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The authors review the epidemiology, pathophysiology, and treatment of alcohol-associated hepatitis, including the evidence for glucocorticoids and liver transplantation.

The prison setting presents not only challenges, but also opportunities, for the prevention and treatment of HIV, viral hepatitis, and tuberculosis. We did a comprehensive literature search of data published between 2005 and 2015 to understand the global epidemiology of HIV, hepatitis C virus (HCV), hepatitis B virus (HBV), and tuberculosis in prisoners. We further modelled the contribution of imprisonment and the potential impact of prevention interventions on HIV transmission in this population. Of the estimated 10·2 million people incarcerated worldwide on any given day in 2014, we estimated that 3·8% have HIV (389 000 living with HIV), 15·1% have HCV (1 546 500), 4·8% have chronic HBV (491 500), and 2·8% have active tuberculosis (286 000). The few studies on incidence suggest that intraprison transmission is generally low, except for large-scale outbreaks. Our model indicates that decreasing the incarceration rate in people who inject drugs and providing opioid agonist therapy could reduce the burden of HIV in this population. The prevalence of HIV, HCV, HBV, and tuberculosis is higher in prison populations than in the general population, mainly because of the criminalisation of drug use and the detention of people who use drugs. The most effective way of controlling these infections in prisoners and the broader community is to reduce the incarceration of people who inject drugs.

BackgroundAdalimumab has been used in patients with moderately to severely active rheumatoid arthritis (RA) for over 10 years and has a well-established safety profile across multiple indications.ObjectiveTo update adverse events (AEs) of special interest from global adalimumab clinical trials in patients with RA.MethodsThis analysis includes 15 132 patients exposed to adalimumab in global RA clinical trials. AEs of interest included overall infections, laboratory abnormalities and AEs associated with influenza vaccination. Pregnancy outcome data were collected from the Adalimumab Pregnancy Registry.ResultsSerious infections and tuberculosis occurred at a rate of 4.7 and 0.3 events/100 patient-years, respectively. Two patients experienced hepatitis B reactivation. No significant laboratory abnormalities were reported with adalimumab-plus-methotrexate compared with placebo-plus-methotrexate. Influenza-related AEs occurred in 5% of vaccinated patients compared with 14% of patients not vaccinated during the study. Relative risk of major birth defects and spontaneous abortions in adalimumab-exposed women were similar between that of unexposed women with RA and healthy women.ConclusionsThis analysis confirms and expands the known safety profile of adalimumab and reports no additional safety risk of laboratory abnormalities, hepatitis B reactivation and pregnancy outcomes, including spontaneous abortions and birth defects. The benefits of influenza vaccination are reinforced.Trial registration numbersNCT00195663, NCT00195702, NCT00448383, NCT00049751, NCT00234845, NCT00650390, NCT00235859, NCT00647920, NCT00649545, NCT00647491, NCT00649922, NCT00538902, NCT00420927, NCT00870467, NCT00650156, NCT00647270, NCT01185288, NCT01185301.

Key Points Hepatitis B virus (HBV) and hepatitis C virus (HCV) are both parenterally transmitted enveloped viruses that induce acute and chronic necroinflammatory liver disease. HBV is a partially double-stranded DNA virus and a member of the hepadnaviridae family, whereas HCV is a positive-stranded RNA virus and constitutes a separate genus in the flaviviridae family. HBV and HCV have a narrow host range, which is limited to humans and chimpanzees. Humans are the main natural host for HBV (a single indigenous HBV strain has been identified in chimpanzees in West Africa) and the only natural host for HCV. The most common cause of chronic hepatitis B is vertical transmission from mother to neonate. Vertical transmission is not common for hepatitis C. More than 90% of those individuals who acquire HBV infection as adults, but only 20–40% of those who acquire HCV infection as adults spontaneously recover from all clinical symptoms. Studies of experimentally infected chimpanzees showed that HBV does not induce any detectable changes in the expression of intrahepatic genes in the first weeks of infection. By contrast, HCV upregulates the expression of many intrahepatic genes early after infection. Hepatocytes in which HBV is replicating can be removed by cytotoxic mechanisms or cured by cytokine-mediated, non-cytolytic mechanisms, as shown in transgenic mice (by adoptive transfer of HBV-specific, interferon-γ (IFN-γ)-secreting T cells) and in chimpanzees (by a temporal relationship between HBV clearance and upregulation of intrahepatic IFN-γ expression in the early phase of HBV infection). A reduction in HCV titre at the time of intrahepatic IFN-γ expression has also been shown in HCV infection. Humoral responses in HBV infection are important. HBV core antigen (HBcAg)-specific IgM is an early marker of infection, and the appearance of HBV e antigen (HBeAg)-specific antibodies indicates a reduction in viral titre in chronically infected patients. HBcAg- and HBV surface antigen (HBsAg)-specific IgG persist for life in recovered patients. By contrast, the appearance of HCV-specific antibodies is much more variable: no antibodies develop early after infection, and in some cases, they might not develop at all. HCV-specific antibody titres might decrease to undetectable levels 10–20 years after recovery. Trace amounts of HBV persist after clinical recovery and are controlled by HBV-specific humoral and cellular immune responses. Whether trace amounts of HCV persist long-term after clinical recovery is controversial and requires studies of large patient cohorts. HBV-specific immunity is observed in all clinically recovered patients and is mediated by neutralizing antibodies and T cells. HCV-specific immunity has been described for some, but not all, chimpanzees that recover from an experimental infection, and it is mediated by T cells. HBV- and HCV-specific T-cell responses contribute not only to viral clearance and clinical recovery but also to immune-mediated acute and chronic liver disease. Spontaneous viral clearance, generation of HBsAg-specific-antibody and resolution of disease occurs in ∼2% of patients with chronic hepatitis B each year, and it is temporally correlated with the appearance of HBV-specific T cells in the blood. By contrast, there is no spontaneous viral clearance in patients with chronic hepatitis C. More than 500 million people worldwide are persistently infected with the hepatitis B virus (HBV) and/or hepatitis C virus (HCV) and are at risk of developing chronic liver disease, cirrhosis and hepatocellular carcinoma. Despite many common features in the pathogenesis of HBV- and HCV-related liver disease, these viruses markedly differ in their virological properties and in their immune escape and survival strategies. This review assesses recent advances in our understanding of viral hepatitis, contrasts mechanisms of virus–host interaction in acute hepatitis B and hepatitis C, and outlines areas for future studies.

Renal transplantation is the most beneficial treatment in patients with chronic kidney disease (CKD), increasing life expectancy and improving quality of life. A better understanding of organ and tissue functions, the development of surgical techniques, and new and effective immunosuppressive and antimicrobial drugs increase the success of transplantation. However, the number of renal transplantations from living and cadaveric donors is not at the desired frequency. Among the leading causes of the restrictions for transplantation are both the recipients’ and donors’ chronic diseases. While hepatitis B and C infections are a significant problem affecting the number and success of renal transplantations, the innovation of hepatitis C virus treatments has improved outcomes. Thus, the recipient and donor hepatitis B and C virus infections are no longer considered as relative contraindications for renal transplantation. This review discusses the management of patients and donors with hepatitis B and hepatitis C in renal transplantation.

Background In Luxembourg, viral hepatitis and HIV infection data in problem drug users (PDUs) are primarily based on self-reporting. Our study aimed to determine the prevalence of HAV, HBV, HCV and HIV infections in ever injecting (IDUs) and non-injecting drug users (nIDUs) including inherent risk factors analysis for IDUs. Secondary objectives were immunisation against HAV and HBV, referral to care and treatment facilities as well as reduction in risk behaviour. Methods A nationwide, cross-sectional multi-site survey, involving 5 in-, 8 out-treatment and 2 prison centres, included both an assisted questionnaire (n = 368) and serological detection of HIV and Hepatitis A, B, C (n = 334). A response rate of 31% resulted in the participation of 310 IDUs and 58 nIDUs. Risk factors such as drug use, sexual behaviour, imprisonment, protection and health knowledge (HAV, HBV status and immunisations, HCV, HIV), piercing/tattoo and use of social and medical services were studied by means of chi2 and logistic models. Results Seroprevalence results for IDUs were 81.3% (218/268, 95%CI=[76.6; 86.0]) for HCV, 29.1% (74/254, 95%CI=[25.5;34.7 ]) for HBV (acute/chronic infection or past cured infection), 2.5% (5/202, 95%CI=[0.3; 4.6]) for HIV-1 and 57.1% (108/189, 95%CI=[50.0; 64.1]) for HAV (cured infections or past vaccinations). Seroprevalence results for nIDUs were 19.1% (9/47, 95%CI=[7.9;30.3]) for HCV, 8.9% (4/45, 95%CI=[0.6;17.2]) for HBV (acute/chronic infection or past cured infection), 4.8% (2/42, 95%CI=[-1.7;11.3]) for HIV-1 and 65.9% (27/41, 95%CI=[51.4;80.4]) for HAV. Prisoners showed the highest rates for all infections. Age, imprisonment and setting of recruitment were statistically associated with HCV seropositivity. Age, speedball career and nationality were significantly associated with HBV seropositivity. Only 56% of the participants in outpatient centres collected their serology results and 43 doses of vaccine against HAV and/or HBV were administered. Conclusions Despite the existing national risk-reduction strategies implemented since 1993, high prevalence of HCV and HBV infections in injecting drug users is observed. Our study showed that implementing risk-prevention strategies, including immunisation remains difficult with PDUs. Improvement should be looked for by the provision of field healthcare structures providing tests with immediate results, advice, immunisation or treatment if appropriate.

ObjectivesEffective oral therapies for hepatitis B and C have recently been developed, while there are no approved pharmacological therapies for alcoholic and non-alcoholic fatty liver diseases (ALD and NAFLD). We hypothesise that fewer advances in fatty liver diseases could be related to disparities in research attention.MethodsWe developed the Attention-to-Burden Index (ABI) that compares the research activities during 2010–2014, and an estimate of disease burden of these 4 major liver diseases. The resulting ratio reflects either overattention (positive value) or inadequate attention (negative value) compared with disease burden. The mean research attention and disease burden were calculated from 5 and 6 different parameters, respectively. The efficacy rate of current pharmacological therapies was assessed from published clinical trials.FindingsThe mean research attention for hepatitis B and C was 31% and 47%, respectively, while NAFLD and ALD received 17% and 5%. The overall burden was 5% and 28% for hepatitis B and C, and 17% and 50% for NAFLD and ALD. The calculated ABI for hepatitis B and C revealed a +6.7-fold and +1.7-fold overattention, respectively. NAFLD received an appropriate attention compared with its burden, while ALD received marked inadequate attention of −9.7-fold. The efficacy rate of current pharmacological agents was 72% for hepatitis B, 89% for hepatitis C, 25% for non-alcoholic steatohepatitis and 13% for alcoholic hepatitis. Importantly, we found a positive correlation between the mean attention and the efficacy rate of current therapies in these 4 major liver diseases.InterpretationThere are important disparities between research attention and disease burden among the major liver diseases. While viral hepatitis has received considerable attention, there is a marked inadequate attention to ALD. There is a critical need to increase awareness of ALD in the liver research community.

An estimated 240 million people are chronically infected with hepatitis B virus, and between 130 and 150 million people globally have chronic hepatitis C infection (1,2). The 63rd (2010) and 67th (2014) Sessions of the World Health Assembly recognized the serious burden of viral hepatitis on global health, and called for Member States of the World Health Organization to develop and implement national strategies for preventing, diagnosing, and treating viral hepatitis. The action plan prioritizes evidence-based effective interventions, including hepatitis B vaccination, blood and injection safety, harm reduction for injecting drug users and hepatitis B and C diagnosis and treatment, and has set regional targets (22). The contributions of hepatitis B virus and hepatitis C virus infections to cirrhosis and primary liver cancer worldwide.

HIV, hepatitis B and C, and syphilis share common transmission routes of which primarily unsafe sexual contact and injecting drug use are important. Impulsivity is a major factor contributing to this transmission risk behavior; however comprehensive studies within female, prison, and Asian populations are scarce. This cross-sectional study aims to delineate the contributions of different aspects of impulsivity to risk behavior, among female inmates living in a prison in Jakarta (N = 214). The relationships between various aspects of impulsivity, risk behaviors and seropositivity were tested using analyses of variance and logistic regression analyses. Motor impulsivity was related to alcohol use, reward-related impulsivity to drug use, and cognitive/goal-directed impulsivity to sexual risk behavior. Finally, goal-directed impulsivity was also directly associated with seropositivity. Specific aspects of impulsivity are associated with different types of risk behavior in Indonesian female prisoners, which can be relevant for future studies on infection prevention strategies for such a population.

Background During 2022, a new public health threat emerged when cases of paediatric acute hepatitis of unknown aetiology (HUA) were identified in children aged under 16 years old in the United Kingdom (UK). At the time, the epidemiology and extent of cases was based upon limited and non-standardised reporting from hospitals and liver units. We aimed to adapt existing real-time syndromic surveillance systems to support the epidemiological investigation of cases of HUA presenting to emergency departments (EDs) in England. Methods Syndromic surveillance is generally based on the collection of patient symptoms or chief complaints, which are collected using automated routines in near real-time. Here, we used an existing ED syndromic surveillance system monitoring daily patient attendances across a network of approximately 150 EDs in England. Clinical diagnosis codes related to the potential symptoms associated with the HUA incident were selected and attendance data monitored retrospectively and prospectively during the incident. Results From 2 April 2018 to 31 December 2021, there were small sporadic numbers of daily ED attendances for ‘liver conditions’ in children with no observed secular trends or seasonality across the 1 to 4 and 5 to 14 years age groups. The period 2 April to 29 July was compared across each year included in the analysis. Mean daily HUA attendances during 2018 to 2021 was 0.05 and 0.22 for 1 to 4 and 5 to 14 years respectively, however in 2022 there were 0.26 and 0.42 mean daily attendances. This represented an increase of 377% and 94% in the 1 to 4 and 5 to 14 years age groups, respectively. From June 2022, daily syndromic ‘liver condition’ attendances appeared to decrease and the rate of increase in cumulative attendances slowed. Conclusions We demonstrate how syndromic surveillance provided support to the HUA outbreak using an existing syndromic surveillance framework to develop new indicators based on the newly emerging clinical symptoms. The outputs from the syndromic tool matched clinical and epidemiological findings with respect to trends in other HUA-related data, including clinical and laboratory reports, over time. This work demonstrates the potential for syndromic surveillance supporting the epidemiological surveillance of hepatitis and providing a valuable tool for the real-time management of future unknown health threats.