Elimination of Hepatitis C Infection along with Primary Care Practitioners

Abstract

Objectives: Chronic hepatitis C virus (HCV) infection remains a major public health challenge around the world including Myanmar and whole Asia. This article outlines awareness and understanding of swiftly evolving newer regimens of Direct Acting Antiviral (DAA) from international guidelines, for Primary Care Practitioners (PCPs)/General Practitioners (GPs). This piece also discusses minimal required tests which still remain as a barrier for treatment access even in developed countries let alone countries/regions with limited resources.

Methods: Literature (from 2016 onwards from PubMed) and the latest major guidelines (updated 2017) from North America, Europe, Asia-Pacific, Australasia and the World Health Organization were reviewed using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system.

Results: The regimens of DAA including Pangenotypic options (covering all genotypes) are well promising with cure rate over 95% plus well tolerability, fewer side effects and shorter course. Its viral eradication also gives multiple clinical benefits- improvement in quality of life, loss of infectivity, regression of liver fibrosis/cirrhosis, and lower risk of liver failure & cancer (hepatocellular carcinoma) and reduced mortality.

Conclusion: PCPs/GPs in the community including from remote areas, are actively encouraged to treat those infected persons, given high prevalence and increasing burden if treatment uptake is low. Pangenotypic option offers some advantages with greater simplicity.

Keywords: Direct Acting Antiviral, DAA, HCV, Hepatitis C, Primary care practitioner.

Introduction

Although reportedly declining from old studies of 185 million people (2-3%) to 130–150 million globally with chronic HCV infection, death from HCV-related liver diseases continues surge from 333,000 in 1990, to 500,000 in 2010 and 700,000 in 2013.^[6^] Significant number of the HCV infected develop liver cirrhosis or liver cancer leading to increased morbidity and mortality. HCV infection is the most common cause of liver transplantation in western countries and could also be one of leading causes for cirrhotic liver in developing countries. The HCV-related disease burden is already high and is projected to rise steeply over the coming decades if no improvement in management is made.^[6,^27,28]

The prevalence in Myanmar is difficult to validate, nevertheless recent publication indicates 2.65% (n = 5547, DMR).^[30] However, the rate could be higher in provincial states and border towns by citing 11.6% (n = 1333, study of four border towns/cities in 2007).^[31] In comparison, the whole of Southeast Asia region has 2.15% (32.3 million), Australasia 1.5- 2%, USA 1.8-2% and China 2-3%.^[32-34]

Diagnosis and Pre-treatment Assessment

First of all, diagnosis for HCV infection is to be established as in figure 1 with initial HCV antibody (Ab) test. If positive, then HCV RNA test (qualitative/quantitative) which will indicate current or active infection, those who require treatment. Next step is to identify Genotype (Gt) and ± fibrosis/cirrhosis, as selection of drug regimen depends on HCV genotype and in a genotype specific manner, the presence of cirrhosis and/or prior HCV treatment failure, and please refer to below Table 2 for details.

Figure1. Test flow diagram for HCV Infection

The gold standard to rule out fibrosis/cirrhosis is liver biopsy which is an invasive procedure with risks and unfeasible even in developed countries. Thus, non-invasive tests are becoming more favourable. Serum biomarker-based fibrosis assessment (such as APRI, Fib-4 score, in table 1) are cost-effectively useful if imaging is inaccessible. Details of pre-treatment assessment is to be referred to local administration body or “Revolution in Hepatitis C Treatment: Cured plus other benefits” of Myanmar Medical Journal, September 2016, and consensus statement 2017 from Gastroenterological Society of Australia (GESA).[4,29]

Treatment and Medications

The goal of treatment is cure, or SVR (Sustained Virological Response), defined as undetectable plasma HCVRNA at least 12weeks after treatment. Latest treatment options are simplified and compiled with based on level of evidence and strength of the recommendation (table 2) from: AASLD (American Association for the Study of Liver Diseases) and IDSA (Infectious Diseases Society of America), EASL (European Association for the Study of the Liver), APASL (Asian Pacific Association of Study of Liver), GESA (Gastroenterological Society of Australia),WHO (World Health Organization), and a number of literatures review.^[1-23456789²⁰23456789^]

As per several updated guidelines and reviews, sofosbuvir/velpatasvir (400/100mg) or glecaprevir/pibrentasvir (300/120mg) one tablet daily was recommended as a truly pangenotypic treatment option (Gt 1 – 6) regardless of fibrosis/cirrhosis status with strong evidence.^[1-23456789²⁰23456789^]This is a good newsflash for regions with lack of full resources for pre-treatment assessment.2346789

Genotype (Gt) 3, 6 and 1 are common in Myanmar in order ^[31], although type 1 (46%-49%)is highly prevalent worldwide, followed by 3, 2, 4, 6 and 5 in order.^[32-34]Gt 6 is mostly confined to Southeast Asia and South western part of China, 4 to North Africa and Middle-east, and 5 to South Africa. Of note, Gt3 may pose a treatment challenge due to relatively faster progression to fibrosis or cirrhosis, and highly associated with steatosis and hepatocellular carcinoma.^[35,36]In general, regimens for difficult or complicated cases are longer duration (24 weeks) with ±Ribavirin and/or addition of Interferon.

Treatment Monitoring and Follow-up ^[4,29]

On-treatment, monitoring for medication adherence, side effects (figure 2) and liver function should be performed. Quantitative HCV PCR testing should be considered if there are concerns about adherence or viral resistance. Qualitative HCV PCR testing at the end of treatment is reasonable to confirm an end-of-treatment response, however given the high efficacy of DAA therapy, such monitoring is not mandated in all individuals. All patients should have drug-drug interactions assessed prior to and on-treatment. For more information, please refer at University of Liverpool web site, http://www.hep-druginteractions.org/. In order of blood test monitoring are:

• Week0: FBC, RFT, LFTs, PT, HCVRNA level (quantitative/viral load)
• Week4: FBE,LFTs
• Week12±24 (EOT= end of treatment): FBE, LFTs, HCVPCR (qualitative/viral detection test).

(FBC= Full Blood Count, RFT= Renal Function Test, LFTs= Liver Function Test, PT= Prothrombin Time).

Discussion

Globally, liver diseases and its consequences (e.g. cirrhosis, cancer) remain as major morbidity and mortality. In most countries, disparity in health-care delivery and public access exists, especially in small towns and rural and remote areas. This is not the case in metropolitan cities where teaching medical schools/hospitals and specialists practice. Lack of an imaging-based fibrosis test should not hinder the treatment accessibility. PCPs are well positioned in the delivery of better access treatment for patients across the country. Pangenotypic options are simply opportunistic regimes to apply either genotype if there is lack of resources to carry out the full pre-treatment assessment. There are also growing pangenotypic options (e.g., Sofosbuvir/Velpatasvir/Voxilaprevir), which should be reserved for drug resistance cases. It is reasonable to choose cost-effective regimes or following local guidelines to minimise the cost barrier. Elimination of HCV by 2030 as per WHO seems possible to achieve for each region and worldwide, provided there is improvement in screening, diagnosis and access to treatment.

Acknowledgement: Author is grateful to Prof Tha Hla Shwe (Rtd Rector), Prof Win Myaing (Urologist), and Dr P J Clark (FRACP), Hepatologist and Gastroenterologist, Princess Alexandra Hospital & University of Queensland of Brisbane, QLD, Australia for their motivation and encouragement.

Disclosure: There is no conflict of interest and no financial grant from any organisation and individual.

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