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Background & Aims: Hepatitis C virus (HCV) genotype (GT) 4 infection is prevalent in sub‐Saharan Africa and the Middle East, particularly in Egypt. This study evaluated the safety and efficacy of elbasvir/grazoprevir administered for 8 and 12 weeks in participants with HCV GT4 infection. Methods: In this partially randomized, open‐label multicentre study conducted in France (NCT03111108; Protocol MK5172‐096), treatment‐naive participants with GT4 infection and F0‐F2 fibrosis were randomized 2:1 to elbasvir (50 mg)/grazoprevir (100 mg) for 8 or 12 weeks. Treatment‐naive participants with F3‐F4 fibrosis and all treatment‐experienced participants (F0‐F4) were assigned to elbasvir/grazoprevir for 12 weeks. The primary endpoint was sustained virologic response (SVR) 12 weeks after the end of therapy. Results: One hundred and seventeen participants were enrolled. Among treatment‐naive participants with F0‐F2 fibrosis, SVR was achieved by 94% (50/53) and 96% (26/27) of those receiving elbasvir/grazoprevir for 8 or 12 weeks, respectively, and four participants relapsed. In the 12‐week arm, 95% (35/37) achieved SVR and two participants relapsed. NS5A resistance‐associated substitutions were present at baseline and virologic failure in five of the participants with relapse. Drug‐related adverse events occurred in 42% (n = 22) and 50% (n = 32) of participants receiving 8 and 12 weeks of treatment, respectively. No participant discontinued treatment owing to an adverse event. Conclusion: These data confirm the efficacy of elbasvir/grazoprevir administered for 12 weeks in treatment‐experienced individuals with HCV GT4 infection and those with advanced fibrosis. Treatment‐naive individuals with mild fibrosis can be treated effectively with an 8‐week regimen. [ABSTRACT FROM AUTHOR]

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Background: Hepatitis C virus (HCV) is the aetiological agent for most cases of cryoglobulinaemia vasculitis. Interferon-containing regimens are associated with important side effects and may exacerbate the vasculitis.Objective: To evaluate safety and efficacy of an oral interferon-free regimen, sofosbuvir plus ribavirin, in HCV-cryoglobulinaemia vasculitis.Patients and Methods: We enrolled 24 consecutive patients (median age of 56.5 years and 46% of women) with HCV-cryoglobulinaemia vasculitis. Sofosbuvir (400 mg/day) was associated with ribavirin (200-1400 mg/day), for 24 weeks. The primary efficacy end point was a complete clinical response of the vasculitis at the end of treatment (week 24).Results: Main features of HCV-cryoglobulinaemia vasculitis included purpura and peripheral neuropathy (67%), arthralgia (58%), glomerulonephritis (21%) and skin ulcers (12%). Twenty-one patients (87.5%) were complete clinical response at week 24. Complete clinical response was achieved in six (25%) patients at week 4, four (16.6%) at week 8, seven (29.2%) at week 12, three (12.5%) at week 16 and one (4.2%) at week 20. The cryoglobulin level decreased from 0.35 (0.16-0.83) at baseline to 0.15 (0.05-0.45) g/L at week 24. The C4 serum level increased from 0.10 (0.07-0.19) to 0.17 (0.09-0.23) g/L at week 24. Seventy-four per cent of patients had a sustained virological response at week 12 post treatment. The most common side effects were fatigue, insomnia and anaemia. Two serious adverse events were observed.Conclusions: Sofosbuvir plus ribavirin combination was associated with a high rate of complete clinical response and a low rate of serious adverse events in HCV-cryoglobulinaemia vasculitis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Severe pulmonary arterial hypertension in patients treated for hepatitis C with sofosbuvirm," by S. Renard and colleagues in the 2016 issue.

Background: The nonstructural (NS) 5A protein of hepatitis C virus (HCV) has been suggested to contain an interferon (IFN) sensitivity-determining region (ISDR).Methods: We studied whether the degree of viral decline on day 1 is associated with differences in NS5A amino acid sequences among patients receiving IFN- alpha.Results: Phylogenetic analyses of the full-length protein and of functional domains showed no relationship between the baseline protein sequence and the antiviral response. NS5A quasispecies sequences showed no differences in the number of mutations in the putative ISDR relative to a prototype sequence between responders and nonresponders or according to IFN- alpha antiviral efficacy. No relationship was found between antiviral efficacy at 24 h and the baseline sequence of any NS5A region. Amino acid changes were observed in a few cases at 24 h in both responders and nonresponders, but no consistent pattern of amino acid shifts was observed, ruling out the possibility that IFN- alpha selected IFN-resistant variants.Conclusion: Our findings show that there is no ISDR in the HCV genotype 1 NS5A protein and that the NS5A sequence does not influence the capacity of IFN- alpha to block viral replication. The findings do not rule out a role for NS5A in subsequent viral clearance. [ABSTRACT FROM AUTHOR]

Background. The nonstructural (NS) 5A protein of hepatitis C virus (HCV) has been suggested to contain an interferon (IFN) sensitivity-determining region (ISDR). Methods. We studied whether the degree of viral decline on day 1 is associated with differences in NS5A amino acid sequences among patients receiving IFN-α. Results. Phylogenetic analyses of the full-length protein and of functional domains showed no relationship between the baseline protein sequence and the antiviral response. NS5A quasispecies sequences showed no differences in the number of mutations in the putative ISDR relative to a prototype sequence between responders and nonresponders or according to IFN-α antiviral efficacy. No relationship was found between antiviral efficacy at 24 h and the baseline sequence of any NS5A region. Amino acid changes were observed in a few cases at 24 h in both responders and nonresponders, but no consistent pattern of amino acid shifts was observed, ruling out the possibility that IFN-α selected IFN-resistant variants. Conclusion. Our findings show that there is no ISDR in the HCV genotype 1 NS5A protein and that the NS5A sequence does not influence the capacity of IFN-α to block viral replication. The findings do not rule out a role for NS5A in subsequent viral clearance. [ABSTRACT FROM AUTHOR]

LINKED CONTENT This article is linked to Singh et al and Singh and Shalimar papers. To view these articles, visit https://doi.org/10.1111/apt.15633 and https://doi.org/10.1111/apt.16011 [ABSTRACT FROM AUTHOR]

Two distinct forms of hepatocellular steatosis can be seen in patients with chronic hepatitis C virus (HCV) infection. Classical metabolic risk factors for hepatocellular steatosis account for the vast majority of cases of steatosis in patients infected by non-genotype 3 HCV strains. In contrast, in patients infected by HCV genotype 3, steatosis is generally induced by the virus itself through a direct cytopathic effect, the mechanisms of which remain debated. Mixed forms of steatosis can also be seen in HCV genotype 3-infected patients with metabolic risk factors. Hepatocellular steatosis appears to be associated with more rapid progression of hepatic fibrosis. However, it is unclear whether this association is due to steatosis itself, or rather to metabolic and host factors that promote steatosis and fibrosis concomitantly. This review discusses current knowledge of HCV-induced steatosis and its relation to chronic HCV-associated liver disease.(Am J Gastroenterol 2005;100:1–5) [ABSTRACT FROM AUTHOR]

Background: Although real-life results of sofosbuvir/simeprevir have been extensively reported from the United States, data from other geographical areas are limited. In the French observational cohort, ANRS CO22 HEPATHER, 9432 patients were given the new oral antivirals from December 2013 to June 30, 2018. We report the results of sofosbuvir/simeprevir in genotypes 1- and 4-infected patients.Methods: Demographics and history of liver disease were collected at entry in the cohort. Clinical, adverse events, and virological data were collected throughout treatment and post-treatment follow-up. The choice of treatment duration or addition of ribavirin was left up to the physician.Results: Five hundred ninety-nine HCV (467 genotype 1 and 132 genotype 4) mono-infected, naïve for all oral-DAAs regimen patients were given sofosbuvir/simeprevir with (n = 63) or without ribavirin (n = 536) for 12 or 24 weeks; 56% had cirrhosis (4% decompensated) and 71% had prior treatment failure to interferon-based regimen. 7 patients (1.16%) were lost to follow-up. The overall SVR12 rate was 92.6%. The SVR12 was 90% in GT1a, 94.2% in GT1b and 91.6% in GT4 with no significant difference for genotype, treatment duration or ribavirin addition. Severity of liver disease was not associated with a lower SVR12 rate on multivariate analysis but was associated with a higher rate of severe side effects. Early treatment discontinuations were rare; no new safety signals were reported.Conclusion: In this real life, observational, prospective cohort study, the 12-week sofosbuvir/simeprevir+/-ribavirin combination appears to be efficient and safe.Trial Registration: Trial registration with ClinicalTrials.gov NCT01953458 . [ABSTRACT FROM AUTHOR]