Nonviral Liver Disease Burden in People Living With HIV and Elevated Transaminases: A Cross-Sectional Study.

INTRODUCTION: Because of improved life expectancy in people living with HIV (PLWH), liver disease is increasingly being recognized. We assessed nonviral chronic liver disease burden in PLWH. METHODS: The HIV non-virAL liver disease study (2014-2021) prospectively recruited PLWH with elevated serum alanine aminotransferase levels and negative hepatitis serology. Clinically significant hepatic fibrosis (CSHF) was defined as liver stiffness measurement of >7.1 kPa and hazardous alcohol use as Alcohol Use Disorders Identification Test score ≥ 8. Primary outcome was prevalence/predictors of CSHF. RESULTS: Total recruited were n = 274, 92% male, median age 52 (45-59) years, and 96% having undetectable HIV viral load. Overall, n = 97 (35%) had hazardous alcohol use, n = 72 (26%) had metabolic syndrome, and 17%-27% had exposure to hepatotoxic antiretrovirals. Prevalence of CSHF was 20% (n = 54), prevalence of cirrhosis (liver stiffness measurement > 12.5 kPa) being 7% (19/274). Risk factors for CSHF were hazardous alcohol use in 44% (n = 24), metabolic syndrome in 46% (n = 25), and hepatotoxic antiretrovirals in 56% (n = 30), most having more than one risk factor. Independent predictors of CSHF were serum high-density lipoprotein (odds ratio [OR] 0.220; 95% confidence interval [CI]: 0.061 to 0.790, P = 0.020) (inverse relationship); serum aspartate aminotransferase (OR 1.033, 95% CI: 1.001 to 1.067, P = 0.045), and didanosine use (OR 2.878, 95% CI: 1.228 to 6.774, P = 0.015). Moderate-severe hepatic steatosis was identified in 52% (n = 142). FIB-4 and aspartate aminotransferase-to-platelet ratio index performed poorly in predicting CSHF (positive predictive value 27.3% and 30.6%, respectively) and advanced fibrosis (≥F3) (positive predictive value 17.6% and 5.9%, respectively). CONCLUSION: In this study, 20% of PLWH had CSHF associated with high prevalence of hazardous alcohol use/metabolic syndrome/potentially hepatotoxic antiretrovirals. These potentially modifiable risk factors need addressing.

Comparative effectiveness of a second-line biologic in patients with ulcerative colitis: vedolizumab followed by an anti-TNF versus anti-TNF followed by vedolizumab.

Background: Sequential drug treatment with biological agents in ulcerative colitis (UC) is becoming increasingly complex. There are few studies comparing head-to-head outcomes in second-line treatments. The study assesses whether using anti-tumour necrosis factor (anti-TNF)-α therapy following the α4ß7 integrin blocker vedolizumab (VDZ) or VDZ after an anti-TNF has more favourable clinical outcomes in UC in a real-world outpatient setting. Methods: Patients with UC who were exposed to first-line anti-TNF (adalimumab or infliximab) or VDZ who subsequently switched to the alternate class between May 2013 and August 2020 were identified by reviewing patient databases at 10 hospitals. Data were collected retrospectively using patient records. Baseline demographics, disease activity indices, biochemical markers, endoscopic Mayo score, colectomy rates, treatment persistence and urgent hospital utilisation composite endpoint (UHUC) rates were examined over a 52-week period. Results: Second-line week 52 treatment persistence was higher in the VDZ group (71/81, 89%) versus the anti-TNF group (15/34, 44%; p=0.0001), as were week 52 colectomy-free survival (VDZ: 77/80, 96%, vs anti-TNF: 26/32, 81%; p=0.009), week 52 UHUC survival (VDZ: 68/84, 81%, vs anti-TNF: 20/34, 59%; p=0.002) and week 52 corticosteroid-free clinical remission (CFCR) rates (VDZ: 22/34, 65%, vs anti-TNF: 4/20, 20%; p=0.001). Conclusion: Compared with second-line anti TNF usage, the VDZ second-line cohort had significantly higher 52-week treatment persistence, UHUC survival, higher colectomy-free survival rates and higher week 52 CFCR. These data suggest that VDZ is an effective biologic in UC as a second-line therapy after anti-TNF exposure. It highlights the effect of biological order on clinically important outcomes.

Chronic liver disease in homeless individuals and performance of non-invasive liver fibrosis and injury markers: VALID study.

BACKGROUND/AIMS: Community-based assessment and management of chronic liver disease (CLD) in people who are homeless (PWAH) remain poorly described. We aimed to determine prevalence/predictors of CLD in PWAH and assess the performance of non-invasive liver fibrosis and injury markers. METHODS: The Vulnerable Adult LIver Disease (VALID) study provided a "one-stop" liver service based at homeless hostels. Our primary outcome was the prevalence of clinically significant hepatic fibrosis (CSHF; liver stiffness measurement (LSM) ≥8 kPa). RESULTS: Total individuals recruited were 127, mean ± SD age 47 ± 9.4 years, 50% (95% CI 41%-59%) and 39% (95% CI 31%-48%) having alcohol dependence and a positive HCV RNA respectively. CSHF was detected in 26% (95% CI 17%-35%), independent predictors being total alcohol unit/week (OR 1.01, 95% CI 1.00-1.02, P = .002) and HCV RNA positivity (OR 2.93, 95% CI 1.12-7.66, P = .029). There was moderate agreement between LSM and Enhanced Liver Fibrosis (ELF) score (kappa 0.536, P < .001) for CSHF as assessed by LSM ≥8 kPa. Those with CSHF had significantly higher levels of IFN-γ (P = .002), IL-6 (P = .001), MMP-2 (P = .006), ccCK-18 (P < .001) and ELF biomarkers (P < .001), compared to those without CSHF. Service uptake was ≥95%. Direct acting antiviral (DAA) treatment completion was 93% (95% CI 77%-99%), sustained virological response (SVR) being 83% (95% CI 64%-94%). CONCLUSION: There is a significant liver disease burden from HCV and alcohol in PWAH. Non-invasive liver fibrosis and injury markers can help in identifying such individuals in the community. Despite a challenging cohort, excellent service uptake and high DAA-based SVRs can be achieved.

Longterm Outcomes of Patients Undergoing Liver Transplantation for Acute-on-Chronic Liver Failure.

Recent data have demonstrated >80% 1-year survival probability after liver transplantation (LT) for patients with severe acute-on-chronic liver failure (ACLF). However, longterm outcomes and complications are still unknown for this population. Our aim was to compare longterm patient and graft survival among patients transplanted across all grades of ACLF. We analyzed the United Network for Organ Sharing database for the years 2004-2017. Patients with ACLF were identified using the European Association for the Study of the Liver-Chronic Liver Failure criteria. Kaplan-Meier and Cox regression methods were used to determine patient and graft survival and associated predictors of mortality in adjusted models. A total of 56,801 patients underwent transplantation of which 31,024 (54.6%) had no ACLF, 8757 (15.4%) had ACLF grade 1, 9039 (15.9%) had ACLF grade 2, and 7891 (14.1%) had ACLF grade 3. The 5-year patient survival after LT was lower in the ACLF grade 3 patients compared with the other groups (67.7%; P < 0.001), although after year 1, the percentage decrease in survival was similar among all groups. Infection was the primary cause of death among all patient groups in the first year. Infection was the primary cause of death among all patient groups in the first year. After the first year, infection was the main cause of death in patients transplanted with ACLF grade 1 (32.1%), ACLF grade 2 (33.9%), and ACLF grade 3 (37.6%), whereas malignancy was the predominant cause of death in those transplanted with no ACLF (28.5%). In conclusion, patients transplanted with ACLF grade 3 had lower 5-year survival as compared with patients with ACLF grades 0-2, but mortality rates were not significantly different after the first year following LT. Graft survival was excellent across all ACLF groups.