What are the differences in treatment duration and side effects between current therapies for hepatitis C (Hepatitis C Virus, HCV) and prior treatments?

From the Guidelines

Current treatments for hepatitis C are dramatically improved compared to prior treatments, with modern direct-acting antiviral (DAA) regimens offering shorter treatment durations and fewer side effects. The most recent and highest quality study, published in 2020 1, supports the use of DAA combinations for 8-12 weeks, with cure rates exceeding 95%. These medications, such as Epclusa (sofosbuvir/velpatasvir) and Mavyret (glecaprevir/pibrentasvir), are taken orally once daily and have minimal side effects, usually limited to mild headache, fatigue, or nausea.

Comparison of Treatment Durations

In contrast, older treatments relied on interferon-based therapy combined with ribavirin, which required 24-48 weeks of treatment, had cure rates of only 40-50%, and caused severe side effects including flu-like symptoms, depression, anemia, and autoimmune disorders, as noted in a 2011 study 1. A 2019 study 1 also highlights the improved feasibility of hepatitis C treatment among people who inject drugs (PWID) with DAA therapies, given their limited psychiatric side-effects, simpler administration (oral, once-daily vs. weekly injections), and shorter duration (8–12 weeks vs. 24–48 weeks).

Side Effects and Tolerability

The improved tolerability of modern treatments is a significant advantage, with the 2020 study 1 reporting that fatigue and headache were the most common adverse events in patients receiving sofosbuvir and velpatasvir for 12 weeks. The addition of voxilaprevir was associated with more frequent benign diarrhea, but overall, the side effect profile of DAA regimens is significantly better than that of older treatments.

Treatment Outcomes and Recommendations

The current recommendation is to treat patients with chronic hepatitis C using DAA combinations for 8-12 weeks, pending additional data on the ideal treatment duration in certain groups. This approach is supported by the 2020 study 1, which notes that at least 8 weeks of therapy are required to maximize sustained virologic response (SVR) rates in patients with chronic hepatitis C. Overall, the improved efficacy, tolerability, and shorter duration of modern treatments have dramatically increased the number of patients who can successfully complete therapy and achieve SVR, which is considered a cure for hepatitis C.

From the FDA Drug Label

Table 1. Recommended Duration for Treatment-Naïve Patients HCV GenotypeTreatment Duration No CirrhosisCompensated Cirrhosis (Child-Pugh A) 1,2,3,4,5, or 68 weeks8 weeks

Table 2 Recommended Duration for Treatment-Experienced Patients Treatment Duration HCV GenotypePatients Previously Treated with a Regimen Containing:No CirrhosisCompensated Cirrhosis (Child-Pugh A) 1An NS5A inhibitor1 without prior treatment with an NS3/4A protease inhibitor (PI) 16 weeks16 weeks An NS3/4A PI2 without prior treatment with an NS5A inhibitor 12 weeks12 weeks 1,2,4,5, or 6PRS38 weeks12 weeks 3PRS316 weeks16 weeks

The current therapy for hepatitis C, as described in the label for glecaprevir (PO) 2, has treatment durations ranging from 8 weeks to 16 weeks, depending on the patient's HCV genotype, treatment history, and presence of cirrhosis.

• Treatment-naive patients with no cirrhosis or compensated cirrhosis can be treated for 8 weeks.
• Treatment-experienced patients may require longer treatment durations, up to 16 weeks, depending on their prior treatment regimen and presence of cirrhosis. The label does not provide a direct comparison of side effects between current and prior treatments.

From the Research

Treatment Duration

• The treatment duration for hepatitis C has significantly decreased over the years, from 48 weeks or 24 weeks in patients infected with HCV genotype 1 or 2/3, respectively, using peginterferon alfa-2a/-2b with ribavirin 3, to 8 to 12 weeks using direct-acting antivirals (DAA) 4.
• The current treatment strategies for different groups of patients can be tailored based on liver and kidney function, prior treatment experience, and potential drug-drug interactions, with treatment duration ranging from 8 to 12 weeks 4.
• A study comparing the efficacy and safety of sofosbuvir/daclatasvir versus sofosbuvir/ledipasvir for the treatment of non-cirrhotic naïve patients with chronic Hepatitis C Virus (HCV) genotype 4 infection found that both treatments were administered for 12 weeks 5.

Side Effects

• Prior treatments for hepatitis C, such as peginterferon alfa-2a/-2b with ribavirin, were associated with side effects, complications, and poor patient tolerability 3.
• The first generation protease inhibitors, telaprevir and boceprevir, had substantial side effects 6.
• In contrast, current therapies using direct-acting antivirals (DAA) have been found to be well-tolerated, with common adverse events including headache and fatigue 4, 5, 7.
• A systematic review and meta-analysis of DAA regimens for patients with hepatitis C virus genotype 2 found that fatigue was the most common adverse event (14.0%), followed by headache (13.1%) 7.