Efficacy of Generic Oral Directly Acting Agents in Patients With Hepatitis C Virus Infection

S. Gupta; G. Rout; A. H. Patel; M. Mahanta; N. Kalra; P. Sahu; R. Sethia; A. Agarwal; G. Ranjan; S. Kedia; S. K. Acharya; B. Nayak; Shalimar


J Viral Hepat. 2018;25(7):771-778. 

In This Article


Baseline Characteristics

A total of 683 HCV–positive patients were evaluated during the study period and recommended to initiate DAA therapy. Of these patients, 193 were excluded because of an inability to afford therapy or incomplete follow–up after the 1st visit (n = 65), ongoing therapy (n = 90), chronic kidney disease (n = 28), co–infection with HBV (n = 8) and HIV (n=2) (Figure 1). Of the 490 patients included (mean age 38.9 ± 12.7 years), clinical presentations included chronic hepatitis (n = 339, 69.2%), compensated cirrhosis (n = 120, 24.5%) and decompensated cirrhosis (n = 31, 6.3%). Genotype 3 was most common in 372 (75.9%) patients followed by genotype 1 in 97 (19.8%). There were 432 (88.2%) treatment naïve and 58 (11.8%) treatment–experienced (defined as previous treatment with peginterferon and ribavirin) patients. Pretreatment high viral load was observed in 242 (49.4%) patients. The clinical and demographic details are shown in Table 1.

Figure 1.

SVR12 in various combinations of oral directly acting agents. HCV, hepatitis C virus; CHC, chronic hepatitis C; HIV, human immunodeficiency virus; NOS, not otherwise specified; SVR12, sustained viral response at 12 wks; SOF, Sofosbuvir; RBV, ribavirin; DAC, daclatasvir; LDV, ledipasvir

SVR According to Genotype, Underlying Liver Disease and Type of Regimen

Overall SVR12 was seen in 95.9% (470/490). SVR12 for treatment–naïve and treatment–experienced patients was 97.0% (419/432) and 87.9% (51/58), respectively, P = .005.

The details of various combinations using sofosbuvir are shown in Figure 1. The SVR12 in genotype 1 CHC and cirrhosis were 92.4% (61/66) and 85.7% (18/21), respectively. Only six genotype 1 patients received the sofosbuvir plus ledipasvir plus ribavirin regimen. Among these, the SVR12 in CHC and cirrhosis were 50% (1/2) and 75% (3/4), respectively.

With the various sofosbuvir–based regimens, SVR12 was 95.8–100% in genotype 3 cirrhosis and 91.7–100% in decompensated cirrhosis. The SVR12 in genotype 3 CHC was 97.5% (177/120) in the sofosbuvir plus daclatasvir regimen and 75% (6/8) in the sofosbuvir plus daclatasvir plus ribavirin regimen. SVR12 rates observed with various regimens, according to genotype and underlying liver disease status are shown in Figure 1 and Table 2. There were no differences in the SVR12 with 12 weeks and 24 weeks therapy (Table 3). The details of SVR12 in different sofosbuvir–based regimens, according to genotype 1 and 3, underlying liver disease and duration of therapy, are shown in Table S1 and Table S2.

Predictors of SVR12

In univariate analysis, treatment–experienced patients (relapsers and nonresponders to peginterferon and ribavirin) had a lower SVR12 (87.9%) as compared to treatment–naïve patients (97.0%), odds ratio (OR) 0.226, 95% CI (0.086–0.593). The rates of SVR12 with the treatment regimen of sofosbuvir, ledipasvir and ribavirin in combination therapy was 66.7% (4/6) and lower as compared to other regimens (>90%). No differences were found among patients who achieved or those who did not achieve SVR12 (Table 4), in terms of factors related to the virus (including genotype, viral load) or host factors {including age, sex, presence of diabetes, body mass index, underlying liver disease status (CHC, cirrhosis and decompensated cirrhosis), liver stiffness measurement (LSM) or controlled attenuation parameter (CAP) on fibroscan} or duration of therapy (12 vs 24 weeks). Multivariate analysis for predictors of SVR12 was not carried out due to small number of patients in the treatment regimen consisting of sofosbuvir, ledipasvir and ribavirin. There was no change in SVR12 when the analysis was performed after excluding patients who were lost to follow–up.

Patients Lost to Follow–up and Relapsers

Seven patients (including one breakthrough) were documented to have relapsed on the basis of positive HCV RNA after 12 weeks of therapy. Thirteen treatment–naïve patients were lost to follow–up and were treated as nonresponders when analysing outcomes (total n = 20). There were no treatment–experienced patients who were lost to follow–up. All relapsers to sofosbuvir–based therapy were treatment–experienced and had previously received peginterferon and ribavirin–based therapy. The characteristics of patients lost to follow–up and relapsers according to underlying liver disease are shown in Table S3. The details of patients lost to follow–up and relapsers according to underlying liver disease and genotype are shown in Table S4 and Table S5, respectively. There were no differences in genotype, viral load, age, diabetes, BMI, fibroscan values, CAP, underlying liver disease status, duration of therapy and treatment regimen used.

Change in MELD Score at 12 Weeks Post–therapy

The baseline model for end–stage liver disease (MELD) score in patients with compensated cirrhosis at baseline was 8.5 ± 2.4 and at end of 12 weeks of treatment was 8.4 ± 2.4; P = .672. MELD score in patients with decompensated cirrhosis at baseline was 10.3 ± 3.5 and at end of 12 weeks of treatment was 10.3 ± 3.4; P = .957.

Adverse Events

No major adverse events requiring treatment stoppage occurred. Among the 357 patients with available paired samples (at baseline and after therapy), 37/357 (10.4%) had worsening anaemia with a haemoglobin below 10 g/dL.