Cirrhosis of the Liver

History and Epidemiology

Cirrhosis is a chronic condition involving the development of fibrosis and nodule formation in the liver.¹ Between 1999 and 2010, the prevalence of cirrhosis of the liver was estimated to be 0.27% in the United States and was higher in people living below the poverty level.² In 2018, 4.5 million adults, or 1.8% of US adults, were diagnosed with liver disease, and, between 2018 and 2021, 56,585 died from chronic liver disease and cirrhosis.³ 

Causes of liver cirrhosis include¹:

• Hepatitis B, C, or D virus
• Cardiac fibrosis
• Autoimmune hepatitis, primary biliary cholangitis, or primary sclerosing cholangitis
• Alcohol consumption
• Arsenic poisoning
• Wilson disease
• Hemochromatosis
• 𝛼-1 antitrypsin deficiency
• Galactosemia
• Glycogen storage disease
• Nonalcoholic fatty liver disease (NFLD) and nonalcoholic steatohepatitis (NASH)
• Budd-Chiari syndrome
• Gallstones, biliary tumors or blockage, or injury to the bile duct
• Cystic fibrosis
• Lysosomal acid lipase deficiency
• Medications, including methotrexate and high-dose vitamin A

Liver fibrosis may be classified based on the following histologic findings¹:

• Stage 0: the portal tract, portal vein branch, hepatic artery branch, and interlobular bile duct are normal; there is mild steatosis (fatty liver) of the acinar parenchyma and no fibrosis
• Stage 1: collagen is increased in the portal tract; fibrosis is present in the portal tract but does not affect the acinar parenchyma 
• Stage 2: collagen is increased in the portal tract and extends to involve the acinar parenchyma
• Stage 3: fibrous bridges are seen in the portal tracts
• Stage 4: cirrhosis of the liver, the structure of which has been replaced with nodules separated by fibrous septa

Cirrhosis also may be described as compensated or decompensated. In this classification, stages 1 and 2 are considered compensated and stages 3 and 4 are considered decompensated. In decompensated cirrhosis, the following signs may be present¹: 

• Encephalopathy
• Jaundice
• Ascites
• Variceal hemorrhage
• Hepatocellular carcinoma

Patients with compensated cirrhosis do not have the above findings.¹ 

Under this classification, patients in stage 1 cirrhosis do not have ascites or varices. Patients in stage 2 cirrhosis have varices with no bleeding and no ascites. In stage 3 cirrhosis, patients have ascites with or without varices. In stage 4 cirrhosis, patients have bleeding of varices with or without ascites.¹

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Diagnosis of Cirrhosis of the Liver

Diagnosis of cirrhosis of the liver is typically based on findings from histologic examination. Physical examination findings also play a role in diagnosis and may include¹: 

• Palmar erythema
• Changes in the nails, such as clubbing and Terry nails (white discoloration of the nails [leukonychia] with a darker band at the tip)
• Gynecomastia (enlargement of the breasts in men or boys)
• Telangiectasia (dilated small blood vessels in the skin or mucous membranes)
• Caput medusae (large swollen veins visible in the mid abdomen)
• Enlargement of the parotid glands
• Gastroesophageal varices (dilated veins in the esophagus and/or stomach)
• Ascites (abdominal fluid collection)
• Hepatic encephalopathy
• Enlarged left lobe of the liver
• Enlarged spleen (splenomegaly)

The following findings on laboratory assessment may be indicative of cirrhosis when combined with the physical signs listed above¹: 

• Thrombocytopenia (low platelet count)
• Hypoalbuminemia
• Prolonged prothrombin time

Additional studies that may aid in confirming a diagnosis of cirrhosis include¹: 

• Vibration-controlled transient elastography

• Liver stiffness of more than 14 kPa indicates cirrhosis
• Liver stiffness of more than 21 kPa indicates portal hypertension 
• Acoustic radiation force impulse elastography
• Values more than 2.6 m/sec indicate cirrhosis
• Magnetic resonance elastography
• Liver stiffness of more than 5.9 kPa indicates cirrhosis

Although liver biopsy is the benchmark for diagnosing cirrhosis, it is also costly, prone to error, and comes with possible risks to the patient. Various scoring systems are available to aid in staging of cirrhosis. Some include¹: 

• Serum aspartate aminotransferase (AST) to platelet ratio index (APRI)
• Score of >2 suggests cirrhosis
• Bonacini cirrhosis discriminant score 
• Score of ≥7 suggests cirrhosis

• Platelet score, alanine transaminase (ALT)/AST ratio, and international normalized ratio (INR) 
• Lok index

In patients with hepatitis B or C, alcohol-associated liver disease, or NFLD, transient elastography is a better test than APRI scoring to determine a diagnosis of cirrhosis.¹ 

The differential diagnosis of cirrhosis of the liver includes the following⁴:

• Hepatic adenoma
• Hepatocellular carcinoma
• Focal nodular hyperplasia
• Nodular regenerative hyperplasia

Management of Cirrhosis of the Liver

Patients with compensated cirrhosis should undergo evaluation every 6 months for hepatocellular carcinoma. They also should be monitored for development of esophageal varices. Lifestyle modifications include weight loss and avoidance of alcohol. Exercise is beneficial, but abdominal exercises should be avoided due to the risk of variceal hemorrhage. Vaccinations, such as those to prevent hepatitis A, hepatitis B, pneumonia, and influenza, should be given. Statin drugs may be helpful in patients with chronic viral hepatitis.¹ 

For pain relief, patients with liver cirrhosis may take acetaminophen up to 2 g/d. Patients with decompensated cirrhosis should avoid using aspirin and nonsteroidal anti-inflammatory drugs due to their increased risk for bleeding. Insulin is recommended for patients with diabetes and decompensated cirrhosis.¹ 

Frequent high-calorie snacks are recommended, and levels of fat-soluble vitamins and zinc should be monitored.

Patients with primary biliary cholangitis may be treated with ursodeoxycholic acid with or without obeticholic acid. Contraindications to treatment with obeticholic acid include the following⁵:

• Decompensated cirrhosis (Child-Pugh Class B or C) 
• Previous decompensation
• Compensated cirrhosis (ascites, gastroesophageal varices, and persistent thrombocytopenia) with portal hypertension
• Complete biliary obstruction

The recommended dosage of obeticholic acid is 5 mg once daily for the first 3 months, after which the dosage may be increased to 10 mg once daily, if needed.⁵ 

Monitoring Side Effects Associated With Treatment for Cirrhosis of the Liver

Patients with cirrhosis often experience fatigue, muscle cramps, and sexual dysfunction. Patients with fatigue should be evaluated to rule out causes such as anemia and underactive thyroid. Phosphodiesterase inhibitors are typically not effective in patients with erectile dysfunction and cirrhosis. Female individuals with cirrhosis who become pregnant are at increased risk for variceal bleeding in the third trimester and require monitoring by a high-risk obstetrician, a hepatologist, and an endoscopist.¹ 

Depression may occur in 30% to 40% of patients with cirrhosis. It may be treated with selective serotonin reuptake inhibitors or mirtazepine.¹ 

Patients treated with obeticholic acid with or without ursodeoxycholic acid should be counseled about possible side effects of treatment, including the following⁵:

• Rash, pruritus, and eczema
• Fatigue
• Abdominal pain 
• Oropharyngeal pain
• Dizziness
• Constipation
• Arthralgia
• Palpitations
• Pyrexia
• Peripheral edema
• Abnormal thyroid function

References

1. Kamath PS, Shah VH. Overview of cirrhosis. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran’s Gastrointestinal and Liver Disease. 11th ed. Elsevier, Inc; 2021:1164-1171. 

2. Scaglione S, Kliethermes S, Cao G, et al. The epidemiology of cirrhosis in the United States: a population-based study. J Clin Gastroenterol. 2015;49(8):690-696. doi:10.1097/MCG.0000000000000208

3. Centers for Disease Control and Prevention. Chronic liver disease and cirrhosis. Updated January 17, 2023. Accessed March 8, 2023. https://www.cdc.gov/nchs/fastats/liver-disease.htm 

4. Ducatman BS, Bernacki KD. Liver. In: Cibas ES, Ducatman BS, eds. Cytology. 5th ed. Elsevier, Inc; 2021:425-450. 

5. Ocaliva^® [package insert]. New York, NY: Intercept Pharmaceuticals, Inc; 2016. 

Author Bio

Jen Seabright, PharmD, is a freelance medical writer in Pittsburgh, Pennsylvania.