Hepatitis C Spearman, C Wendy; Dusheiko, Geoffrey M; Hellard, Margaret ...
The Lancet (British edition),
10/2019, Letnik:
394, Številka:
10207
Journal Article
Recenzirano
Hepatitis C is a global health problem, and an estimated 71·1 million individuals are chronically infected with hepatitis C virus (HCV). The global incidence of HCV was 23·7 cases per 100 000 ...population (95% uncertainty interval 21·3–28·7) in 2015, with an estimated 1·75 million new HCV infections diagnosed in 2015. Globally, the most common infections are with HCV genotypes 1 (44% of cases), 3 (25% of cases), and 4 (15% of cases). HCV transmission is most commonly associated with direct percutaneous exposure to blood, via blood transfusions, health-care-related injections, and injecting drug use. Key high-risk populations include people who inject drugs, men who have sex with men, and prisoners. Approximately 10–20% of individuals who are chronically infected with HCV develop complications, such as cirrhosis, liver failure, and hepatocellular carcinoma over a period of 20–30 years. Direct-acting antiviral therapy is now curative, but it is estimated that only 20% of individuals with hepatitis C know their diagnosis, and only 15% of those with known hepatitis C have been treated. Increased diagnosis and linkage to care through universal access to affordable point-of-care diagnostics and pangenotypic direct-acting antiviral therapy is essential to achieve the WHO 2030 elimination targets.
In 2016, WHO member states at the World Health Assembly adopted a Global Health Sector Strategy that included a policy of eliminating viral hepatitis. Clear targets were established to assist in ...achieving this by 2030. The strategy, while achievable, has exposed existing global disparities in healthcare systems and their ability to implement such policies. Compounding this, the regions with most disparity are also those where the hepatitis B prevalence and disease burden are the greatest. Foundational to hepatitis B elimination is the identification of both those with chronic infection and crucially pregnant women, and primary prevention through vaccination. Vaccination, including the birth dose and full three-dose coverage, is key, but complete mother-to-child transmission prevention includes reducing the maternal hepatitis B viral load in the third trimester where appropriate. Innovations and simplified tools exist in order to achieve elimination, but what is desperately required is the will to implement these strategies through the support of appropriate investment and funding. Without this, disparities will continue.
Oral daily preexposure prophylaxis (PrEP) using emtricitabine (FTC)/tenofovir disoproxil fumarate (TDF) is recommended as standard of care for prevention in individuals at high risk for HIV ...infection, including pregnant and postpartum cisgender women. FTC/TDF is also active against hepatitis B virus (HBV); however, concern has been raised that providing PrEP to individuals infected with HBV could lead to hepatitis flares and liver injury, especially in the setting of suboptimal PrEP use. We conducted a cross-sectional analysis of baseline data from the PrEP in pregnant and postpartum women (PrEP-PP) cohort study from February 2020-March 2022 in one antenatal care clinic in Cape Town, South Africa (SA) to evaluate: (1) the field performance of a point of care test (POCT) (Determine II, Abbott Inc., Japan) for diagnosis of hepatitis B surface antigen (HBsAg) in a maternity setting, (2) the prevalence of HBV in a cohort of pregnant women not living with HIV. We enrolled 1194 HIV sero-negative pregnant women at their first antenatal visit. Median age was 26 years (IQR = 22-31 years); 52% were born before 1995 (before universal HBV vaccination had started in South Africa). Median gestational age was 22 weeks (IQR = 16-30 weeks). There were 8 POCT and laboratory confirmed HBV cases among 1194 women. The overall prevalence of 0.67% (95% CI = 0.34-1.32%). In women born before 1995, 8 of 622 women were diagnosed with HBsAg; the prevalence was 1.29% (95% CI = 0.65-2.52%), and in women born in 1995 or after (n = 572); the prevalence was 0% (95% CI = 0.0-0.67%). We confirmed the test results in 99.8% of the rapid HBsAg (Determine II). Sensitivity was 100% (95% CI = 68-100%). Specificity was 100% (95% CI = 99.67-100%). The prevalence of HBV was very low in pregnant women not living with HIV and was only in women born before the HBV vaccine was included in the Expanded Program of Immunization. The Determine II POCT HBsAg showed excellent performance against the laboratory assay. HBV screening should not be a barrier to starting PrEP in the context of high HIV risk communities.
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content ...experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms “nonalcoholic” and “fatty” were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction–associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction–associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction–associated steatotic liver disease, who consume greater amounts of alcohol per week (140–350 g/wk and 210–420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
The principal limitations of the terms NAFLD and NASH are the reliance on exclusionary confounder terms and the use of potentially stigmatising language. This study set out to determine if content ...experts and patient advocates were in favor of a change in nomenclature and/or definition. A modified Delphi process was led by three large pan-national liver associations. The consensus was defined a priori as a supermajority (67%) vote. An independent committee of experts external to the nomenclature process made the final recommendation on the acronym and its diagnostic criteria. A total of 236 panelists from 56 countries participated in 4 online surveys and 2 hybrid meetings. Response rates across the 4 survey rounds were 87%, 83%, 83%, and 78%, respectively. Seventy-four percent of respondents felt that the current nomenclature was sufficiently flawed to consider a name change. The terms "nonalcoholic" and "fatty" were felt to be stigmatising by 61% and 66% of respondents, respectively. Steatotic liver disease was chosen as an overarching term to encompass the various aetiologies of steatosis. The term steatohepatitis was felt to be an important pathophysiological concept that should be retained. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease. There was consensus to change the definition to include the presence of at least 1 of 5 cardiometabolic risk factors. Those with no metabolic parameters and no known cause were deemed to have cryptogenic steatotic liver disease. A new category, outside pure metabolic dysfunction-associated steatotic liver disease, termed metabolic and alcohol related/associated liver disease (MetALD), was selected to describe those with metabolic dysfunction-associated steatotic liver disease, who consume greater amounts of alcohol per week (140-350 g/wk and 210-420 g/wk for females and males, respectively). The new nomenclature and diagnostic criteria are widely supported and nonstigmatising, and can improve awareness and patient identification.
Aims
N‐acetylcysteine (NAC) may be useful in the management of non‐paracetamol drug‐induced liver injury (DILI). Our objective was to review systematically evidence for the use of NAC as a ...therapeutic option for non‐paracetamol DILI.
Methods
We searched for randomized controlled trials (RCTs) and prospective cohort studies. We searched several bibliographic databases, grey literature sources, conference proceedings and ongoing trials. Our pre‐specified primary outcomes were all cause and DILI related mortality, time to normalization of liver biochemistry and adverse events. Secondary outcomes were proportion receiving liver transplant, time to transplantation, transplant‐free survival and hospitalization duration.
Results
We identified one RCT of NAC vs. placebo in patients with non‐paracetamol acute liver failure. There was no difference in the primary outcomes of overall survival at 3 weeks between NAC 70%, 95% confidence interval (CI) = 60%, 81%, n = 81 and placebo (66%, 95% CI = 56%, 77%, n = 92). NAC significantly improved the secondary outcomes of transplant‐free survival compared with placebo: 40% NAC (95% CI = 28%, 51%) vs. 27% placebo (95% CI = 18%, 37%). A subgroup analysis according to aetiology found improved transplant‐free survival in patients with non‐paracetamol DILI, NAC (58%, n = 19) vs. placebo (27%, n = 26), odds ratio (OR) 0.27 (95% CI = 0.076, 0.942). Overall survival was similar, NAC (79%) vs. placebo (65%);, OR 0.50 (95% CI = 0.13, 1.98).
Conclusion
Current available evidence is limited and does not allow for any firm conclusions to be made regarding the role of NAC in non‐paracetamol DILI. We therefore highlight the need for further research in this area.
In sub-Saharan Africa, simple biomarkers of liver fibrosis are needed to scale-up hepatitis B treatment. We conducted an individual participant data meta-analysis of 3,548 chronic hepatitis B ...patients living in eight sub-Saharan African countries to assess the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index and two other fibrosis biomarkers using a Bayesian bivariate model. Transient elastography was used as a reference test with liver stiffness measurement thresholds at 7.9 and 12.2kPa indicating significant fibrosis and cirrhosis, respectively. At the World Health Organization-recommended cirrhosis threshold (>2.0), aspartate aminotransferase-to-platelet ratio index had sensitivity (95% credible interval) of only 16.5% (12.5-20.5). We identified an optimised aspartate aminotransferase-to-platelet ratio index rule-in threshold (>0.65) for liver stiffness measurement >12.2kPa with sensitivity and specificity of 56.2% (50.5-62.2) and 90.0% (89.0-91.0), and an optimised rule-out threshold (<0.36) with sensitivity and specificity of 80.6% (76.1-85.1) and 64.3% (62.8-65.8). Here we show that the World Health Organization-recommended aspartate aminotransferase-to-platelet ratio index threshold is inappropriately high in sub-Saharan Africa; improved rule-in and rule-out thresholds can optimise treatment recommendations in this setting.
People who use drugs including people who inject drugs (PWUD/ID), sex workers (SWs) and men who have sex with men (MSM) are at increased risk of HIV and viral hepatitis infection. Limited ...epidemiological data on the infections exists in key populations (KPs) in South Africa. We investigated the prevalence of hepatitis B (HBV), hepatitis C (HCV) and HIV and selected risk factors among these KPs to inform effective responses. We used convenience sampling to recruit a targeted 3500 KPs accessing HIV-related health services across Cape Town (SWs, MSM, PWUD/ID), Durban (SWs, PWUD/ID), Pietermaritzburg (SWs), Mthatha (SWs), Port Elizabeth (SWs), Johannesburg (MSM) and Pretoria (MSM and PWUD/ID) into a cross-sectional survey. An interviewer questionnaire to assess socio-demographic characteristics, drug use and sexual risk practices, was administered. HBV surface antigen (HBsAg); HCV antibody, viral load and genotype, and HIV antibody, was tested. Among the 3439 people included in the study (1528 SWs, 746 MSM, 1165 PWUD/ID) the median age was 29 years, most participants were black African (60%), and 24% reported homelessness. 82% reported substance use in the last month, including alcohol (46%) and heroin (33%). 75% were sexually active in the previous month, with condom use at last sex at 74%. HIV prevalence was 37% (highest among SWs at 47%), HBsAg prevalence 4% (similar across KPs) and HCV prevalence was 16% (highest among PWUD/ID at 46%). HBV, HCV and HIV pose a health burden for KPs in South Africa. While HIV is key for all included KPs, HCV is of particular importance to PWUD/ID. For KPs, HBV vaccination and behavioural change interventions that support consistent condom and lubricant access and use are needed. Coverage of opioid substitution therapy and needle and syringe services, and access to HCV treatment for PWUD/ID need to be expanded.
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