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

Liver transplantation does not impact the renal function outcome in Alagille syndrome

Objectives and study: Alagille syndrome (AS) is an autosomal dominant multi-systemic disorder caused by pathogenic variants in JAG1 and NOTCH2. Characteristic findings include hepatic involvement with bile duct paucity and 20-50% eventually need a liver transplantation. Post-LT Tacrolimus induced nephropathy is well recognised and 40% of AS patients have an underlying renal anomaly. In the current study we analysed the impact of LT and Tacrolimus on the evolution of renal function (RF) in children with AS. Methods: Retrospective study including 50 children that satisfied 3 of 5 major Alagille syndrome criteria and under regular follow-up at our centre between 1984 and 2016. Clinical, biochemical and radiological data were collected at similar time points of follow-up among the transplanted and non-transplanted children. The time points were at diagnosis or at LT and after 1-2 years, 2-3 years, 3-5 years, 5-7 years and 7-10 years of follow-up. The RF was estimated by glomerular filtration rate (eGFR) using the updated Schwartz formula. The RF outcomes of children with AS having undergone LT were compared with those without LT and also with children having undergone LT for non-AS related indication but without associated nephropathy. Results: 28 of 50 (56%) included AS children underwent LT and were compared with 77 children transplanted for non-AS indications. Mean eGFR post-LT in AS patients and non-AS patients were 93.8 mL/min and 143.2 mL/min, respectively (difference: 49.4 mL/min, p<0.0001). Among children with AS mean eGFR observed in those who did not receive LT was 87.9 mL/min, -5.9 mL/min compared to those who received LT though this was statistically insignificant (p=0.32). Presence of renal ultrasound abnormalities was correlated to RF impairment in AS patients, with or without LT: -14.6 mL/min (98.5 mL/min vs 83.9 mL/min, p=0.03) and -40.9 mL/min (97.8 mL/min vs 56.9 mL/min, p<0.0001), respectively. Conclusion: Post-LT renal function outcomes are significantly worse in children with AS being the primary disease. Among the children with AS, the RF outcome is not worse after LT

Liver transplantation does not impact the renal function outcome in Alagille syndrome

Background and Aims: Alagille syndrome (AS) is an autosomal dominant multi-systemic disorder caused by pathogenic variants in JAG1 and NOTCH2. Characteristic findings include hepatic involvement with bile duct paucity and 20-50% eventually need a liver transplantation. Post-LT Tacrolimus induced nephropathy is well recognised and 40% of AS patients have an underlying renal anomaly. In the current study we analysed the impact of LT and Tacrolimus on the evolution of renal function (RF) in children with AS. Methods: Retrospective study including 50 children that satisfied 3 of 5 major Alagille syndrome criteria and under regular follow-up at our centre between 1984 and 2016. Clinical, biochemical and radiological data were collected at similar time points of follow-up among the transplanted and non-transplanted children. The time points were at diagnosis or at LT and after 1-2 years, 2-3 years, 3-5 years, 5-7 years and 7-10 years of follow-up. The RF was estimated by glomerular filtration rate (eGFR) using the updated Schwartz formula. The RF outcomes of children with AS having undergone LT were compared with those without LT and also with children having undergone LT for non-AS related indication but without associated nephropathy. Results: 28 of 50 (56%) included AS children underwent LT and were compared with 77 children transplanted for non-AS indications. Mean eGFR post-LT in AS patients and non-AS patients were 93.8 mL/min and 143.2 mL/min, respectively (difference: 49.4 mL/min, p<0.0001). Among children with AS mean eGFR observed in those who did not receive LT was 87.9 mL/min, -5.9 mL/min compared to those who received LT though this was statistically insignificant (p=0.32). Presence of renal ultrasound abnormalities was correlated to RF impairment in AS patients, with or without LT: -14.6 mL/min (98.5 mL/min vs 83.9 mL/min, p=0.03) and -40.9 mL/min (97.8 mL/min vs 56.9 mL/min, p<0.0001), respectively. Conclusions: Post-LT renal function outcomes are significantly worse in children with AS being the primary disease. Among the children with AS, the RF outcome is not worse after LT