Factors That Affect Hepatitis C Treatment
Sustained Virologic Response Varies Widely Among Patients
Aug 18, 2009
With the development of pegylated interferon for the treatment of hepatitis C (HCV), more individuals with this chronic viral infection could look forward to successful treatment than had previously been possible. Prior to this advancement, many patients did not even qualify for pharmacologic therapy and were left with few options to deal with their disease.
However, given the clear superiority of current therapy over older methods, the National Institutes of Health (NIH) now suggests that all patients with chronic HCV infection—barring those with absolute contraindications, such as allergy to the medications—are candidates for therapy. (Management of hepatitis C: 2002. NIH Consens State Sci Statement 2002;19:1-46)
Overall, the combination of pegylated interferon and ribavirin provides a “cure”—measured by a sustained virologic response (SVR)—in up to 80% of HCV patients. Unfortunately, successful treatment for the disease can be markedly impaired by various factors, only some of which are modifiable.
Viral Factors that Affect Response to Treatment for Hepatitis C (HCV)
- Viral genotype: Of the six main genotypes of HCV, type 1 accounts for 75% of infections in the US. Type 1 is the least amenable to treatment; approximately 50% of patients with this genotype achieve SVR. (Fried M, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med. 2002;347[13]:975-982 and Hadziyannis S, et al. Peginterferon-α2a and ribavirin combination therapy in chronic hepatitis C: a randomized study of treatment duration and ribavirin dose. Ann Intern Med. 2004;140[5]:346-355)
- Viral load: The presence of higher numbers of viral particles in the bloodstream prior to beginning treatment decreases the likelihood of SVR. Patients with high viral loads and genotype 1 exhibit only a 40 – 45% response rate.
Social Factors that Affect Response to Treatment for Hepatitis C (HCV)
- Adherence to therapeutic regimen: Due to the side effects of treatment or other factors, some patients do not complete the necessary six- to twelve-month course of therapy.
- Substance use: Individuals who continue to use alcohol or other substances demonstrate poorer responses to treatment, higher rates of complications, and a greater likelihood of discontinuing treatment.
- Mental health issues: Preexisting psychiatric conditions may affect compliance with treatment, and some illnesses, such as depression, can be exacerbated by the medications used to treat HCV.
Host Factors that Affect Response to Treatment for Hepatitis C (HCV)
- Age: Individuals over the age of 40 demonstrate more rapid progression of liver disease and exhibit poorer response to treatment.
- Gender: In general, males tend to exhibit more rapid disease progression. There is some evidence that younger women clear HCV more effectively than men or older women.
- Degree of liver scarring (cirrhosis) or fatty liver (steatosis): Only 1 in 5 patients with compensated cirrhosis will achieve SVR with treatment; likewise, the presence of steatosis impairs response to therapy. (Di Marco V, et al. The effect of antiviral therapy on clinical outcome of HCV cirrhosis with portal hypertension: a prospective cohort study. 57th AASLD. Boston, MA. October 27-31, 2006)
- Co-infection with other organisms (hepatitis B, HIV, etc.): Concurrent infection by viruses that impair liver function may complicate therapy and lessen response to treatment for HCV. Co-infection also heightens the risk for progressive liver damage.
- Hyperinsulinemia (e.g., diabetes): HCV infection leads to increased insulin resistance, hyperinsulinemia, and diabetes, and preexisting diabetes often worsens during treatment for HCV. Individuals with impaired fasting glucose or frank diabetes are less likely than non-diabetics to achieve SVR (44% vs 59%). (Highleyman L. Hepatitis Journal Review: a bimonthly publication of the hepatitis support project. June 15, 2008, Volume 5, Issue 6)
- Race: Compared to non-Hispanic whites with HCV genotype 1 (50% SVR), Latinos with genotype 1 exhibit a 34% SVR, and African-Americans achieve only a 28% SVR. The difference may be due to a genetic variant that is more common in Caucasians. (Rodriguez-Torres M, et al. Peginterferon alfa-2a and ribavirin in Latino and non-Latino whites with hepatitis C. N Engl J Med. 2009;360:257-267 and Conjeevaram H, et al. Peginterferon and ribavirin treatment in African Americans and Caucasian patients with hepatitis C genotype 1. Gastroenterology. 2006;131[2]:470-477)
- Weight: For patients across all viral genotypes, 60% of those who weighed less than 85 kg (187 lbs) achieved SVR with treatment; only 49% of those weighing over 85 kg achieved SVR.
- Hepatic iron overload (e.g., hemochromatosis): Damage from excessive iron within hepatocytes lessens the likelihood of attaining SVR and complicates treatment.
Although treatment for HCV has improved significantly in the past 15 years, sustained virologic response may be difficult to achieve in many individuals due to a variety of factors.
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