Background & aims

Acetaminophen overdose is the leading cause of acute liver injury (ALI) and acute liver failure (ALF) in the developed world. Sex differences in acetaminophen-induced hepatotoxicity have not been described.

Methods

We collected data from the Acute Liver Failure Study Group cohort, a national registry of 32 academic medical centers in North America of adults with ALI or ALF, including 1162 patients with acetaminophen-induced ALI (n = 250) or acetaminophen-induced ALF (n = 912) from January 2000 through September 2016. We analyzed data on patient presentation, disease course, demographics, medical and psychiatric history, medication use, substance use, and details of acetaminophen ingestion. Sex differences in continuous and categorical variables were evaluated by Wilcoxon rank-sum and χ² analysis or the Fisher exact test. Our primary aim was to evaluate sex differences in the presentation and clinical course of acetaminophen-induced acute liver injury or liver failure, and our secondary goal was to compare overall and transplant-free survival between sexes.

Results

Most patients with acetaminophen-induced ALI (68%) or ALF (76%) were women. Higher proportions of women than men had psychiatric disease (60% of women vs 48% of men, P < .01) and had co-ingestion with sedating agents (70% of women vs 52% of men, P < .01)-more than half of which were opioids. Higher proportions of women had severe hepatic encephalopathy (HE) (68% of women vs 58% of men), and required intubation (67% of women vs 59% of men, P values <.03). Higher proportions of women used vasopressors (26% of women vs 19% of men, P = .04) or mannitol (13% of women vs 6% of men, P < .01); proportions of male vs female patients with transplant-free survival were similar (68%). On adjusted analysis, women had higher risk of severe HE (adjusted odds ratio [AOR], 1.66; 95% CI, 1.17-2.35). We found a significant interaction between sex and co-ingestion of sedating agents (P < .01); co-ingestion increased odds of severe HE in women 2-fold (AOR, 1.86; 95% CI, 1.28-2.69; P < .01) but not in men (AOR; 0.62; 95% CI, 0.34-1.13; P = .12).

Conclusions

In an analysis of the Acute Liver Failure Study Group cohort, we found acetaminophen-induced ALI and ALF to be more common among women. Women have greater critical care needs than men, and increased risk for severe HE, which could be due in part to increased use of sedatives. Future studies should investigate sex differences in acetaminophen metabolism and hepatotoxicity, particularly among users of opioids.

Hepatitis B e antigen (HBeAg) is an important serological marker of hepatitis B virus (HBV) infection and is associated with higher levels of viraemia, increased risk of infectivity to others and increased risk of hepatocellular carcinoma. We analysed HBeAg status in a large cohort of adults and children enrolled in Cohort Studies of the Hepatitis B Research Network, long-term natural history studies of chronic HBV infection. A cross-sectional analysis examined factors associated with HBeAg positivity, including demographic and virologic data, across the age spectrum. Among 2241 enrolled participants who met criteria for this analysis, 825 (37%) were seropositive for HBeAg. The prevalence of HBeAg was lower in those with older age, ranging from 85% among those up to 10 years of age to only 12% among those older than 50 years. In addition to age, both race and HBV genotype were independently associated with HBeAg positivity. There was a significant interaction between age and race; the prevalence of HBeAg was significantly higher among Asians > 10-30 years old vs Whites or Blacks who were >10 to 30 years old and those infected with HBV genotype C. Conversely, the presence of the basal core promoter and precore variants was associated with significantly lower prevalence of HBeAg, even when adjusted for age, race and genotype. These data will provide a better understanding of factors associated with seropositivity for HBeAg and may lead to better strategies for preventing HBV infection and broader indications for antiviral therapy.

Background

A baseline of hepatitis C virus (HCV) burden and other HCV epidemiological profiles is necessary for HCV micro-elimination in Ho Chi Minh City (HCMC), Viet Nam. This study aimed to determine HCV exposure and prevalence of HCV viremia as well as the proportion of HCV testing and treatment uptake among participants.

Methods

From 2019 to 2020, the probability proportionate to size sampling method was deployed to representatively invite approximately 20,000 adults (18 or older) throughout HCMC to free screening and linkage to care for HCV.

Findings

In HCMC, the weighted prevalence of anti-HCV was 1·3% (95% CI, 1·1%-1·6%). Individuals born from 1945 to 1964 had the anti-HCV prevalence of 3·6% (95% CI, 3·0%-4·2%) and represented 40·4% of all HCV cases. There were wide variations in anti-HCV prevalence in HCMC, including variations between districts, risk factors, and socioeconomic statuses. A baseline HCV continuum of care for the city demonstrated that only 28·5% (85/298, 95%CI 23·4-33·7%) of persons with anti-HCV (+) were aware of their HCV status, with 77.6% (66/85, 95%CI 68·8-86·5%) diagnosing HCV incidentally, 82·7% (62/75, 95%CI 74·1-91·2%) initiating anti-HCV therapy, and 53.6% (30/56, 95%CI 40·5-66·6%) achieving HCV cures.

Interpretation

There remains a considerable disease burden of HCV in HCMC of which a significant proportion was in the age group born between 1945 to 1964. Additionally, there were significant gaps in HCV awareness, screening, and access to care in the community in Viet Nam. Thus, future interventions must have pragmatic targets, be tailored to the local needs, and emphasise screening.

Funding

This work was supported by investigator-sponsored research grants from Gilead Sciences Inc. (Grant No: IN-US-987-5382); Roche Diagnostic International Ltd. (Grant No. SUB-000196); and in-kind donations from Abbott Diagnostic Viet Nam; Hepatitis B Foundation; Medic Medical Center, Viet Nam; Johns Hopkins University School of Medicine's Center of Excellence for Liver Disease in Viet Nam; and the Board of Directors, Viet Nam Viral Hepatitis Alliance (V-VHA).

Background & aims

Chronic hepatitis B virus (HBV) infection is an important cause of cirrhosis and hepatocellular carcinoma worldwide; populations that migrate to the United States and Canada might be affected disproportionately. The Hepatitis B Research Network (HBRN) is a cooperative network of investigators from the United States and Canada, created to facilitate clinical, therapeutic, and translational research in adults and children with hepatitis B. We describe the structure of the network and baseline characteristics of adults with hepatitis B enrolled in the network.

Methods

The HBRN collected data on the clinical characteristics of 1625 adults with chronic HBV infection who are not receiving antiviral therapy from 21 clinical centers in North America.

Results

Half of the subjects in the HBRN are men, and the median age is 42 years; 72% are Asian, 15% are black, and 11% are white; with 82% born outside of North America. The most common HBV genotype was B (39%); 74% of subjects were negative for the hepatitis B e antigen. The median serum level of HBV DNA when the study began was 3.6 log10 IU/mL; 68% of male subjects and 67% of female subjects had alanine aminotransferase levels higher than the normal range.

Conclusions

The HBRN cohort is used to address important clinical and therapeutic questions for North Americans infected with chronic HBV and to guide health policies on HBV prevention and management in North America.