidneys with salt and water retention. Patients with cirrhosis are at increased risk of infections with intestinal bacteria like E.coli.

Causes of cirrhosis

• Alcoholic liver disease
• Hepatitis C
• Hepatitis B
• Fatty liver and non-alcoholic steatohepatitis
• Hemochromatosis
• Wilson’s disease
• Biliary cirrhosis
• AAT deficiency
• Autoimmune hepatitis
• Metabolic and infectious

Micronodular cirrhosis: Nodules are <3 mm in diameter; seen in cirrhosis due to alcoholic liver disease, hemochromatosis, biliary obstruction. Progresses over time to macronodular type.

Macronodular cirrhosis: Nodules >3mm in diameter, seen in Hep B,C, alpha 1 antitrypsin deficiency, primary biliary cholangitis.

Cirrhosis remains asymptomatic for a long time till complications occur. It presents with jaundice, ascites, caput medusae, hematemesis, bleeding esophageal varices, palmar erythema, pruritus, flapping tremors, seizures, spider angiomas, hyperglycemia, clubbing, peripheral edema, hepatomegaly, splenomegaly, gynecomastia, Dupuytren’s contracture, anorexia, fatigue and a characteristic sweet smell called fetor hepaticus.

Portal hypertension occurs when the pressure in the portal vein is >10mmHg or the hepatic venous pressure gradient (HVPG) is > 4mmHg. HVPG correlates directly with bleeding in esophageal varices. PHT presents with hepatosplenomegaly and varices (back pressure into veins) located in the lower esophagus, cardia of the stomach, the anus, umbilicus, the falciform ligament and retroperitoneum.

Characteristic clinical features of cirrhosis and liver failure

Biopsy is the gold standard for diagnosis of cirrhosis. Liver enzymes like AST and ALT may be normal or elevated, gamma glutamyl transferase, alkaline phosphatase and bilirubin are elevated, albumin is low from decreased synthesis, PT increases, PTT is normal initially and prolonged in later stages, IgG increases and hyponatremia may be seen from water retention. Ultrasound, CT and MRI show nodularity of the liver surface, fibrosis and changes of portal hypertension. Elastography scan can assess degree of fibrosis.

Management includes abstinence from alcohol, treatment of the underlying conditions like HCV (interferon and ribavirin), HBV (lamivudine, adefovir, entecavir, telbivudine), which may help to stop progression or even reverse early cirrhosis. Hyponatremia is treated with fluid restriction and conivaptan (vasopressin receptor antagonist). Fresh frozen plasma is given in acute bleeding. Screening should be done for esophageal varices and hepatocellular carcinoma. NSAIDS and hepatotoxic drugs are avoided. Immunizations against Hep A, Hep B, influenza, pneumonia, tetanus, diphtheria, zoster, HPV and meningococci are recommended. Vitamin K injections are given prophylactically. Patients should be evaluated for liver transplantation once complications have appeared.

TIPS or transjugular intrahepatic portosystemic shunt is a minimally invasive procedure that connects the portal vein to the hepatic vein thus bypassing the liver parenchyma. Hence, it decreases pressure in the portal vein, which is useful in portal hypertension. It can be used as a treatment of refractory ascites and variceal bleeding in patients with cirrhosis. Adverse effect is a worsening of hepatic encephalopathy. Alternatively, a surgical porto-systemic shunting can also be done.