Recurrence Rate of Hepatitis C Virus After Achieving a Sustained Virologic Response in Kurdistan Region, Iraq

Background: Hepatitis C virus (HCV) is a public health issue. Successful treatment of HCV infection results in sustained virologic response (SVR) in the majority of subjects. Subsequent recurrence of HCV, either from late relapse or reinfection, may occur. The aim of this study was to assess the recurrence rate of HCV in Iraqi patients. Methods: In this study, 113 patients who completed anti-HCV therapy successfully were recruited. While 23 patients received a classical regimen of peg-interferon plus ribavirin, 90 patients received direct-acting antiviral therapy. Those patients were followed up for three years. HCV recurrence rate was calculated using events/ person years of follow-up (PYFU). Results: Among the recruited patients, HCV RT-PCR was positive in 1 (0.88%) patient giving a recurrence rate of 2.95 per 1000 PYFU. When the data were stratified according to the treatment regimen, the recurrence rate was 14.49 per 1000 PYFU in patients who received the classical regimen of interferon and ribavirin. Conclusions: The overall recurrence rate was low in Iraq. No recurrence was recorded in patients received direct-acting antiviral therapy. Further studies are needed with a larger sample size and longer follow-up to determine the relapse rate in Iraq.


Recurrence of HCV after Treatment Completion
Q thermocycler. In this procedure, the amplification of HCV RNA ranged from 65-10^6 IU/mL for HCV . Then, positive samples were sent for genotype study. The genotyping was carried out using GEN-C 2.0 reverse hybridization strip assay (Nuclear Laser Medicine, Settala, Mi, Italy). In this procedure, the variations in the 5'-UTR and core regions were used to discriminate between HCV genotypes.

Patients
In this study, 113 patients were recruited. While 23 patients received the classical regimen of peg-interferon plus ribavirin, 90 patients received direct-acting antiviral therapy. Among them, 64 (56.63%) were male and 111 (98.23%) were treatment-naive (patients without prior treatment for HCV) ( Table 1). Among these patients, 47 (41.59%) were infected with genotype 1 while 49 (43.36%) were infected with genotype 4 (Table 1). Then, all patients were tested for HBV and HIV. Among them, 1 (0.88%) was HBV positive, whereas all patients were negative for HIV.

HCV RT-PCR and Relapse Rate
In this study, HCV recurrence rate was calculated using events/person years of follow-up (PYFU) (11). Patients were followed up for 3 years. HCV RT-PCR was positive in 1 (0.88%) patient giving a recurrence rate of 2.95 per 1000 PYFU. When the data were stratified according to the treatment regimen, the recurrence rate was 14.49 per 1000 PYFU in patients who received the classical regimen of interferon and ribavirin. The genotype study showed that the patient with relapse was infected with HCV genotype 4. The previous record of the patient showed that he was without co-morbidity and was infected with HCV genotype 4. The patient was treated with the classical regimen of peg-interferon and ribavirin for 48 weeks. The HCV RT-PCR was negative at the end of the treatment (end of treatment response) and HCV RT-PCR was negative 24 weeks after the completion of treatment (sustained virologic response).

Discussion
Infection with HCV is a common public health issue especially in developing countries such as Iraq. Such an infection is associated with deleterious consequences predisposing to liver cirrhosis and hepatocellular carcinoma. Early diagnosis and treatment of this infection can prevent those complications. The prevalence of HCV has been studied thoroughly in Iraq and it has been reported to be low (5,12). Therefore, the approval of new powerful drugs for the treatment of HCV may help the elimination of the virus in the country. Posttreatment relapse or reinfection represents a challenge to the elimination plan. In this study, the overall recurrence rate was 2.95 per 1000 PYFU. The vast majority of the studies investigating HCV recurrence rate recruited patients who received the classical treatment of interferon plus ribavirin. Hence, to avoid the bias of recruiting patients who received direct-acting antiviral therapy, our data were stratified according to the regimen used in the treatment. In patients who received the classical regimen of interferon and ribavirin, the recurrence rate was 14.49 per 1000 PYFU. The patient with recurrent infection was infected with genotype 4 which is the same genotypes that was infected with before treatment. This suggests relapse rather than reinfection. However, sequencebased phylogeny is needed to distinguish between relapse and intra-subtype reinfection (13). In a previous study conducted in Germany, the post-treatment relapse rate was 3.30 per 1000 PYFU in patients who were treated with interferon and ribavirin. In a study conducted in Korea, the recurrence rate was 45.96 per 1000 PYFU. In another study conducted in Spain recruiting patients who were treated with the classical regimen, the recurrence rate was 2.50 per 1000 PYF. In a meta-analysis study analyzing relapse rate in 43 studies, the patients were classified into two groups of high-risk and low-risk patients. The relapse rate in the low-risk group was 22.23 per 1000 PYFU while it was 1.85 per 1000 PYFU in the high-risk group (11). In the same study, the relapse rate for patients with HIV/HCV coinfection was 32.02 per 1000 PYFU (11). The differences among these studies are difficult to explain; however, the patient's genetic makeup and virus genotypes can partially explain the differences. The data about the recurrence rate of HCV after receiving potent direct-acting antivirals are sparse. In this study, no recurrence was found in patients who received directacting antiviral therapy. Further studies are required with a large sample size and monitoring for longer duration is required to determine the recurrence rate after those medications.
To conclude, the overall recurrence rate was low in Iraq. No recurrence was recorded in patients who received direct-acting antiviral therapy. Further studies are needed with a larger sample size and longer follow-up to determine the relapse rate in Iraq.