Hepatitis C Virus Genotype 8 Infection—Successful Treatment With Sofosbuvir/Velpatasvir

Following the recent report of a novel hepatitis C virus (HCV) genotype 8 in 4 Canadian patients from Punjab, India [1], we report 2 further cases in Australia. One patient responded to sofosbuvir/velpatasvir treatment, and infection in the other resolved spontaneously. In June 2017, a 30-year-old woman from Punjab presented to our hospital in Sydney, Australia, with acute hepatitis. She was clinically jaundiced, with an elevated bilirubin level of 45 μmol/L and an elevated alanine transaminase (ALT) level of 661 U/L. Findings of coagulation studies and the albumin level were normal. Results of serologic testing for hepatitis A virus were consistent with previous infection, those for hepatitis E virus were negative, and those for hepatitis B virus were consistent with distant infection (only hepatitis B virus core antigen was detected). Results of an HCV serologic test were positive, with polymerase chain reaction (PCR) analysis and a line-probe assay (LiPA) demonstrating genotype 5a and a viral load of 1.2 × 106 IU/mL. Her symptoms improved spontaneously; 3 months after presentation, HCV PCR results were negative, although HCV serologic test results remained positive. Results of HCV serologic testing 1 year previously (in May 2016) were negative. As the patient denied any risk factors for hepatitis C, her husband was tested and found to have an HCV-positive serologic test result, with genotype 5a detected and viral load of 2.6 × 106 IU/mL. He was previously unaware of his HCV infection and was also born in Punjab. His only risk factor was having travelled to India in 2011 and 2015 for dental work. The husband was treated with sofosbuvir/velpatasvir (400 mg/100 mg) for 12 weeks and achieved a sustained virological response (SVR) with a normal ALT level (baseline, 98 IU/mL). Following the recent report of a novel HCV genotype 8 [1], we analyzed plasma specimens collected from the husband before treatment. As shown in Figure 1, the virus from our patient displayed a high level of homology to the previously reported genotype 8 strains [1], with nucleotide identity in the gene encoding HCV nonstructural protein 5B (NS5B) of 89.2%–94.9%. Nucleotide identity for NS3 and NS5A amplicons was also >90%. Full-genome sequencing was unsuccessful. Phylogenetic analysis of the gene encoding hepatitis C virus nonstructural protein 5B (NS5B). The viral NS5B sequence from a male patient (WM001 NS5B) was aligned against reference sequences of known genotypes. A phylogenetic tree was then estimated using a maximum likelihood approach with support for individual nodes assessed with bootstrapping. Branch labels indicate bootstrap values from 1000 replicates and shown for values >65%. Taxa are labeled with the genotype and GenBank accession number. The scale bar represents the number of substitutions per site. This analysis demonstrated the patient’s sequence clustered with genotype 8 viruses with strong support. HCV is a highly diverse RNA virus that, until recently, was classified into 7 genotypes [2]. Genotype 5 is generally restricted to Africa and accounts for <1% of infections worldwide [3]. In the other report, patients were all originally from Punjab, and virus had been identified as genotype 5 by commercial assays (LiPA or Abbott RealTime PCR). Sequencing demonstrated it to be genetically distinct from previously identified HCV genotypes (ie, genotypes 1–7), with >30% nucleotide sequence divergence [1]. This is the first report of HCV genotype 8 infection being cured by sofosbuvir/velpatasvir. In the previous study [1], all patients also achieved a SVR with sofosbuvir-based therapy, of whom 2 received triple therapy (sofosbuvir/velpatasvir/voxilaprevir) and 2 received sofosbuvir in combination with daclatasvir or ledipasvir plus ribavirin. Although the clinical significance of resistance-associated substitutions (RASs) in HCV genotype 8 is unknown, sequencing of the virus from our patient demonstrated a Y93S substitution in NS5A, a RAS that confers resistance to velpatasvir for HCV genotype 1 [4]. The 4 previously reported genotype 8 isolates also contained the Y93S substitution, along with Q30S, but this did not correlate with resistance to velpatasvir in vitro, and all patients achieved virological cure [1]. Although we were unable to analyze virus from the index patient, her virus was most likely genotype 8. She developed acute hepatitis that resolved spontaneously within 3 months, with the most likely source of acquisition being her husband. Both had genotype 5a infection confirmed by the same LiPA. HCV genotype 5a is rare, found predominantly in southern Africa, and comprises <1% of reported cases in Australia (there were no other cases at our center in the last 2 years). Interestingly, her course was symptomatic with spontaneous resolution. We conclude that the molecular epidemiology of HCV now includes genotype 8, which is present in North India and should be tested for in patients from Punjab who are identified as being infected with genotype 5a. Examining the proportion with genotype 8 in Punjab would be of interest. Financial support. This work was supported by the National Health and Medical Research Council of Australia (program grant 358772), the Western Sydney Local Health District (Research Education Network Internal Grant Scheme), the University of Sydney, Sydney Medical School (Mid Career Researcher Accelerator Grant), and Robert W. Storr Bequest to the Sydney Medical Foundation, University of Sydney. Potential conflicts of interest. All authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.