Search

Background and Aims: People living with HIV (PLWH) are at high risk for advanced chronic liver disease and related adverse outcomes. We aimed to validate the prognostic value of non-invasive scores based on liver stiffness measurement (LSM) and on markers of portal hypertension (PH), namely platelets and spleen diameter, in PLWH., Methods: We combined data from eight international cohorts of PLWH with available non-invasive scores, including LSM and the composite biomarkers liver stiffness-spleen size-to-platelet ratio score (LSPS), LSM-to-Platelet ratio (LPR) and PH risk score. Incidence and predictors of all-cause mortality, any liver-related event and classical hepatic decompensation were determined by survival analysis, controlling for competing risks for the latter two. Non-invasive scores were assessed and compared using area under the receiver operating curve (AUROC)., Results: We included 1695 PLWH (66.8% coinfected with hepatitis C virus). During a median follow-up of 4.7 (interquartile range 2.8-7.7) years, the incidence rates of any liver-related event, all-cause mortality and hepatic decompensation were 13.7 per 1000 persons-year (PY) (95% confidence interval [CI], 11.4-16.3), 13.8 per 1000 PY (95% CI, 11.6-16.4) and 9.9 per 1000 PY (95% CI, 8.1-12.2), respectively. The AUROC of LSM was similar to that of the composite biomarkers, ranging between 0.83 and 0.86 for any liver-related event, 0.79-0.85 for all-cause mortality and 0.87-0.88 for classical hepatic decompensation. All individual non-invasive scores remained independent predictors of clinical outcomes in multivariable analysis., Conclusions: Non-invasive scores based on LSM, spleen diameter and platelets predict clinical outcomes in PLWH. Composite biomarkers do not achieve higher prognostic performance compared to LSM alone., (© 2023 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: A simplified cascade-of-care may improve screening and treatment uptake among incarcerated individuals. We assessed the cost-effectiveness of traditional and simplified screening and treatment in a London remand prison., Methods: Using empirical data from Her Majesty's Prison (HMP) Wormwood Scrubs, London, we designed a decision tree and Markov transition state model using national average data for HCV screening and treatment for the base-case scenario. This compared two alternative strategies; (a) general prison population screening and treatment and (b) prioritising screening and treatment among people who inject drugs (PWID) combined with general prison population screening and treatment. Strategies varied the rates of screening (47%-90%), linkage-to-care (60%-86%) and treatment (21%-85%). Cost, utility and disease transition rates were obtained from existing literature. Outcome measures were as follows: screening, treatment and disease-related costs per admitted individual, quality-adjusted life years (QALYs). Incremental cost-effectiveness ratios (ICERs) were calculated for each intervention. All costs and utilities were discounted at a rate of 3.5% per annum. Both univariate and probabilistic sensitivity analyses have been conducted., Results: In our cohort of 5239 incarcerated individuals with an estimated chronic HCV prevalence of 2.6%, all strategy ICER values (£3565-10 300) fell below the national willingness to pay threshold (£30 000). Increased successful treatment (7%-54%) was observed by an optimising cascade-of-care. A robust sensitivity analysis identified treatment cost of, QALY for mild liver disease and probability of completing treatment as important factors that impact the ICER value., Conclusion: In our remand setting, optimising adherence to the cascade-of-care is cost-effective. Where universal screening is not practical, a stratified approach focused on intensive screening and treatment of PWID also results in increased treatment uptake and is highly cost-effective., (© 2020 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: In Sub-Saharan Africa, chronic hepatitis C (CHC) is a major public health issue. We estimated the long-term clinical benefits of treating CHC with sofosbuvir-based regimens in Cameroon, Côte d'Ivoire and Senegal using Markov model combining data from the literature with estimates of direct-acting antiviral (DAAs) effectiveness in West and Central Africa., Methods: Disease progression was simulated with and without treatment in fictive cohorts of patients "diagnosed" with CHC in Cameroon (n = 3224), Côte d'Ivoire (n = 9748) and Senegal (n = 6358). Lifetime treatment benefits were assessed using (a) life-years saved (LYS); (b) life-years (LY) avoided in compensated cirrhosis (CC), decompensated cirrhosis (DC) and hepatocellular carcinoma; and (c) comparison of the proportions of patients at each disease stage with and without treatment. Probabilistic and determinist sensitivity analyses were performed to address uncertainty., Results: Sofosbuvir-based treatment would save [mean, 95% confidence intervals] 3.3 (2.5; 5.7) LY per patient in Cameroon, 2.7 (2.1; 4.8) in Côte d'Ivoire and 3.6 (2.8; 6.3) in Senegal. With treatment, approximately 6% (1%) of the patients still alive in each of the study countries would be in the CC (DC) health state 11 (15) years after CHC diagnosis, vs 15% (5%) without treatment. Scenario analysis showed earlier diagnosis and treatment initiation would dramatically improve LYS and morbidity., Conclusion: Sofosbuvir-based treatment could significantly reduce CHC-related mortality and help control CHC-related liver disease progression in West and Central Africa. However, the goal of disease elimination necessitates a substantial decrease in DAAs prices, greater political commitment and increases in both national and external health expenditures., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Although novel hepatitis C virus (HCV) RNA point-of-care technology has the potential to enhance the diagnosis in resource-limited settings, very little real-world validation of their utility exists. We evaluate the performance of HCV RNA quantification using the Xpert ® HCV viral load Fingerstick assay (Xpert ® HCV VL Fingerstick assay) as compared to the World Health Organisation pre-qualified plasma Xpert ® HCV VL assay among people who inject drugs (PWID) attending an opioid agonist therapy (OAT) clinic in Dar-es-Salaam, Tanzania., Methods: Between December 2018 and February 2019, consecutive HCV seropositive PWID attending the OAT clinic provided paired venous and Fingerstick samples for HCV RNA quantification. These were processed onsite using the GeneXpert ® platform located at the Central tuberculosis reference laboratory., Results: A total of 208 out of 220 anti-HCV-positive participants recruited (94.5%) had a valid Xpert ® HCV VL result available; 126 (61%; 95% CI 53.8-67.0) had detectable and quantifiable HCV RNA. About 188 (85%) participants had paired plasma and Fingerstick whole blood samples; the sensitivity and specificity for the quantification of HCV RNA levels were 99.1% and 98.7% respectively. There was an excellent correlation (R 2  = .95) and concordance (mean difference 0.13 IU/mL, (95% CI -0.9 to 0.16 IU/mL) in HCV RNA levels between plasma samples and Fingerstick samples., Conclusion: This study found excellent performance of the Xpert ® HCV VL Fingerstick assay for HCV RNA detection and quantification in an African-field setting. Its clinical utility represents an important watershed in overcoming existing challenges to HCV diagnosis, which should play a crucial role in HCV elimination in Africa., (© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.)

Background: In sub-Saharan Africa, it is unknown whether hepatitis E virus (HEV) infection is a common precipitating event of acute-on-chronic liver failure (ACLF)., Aims: To estimate the prevalence of HEV infection in general population and assess whether HEV is a common trigger of ACLF in cirrhotic patients in The Gambia, West Africa., Methods: We first conducted an HEV sero-survey in healthy volunteers. We then tested cirrhotic patients with ACLF (cases) and compensated cirrhosis (controls) for anti-HEV IgG as a marker of exposure to HEV, and anti-HEV IgA and HEV RNA as a marker of recent infection. We also described the characteristics and survival of the ACLF cases and controls., Results: In the healthy volunteers (n = 204), 13.7% (95% CI: 9.6-19.2) were positive for anti-HEV IgG, and none had positive HEV viraemia. After adjusting for age and sex, the following were associated with positive anti-HEV IgG: being a Christian, a farmer, drinking water from wells, handling pigs and eating pork. In 40 cases (median age: 45 years, 72.5% male) and 71 controls (39 years, 74.6% male), ≥70% were infected with hepatitis B virus. Although hepatitis B flare and sepsis were important precipitating events of ACLF, none had marker of acute HEV. ACLF cases had high (70.0%) 28-day mortality., Conclusions: Hepatitis E virus infection is endemic in The Gambia, where both faecal-oral route (contaminated water) and zoonotic transmission (pigs/pork meat) may be important. However, acute HEV was not a common cause of acute-on-chronic liver failure in The Gambia., (© 2015 John Wiley & Sons Ltd.)

Background & Aims: Early age at infection with Hepatitis B virus (HBV) increases the risk of chronic infection. Moreover, early HBV infection may further independently increase the risk of hepatocellular carcinoma (HCC) beyond its effect on chronicity., Methods: The distribution of birth order, a proxy for mode and timing of HBV transmission, was compared in The Gambia between hepatitis B surface antigen (HBsAg)-positive HCC cases recruited from hospitals (n = 72) and two HBsAg-positive control groups without HCC: population-based controls from a community HBV screening (n = 392) and hospital-based controls (n = 63)., Results: HCC risk decreased with increasing birth order in the population-based case-control analysis. Using first birth order as the reference, the odds ratios were 0.52 (95% CI: 0.20-1.36), 0.52 (0.17-1.56), 0.57 (0.16-2.05) and 0.14 (0.03-0.64) for second, third, fourth and greater than fourth birth order respectively (P = 0.01). A similar inverse association was observed in the hospital-based case-control comparison (P = 0.04)., Conclusions: Compared to controls, HCC cases had earlier birth order, a proxy for young maternal age and maternal HBV viraemia at birth. This finding suggests that in chronic HBV carriers perinatal mother-to-infant transmission may increase HCC risk more than horizontal transmission. Providing HBV vaccine within 24 h of birth to interrupt perinatal transmission might reduce the incidence of HCC in The Gambia., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In 2010, the World Health Assembly adopted a resolution calling for interventions for the prevention and control of chronic viral hepatitis. These infectious diseases mostly affect resource-limited countries accounting for 80% of the world's population and facing numerous obstacles to contain the epidemic. At a time when morbidity and mortality of chronic liver disease have been considerably improved in wealthy countries by new innovative strategies and new potent antiviral drugs, it is now urgent to recall for concrete actions from stakeholders of global health policy to reduce the burden in resource-limited countries., (© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: By increasing the hepatic blood circulation, food intake has been suggested to increase liver stiffness measurement (LSM) values in HCV-infected patients., Aim: To investigate prospectively the effects of food intake on LSM in hepatitis B virus (HBV)-infected patients and healthy controls., Methods: In The Gambia, patients included in the PROLIFICA project are screened for HBV at the community level and then invited for fasting assessment including LSM. Between April 2012 and October 2012, each day, the first five participants were invited to participate in this study. After the initial examination, a standardised 850 Kcal breakfast was provided. Effect of food intake was assessed by examining mean difference of LSM, IQR and IQR/LSM at T0 (fasting LSM1), T30min (LSM2) and T120min (LSM3) respectively., Results: A total of 209 subjects were enrolled in this study (133 were HBV positive, 76 healthy controls). Unreliable measurements occurred more frequently after food intake (5%, 24% and 18% at T0, T30min and T120min respectively). In both groups, median LSM2 was significantly higher than LSM1 [6.2 (IQR: 5.4, 7.9)] vs. 4.9 (4.2, 6.2), P < 0.0001. LSM3 was still higher than the baseline, but lower than LSM2. In multivariable analysis, no factor modified the effect of breakfast on LSM. In a subgroup of patients having liver biopsies, we confirmed that food intake can overestimate liver fibrosis., Conclusions: Food intake significantly increases liver stiffness measurement and its IQR values in patients with chronic hepatitis B as well as healthy individuals; and also the number of unreliable liver stiffness measurement values., (© 2013 John Wiley & Sons Ltd.)

The main thesis of this paper is that mental health practitioners can legitimately infer that a patient's given condition is a case of mental disorder without having diagnosed any specific mental disorder. The article shows how this is justifiable by relying either on psychopathological reasoning, on 'intentional' analysis or possibly on other modes of reasoning. In the end, it highlights the clinical and philosophical consequences of the plurality of modes of 'inferences to mental disorder'., (© 2012 Blackwell Publishing Ltd.)

Aims: The aim of this study was to determine whether serum levels of adipokines, including the ratio of serum adiponectin to leptin (A/L) levels could predict the severity of liver injury in patients with non-alcoholic fatty liver disease (NAFLD)., Patients and Methods: Fifty-seven patients with biopsy-proven non-alcoholic steatohepatitis (NASH) (mean age 51+/-12, sex ratio 1), 17 with simple steatosis (mean age 47+/-12, sex ratio 1.4) and 10 controls without steatosis (mean age 51+/-11, sex ratio 4) were investigated. In all subjects, serum concentrations of triglycerides, ultrasensitive C reactive protein, leptin, adiponectin, soluble tumour necrosis factor receptor 1, interleukin (IL)-6 and Homeostasis Model Assessment Method (HOMA) were measured. Hepatic expression of adiponectin and its two receptors was assessed by quantitative reverse transcriptase polymerase chain reaction., Results: Body mass index (BMI) and HOMA were correlated positively with leptin levels (r=0.44 and 0.28 respectively) and negatively with the A/L ratio (r=0.51 and 0.41 respectively). Independent parameters associated with NASH vs steatosis were HOMA>3 [odds ratio (OR)=6.9] and A/L ratio <1.4 10(3) (OR=5.2). The combination of HOMA with A/L ratio showed an area under the receiver operating characteristic curve of 0.82 for distinguishing between NASH and steatosis. Extensive portal fibrosis was present in 17 (23%) patients with NAFLD. Three independent parameters were associated with fibrosis: age (OR=1.1), BMI (OR=1.3) and high IL-6 levels (OR=1.6). The hepatic expression of adiponectin receptor 2 was significantly higher in patients with NASH compared with controls and was related with necroinflammatory injury., Conclusions: This study shows that in patients with NAFLD, the combination of HOMA with A/L ratio may be a useful non-invasive approach to appreciate the severity of liver damage.

Background: Hepatic venous pressure gradient (HVPG) is the gold standard for assessing the presence and the severity of portal hypertension (PHT). Liver stiffness measurement (LSM) is a non-invasive method for liver fibrosis assessment., Aims: To assess the relationship between LSM and HVPG in patients with compensated cirrhosis related to hepatitis C virus (HCV) or alcohol and to define the performance and the best cut-off of LSM for the diagnosis of PHT in these patients., Methods: Between January 2004 and September 2006, we studied all the consecutive patients with compensated HCV or alcohol-related-cirrhosis referred for transjugular liver biopsy with HVPG measurement and LSM performed the same day., Results: Ninety-two patients were eligible, 44 had HCV related-cirrhosis and 48 alcoholic cirrhosis. LSM was positively correlated to HVPG in both groups. The area under the receiver operating characteristic curve for the diagnosis of significant PHT was 0.76 +/- 0.07 in HCV patients (best cut-off at 20.5 kPa) and 0.94 +/- 0.03 (best cut-off at 34.9 kPa) in alcoholic patients., Conclusions: Liver stiffness measurement and HVPG were significantly correlated in patients with compensated cirrhosis because of HCV infection or alcohol. LSM could predict significant PHT in both these groups of patients with a higher cut-off and a better performance in alcoholic patients.