Residency · Residency · Family Medicine

Hepatitis B and C: Screening, Vaccination, and Treatment Referral

Introduction

Viral hepatitis B (HBV) and hepatitis C (HCV) are major causes of chronic liver disease, cirrhosis, and hepatocellular carcinoma worldwide. Family physicians are essential for implementing universal screening recommendations, ensuring vaccination coverage for HBV, and facilitating treatment for HCV, which is now curable in over 95% of cases with direct-acting antivirals.

Hepatitis B

Epidemiology

Approximately 296 million people live with chronic HBV globally, with an estimated 880,000 to 1.4 million chronically infected in the United States. Transmission occurs via percutaneous, sexual, and vertical (mother to child) routes. Risk groups include persons born in high-prevalence regions, injection drug users, MSM, household contacts of HBV-positive persons, and healthcare workers.

Screening

The USPSTF recommends universal HBV screening for all adolescents and adults aged 15 to 65 and all pregnant persons. Screening uses a triple panel: HBsAg, anti-HBs, and anti-HBc (total).

Interpretation is as follows: immunity from vaccination shows HBsAg negative, anti-HBs positive, and anti-HBc negative; immunity from prior infection shows HBsAg negative, anti-HBs positive, and anti-HBc positive; chronic infection shows HBsAg positive, anti-HBs negative, and anti-HBc positive; susceptibility is indicated when all three are negative, and the patient should be vaccinated.

Vaccination

Universal infant vaccination begins at birth, with hepatitis B immune globulin (HBIG) plus vaccine for infants born to HBsAg-positive mothers. All unvaccinated adults should be vaccinated per the ACIP universal adult recommendation. Available vaccines include Engerix-B and Recombivax (3-dose series), Heplisav-B (2-dose series), and PreHevbrio (3-dose series). Post-vaccination serologic testing for anti-HBs is recommended for healthcare workers and other high-risk groups, with a protective level of 10 mIU/mL or greater.

Chronic HBV Management

Patients with chronic HBV should be referred to hepatology or infectious disease for treatment consideration. Indications for treatment include elevated ALT, high HBV DNA levels, evidence of significant fibrosis, and cirrhosis. First-line therapies are tenofovir (TDF or TAF) or entecavir, typically requiring lifelong treatment. Monitoring every 6 months with ALT, HBV DNA, and hepatocellular carcinoma (HCC) surveillance using ultrasound with or without AFP is recommended for at-risk patients. Family members and sexual contacts should be screened and vaccinated if susceptible.

Hepatitis C

Epidemiology

Approximately 58 million people have chronic HCV globally, with approximately 2.4 million chronically infected in the United States, many of whom are undiagnosed. Transmission is primarily percutaneous, with injection drug use accounting for 60 to 70% of new infections. Other risk factors include blood transfusion before 1992, incarceration, intranasal drug use, needlestick injuries, and vertical transmission.

Screening

The USPSTF and CDC recommend universal HCV screening for all adults aged 18 and older at least once, and for all pregnant persons during each pregnancy. Screening uses the anti-HCV antibody, and positive results are confirmed with HCV RNA (viral load). Anti-HCV positive with RNA positive indicates active (current) infection. Anti-HCV positive with RNA negative indicates cleared infection, either spontaneous or treated, and no further treatment is needed. Repeat screening should be performed for persons with ongoing risk factors such as active injection drug use.

Natural History

Acute HCV is often asymptomatic, and 75 to 85% of infected individuals develop chronic infection. Chronic HCV progresses slowly over decades, with 15 to 30% developing cirrhosis within 20 to 30 years. Cirrhosis carries a 1 to 5% annual risk of hepatocellular carcinoma and risk of decompensation. Extrahepatic manifestations include cryoglobulinemia, membranoproliferative glomerulonephritis, porphyria cutanea tarda, and lymphoma.

Treatment

Direct-acting antivirals (DAAs) achieve sustained virologic response (SVR, or cure) in over 95% of patients. Pan-genotypic regimens simplify treatment, often eliminating the need for genotyping. Sofosbuvir/velpatasvir (Epclusa) is given for 12 weeks and covers all genotypes. Glecaprevir/pibrentasvir (Mavyret) is given for 8 weeks in treatment-naive non-cirrhotic patients and is pan-genotypic. Pre-treatment assessment includes HCV genotype (if required by insurer), fibrosis staging (FibroScan or FIB-4 score), hepatic function panel, CBC, and renal function. Drug interactions should be checked, particularly with acid-reducing agents, statins, and certain anticonvulsants. There is no contraindication to treating active injection drug users, as treatment in this population prevents ongoing transmission.

Post-Treatment Follow-Up

SVR is confirmed by checking HCV RNA at 12 weeks after completing treatment (SVR12). SVR12 equals cure, though reinfection risk exists with ongoing risk behaviors. Patients with cirrhosis require lifelong HCC surveillance with ultrasound every 6 months even after SVR. Patients without cirrhosis who achieve SVR generally do not require ongoing hepatology follow-up.

Fibrosis Assessment

The FIB-4 index is a non-invasive calculation using age, AST, ALT, and platelet count. A score below 1.45 indicates low probability of advanced fibrosis, while a score above 3.25 indicates high probability. Intermediate values should be followed by FibroScan or imaging. FibroScan (transient elastography) measures liver stiffness and is widely available and non-invasive. Liver biopsy remains the gold standard but is invasive and rarely needed with current non-invasive tools.

Role of the Family Physician

Family physicians should implement universal screening for HBV and HCV in primary care and ensure all adults are vaccinated against HBV. Family physicians can prescribe DAAs for uncomplicated HCV in non-cirrhotic, treatment-naive patients, with training programs and simplified protocols available. Referral to hepatology is appropriate for patients with cirrhosis, decompensated liver disease, prior treatment failure, or HBV/HCV co-infection. Barriers to care including insurance coverage, stigma, and the need for substance use disorder treatment integration should be actively addressed.

Key Clinical Pearls

Universal screening for both HBV and HCV is now recommended for all adults; risk-based screening alone misses many infections. HCV is curable with 8 to 12 weeks of oral DAAs in over 95% of patients, and family physicians should be comfortable initiating treatment for uncomplicated cases. The 2-dose Heplisav-B series simplifies HBV vaccination completion for adults. Patients with cirrhosis from HBV or HCV require lifelong HCC surveillance with ultrasound every 6 months, even after successful treatment.

References

1. USPSTF. Screening for Hepatitis B Virus Infection in Adolescents and Adults. JAMA. 2023;330(23):2293-2301.
2. USPSTF. Screening for Hepatitis C Virus Infection in Adolescents and Adults. JAMA. 2020;323(10):970-975.
3. AASLD-IDSA. HCV Guidance: Recommendations for Testing, Managing, and Treating Hepatitis C. https://www.hcvguidelines.org. Updated 2024.
4. Terrault NA, et al. AASLD guidelines for treatment of chronic hepatitis B. Hepatology. 2018;67(4):1560-1599.

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