Hepatitis C — The Primary Care Physician’s Role in Reducing the Epidemic’s Impact

Sax, Paul E., MD
Clinical Director of the Division of Infectious Diseases
Brigham and Women's Hospital
Professor of Medicine
Harvard Medical School
Boston, MA
Also by this Author 

Hepatitis C virus (HCV) infection is the most common chronic blood borne infection in the United States affecting approximately 3.2 million people. The majority are asymptomatic and remain undiagnosed for many years but 60%-70% develop chronic liver disease due to their infection.1

To address the impact of this epidemic, the Centers for Disease Control and Prevention and the United States Preventive Services Task Force both recently issued recommendations to screen those at high risk of infection and adults born between 1945-1965 for HCV infection.2, 3

Dr. Paul Sax, Clinical Director, Division of Infectious Disease, Brigham and Women’s Hospital, and Professor of Medicine at Harvard Medical School, discusses the critical role of primary care physicians in identifying those infected with HCV and reducing the burden of chronic liver disease through timely intervention.

Screening Recommendations

“It’s critically important for physicians in the primary care setting to be aware that the large majority of people with hepatitis C are asymptomatic and don’t know they have the infection,” says Dr. Sax. “They should order a screening hepatitis C antibody test for all their patients in the baby-boom generation, because that group represents the largest proportion of undiagnosed cases by far.”

In addition to population based screening, Dr. Sax stresses the importance of screening specific high-risk groups. “The primary way people acquire hepatitis C is through unsafe intravenous drug use,” he notes. “This could just have been a one-time use of injection drugs back in the 1970s, as the virus is highly transmissible.”

Screening should also be performed for individuals who received blood transfusions before 1992; anyone who’s received a blood transfusion in a developing country; anyone who has HIV, in particular HIV-positive injection drug users and HIV – positive gay men. Dr. Sax also suggests it would be prudent to screen gay men, as HCV appears to be a sexually transmitted infection among that group.

The Impact of Undiagnosed HCV

Unlike those infected with hepatitis A and hepatitis B, most people infected with HCV, approximately 80%, have chronic disease.1“Chronic hepatitis C is a lifelong infection that’s characterized by viremia, a variety of other non-hepatic complications, and most importantly by a slowly progressive inflammatory condition in the liver that eventually leads to fibrosis, and possibly hepatocellular carcinoma,” says Dr. Sax. “This progression typically happens over a period of decades, but you can prevent it through treatment, if you catch it early.”

There are also less common extra-hepatic complications of HCV. These include cryoglobulinemia, where people get skin rashes and vascuitis, lymphoma, increased risk of diabetes, and a variety of kidney problems.

Diagnostic Testing

“For an initial diagnosis, physicians only need to order one test – an assay for HCV antibody in blood,” says Dr. Sax. “It’s a very easy test, with low complexity, fast turnaround and good accuracy.”

This antibody test indicates exposure, so a reactive result could indicate current HCV infection, past HCV infection that has resolved, or false positivity. A reactive result therefore needs to be followed up with further testing to confirm whether the patient has cleared the disease or whether there is active infection. This is achieved by nucleic acid testing (NAT) to identify HCV RNA in blood.4 An HCV antibody with reflex to quantitative testing to confirm infectivity is available from certain laboratories, eliminating the need to order a separate follow-up test. The quantitative test also provides the clinician with a baseline viral load.

If active infection is confirmed, physicians should also order a HCV genotype test. “Genotyping is important,” notes Dr. Sax, “because the genotype is an indicator of how well someone will respond to treatment. In addition, in the future some treatments will only be active against specific genotypes, so it will also help direct therapy.”

Following diagnostic testing, a complete clinical assessment for liver disease is performed before initiating therapy. In addition to a physical examination and standard blood tests, this may include testing for indirect markers of liver damage, and, in rare cases, performing a liver biopsy.

Advances in Treatment

The urgency of treatment is dictated by the stage of liver disease. Urgency is low for those with early stage disease, but higher for those with more advanced fibrosis. This distinction has become very important, notes Dr. Sax, because of the imminent availability of new HCV therapies: “Traditional treatment of hepatitis C consists of 24 – 48 weeks of interferon based therapy given with ribavirin, plus a protease inhibitor, which has significant side effects. This is going to change with the recent approval of two new drugs, which will improve and simplify treatment significantly.”

These new drugs, approved in late 2013, are simeprevir, a protease inhibitor taken once a day, which has fewer side effects than the existing drugs in this class, and sofosbuvir, a nucleotide analog. Dr. Sax considers the introduction of these drugs a major leap forward in HCV therapy: “In combination with interferon and ribavirin, sofosbuvirwill shorten treatment from 24 to 12 weeks. Even more exciting is the potential to use these drugs without interferon in some cases - something which is currently being investigated.”

The new drugs offer greater efficacy with less side effects than traditional treatments. “For those with Genotype 1, the most common genotype in the United States and the most difficult to treat, the cure rate is about 75% with the existing standard of care,” observes Dr. Sax. “Most of the non-cures are due to patients’ inability to tolerate the regimen. The new treatment achieves response rates of 80-90%, even 95%, with a shorter course of therapy and fewer side effects. Genotype 2 is much easier to treat so we’ll probably be able to treat genotype 2 with sofosbuvir and ribavirin interferon and achieve 90% cure rates. Genotypes 3 and 4 are somewhat less responsive to treatment."

To assess how patients respond to treatment, the viral load is measured at regular intervals during treatment, at the end of treatment and after treatment. “If they have an undetectable viral load 12 weeks after stopping treatment, some would say 24 but most would say 12, they’re considered cured,” notes Dr. Sax.

Physicians are very keen to reduce interferon treatment because of its toxicity and consequent side effects. It causes flu-like symptoms, low-grade fevers, muscle pains, myalgias and fatigue. “But more importantly,” stresses Dr. Sax, “it’s extremely active in a neuro-psychiatric way. It causes a very high rate of depressive symptoms and irritability and these symptoms associated with interferon therapy worsen over time. So reducing the potential for these side-effects is very important in reducing non-compliance.”

Post-Treatment Management

For patients who have a history of hepatitis and have some degree of cirrhosis there are recommendations to monitor periodically for hepatocellular carcinoma. “The most common recommendation is to do periodic ultrasounds, says Dr. Sax. “Some people say they should also check an alpha-fetoprotein but that’s more debatable. These patients should be managed in conjunction with a hepatologist.”

Finally, Dr. Sax stresses the importance of both HBV and HAV immunization: “Universal immunization is now recommended for hepatitis B. Some adults have not been immunized and are at risk of being infected since hepatitis B is sexually transmitted. They should definitely be immunized. There’s also a very broad range of patients who should get hepatitis A immunization. They include anyone with underlying liver disease, anyone who’s going to travel to an endemic area for hepatitis A, which includes most tropical regions, and sexually active gay men.”


  1. Centers for Disease Control and Prevention. Hepatitis C Information for Health Professionals http://www.cdc.gov/hepatitis/HCV/index.htm. Accessed 11/20/13
  2. Centers for Disease Control and Prevention. Recommendations for the Identification of Chronic Hepatitis C Virus Infection Among Persons Born During 1945–1965. MMWR. Vol. 61 / No. 4 August 17, 2012.
  3. U.S. Preventive Services Task Force Recommendation Statement. Screening for Hepatitis C Virus Infection in Adults http://www.uspreventiveservicestaskforce.org/uspstf12/hepc/hepcfinalrs.htm#copyright Accessed 11/20/13
  4. Testing for HCV Infection: An Update of Guidance for Clinicians and LaboratoriansMMWR / May 7, 2013 / Vol. 62

Released on Tuesday, December 10, 2013