Global prevalence and genotype distribution of hepatitis C virus infection in 2015 : A modelling study

Publisher Copyright: © 2017 Elsevier LtdBackground The 69th World Health Assembly approved the Global Health Sector Strategy to eliminate hepatitis C virus (HCV) infection by 2030, which can become a reality with the recent launch of direct acting antiviral therapies. Reliable disease burden estimates are required for national strategies. This analysis estimates the global prevalence of viraemic HCV at the end of 2015, an update of—and expansion on—the 2014 analysis, which reported 80 million (95% CI 64–103) viraemic infections in 2013. Methods We developed country-level disease burden models following a systematic review of HCV prevalence (number of studies, n=6754) and genotype (n=11 342) studies published after 2013. A Delphi process was used to gain country expert consensus and validate inputs. Published estimates alone were used for countries where expert panel meetings could not be scheduled. Global prevalence was estimated using regional averages for countries without data. Findings Models were built for 100 countries, 59 of which were approved by country experts, with the remaining 41 estimated using published data alone. The remaining countries had insufficient data to create a model. The global prevalence of viraemic HCV is estimated to be 1·0% (95% uncertainty interval 0·8–1·1) in 2015, corresponding to 71·1 million (62·5–79·4) viraemic infections. Genotypes 1 and 3 were the most common cause of infections (44% and 25%, respectively). Interpretation The global estimate of viraemic infections is lower than previous estimates, largely due to more recent (lower) prevalence estimates in Africa. Additionally, increased mortality due to liver-related causes and an ageing population may have contributed to a reduction in infections. Funding John C Martin Foundation.publishersversionPeer reviewe

Multiple sporadic gastrointestinal stromal tumours arising at different gastrointestinal sites: pattern of involvement of the muscularis propria as a clue to independent primary GISTs

Multifocal sporadic gastrointestinal stromal tumours (GISTs) may be misinterpreted as recurrent or metastatic disease, leading to inappropriate treatment. As molecular analysis is generally not available in routine practise, histological criteria that would facilitate diagnosis of multiple primary GISTs in routine slides are needed. We studied 14 GISTs (mean size, 2.7 cm) from six men and one woman (mean age, 70 years) applying morphological features and direct sequencing of KIT, PDGFRA, BRAF, and KRAS. Diagnosis was synchronous in five and metachronous in two patients. Paired tumours originated in stomach/small bowel (n = 5), duodenum/jejunum (n = 1), and stomach/oesophagus (n = 1) and revealed spindle (n = 10) and mixed spindle and epithelioid (n = 4) phenotype. Tumours were well circumscribed and have involved the muscularis propria in a pattern typical of primary GISTs. Different somatic KIT mutations were found in tumours from four patients. One patient had a KIT-mutated and a BRAF-mutated (V600E) tumour. Two patients had wild-type tumours. No PDGFRA or KRAS mutations were detected. Our results underscore the molecular heterogeneity of sporadic multifocal GISTs. The characteristic involvement of the muscularis propria and the site-typical morphology and immunophenotype facilitated the diagnosis of primary GISTs in all cases and correlated with molecular findings, emphasising the value of conventional histology in recognising independent primary GISTs

Kaposi sarcoma herpes virus antibody response and viremia following highly active antiretroviral therapy in the Swiss HIV Cohort study

OBJECTIVE: To describe the effect of HAART on Kaposi sarcoma herpes virus (KSHV) antibody response and viremia among HIV-positive MSM. DESIGN: A follow-up study of 272 HIV-positive MSM (including 22 with Kaposi sarcoma) who first initiated HAART between January 1996 and July 2004 in the Swiss HIV Cohort Study. METHODS: For each individual, two serum samples, one at HAART initiation and another 24 months later, were tested for latent and lytic KSHV antibodies using immunofluorescence assays, and for KSHV viremia using PCR. Factors associated with changes in KSHV antibody titers and viremia were evaluated. RESULTS: At HAART initiation, 69.1 and 75.0% of patients were seropositive to latent and lytic KSHV antibodies, respectively. Seropositivity was associated with the presence of Kaposi sarcoma, older age, lower CD8 cell count and higher CD4/CD8 ratio. Prevalence of KSHV viremia at HAART initiation was 6.4%, being significantly higher among patients with Kaposi sarcoma (35.0%), and those with HIV viral loads 100 000 copies/ml (11.7%) or higher. At 24-month follow-up, geometric mean titers (GMTs) among KSHV seropositive patients increased and antibody seroprevalence was higher. Having Kaposi sarcoma and/or CD4 cell counts less than 50 cells/microl at HAART initiation was associated both with higher probability for antibody titers to increase (including seroconversion) and larger increases in GMTs. Only one of 17 viremic patients at HAART initiation had viremia at 24-month follow-up. CONCLUSION: HAART increases KSHV-specific humoral immune response and clearance of viremia among HIV-infected MSM, consistent with the dramatic protection offered by HAART against Kaposi sarcoma