Hepatitis Overview

More than 300 million people globally have viral hepatitis. Predominantly caused by hepatitis A, B, and C viruses, viral hepatitis continues to confer high levels of morbidity and mortality despite the availability of vaccines and advances in therapies. Symptom severity varies during acute infection, with management focused on stabilization and serial monitoring to ensure resolution of liver injury. Infection with hepatitis A virus is generally self-limited, with low but increasing rates of mortality and hospitalization due to factors such as poorer baseline health status, older age, and coexisting liver disease. About 95% of acute hepatitis B cases in adults resolve spontaneously; treatment is rarely needed in acute infection. In contrast, only about 25% of acute hepatitis C cases resolve spontaneously, and immediate initiation of treatment at diagnosis is recommended. Screening for hepatitis B and C is recommended for all adults. Hepatocellular carcinoma screening is recommended for those with hepatitis B and cirrhosis or specific risk factors, and for those with hepatitis C and advanced liver fibrosis or cirrhosis. Treatment of hepatitis B involves assessment of specific factors to determine antiviral need; the goal of treatment is suppression of viral replication, thereby reducing risks of liver disease progression and hepatocellular carcinoma. Curative medications are available for hepatitis C.

Alcohol-associated liver disease is the leading cause of cirrhosis in the United States and has become the top indication for liver transplantation since direct-acting antivirals allowed for cure of hepatitis C. The COVID-19 pandemic compounded existing concerns about a rising prevalence of alcohol-associated hepatitis, with a notable increase in women in their 30s and 40s. Insufficient access to health care continues to exacerbate socioeconomic disparities in screening and treatment. People identifying as American Indian or Alaska Native have had the greatest increase in mortality due to alcohol-associated liver disease. Alcohol use screening is essential for all adults. Abstinence from alcohol remains the cornerstone intervention for alcohol-associated liver disease, although pharmacotherapies are under evaluation. Noninvasive liver disease assessment, including serum and imaging modalities, is expanding access to advanced liver disease evaluation in primary care settings. Other causes of substance-based liver injury include prescription and nonprescription medications, herbal products, and dietary supplements.

Although metabolic, viral, and drug- and alcohol-related etiologies are a familiar part of the evaluation of elevated liver enzymes, less common causes include autoimmune hepatitis, Wilson disease, and hereditary hemochromatosis. Each has a progressive course to end-organ damage underscoring the importance of early recognition, as effective therapies are available. Autoimmune hepatitis is an immune-mediated liver disease, with a female predominance and autoantibodies present in about 80% of cases. It can progress rapidly without treatment. Liver biopsy featuring lymphoplasmacytic hepatitis is needed for diagnosis and to determine the intensity of immunosuppression. Wilson disease is caused by biallelic variants in the ATP7B gene resulting in copper accumulation in the liver, brain, kidneys, and corneas. Diagnosis relies on clinical findings, laboratory data, and genetic testing results. Lifelong chelation therapy is required. Hereditary hemochromatosis is characterized by iron overload, usually due to a common variant in the HFE gene with variable disease penetrance; it is prevalent in people of Northern European ancestry. Untreated hemochromatosis leads to cirrhosis and hepatocellular carcinoma. Early diagnosis and initiation of phlebotomy can result in normal life expectancy. To facilitate early diagnosis, genetic testing of first-degree relatives is recommended for those with Wilson disease or hemochromatosis.