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INTRODUCTION: Several scoring systems predict mortality in alcohol-associated hepatitis (AH), including the Maddrey discriminant function (mDF) and model for end-stage liver disease (MELD) score developed in the United States, Glasgow alcoholic hepatitis score in the United Kingdom, and age, bilirubin, international normalized ratio, and creatinine score in Spain. To date, no global studies have examined the utility of these scores, nor has the MELD-sodium been evaluated for outcome prediction in AH. In this study, we assessed the accuracy of different scores to predict short-term mortality in AH and investigated additional factors to improve mortality prediction. METHODS: Patients admitted to hospital with a definite or probable AH were recruited by 85 tertiary centers in 11 countries and across 3 continents. Baseline demographic and laboratory variables were obtained. The primary outcome was all-cause mortality at 28 and 90 days. RESULTS: In total, 3,101 patients were eligible for inclusion. After exclusions (n = 520), 2,581 patients were enrolled (74.4% male, median age 48 years, interquartile range 40.9-55.0 years). The median MELD score was 23.5 (interquartile range 20.5-27.8). Mortality at 28 and 90 days was 20% and 30.9%, respectively. The area under the receiver operating characteristic curve for 28-day mortality ranged from 0.776 for MELD-sodium to 0.701 for mDF, and for 90-day mortality, it ranged from 0.773 for MELD to 0.709 for mDF. The area under the receiver operating characteristic curve for mDF to predict death was significantly lower than all other scores. Age added to MELD obtained only a small improvement of AUC. DISCUSSION: These results suggest that the mDF score should no longer be used to assess AH's prognosis. The MELD score has the best performance in predicting short-term mortality.
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Enfermedad Hepática en Estado Terminal/etiología , Hepatitis Alcohólica/mortalidad , Hígado/fisiopatología , Adulto , Análisis Discriminante , Enfermedad Hepática en Estado Terminal/mortalidad , Enfermedad Hepática en Estado Terminal/fisiopatología , Femenino , Estudios de Seguimiento , Salud Global , Hepatitis Alcohólica/complicaciones , Hepatitis Alcohólica/fisiopatología , Humanos , Pruebas de Función Hepática , Masculino , Persona de Mediana Edad , Pronóstico , Curva ROC , Factores de Riesgo , Índice de Severidad de la Enfermedad , Tasa de Supervivencia/tendencias , Factores de TiempoRESUMEN
BACKGROUND: In 2016, the first global viral hepatitis elimination targets were endorsed. An estimated one-third of the world's population of individuals with chronic hepatitis B virus (HBV) infection live in China and liver cancer is the sixth leading cause of mortality, but coverage of first-line antiviral treatment was low. In 2015, China was one of the first countries to initiate a consultative process for a renewed approach to viral hepatitis. We present the investment case for the scale-up of a comprehensive package of HBV interventions. METHODS: A dynamic simulation model of HBV was developed and used to simulate the Chinese HBV epidemic. We evaluated the impact, costs, and return on investment of a comprehensive package of prevention and treatment interventions from a societal perspective, incorporating costs of management of end-stage liver disease and lost productivity costs. RESULTS: Despite the successes of historical vaccination scale-up since 1992, there will be a projected 60 million people still living with HBV in 2030 and 10 million HBV-related deaths, including 5.7 million HBV-related cancer deaths between 2015 and 2030. This could be reduced by 2.1 million by highly active case-finding and optimal antiviral treatment regimens. The package of interventions is likely to have a positive return on investment to society of US$1.57 per US dollar invested. CONCLUSIONS: Increases in HBV-related deaths for the next few decades pose a major public health threat in China. Active case-finding and access to optimal antiviral treatment are required to mitigate this risk. This investment case approach provides a real-world example of how applied modeling can support national dialog and inform policy planning.
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Hepatitis B Crónica , Hepatitis B , Antivirales/uso terapéutico , China/epidemiología , Hepatitis B/tratamiento farmacológico , Hepatitis B/epidemiología , Hepatitis B/prevención & control , Vacunas contra Hepatitis B/uso terapéutico , Virus de la Hepatitis B , Hepatitis B Crónica/tratamiento farmacológico , Hepatitis B Crónica/epidemiología , Hepatitis B Crónica/prevención & control , HumanosRESUMEN
Severe malaria is a major cause of childhood mortality in sub-Saharan Africa but the factors predisposing children to severe forms of malaria have not been fully elucidated. In a case-control study of over 1,200 Gambian children hepatitis B virus carriage was significantly increased amongst cases of severe malaria compared to matched controls. We suggest that this association may relate to impaired clearance of liver stage parasites in the presence of the reduced level of HLA class I antigen expression on hepatocytes infected by hepatitis B virus. If this association is causal and viral carriage predisposes to severe malaria, widespread vaccination against hepatitis B virus may reduce mortality from severe malaria.
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Portador Sano , Antígenos de Superficie de la Hepatitis B/sangre , Virus de la Hepatitis B/inmunología , Hepatitis B/complicaciones , Malaria Cerebral/complicaciones , Malaria Falciparum/complicaciones , Animales , Portador Sano/epidemiología , Portador Sano/inmunología , Estudios de Casos y Controles , Niño , Preescolar , Ensayo de Inmunoadsorción Enzimática , Gambia/epidemiología , Hepatitis B/epidemiología , Hepatitis B/inmunología , Humanos , Hígado/parasitología , Hígado/virología , Malaria Cerebral/epidemiología , Malaria Cerebral/inmunología , Malaria Falciparum/epidemiología , Malaria Falciparum/inmunología , Oportunidad Relativa , Plasmodium falciparum/fisiología , PrevalenciaAsunto(s)
Genes MHC Clase II , Hepatitis B/genética , Hepatitis B/inmunología , Adulto , Genes MHC Clase I , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Heterocigoto , Homocigoto , Humanos , Inmunidad Innata/genética , Oportunidad RelativaRESUMEN
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.
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Insuficiencia Hepática Crónica Agudizada/epidemiología , Hepatitis E/epidemiología , Cirrosis Hepática/epidemiología , Adulto , Agricultura , Estudios de Casos y Controles , Femenino , Gambia/epidemiología , Anticuerpos Antihepatitis/sangre , Virus de la Hepatitis E/genética , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , ARN Viral , Factores Socioeconómicos , Abastecimiento de AguaRESUMEN
We prospectively assessed the implementation of venous thromboembolism (VTE) prophylaxis guidelines and the impact of grand round presentation of the data in changing clinical practice. Two NHS teaching hospitals were studied for 24 months from January 2003. Patients were risk stratified according to the THRIFT (thromboembolic risk factor) consensus group guidelines and compared with the recommendations of the THRIFT and ACCP (American College of Chest Physicians) consensus groups. Six months following presentation of the initial results, a further analysis was made to assess changes in clinical practice. 1128 patients were assessed of whom 1062 satisfied the inclusion criteria for thromboprophylaxis. 89% of all patients were stratified as having high or moderate risk of developing VTE. Of these only 28% were prescribed some form of thromboprophylaxis-4% received the THRIFT-recommended and 22% received the ACCP-recommended thromboprophylaxis. The vast majority (72%) received no thromboprophylaxis at all. Reassessment, following data presentation at grand rounds, showed a significant increase to 31% inpatients receiving THRIFT (P<0.0001) and ACCP (P=0.002) recommended thromboprophylaxis. However,the proportion of patients receiving no form of prophylaxis barely changed (72% to 69%: P=0.59). We found a gross underutilization of thromboprophylaxis in hospitalized medical patients. A simple grand-round presentation of the data and recommended guidelines to clinicians significantly increased the proportion of patients receiving recommended thromboprophylaxis but did not increase the overall proportion of patients receiving it. We therefore conclude that a single presentation of guidelines is not enough to achieve the desired levels. Such presentations may only serve to make DVT (deep venous thromboembolism) aware clinicians prescribe prophylaxis more accurately.
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Anticoagulantes/uso terapéutico , Vendajes , Heparina de Bajo-Peso-Molecular/uso terapéutico , Hospitalización , Tromboembolia/prevención & control , Trombosis de la Vena/prevención & control , Enfermedad Aguda , Análisis Costo-Beneficio , Hospitales de Enseñanza , Humanos , Guías de Práctica Clínica como Asunto , Estudios Prospectivos , Factores de RiesgoRESUMEN
Faecal microbiome transplantation (FMT) has generated huge recent interest as it presents a potential solution to a significant clinical problem--the increasing incidence of Clostridium difficile infection (CDI). In the short term, however, there remain many practical questions regarding its use, including the optimal selection of donors, material preparation and the mechanics of delivery. In the longer term, enhanced understanding of the mechanisms of action of FMT may potentiate novel therapies, such as targeted manipulation of the microbiome in CDI and beyond.
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Clostridioides difficile/patogenicidad , Infecciones por Clostridium/terapia , Trasplante de Microbiota Fecal , Microbiota , Selección de Donante , Trasplante de Microbiota Fecal/efectos adversos , HumanosRESUMEN
Hepatitis C is now recognized as the most common infection causing chronic liver disease in the European population. Our aim was to assess the prevalence of the antibody to hepatitis C virus (HCV), and the incidence of HCV seroconversion in the general population and the main risk groups, namely intravenous drug users, haemodialysis and transfused patients, in seven countries of the European Union, by carrying out a critical analysis of the literature. Data sources used were the Medline database and a manual search using the key words: hepatitis C, prevalence, incidence, transmission, risk factors and epidemiology. Articles published between January 1990 and March 1997 were reviewed. Articles were reviewed according to a critical analysis method regarding title, type of article, study design, period and population, tests, results and their consistency with data. The tests performed were mainly second- or third-generation serological tests. The average prevalence rate in blood donors was 1%, with a north-south gradient ranging from 0.04% to 2%. Prevalence varied from 20% to 30% in haemodialysis patients. The incidence in transfused patients was less than 1% after 1991. The prevalence in intravenous drug users was about 80%. Multicentre studies conducted in larger samples are needed to obtain more accurate and reliable results, in particular. However, the epidemiological studies available allowed us to assess the magnitude of HCV infection in Europe.
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Hepatitis C/epidemiología , Europa (Continente)/epidemiología , Unión Europea , Hepatitis C/transmisión , Anticuerpos contra la Hepatitis C/análisis , Humanos , Incidencia , Prevalencia , Factores de Riesgo , Estudios SeroepidemiológicosRESUMEN
Hepatitis C infection is characterised by three key features, which are the consequence of a complex interaction between genetic determinants of immune and other host factors and viral characteristics: 1. A high rate of viral persistence after acute infection resulting from a combination of weak T cell responsiveness and specific viral mechanisms of immune escape. 2. Marked interindividual variability in end-organ damage (fibrosis and cirrhosis), probably due to host genetic polymorphisms in genes governing the immune response and fibrosis pathways in addition to viral pathogenicity factors. 3. Significant resistance to antiviral therapies. Viral mechanisms of antiviral resistance parallel those of viral persistence, and include the intriguing possibility that hepatitis C may infect immunologically privileged sites such as the central nervous system.
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Hepatitis C Crónica , Antivirales/farmacología , Progresión de la Enfermedad , Farmacorresistencia Microbiana , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C Crónica/genética , Hepatitis C Crónica/inmunología , Hepatitis C Crónica/patología , Humanos , Cirrosis Hepática/virología , Polimorfismo Genético , Factores de RiesgoRESUMEN
BACKGROUND: The scale of depression in patients with chronic liver disease (CLD) and those who have received orthotopic liver transplantation (OLT) is poorly characterised. Clinicians are uncertain of how best to manage depression within these patients. AIMS: To review the literature evaluating both the prevalence and impact of depression in patients with CLD and post-OLT, and to assess the safety and efficacy of antidepressant use within this context. METHODS: A PubMed search using the phrases 'chronic liver disease', 'cirrhosis', 'liver transplantation', 'depression', 'antidepressant' and the names of specific causes of liver disease and individual antidepressants. RESULTS: Over 30% of cirrhotic patients have depressive features, and they experience worse clinical outcomes than nondepressed cirrhotic patients. CLD patients with chronic hepatitis C are particularly prone to depression, partly related to the use of interferon therapy. OLT patients with depression have higher mortality rates than nondepressed patients; appropriate antidepressant use reverses this effect. Selective serotonin reuptake inhibitors (SSRIs) and selective noradrenaline reuptake inhibitors (SNRIs) are effective and generally safe in both CLD and OLT patients. CONCLUSIONS: Depression is much more prevalent in CLD or OLT patients than is generally recognised, and it adversely affects clinical outcomes. The reasons for this relationship are complex and multifactorial. Antidepressants are effective in both CLD and post-OLT, although lower doses or a reduced dosing frequency may be required to minimise side effects, e.g. exacerbation of hepatic encephalopathy. Further research is needed to establish optimal management of depression in these patients, including the potential role of nonpharmacological treatments.
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Antidepresivos/uso terapéutico , Depresión/tratamiento farmacológico , Hepatopatías/tratamiento farmacológico , Trasplante de Hígado , Humanos , Hepatopatías/psicología , Trasplante de Hígado/psicología , Inhibidores de la Captación de Neurotransmisores/uso terapéuticoAsunto(s)
Investigación Biomédica/organización & administración , Carcinoma Hepatocelular , Hepatitis B , Cooperación Internacional , Neoplasias Hepáticas , África Occidental/epidemiología , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/epidemiología , Carcinoma Hepatocelular/terapia , Estudios de Casos y Controles , Europa (Continente) , Hepatitis B/diagnóstico , Hepatitis B/epidemiología , Hepatitis B/terapia , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/epidemiología , Neoplasias Hepáticas/terapia , Estudios Longitudinales , Evaluación de Necesidades/organización & administración , Desarrollo de Programa , Evaluación de Programas y Proyectos de Salud , Apoyo a la Investigación como AsuntoRESUMEN
BACKGROUND: There is strong evidence demonstrating that coagulation system activation contributes to wound healing and promotes organ fibrosis. Several epidemiological studies have now shown that prothrombotic status, including carriage of the factor (F)V Leiden mutation, is associated with rapid progression of hepatic fibrosis. OBJECTIVES: To assess the effect of a procoagulant state on progression of hepatic fibrosis in a controlled environment and to test whether anticoagulation could attenuate fibrogenesis. METHODS: We investigated the effects of coagulation status on liver fibrosis development in a mouse model of chronic toxic liver injury. Prothrombotic FV Leiden mutant mice, C57BL/6 control animals and anticoagulated mice were studied after chronic exposure to carbon tetrachloride. RESULTS: Carriage of the FV Leiden mutation caused a significant increase in hepatic fibrosis. Anticoagulation with warfarin significantly reduced fibrosis progression in wild-type mice but was less effective against the profibrotic FV Leiden mutation. Changes in the fibrosis scores were mirrored by changes in liver hydroxyproline content and hepatic stellate cell activation detected by alpha-smooth muscle actin expression. CONCLUSIONS: These results demonstrate that coagulation status has a strong influence on hepatic fibrogenesis. It is likely that thrombin signaling through the proteinase-activated receptor 1 (PAR(1)) receptor expressed on hepatic stellate cells is responsible for this relationship. These results represent the first reported use of anticoagulation to slow hepatic fibrogenesis and suggest a potential novel anti-fibrotic therapeutic approach for the future.
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Cirrosis Hepática Experimental/sangre , Cirrosis Hepática Experimental/tratamiento farmacológico , Actinas/metabolismo , Animales , Anticoagulantes/uso terapéutico , Tetracloruro de Carbono/toxicidad , Factor V/genética , Expresión Génica/efectos de los fármacos , Hidroxiprolina/metabolismo , Peroxidación de Lípido/efectos de los fármacos , Hígado/efectos de los fármacos , Hígado/metabolismo , Hígado/patología , Cirrosis Hepática Experimental/etiología , Masculino , Ratones , Ratones Congénicos , Ratones Endogámicos C57BL , Ratones Mutantes , Ratones Transgénicos , Mutación Puntual , Warfarina/uso terapéuticoRESUMEN
A strong genetic component determining the outcome of hepatitis B virus (HBV) infection has been established through twin studies. The immunopathogenesis of HBV infection is well described and it has therefore been possible to predict some gene loci, exhibiting polymorphism, may influence the outcome of HBV infection. As expected, the immune response genes in the major histocompatibility complex (MHC) on the short arm of chromosome 6 have provided confirmed susceptibility genes. In hepatitis C virus (HCV) infection the picture is not so clear although comparison of the known immunological phenomena with those of HBV suggest that polymorphisms in the MHC may also influence disease outcome. Identification of susceptibility genes, which modify disease phenotype, may assist in predicting natural outcome of infection or response to therapy.
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Hepatitis B/genética , Hepatitis C/genética , Complejo Mayor de Histocompatibilidad/inmunología , Susceptibilidad a Enfermedades , Hepatitis B/inmunología , Hepatitis C/inmunología , HumanosRESUMEN
The clinical outcomes of both hepatitis B and C virus infection are immensely variable, ranging from subclinical, self-limiting infection to end-stage liver disease with hepatocellular carcinoma. Knowledge of the host factors that determine these outcomes is important for the understanding and management of these diseases and may in the future guide rational drug development. Epidemiologic studies have elucidated the role of age (at the time of infection) and sex on disease outcome and the complex role of HIV coinfection has become clearer with time. More recently, investigation of genetic susceptibility to the most adverse outcomes of infection has identified the importance of polymorphisms in the MHC class I and II loci, mannose-binding protein, and the TNF alpha promoter. However, relative to malaria, the study of genetic susceptibility in viral hepatitis is still in its infancy.
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Hepatitis Crónica/fisiopatología , Hepatitis Viral Humana/fisiopatología , Adolescente , Adulto , Distribución por Edad , Anciano , Niño , Susceptibilidad a Enfermedades , Femenino , Hepatitis Crónica/epidemiología , Hepatitis Viral Humana/epidemiología , Humanos , Inmunidad/genética , Inmunidad/fisiología , Incidencia , Masculino , Persona de Mediana Edad , Factores de Riesgo , Distribución por SexoRESUMEN
BACKGROUND: In murine Helicobacter infection it has been demonstrated that the degree of gastric mucosal inflammation is determined by mouse strain. This is a valuable tool for investigating genetic, immunological or bacterial determinants for the outcome of human Helicobacter infection. This study aims to devise a robust method to facilitate these investigations. MATERIALS AND METHODS: C57BL/6, BALB/c and (C57BL/6 x BALB/c) F1 mice were given 10(8)H. felis by gavage on days 1, 3 and 5 of the experiment Sections of the lesser and greater curve of stomach were examined at 12 weeks to assess active gastritis using a semi-quantitative and a quantitative method by counting neutrophils in glands in four zones of the mucosa. RESULTS: Semi-quantitative scoring for active inflammation, based on the Sydney System, was inadequate with little discrimination between strains. Quantifying the level of active inflammation, counting the number of neutrophils in inflamed gastric glands and taking the total number of neutrophils in three inflamed pits within each zone (cardia, body, transitional zone and antrum) showed clear differences between the two parental strains for the degree of active gastritis and furthermore, using this system the phenotype of the (C57BL/6 x BALB/c) F1 was found to be between the two parental extremes. CONCLUSIONS: This novel method provides a numerical value for active inflammation in the stomach that is accurate, reproducible and discriminatory.
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Gastritis/patología , Infecciones por Helicobacter/genética , Helicobacter/patogenicidad , Neutrófilos/fisiología , Animales , Modelos Animales de Enfermedad , Gastritis/genética , Gastritis/microbiología , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/patología , Humanos , Inflamación/clasificación , Inflamación/genética , Inflamación/microbiología , Inflamación/patología , Recuento de Leucocitos , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Especificidad de la EspecieRESUMEN
Barrett's oesophagus predisposes to oesophageal adenocarcinoma. In vitro, laminin, a component of the epithelial basement membrane (BM), is important in regulation of cell differentiation. There is limited information on the distribution of laminin chains in the upper gastrointestinal tract (GIT) and none in Barrett's oesophagus. This study aimed to investigate qualitatively the distribution of laminins in the normal upper GIT mucosa and Barrett's oesophagus in order to understand the role of laminins in metaplasia. Immunoperoxidase staining for laminin chains alpha1, alpha2, alpha3, alpha5, beta1, beta2, beta3, gamma1, and gamma2 was performed on frozen endoscopic squamous and Barrett's oesophageal biopsies and surgical resection specimens from squamous oesophagus (in resection specimens for oesophageal cancer), and in oesophageal and gastric biopsies from control subjects. alpha1 laminin was expressed in the BM of submucosal glands and ducts in squamous oesophagus and Brunner's glands in the duodenum, but not in Barrett's oesophagus or elsewhere in the upper GIT. alpha2 laminin chain was expressed in a granular distribution in the BM of squamous epithelium. In columnar epithelium, including Barrett's oesophagus, alpha2 laminin chain was expressed continuously in the BM of glands and deeper pits, but expression was reduced and granular in the surface epithelial BM. beta2 laminin was continuous in squamous epithelial BM, but in Barrett's and cardia, gastric body, and duodenum, it was expressed faintly in the surface but continuously in the BM of glands and deeper pits. The constituents of laminin-5 were continuously expressed in the BM of squamous epithelium, but in the cardia, gastric body, duodenum, and Barrett's, they were expressed only in the BM of surface epithelium, with a sharp decline in the glandular and deeper pit BM. Site-specific distribution of the alpha2 and beta2 laminin chains may therefore have an important role in Barrett's metaplasia. However, the absence of alpha1 laminin in Barrett's mucosa suggests that this is unlikely to play an important role in columnar metaplasia.
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Esófago de Barrett/metabolismo , Membrana Basal/química , Esófago/química , Laminina/análisis , Estudios de Casos y Controles , Duodeno , Mucosa Gástrica/química , Humanos , Inmunohistoquímica/métodos , Mucosa Intestinal/químicaRESUMEN
BACKGROUND: The course of hepatitis B virus (HBV) infection does not appear to be determined by variations in viral virulence and may be influenced by the host immune response. We studied the distribution of human leukocyte antigens in children and adult men in the Gambia who spontaneously recovered from HBV infection as compared with the distribution of these antigens in subjects with persistent infection. METHODS: In a two-stage, case-control study, we analyzed the frequency of MHC class I antigens and class II haplotypes in people with either transient or persistent HBV infection. MHC class I typing was performed by microlymphocytotoxicity assays. MHC class II typing was performed with analysis of restriction-fragment-length polymorphisms (RFLPs), supplemented by other techniques. RESULTS: In the first stage (the study of children up to the age of 10 years), the RFLP pattern 25-1, which includes the class II allele HLA-DRB1*1302, was found in 58 of 218 subjects with transient HBV infection (26.6 percent) and 30 of 185 subjects with persistent infection (16.2 percent) (relative risk of carrying the 25-1 pattern in the persistently infected group as compared with the transiently infected group, 0.53; 95 percent confidence interval, 0.32 to 0.90; P = 0.012). In the second stage (the study of adults), HLA-DRB1*1302 was found in 50 of 195 subjects with transient HBV infection (25.6 percent) and in 3 of 40 subjects with persistent infection (7.5 percent) (relative risk, 0.24; 95 percent confidence interval, 0.04 to 0.80; P = 0.012). The RFLP pattern 13-2, which includes the class II allele DRB1*1301, was less frequent in children with persistent infection than in those with transient infection, an association that was neither confirmed nor excluded by the data on adults. Possible associations with HLA class I antigens found in children were not supported by the data on adults. CONCLUSIONS: The MHC class II allele DRB1*1302 was associated with protection against persistent HBV infection among both children and adults in the Gambia.