Graphical abstract AuthorsHighlights Unusual genotypes (G1 non 1a/1b or G4 non 4a/4d) were common in African patients.11 previously unclassified HCV subtypes were represented including novel G1p.Patients with unusual G1 subtypes had a lower SVR rate than any other genotype.Failures were driven by patients treated with a first generation NS5A inhibitor.Background & Aims: HCV subtypes which are unusual in Europe are more prevalent in the African region, but little is known of their response to direct-acting antivirals (DAAs). These include non-1a/1b/ non-subtypeable genotype 1 (G1) or non-4a/4d (G4). In this report we aimed to describe the genotype distribution and treatment outcome in a south London cohort of African patients. Methods:We identified all patients born in Africa who attended our clinic from 2010-2018. Information on HCV genotype, treatment regimen and outcome were obtained. Non-subtypeable samples were analysed using Glasgow NimbleGen nextgeneration sequencing (NGS). Phylogenetic analysis was carried out by generating an uncorrected nucleotide p-distance tree from the complete coding regions of our sequences. Results: Of 91 African patients, 47 (52%) were infected with an unusual subtype. Fourteen novel, as yet undesignated subtypes (G1*), were identified by NGS. Three individuals were infected with the same subtype, now designated as subtype 1p. Baseline sequences were available for 22 patients; 18/22 (82%) had baseline NS5A resistance-associated substitutions (RASs). Sustained virological response (SVR) was achieved in 56/63 (89%) overall, yet only in 21/28 (75%) of those with unusual G1 subtypes, with failure in 3/16 G1*, 1/2 G1p and 3/3 in G1l. Six treatment failures occurred with sofosbuvir/ledipasvir compared to 1 failure on a PI-based regimen. The SVR rate for all other genotypes and subtypes was 35/35 (100%). Conclusions: Most individuals in an unselected cohort of African patients were infected with an unusual genotype, including novel subtype 1p. The SVR rate of those with unusual G1 subtypes was 75%, raising concern about expansion of DAAs across Africa. Depending on the regimen used, higher failure rates in African cohorts could jeopardise HCV elimination. Lay summary: Direct-acting antiviral medications are able to cure hepatitis C in the majority of patients. The most common genotype of hepatitis C in Europe and the United States is genotype 1a or 1b and most clinical trials focused on these geno-types. We report that in a group of African patients, most of them had unusual (non-1a/1b) genotype 1 subtypes, and that the cure rate in these unusual genotypes was lower than in genotypes 1a and 1b.

HBeAg seroconversion marks an important spontaneous change and treatment end-point for HBeAg-positive patients and is a pre-requisite for HBsAg loss or functional cure. In this retrospective analysis, we aimed to identify predictors of seroconversion using serum quantitative HBsAg and HBcrAg, in HBeAg-positive patients treated with nucleos(t)ide analogues (NA). Data and samples from 118 HBeAg-positive adults (genotypes A-G) started on NA between Jan 2005 and Sept 2016 were retrospectively analysed at several time-points. The predictive power of on-treatment levels of HBsAg and HBcrAg was determined using receiver operating curve (ROC) analysis and cut-off values determined by maximized Youden's index. About 36.4% of patients achieved HBeAg seroconversion after a median of 39 months' treatment. On treatment kinetics of HBV DNA, HBsAg and HBcrAg differed between HBeAg seroconverters and nonseroconverters. A combination of HBsAg and HBcrAg had the greatest predictive value for HBeAg seroconversion: at 6 months, HBsAg of 3.9 log IU/mL and HBcrAg of 5.7 log U/mL had a sensitivity of 71.4%, specificity of 79.5%, positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 83.8%, with AUROC of 0.769 (0.668, 0.869; 95%CI), and at 12 months, HBsAg 3.8 log IU/mL and HBcrAg 5.5 log U/mL had a sensitivity of 73.7%, specificity of 79.5%, PPV of 63.6% and NPV of 86.1%, with AUROC 0.807 (0.713, 0.901; 95% CI). In conclusion, our results may be used to identify patients who are unlikely to achieve treatment end-points, which will be important as the future management of chronic hepatitis B looks to therapies that offer functional cure.

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Background: direct-acting antiviral (DAA) therapy is highly efficacious in the treatment of hepatitis C (HCV). The literature to date has focused primarily on the physical health benefits of viral eradication. Aims: this study explored patient emotions during and after DAA therapy for HCV. Methods: over a 6-month period, 178 patients attending a viral hepatitis clinic for treatment of HCV were posed a single question: ‘How do you feel about your diagnosis of hepatitis C today?’ Responses were transcribed verbatim, thematically coded and visualised using WordArt software. Findings: the images depict the evolution of patients' perceptions of HCV before, during and after DAA therapy. Responses before treatment were predominantly negative, often describing the fear of contagion and feelings of isolation, secrecy and loneliness. After treatment, patients often described feeling positive and more motivated. Conclusions: the results demonstrate that treatment of HCV has a transformative effect on patients' perception of the impact of HCV on their wellbeing. This may promote a more positive outlook and, in turn, facilitate patient engagement with healthcare.