Metabolic dysfunction-associated steatohepatitis exhibits sex differences in people with HIV.

OBJECTIVES: People with HIV are at increased risk for metabolic dysfunction-associated steatohepatitis (MASH). Although sex differences are documented in the general population, their role in the context of HIV is less understood. METHODS: This was a multicentre cohort study including people with HIV without viral hepatitis coinfection. A FibroScan-AST (FAST) score >0.35 was used to diagnose MASH with significant liver fibrosis (stage F2-F4). We investigated sex-based differences in MASH trends as a function of age using a segmented linear mixed-effects model. Random effects accounted for clustering by the four sites. Adjusted models included ethnicity, diabetes, hypertension, and detectable HIV viral load. RESULTS: We included 1472 people with HIV (25% women). At baseline, the prevalence of MASH with fibrosis by FAST score was lower in women than in men (4.8% vs. 9.2%, p = 0.008). Based on the adjusted model, male sex (+0.034; p = 0.04), age per year (+0.003; p = 0.05), detectable HIV viral load (+0.034; p = 0.02), and hypertension (+0.03; p = 0.01) were positively associated with MASH with fibrosis. Although men exhibited generally higher FAST scores, FAST scores increased in women during the critical biological age of presumed perimenopause to menopause (between 40 and 50 years), reaching levels similar to those in men by the age of 55 years. CONCLUSION: Despite women with HIV having a lower prevalence of MASH with fibrosis than men, they exhibit an acceleration in FAST score increase around the perimenopausal age. Future studies should target adequate consideration of sex differences in clinical investigation of metabolic dysfunction-associated steatotic liver disease to fill current gaps and implement precision medicine for people with HIV.

Trace Mineral Source Influences Trace Mineral Solubility in Water and Mineral Binding Strength to Ruminal Digesta.

Two experiments were conducted to examine the impact of trace mineral (TM) source on in vitro and in vivo solubility characteristics. Experiment 1: Hydroxy TM (HTM) and sulfate TM (STM) sources of Cu, Mn, and Zn were incubated separately in water for 24 h. Immediately after mixing, initial pH of each solution was greater (P < 0.03) for HTM compared to STM for all elements. Final pH tended to be greater for Cu (P = 0.09) and Zn (P = 0.07) from HTM compared to STM. Water solubility of Cu, Mn, and Zn from STM was greater (P < 0.01) than HTM sources. Experiment 2: Eight steers fitted with rumen cannula were blocked by body weight and randomly assigned to treatments. Treatments consisted of 10 mg Cu, 40 mg Mn, and 60 mg Zn/kg DM from either STM or HTM sources. Steers were individually fed a cracked corn-corn silage-based diet. Treatments were top-dressed daily. Rumen contents were collected at 0, 2, and 4 h post-feeding on d 1 and 14. On d 15, strained ruminal fluid and particle-associated microorganisms were obtained. Zinc was more tightly bound (P = 0.01) to the digesta in HTM-supplemented steers compared to STM on d 14. These data indicate that TM source influences pH and solubility of Cu, Mn, and Zn in water and may affect rumen soluble Cu concentrations and binding strength of Zn to solid digesta.

Frequent Disengagement and Subsequent Mortality Among People With HIV and Hepatitis C in Canada: A Prospective Cohort Study.

Background: The cascade of care, commonly used to assess HIV and hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals' engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people with HIV and HCV. Methods: We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers biannually. Markov multistate models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) reengaged (reentry into cohort after being LTFU); (3) withdrawn from the study (ie, moved); (4) death; otherwise remained (5) engaged-in-care. Results: A total of 1809 participants met the eligibility criteria and contributed 12 591 person-years from 2003 to 2022. LTFU was common, with 46% experiencing at least 1 episode, of whom only 57% reengaged. One in 5 (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (adjusted hazards ratio [aHR], 1.37; 95% confidence interval [CI], 1.13-1.67), evidence of HCV treatment but no sustained virologic response result (aHR, 1.99; 95% CI, 1.56-2.53), and recent incarceration (aHR, 1.94; 95% CI, 1.58-2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Interpretation: Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.

Geographical disparities in gastroenterologists and transient elastography across Canada.

Background: In the next decade, the incidence and prevalence of advanced liver disease are expected to increase across Canada. However, little is known about the country's resources for monitoring patients requiring specialized care. A resource assessment was conducted to evaluate regional disparities of specialists and transient elastography machines across Canada. Methods: Demographic data on licenced gastroenterologists were obtained from Scott's Medical Directory as of October 2022. The primary location of each specialist was linked to 2016 Statistics Canada to obtain the population size and density of provinces/territories and census division (CD). Results were summarized per 100,000 persons. CDs were classified as resource scare or approaching resource scarcity. A list of transient elastography (TE) was provided by KNS Canada Inc. and summarized per 1,000,000 persons by province. Results: Eight hundred fifty-three specialists were identified. Rates of gastroenterologists per 100,000 people ranged from 0 in the territories to 2.9 in Quebec. Half the provinces had fewer than 2.0 gastroenterologists per 100,000 persons. Gastroenterologists were concentrated in 24% (71/293) of the CDs across Canada. We identified resource-scarce CDs as areas with no gastroenterologists and in the highest tercile of population density, which accounted for 33% (1 of 3) in Prince Edward Island, 32% in Quebec, 25% in Ontario, 7% in British Columbia, and 4% in Manitoba. Only 94 TEs were identified nationwide. Conclusion: We found significant variation in liver-specific resources across Canada. Given the increasing number of people living with liver disease, policies must be implemented to address access to specialized care.