The Evolution of Hepatitis C Treatment

Hepatitis C is one of the important causes of liver disease in the world. It seems that HCV will emerge as the leading cause of viral hepatitis-related advanced liver diseases and death in the near future. There are approximately 71 million chronically infected individuals worldwide, many of whom are unaware of their infection (1).
It has been estimated that the prevalence of HCV in the Iranian general population is less than 0.5%. In Iran, the average prevalence of HCV is among thalassemia patients (16.6%), hemophilia patient (54%), individuals under dialysis (8.3%) and among injection drug users (51.4 percent).
After screening of blood donors for HCV in Iran, the burden of HCV infection decreased significantly in hemophilia, thalassemia and patients on hemodialysis. Unfortunately, injecting illicit drugs still continues to be a major source of infection in Iran (2, 3).
Iran has the lowest prevalence for HCV infection in the Middle East. Countries such as Pakistan and Azerbaijan with high prevalence of HCV infection are neighbors of Iran (2).
The main populations at risk of HCV infection in Iran include intravenous drug users (IDUs) followed by people with tattoos, use of common razor, multi partner, homosexuality, receiving blood, and patients on hemodialysis (2).
Clinical care for patients with hepatitis c infection has advanced considerably thanks to an enhanced understanding of the pathophysiology of the disease and because of developments in diagnostic procedures and improvement in therapy and prevention, and HCV elimination has been considered by the World Health Organization till 2030 (2,3).
Screening and treating patients is necessary to eradicate HCV, So, EIA test is used for initial screening and detecting antibody against hepatitis C. Rapid diagnostic tests (RDTs) using serum, plasma, finger stick, whole blood or saliva as matrices can be used for initial screening. If anti-HCV antibodies are detected, the presence of HCV RNA or alternatively HCV core antigen in serum or plasma should be determined to identify patients with ongoing infection. Although the sensitivity of the core antigen assay is less than HCV RNA assay, but because of low cost and good sensitivity, it is a valuable test for HCV. The positive Anti HCV by EIA and negative PCR may be occurred by following reasons: 1-false positive 2-spontaneous viral clearance 3- treatment –induced viral clearance, 4- low levels of virus DNA in the Blood that is not determined by PCR. Following spontaneous or treatment –induced viral clearance, anti HCV antibodies may be persist lifelong. Thus, the follow of treated patient use of PCR or core Ag is necessary (1). HCV has a high rate of genetic heterogeneity (1-7 genotype), therefore, no vaccine to prevent this infection today. Genotype 1a and 3a are the most prevalent genotypes in Iran. HCV reinfection can occur after spontaneous or treatment induced viral clearance, essentially if patient at high risk of infection and re exposure (4).
Strategies to promote diagnosis, screening, and treatment should be targeted to high-risk groups rather than the general population. Annual screening is recommended for Individuals with a history of injecting illicit drug. In the past, treatment of HCV was interferon and ribavirin for 24 to 48 weeks. This treatment regimen associated with low response to treatment, high drug complication and high drug cost. In 2011, protease inhibitors, the first generation of DAAs (Telaprevir and Boceprevir), were emerged as the third component of the standard of care. These drugs had a lot of complications such as drug-drug interactions, severe skin rashes/pruritus and anemia. In 2013, Sofosbuvir, a new DAA, was introduced for treatment of HCV infection. SOF-containing regimens had a shorter duration of therapy, with fewer side effects in comparison with protease inhibitor-based triple therapy (5).
At present, in Iran, the basis of treatment is sofosbovir 400 milligram that combined with second drug daclatasvir (60 mg) or velpatasvir in pan genotype and or ledipasvir (90 mg) in genotype 1a. These drugs exist in separated or combination form with different brand names. In fact, the patient with hepatitis C in both treatment-naive and non-cirrhotic, taking a combination pill daily for 12 weeks associated with high treatment response. However, in cirrhotic patients or patients with previous treatment experience, treatment prolongs 24 weeks or ribavirin (1000 -1200 mg, 5-6 200mg tablets) is added to 12 weeks of treatment according patient weight. Accurate assessment of liver fibrosis and cirrhosis is essential for predicting prognosis and for planning treatment duration and adding RBV to the standard therapy of patients with chronic HCV infection. So, percutaneous liver biopsy or elastography non-invasive methods have been considered as the gold standard for assessing hepatic fibrosis. If biopsy or elastography not available, platelet count, liver sonography and liver enzyme level is helpful for determination of liver fibrosis (6).
In EASL Recommendations on Treatment of Hepatitis C 2018, other drugs of DAAs like pibrentasvir, glecaprevir, elbatasvir and grazoprevir are recommended. Also 8, 16 and 28 weeks of treatments are suggested in special cases and treatment without sofosbovir is mentioned (1).
Determination of viral load by quantitative PCR and genotyping of HCV recommend before the treatment, if viral load and genotyping is not available, qualitative PCR without genotyping is sufficient for treatment with pan genotyping drugs (1, 5).
New treatments are free-INF and these drugs have low cost and low adverse effect (5, 7). Todays, HCV is treated very simply by consuming only one pill daily for 12 weeks. Sustained viral response (SVR) that defined negative PCR 12-24 weeks after discontinuing treatment occurred in more than 90% of patients (1, 4). In patients with cirrhosis, despite SVR, sonography of liver and αFP level test for screening of liver malignancy is recommended every 6 months (1).
It seems that the best strategy for HCV prevention in the community is increasing case finding and therapy with the ultimate goal of stopping the vicious cycle in the community. Todays, there is no vaccine for HCV prevention yet. The incidence of HCV infection should be reduced by providing safe blood transfusion and medical procedures in hospitals and out-patient clinics, increasing people awareness and public education regarding the risks of exposure such as unsafe tattooing and unsafe sexual contacts and finally implementation of harm