For the past decade, pegylated interferon (or peginterferon) combined with ribavirin has been considered the standard of care for HCV; treatment response rates, depending on race and genotype, can range from 35% to 80%.36,37 Two forms of peginterferon, alfa-2a and alfa-2b, are FDA approved for treatment of chronic hepatitis C; both forms are administered subcutaneously in combination with oral ribavirin.1,38
The choice between peginterferon alfa-2a and alfa-2b and the recommended duration of treatment are dependent on the patient's HCV genotype (see Table 21,39-45) and prior exposure to treatment. These complex regimens are best managed by specialists in gastroenterology, hepatology, or infectious disease—clinicians who are familiar with the agents' associated adverse effects, the elements of attentive monitoring, and protocols for dosing adjustments.46
As noted in the AASLD guidelines,1 alcohol consumption constitutes a risk for worsening fibrosis and possibly for HCC. Additionally, drinking in excess may facilitate replication of HCV RNA, interfering with therapy.
Thus, patients should be urged to discontinue alcohol use during treatment for HCV—or at least restrict it to an occasional drink.
New Agents to Improve Cure Rates
HCV genotype 1 accounts for 70% to 75% of cases in the US, but with current standard treatment, a sustained virologic response is achieved in only 45% to 50% of these patients37 (including 30% of black patients and 50% of whites).1,36,38 However, adding one of two new protease inhibitors to the current peginterferon/ribavirin regimen has the potential to increase sustained virologic response rates to as high as 90% to 95% in early virologic responders with genotype 1 infection, both treatment-naïve and previously treated; and in some patients, to shorten treatment to 24 weeks.41,42,44,45 Both boceprevir and telaprevir were approved by the FDA in May 2011.
Both agents are given for 12 weeks during standard peginterferon/ribavirin therapy. Depending on the patient's viral response, the overall regimen may be shortened or extended. Neither telaprevir nor boceprevir is administered as monotherapy,47,48 nor are they ever administered together. As with any protease inhibitor, resuming treatment after the agent has been stopped incurs a risk for drug resistance.40
Both new agents are taken every 7 to 9 hours, with a meal or snack.47,48 The telaprevir dose should be taken with non-low-fat food.47
Drug interactions are common. Patients also being treated for HIV and those being treated for HCV genotype 1 infection with either of the two new protease inhibitors must very carefully communicate any prescription drug changes to their treating provider. Substances of greatest concern act via the cytochrome P450 3A (CYP3A) pathway. Examples include ritonavir, St. John's wort, statins, and daily-dosed sildenafil (as used to treat patients with pulmonary hypertension).
Package inserts accompanying all agents used should be reviewed for monitoring parameters and associated recommendations.
Monitoring for Treatment Effectiveness and Complications
Patients are closely monitored for treatment effectiveness by repeated measurements of HCV RNA (ie, weeks 4, 12, 24, then at four- to 12-week intervals; at end of treatment; and 24 weeks after treatment ends). A viral load not detectable at week 4 indicates a good chance for a cure.1 If at week 12 the viral load remains detectable, the patient with HCV genotype 1 is unlikely to respond to triple therapy; similarly, dual therapy is not likely to produce a cure in patients with HCV genotype 2 or 3. Without a 2-log drop in viral load by week 12, the patient has only an 8% chance of achieving a sustained virologic response.49-51 In these cases, treatment should be discontinued or modified.51
Regular visits and frequent blood testing make it possible to avoid potential disease- and treatment-related complications. At a minimum, it is recommended that a CBC, serum creatinine, and ALT level be measured at weeks 2, 4, 8, 12, 16, 20, and 24 of therapy.1 If significant abnormalities are detected (eg, anemia, thrombocytopenia, neutropenia), the clinician may decide to monitor the patient more closely. Measures of liver and kidney function, electrolytes, and coagulation times are part of the recommended monitoring parameters at regular intervals. In addition, interferon therapy is associated with thyroid dysfunction, so relevant monitoring is advised every 12 weeks.1
Anemia, neutropenia, thrombocytopenia, and other hematologic complications are known adverse effects of HCV therapy—particularly in cirrhotic patients.1,52 Ribavirin use (especially aggressive use, as for patients with recurrent infection or post-liver transplantation53) is associated with hemolytic anemia,54 as is protease inhibitor use.41,45 In cases of profound anemia, dosing reduction or treatment discontinuation may be necessary. Severe cases of hemolysis may require transfusion, but treatment with epoietin alfa has been found helpful in some patients.52,53 Conventional iron supplementation is not an effective treatment for hemolytic anemia resulting from ribavirin use.
