Laboratory Tests for Cirrhosis
Cirrhosis is defined as the fibrotic replacement of liver tissue that can result from any chronic liver disease. Cirrhosis affects approximately 2.2 million adults in the United States and is associated with mortality rates of 21.9 per 100 000 people. Complications of cirrhosis include variceal hemorrhage, ascites, and hepatic encephalopathy.
The most common causes of cirrhosis are alcohol use disorder (45% of cases), hepatitis C (41%), and nonalcoholic fatty liver disease (26%). Many patients have overlapping causes. Since hepatitis C has become curable with direct-acting antiviral medications, most newly diagnosed cases of cirrhosis are due to nonalcoholic fatty liver disease (NAFLD) (62% of incident cases) and alcohol use disorder (20.0%). NAFLD was recently renamed metabolic dysfunction-associated steatotic liver disease (MASLD).
Screening for cirrhosis in the general population is not currently recommended. However, patients with established chronic liver disease, hepatic steatosis, or viral hepatitis should be evaluated for cirrhosis. Liver biopsy has been considered the gold standard to diagnose cirrhosis but is being increasingly replaced by blood tests and imaging-based indices. Biopsy is reserved for patients with inconclusive or technically inadequate noninvasive testing.
A few common blood tests provide indirect signs of liver fibrosis and dysfunction. For example, thrombocytopenia reflects reduced platelet production due to decreased thrombopoietin synthesis by the liver and splenic sequestration. A higher ratio of aspartate aminotransferase to alanine aminotransferase is seen in alcoholic liver disease and cirrhosis.
The fibrosis-4 index (FIB-4) is a widely accepted risk-stratification tool that incorporates age, alanine aminotransferase (ALT), aspartate aminotransferase (AST), and platelet count. Separate cutoffs have been derived based on the underlying etiology of chronic liver disease. For people with either NAFLD or alcohol-related liver disease, FIB-4 classifies scores as low (<1.30), intermediate (1.30-2.67), and high (>2.67). FIB-4 scores are also adjusted for age. The lower risk threshold is raised to 2.0 or less for patients older than 65 years, while the high-risk threshold remains the same. Cutoffs of less than 1.45 and greater than 3.25 have been developed for hepatitis C. FIB-4 has a high negative predictive value (96%) but low positive predictive value (63%) for cirrhosis.
Additional testing is needed for patients with an elevated FIB-4 score (eg ≥1.3 for patients with NAFLD, ≥2.0 for patients >65 years old). Elastography measures liver stiffness that correlates with the degree of fibrosis. A liver stiffness measurement of 15 kPa or greater by vibration-controlled transient elastography (VCTE) identifies cirrhosis with 95.5% specificity and 62% positive predictive value. Conversely, a LSM of 10 kPa or greater has a sensitivity of 74.9% and 88% negative predictive value. Liver inflammation (ie, alanine aminotransferase >120 IU/L) and central venous congestion from heart failure can increase liver stiffness and lead to false-positives from elastography.
Laboratory tests can be used to determine prognosis in patients with cirrhosis. Lower serum levels of albumin, higher international normalized ratios (INRs), and elevated bilirubin levels are associated with reduced survival. These are 3 components of the Child-Turcotte-Pugh (CTP) score, which also includes ascites and hepatic encephalopathy. CTP scores range from 5 (75% 5-year survival) to 15 (20% 5-year survival if >12). CTP is used for long-term prognostication.
Bilirubin and INR are included in the Model for End-stage Liver Disease–Sodium (MELD-Na) score along with creatinine and sodium levels. MELD-Na scores range from 6 (1.9% 90-day mortality) to 40 (71.3% 90-day mortality). MELD is best suited to determine short-term prognostication for patients with decompensated cirrhosis. It is primarily used to prioritize organ allocation for patients on the liver transplant waitlist.
Reference
Tapper EB, Parikh ND. Diagnosis and Management of Cirrhosis and Its Complications: A Review. JAMA. 2023;329(18):1589–1602. doi:10.1001/jama.2023.5997.
