Can chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection cause anemia in a patient with low hemoglobin?

Does Hepatitis Cause Anemia?

Chronic hepatitis B or C infection itself does not directly cause anemia in most patients, but anemia can develop through several indirect mechanisms including hypersplenism from portal hypertension, gastrointestinal bleeding, and nutritional deficiencies associated with advanced liver disease. 1

Mechanisms of Anemia in Chronic Hepatitis

Direct Viral Effects (Rare)

• Hemolytic anemia can occur as a rare complication of acute viral hepatitis, where the virus may directly injure red cell membranes or trigger autoimmune hemolytic anemia through immunological abnormalities. 2
• This mechanism is uncommon and typically associated with acute hepatitis A or B rather than chronic HBV/HCV infection. 2

Indirect Mechanisms in Chronic Disease

• Portal hypertension leading to hypersplenism causes sequestration and destruction of red blood cells, contributing to anemia in patients with cirrhosis. 1
• Acute or chronic gastrointestinal hemorrhage from varices or portal hypertensive gastropathy is a major cause of anemia in advanced liver disease. 1
• Impaired coagulation factor synthesis by damaged hepatocytes predisposes to bleeding and subsequent anemia. 1
• Nutritional deficiencies (folate, vitamin B12) from inadequate dietary intake or malabsorption can exacerbate anemia in chronic liver disease. 1

Treatment-Related Anemia (Critical Distinction)

Interferon-Based Regimens (Older Therapy)

• Ribavirin causes significant hemolytic anemia in 29-49% of patients receiving combination therapy with pegylated interferon, with hemoglobin dropping below 10 g/dL. 3
• The hemolytic effect of ribavirin, combined with interferon-induced bone marrow suppression, was the primary cause of treatment-related anemia. 3, 4
• In cirrhotic patients, treatment-related anemia was more severe, with 67% developing significant anemia compared to 46% in non-cirrhotic patients. 3

Modern Direct-Acting Antivirals (Current Standard)

• Modern DAA regimens (sofosbuvir/velpatasvir, glecaprevir/pibrentasvir) do NOT cause anemia and are safe in patients with pre-existing anemia. 5
• The American Association for the Study of Liver Diseases emphasizes that modern DAAs are well-tolerated and do not cause the severe anemia associated with older interferon-based regimens. 5
• Patients with hemoglobinopathies should be treated with interferon-free, ribavirin-free regimens to avoid exacerbating their baseline anemia. 3

Clinical Implications

For Patients NOT on Treatment

• Evaluate for complications of chronic liver disease including portal hypertension, varices, and nutritional deficiencies if anemia is present. 1
• Anemia in untreated chronic hepatitis suggests advanced disease or alternative causes rather than direct viral effects. 1

For Patients on Treatment

• If using ribavirin-containing regimens (now rare), expect hemoglobin drops of 3-4 g/dL, with the nadir occurring at weeks 12-14. 3
• Modern DAA therapy should NOT be delayed due to anemia concerns, as these agents do not worsen anemia. 5

Common Pitfalls to Avoid

• Do not attribute anemia directly to HBV/HCV infection without evaluating for complications of liver disease (bleeding, hypersplenism) or alternative causes. 1
• Never use interferon/ribavirin-based regimens in patients with baseline anemia when modern DAAs are available, as ribavirin-induced hemolysis would be catastrophic. 5
• Do not assume all hepatitis patients on treatment will develop anemia—this only applies to older ribavirin-containing regimens, not modern DAAs. 5