Karagozian, Raffi

ABSTRACT Introduction Metabolic dysfunction‐associated steatotic liver disease (MASLD) and steatohepatitis (MASH) represent a spectrum of liver conditions that can gradually progress to cirrhosis. Sodium‐glucose co‐transporter‐2 (SGLT‐2) inhibitors have shown benefits in reducing hepatic steatosis and liver‐related events in MASLD. This study aims to assess whether SGLT‐2 inhibitors are associated with a reduced risk of all‐cause mortality and disease‐specific outcomes in patients with MASH cirrhosis and type 2 diabetes (T2D). Methods A retrospective cohort study was performed using TriNetX. Patients with T2D and MASH cirrhosis on SGLT‐2 inhibitors were matched 1:1 with other glucose‐lowering drugs (oGLDs) based on demographics, comorbidities and medications. Primary outcomes included all‐cause mortality, hepatic decompensation and major adverse liver outcomes (MALO). Cox‐proportional hazards models were used to estimate hazard ratios (HRs) with 95% confidence interval (CI). Results A total of 51 427 patients with MASH cirrhosis and T2D were identified, of which 6833 (13.28%) were on SGLT‐2 inhibitors. Patients on SGLT‐2 inhibitors ( n = 6449, mean age 63.7 years, 52.9% female) were matched with 6449 individuals (mean age 63.9 years, 53.5% female) on oGLDs. The SGLT‐2 inhibitors cohort had statistically significantly lower risk of all‐cause mortality (HR: 0.58, 95% CI: 0.53–0.63), hepatic decompensation (HR: 0.85, 95% CI: 0.81–0.90) and MALO (HR: 0.88, 95% CI: 0.83–0.93). Conclusion SGLT‐2 inhibitors are associated with a reduced risk of all‐cause mortality in patients with MASH cirrhosis and T2DM, which may be partly attributable to a lower risk of hepatic decompensation and subsequent events. Further studies are warranted as SGLT‐2 inhibitors may serve as an adjunctive therapy for patients with MASH cirrhosis.

Abstract Introduction Pouchitis is the most common complication in patients with ileal pouch-anal anastomosis (IPAA), which can develop in up to 66% of patients. There is limited data on the effect of orthoptic liver transplantation (OLT) on the risk of developing pouchitis. We aimed to objectively assess whether OLT itself significantly modifies the risk of developing pouchitis in patients with overlap PSC and inflammatory bowel disease (IBD). Method We searched Medline, Scopus, and Embase databases from inception through September 2023 for studies that describe the outcomes of IPAA in patients with PSC and IBD who also have a history of OLT. Pooled proportions, Odds Ratio (OR), and 95% confidence intervals (CI) for data were calculated utilizing a random effects model. Using the Freeman-Turkey double arcsine transformation (FTT) method, the pooled weight-adjusted estimate of event rates for clinical outcomes in each group was also calculated. Heterogeneity between studies was assessed using the Cochrane Q statistic (I2). Results Seven studies with a total of 291 patients with a history of PSC, IBD, and OLT were identified. The pooled overall risk of pouchitis in PSC/IBD patients with a history of OLT was 65% (95% CI: 0.57–0.72), with no heterogeneity observed in the analysis (I2 = 0%). In a subgroup analysis of patients who had IPAA followed by OLT, 3 studies with 28 patients were included; the pooled risk of pouchitis after IPAA and OLT was 83% (95% CI: 0.71–0.94; I2 = 0%), which was significantly higher (P < .001) than the OLT followed by IPAA group (59%; 95 CI: 0.48–0.71; I2 = 0%). There was no difference in the risk of pouchitis between OLT and non-OLT groups (OR = 1.36; 95% CI: 0.37–5.0). Conclusions Our meta-analysis revelaed that pouchitis is common in patients who underwent OLT for PSC, especially in those who had IPAA before the OLT. OLT before IPAA may reduce the risk of pouchitis. Further larger studies are warranted to reproduce this and investigate the reason behind this difference.

Background: The natural history of primary sclerosing cholangitis (PSC) among African Americans (AA) is not well understood. Methods: Transplant-free survival and hepatic decompensation–free survival were assessed using a retrospective research registry from 16 centers throughout North America. Patients with PSC alive without liver transplantation after 2008 were included. Diagnostic delay was defined from the first abnormal liver test to the first abnormal cholangiogram/liver biopsy. Socioeconomic status was imputed by the Zip code. Results: Among 850 patients, 661 (77.8%) were non-Hispanic Whites (NHWs), and 85 (10.0%) were AA. There were no significant differences by race in age at diagnosis, sex, or PSC type. Inflammatory bowel disease was more common in NHWs (75.8% vs. 51.8% p =0.0001). The baseline (median, IQR) Amsterdam-Oxford Model score was lower in NHWs (14.3, 13.4–15.2 vs. 15.1, 14.1–15.7, p =0.002), but Mayo risk score (0.03, −0.8 to 1.1 vs. 0.02, −0.7 to 1.0, p =0.83), Model for End-stage Liver Disease (5.9, 2.8–10.7 vs. 6.4, 2.6–10.4, p =0.95), and cirrhosis (27.4% vs. 27.1%, p =0.95) did not differ. Race was not associated with hepatic decompensation, and after adjusting for clinical variables, neither race nor socioeconomic status was associated with transplant-free survival. Variables independently associated with death/liver transplant (HR, 95% CI) included age at diagnosis (1.04, 1.02–1.06, p <0.0001), total bilirubin (1.06, 1.04–1.08, p <0.0001), and albumin (0.44, 0.33–0.61, p <0.0001). AA race did not affect the performance of prognostic models. Conclusions: AA patients with PSC have a lower rate of inflammatory bowel disease but similar progression to hepatic decompensation and liver transplant/death compared to NHWs.

Background Alcohol-associated liver disease is increasing among females with an earlier onset and more severe disease at lower levels of exposure. However, there is paucity of literature regarding sex differences related to alcoholic hepatitis. Methods Hospitalized patients with alcoholic hepatitis were selected from the US Nationwide readmissions database 2019. In this cohort, we evaluated sex differences in baseline comorbidities, alcoholic hepatitis related complications and mortality. A subset of patients with alcoholic hepatitis who were hospitalized between January and June 2019 were identified to study sex differences in 6 month readmission rate, mortality during readmission, and composite of mortality during index hospitalization or readmission. Results Among 112 790 patients with alcoholic hepatitis, 33.3% were female. Female patients were younger [48 (38–57) vs. 49 (39–58) years; both P < 0.001] but had higher rates of important medical and mental-health related comorbidities. Compared with males, females had higher rates of hepatic encephalopathy (11.5% vs. 10.1; P < 0.001), ascites (27.9% vs. 22.5%; P < 0.001), portal hypertension (18.5% vs. 16.4%; P < 0.001), cirrhosis (37.3% vs. 31.9%; P < 0.001), weight loss (19.0% vs. 14.5%; P < 0.001), hepatorenal syndrome (4.4% vs. 3.8%; P < 0.001), spontaneous bacterial peritonitis (1.9% vs. 1.7%; P = 0.026), sepsis (11.1% vs. 9.5%; P < 0.001), and blood transfusion (12.9% vs. 8.7%; P < 0.001). Females had a similar in-hospital mortality rate (4.3%) compared to males (4.1%; P = 0.202; adjusted odds ratio (OR) 1.02, 95% CI (cardiac index) 0.89–1.15; P = 0.994). In the subset of patients (N = 58 688), females had a higher 6-month readmission rate (48.9% vs. 44.9%; adjusted OR 1.12 (1.06–1.18); P < 0.001), mortality during readmission (4.4% vs. 3.2%; OR 1.23 (1.08–1.40); P < 0.01), and composite of mortality during index hospitalization or readmission (8.7% vs. 7.2%; OR 1.15 (1.04–1.27); P < 0.01). Conclusion Compared to their male counterparts, females with alcoholic hepatitis were generally younger but had higher rates of comorbidities, alcoholic hepatitis related complications, rehospitalizations and associated mortality. The greater risks of alcohol-associated liver dysfunction in females indicate the need for more aggressive management.

Background: Studies have demonstrated an increased risk of herpes zoster (HZ) in patients with inflammatory bowel disease (IBD). Most recently, the Advisory Committee on Immunization Practices recommended HZ vaccination for adults aged 19 years and older who are at increased risk of shingles due to their disease or drug-related immunosuppression. We aimed to assess the burden of HZ in IBD inpatients and contribute with scientific evidence for an appropriate age cut-off vaccination recommendation. Materials and Methods: Population-based cross-sectional analysis using the 2014 US National Inpatient Sample (NIS). We measured the frequencies and demographics of adult patients with IBD admitted to the hospital with an HZ diagnosis. Age-stratification analysis was performed, and age groups were compared with non-IBD inpatients with an HZ diagnosis. Results: From 307,260 IBD discharges, 1110 (0.35%) patients were found to have HZ as follows: shingles 63%; post-herpetic neuralgia 26%; HZ with ophthalmic involvement 7%; HZ with neurological involvement 4%. Women with IBD were more likely to have shingles (P=0.002) and post-herpetic neuralgia (P=0.001) than men with IBD. The shingles distribution by age in IBD inpatients was 18 to 39 (13%), 40 to 49 (19%), 50 to 59 (18%), 60 to 99 (50%) compared with 18 to 39 (8%), 40 to 49 (6%), 50 to 59 years (14%), 60 to 99 (72%) in non-IBD inpatients (P=0.0004). Conclusions: Hospitalized patients with IBD were found to have a higher frequency of shingles at younger ages when compared with hospitalized patients without IBD. Shingles is more frequent in women, and their prevalence steadily increases with aging though 32% of cases were seen in patients younger than age 50.