A patient who received blood transfusions before 2000 presents with chronic hepatitis; hepatitis B surface antigen is negative, hepatitis B antibody is positive, and hepatitis C antibody is positive. Which hepatitis virus is most likely responsible for his chronic hepatitis?

Hepatitis C is Responsible for This Patient's Chronic Hepatitis

The patient's chronic hepatitis is caused by hepatitis C virus (HCV), not hepatitis B. The serologic pattern—negative HBsAg with positive HBV antibodies—indicates resolved or vaccinated HBV immunity, while positive HCV antibodies in a patient with pre-1992 transfusion history and chronic hepatitis symptoms strongly implicates active HCV infection 1, 2.

Serologic Interpretation

Hepatitis B Status

• Negative HBsAg rules out chronic hepatitis B infection, as chronic HBV requires persistent HBsAg positivity for >6 months 1, 2
• Positive HBV antibodies (anti-HBs) indicate immunity from either past resolved infection or vaccination, not active disease 2, 3
• This serologic pattern (HBsAg negative, anti-HBs positive) represents past HBV exposure with recovery or vaccine-induced immunity, definitively excluding chronic HBV as the cause 1, 2

Hepatitis C Status

• Positive HCV antibodies in a patient with transfusion history before 1992 strongly suggests chronic HCV infection 4, 1
• Anti-HCV antibodies alone cannot distinguish between resolved and active infection—HCV RNA PCR testing is mandatory to confirm active chronic infection 2
• Approximately 75-85% of HCV-infected individuals develop chronic infection, making chronicity the expected outcome 2, 5

Historical Context: Pre-1992 Transfusion Risk

Blood transfusions performed before 1992 carried extremely high risk for HCV transmission because routine donor screening was unavailable 4, 1:

• In the pre-screening era (1960s-1970s), post-transfusion hepatitis rates exceeded 20%, with 90% caused by non-A, non-B hepatitis (later identified as HCV) 4
• HCV was the predominant cause of transfusion-transmitted viral hepatitis before screening implementation 1
• Among transfusion-dependent populations, HCV antibody prevalence ranges from 4.4% to 85.4%, with genotype 1b most common 4

Natural History Supporting HCV as the Culprit

HCV characteristically causes chronic hepatitis with the following progression 1, 2:

• Approximately 77% of transfusion-acquired HCV infections become chronic 1
• About 50% develop biochemical evidence of chronic liver disease within 12 months 1, 2
• Within 5 years, ≥40% develop chronic active hepatitis and 10-20% show cirrhosis on biopsy, often with minimal symptoms 1, 2
• The majority remain asymptomatic for years despite ongoing liver damage 2
• Median interval from HCV acquisition to cirrhosis is approximately 30 years 1

Recommended Diagnostic Confirmation

To definitively establish HCV as the cause, perform the following algorithm 1, 2:

1. Obtain quantitative HCV RNA PCR to confirm active viral replication (detectable RNA = chronic infection) 1, 2
2. Measure liver transaminases (ALT/AST), which are typically elevated in chronic active HCV 1
3. Determine HCV genotype (most commonly 1b in transfusion cases) to guide future antiviral therapy 1
4. Assess comprehensive liver panel including bilirubin, albumin, and prothrombin time to evaluate hepatic injury extent 2

Critical Pitfall to Avoid

Do not assume positive HCV antibodies alone prove chronic infection—approximately 15-25% of HCV-infected individuals spontaneously clear the virus but retain antibodies 5. Only detectable HCV RNA confirms ongoing chronic infection requiring treatment 2.

Answer to Multiple Choice Question

The answer is 3 (Hepatitis C) based on:

• Negative HBsAg excluding chronic HBV 1, 2
• Positive HCV antibodies in high-risk transfusion recipient 4, 1
• Clinical presentation of chronic hepatitis consistent with HCV natural history 1, 2
• Historical epidemiology showing HCV as the predominant transfusion-transmitted hepatitis before 1992 4, 1