Hepatitis C: An Update

A Recent paper has recommended that swallowability assessment should be done before starting the direct acting antivirals.

About 3.2 million children and adolescents live with hepatitis C virus (HCV) (1). There is not much data available regarding the prevalence of HCV in children in India. However, Chowdhury, et al. did a community-based study and has shown prevalence of HCV 0.31% in children less than 10 years of age and 0.83% in adolescents (10-19 years) (2). Mother to child transmission is the primary route of transmission in young children with transmission rate of 5%. Other route of transmission include parenteral route, sexual contact, tattooing reuse or unsterilized medical instruments and blood not screened before transfusion. Children with history of multiple transfusion are at higher risk of contracting HCV infection (13-65%) (3).

HCV is hepatotropic RNA virus single stranded and belongs to Flaviviridae family. It is classified into 7 genotypes based on sequence variations. In India genotype 3 is predominant comprising of 80% cases (1). Genotype 1 is prevalent in Europe, American and Australia and genotype 4 is seen in middle east and Africa. HCV such genetic diversity and ability to mutate rapidly has hindered the development of pan genotype HCV vaccines.

Screening of HCV is done by antibody testing, and a positive HCV antibody test will not differentiate between remote or recent infection. Hence quantitative or qualitative nucleic acid amplification test (NAAT) for detection of HCV RNA should be done after all positive HCV antibody test (4). Post exposure if the HCV antibody test is negative a repeat antibody testing or NAAT should be done within 6 months of the exposure (5). Recommendation for perinatally exposed young infants is that only NAAT should be done till 18 months age, with serological testing after 18 months of age as maternal antibodies persist till 18 months of life (6). There has been latest WHO recommendations for HCV screening to improve diagnosis which includes viral load NAAT assays, HCV core antigen detection where NAAT is not easily available, mandatory RNA HCV testing in all HCV antibody positive patients, use of dried blood spot specimens for testing and HCV self-testing kits(7).

Treatment

The natural progression of HCV in children is usually benign but it can progress in 10 years to chronic hepatitis and eventually can lead to cirrhosis or hepatocellular carcinoma (8). The objective of anti-HCV treatment is to eliminate the infection and avoid progression of the liver disease. Oral direct acting antivirals (DAAs) are highly effective and their evolution has changed the game in management and outcome of HCV infection. Sustained virological response (SVR12) is defined as non-appearance of HCV RNA 12 weeks after the end of treatment, and this the endpoint of therapy with DAA.

In consensus WHO, IDSA, ESPGHAN and EASL have recently recommended antiviral treatment for children and adolescents above 3 years of age irrespective of the disease severity. Both pangenotypic and genotype specific DAA regimen are recommended. The accessibility of pangenotypic regimens is easy and does not require assessment of genotype hence are preferred. Regimens with shorter duration are preferred to increase compliance. Patients who have failed the regimen they were started on are then shifted to second line treatment which consists of Sofosbuvir/ Velpatasvir / Voxilaprevir. The combination of sofosbuvir plus daclatasvir is recommended by WHO as pediatric pangenotypic DAA regimen and is less expensive and easily available increasing the accessibility to treatment in lower- and middle-income countries. However, it is not approved by the United States Food and Drug Administration and the European Medicines Agency (7).

Although the efficacy and tolerability of oral DAA is good there is difficulty in taking oral medication leading to poor compliance and treatment failure. ESPGHAN has recently recommended in a paper that before starting the oral DAAs swallowability evaluation should be done and tailor the formulation and regimen in accordance to the result (9).

To conclude WHO is aiming for elimination of HCV through various initiatives like increasing diagnosis through screening and making shorter and more compliant regimen available. The recommendation of treating all children above 3 years of age and adolescents irrespective of the disease severity is playing pivotal role in HCV elimination.

Figure1: Oral DAAs with formulations, dose and duration.( Table 1 - ESPID Reports and reviews – Management of Hepatitis C in Children and Adolescents :An Update)

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