Cirrhosis is an irreversible, end-stage liver disease characterized by progressive fibrosis, formation of regenerative nodules, and loss of the liver’s normal architecture. Fibrotic bands link portal tracts to one another. The space of Disse becomes filled with scar tissue, and endothelial fenestrations are lost (capillarization of sinusoids) due to fibrosis.
Kupffer cells, inflammatory cells, and bile duct epithelial cells secrete cytokines and growth factors (for example, transforming growth factor beta), which drive fibrosis. Activated myofibroblasts - derived from perisinusoidal hepatic stellate cells and from portal or central vein fibroblasts - proliferate and produce excess extracellular matrix.
As fibrosis progresses, blood is shunted from the portal veins and hepatic arteries toward central veins. Intrahepatic resistance rises, leading to portal hypertension with splanchnic vasodilation, kidney hypoperfusion, and salt and water retention. Patients with cirrhosis are also at increased risk of infections with intestinal bacteria such as E.coli.
Micronodular cirrhosis: Nodules are <3 mm in diameter; seen in cirrhosis due to alcoholic liver disease, hemochromatosis, and biliary obstruction. Over time, it can progress to the macronodular type.
Macronodular cirrhosis: Nodules are >3 mm in diameter; seen in Hep B, Hep C, alpha 1 antitrypsin deficiency, and primary biliary cholangitis.
Cirrhosis can remain asymptomatic for a long time, and symptoms often appear when complications develop. It may present 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 >10 mmHg or the hepatic venous pressure gradient (HVPG) is >4 mmHg. HVPG correlates directly with bleeding in esophageal varices. Portal hypertension presents with hepatosplenomegaly and varices (from back pressure into veins). Varices can occur in the lower esophagus, the cardia of the stomach, the anus, the umbilicus, the falciform ligament, and the retroperitoneum.
| Feature | Description |
| Spider angioma | Appears as a central arteriole with radiating vessels; due to elevated estradiol from decreased breakdown by the liver |
| Caput medusae | Dilated veins radiating from the umbilicus, due to portal hypertension, shunting between portal vein and umbilical vein |
| Palmar erythema | Distinctive redness of the palms that spares the center of the palm, due to elevated estradiol from decreased breakdown by the liver |
| Gynecomastia | Enlargement of male breast, due to elevated estradiol; substitute amiloride for spironolactone |
| Flapping tremor or asterixis | Flapping tremor elicited on wrist dorsiflexion, due to temporary decreased muscle tone, negative myoclonus, seen in hepatic encephalopathy |
Biopsy is the gold standard for diagnosing cirrhosis. Liver enzymes such as AST and ALT may be normal or elevated. Gamma glutamyl transferase, alkaline phosphatase, and bilirubin are elevated. Albumin is low due to decreased synthesis. PT increases. PTT is normal initially and becomes prolonged in later stages. IgG increases, and hyponatremia may be seen due to water retention.
Ultrasound, CT, and MRI can show nodularity of the liver surface, fibrosis, and changes of portal hypertension. Elastography scan can assess the degree of fibrosis.
Management includes abstinence from alcohol and treatment of underlying conditions such as HCV (interferon and ribavirin) and HBV (lamivudine, adefovir, entecavir, telbivudine). These treatments may help stop progression or even reverse early cirrhosis. Hyponatremia is treated with fluid restriction and conivaptan (a 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, bypassing the liver parenchyma. This decreases pressure in the portal vein, which is useful in portal hypertension. It can be used to treat refractory ascites and variceal bleeding in patients with cirrhosis. An adverse effect is worsening hepatic encephalopathy. Alternatively, a surgical porto-systemic shunt can also be done.