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Background: Acute-on-chronic liver failure (ACLF) is a syndrome in patients with cirrhosis with high short-term mortality. Infection is a frequent precipitant of ACLF; however, it is unclear if prognosis varies by difference infectious sources. To address this knowledge gap, we utilized a large national database of patients with cirrhosis. Methods: This was a retrospective cohort study of patients with cirrhosis in the Veterans Health Administration between 2008 and 2016. First ACLF hospitalizations were identified and infections were classified using validated algorithms, categorized as bacteremia, fungal, spontaneous bacterial peritonitis (SBP), pyelonephritis/urinary tract infection, or skin and soft tissue/musculoskeletal infection (SST/MSK). Inverse probability treatment weighing for infection-associated ACLF followed by multivariable logistic regression was used to evaluate the association between infection type and 90-day mortality. Results: A total 22,589 ACLF hospitalizations were included, 3998 (17.7%) of which had ACLF grade 3. Infection was associated with 12,405 (54.9%) of ACLF hospitalizations. In regression models, SBP was associated with a 1.79-fold increased odds of 90-day mortality vs. no infection (95% confidence interval [CI] 1.58–2.02, p < 0.001), whereas SST/MSK infections had a lower relative odds of mortality (odds ratio 0.48, 95% CI 0.42–0.53, p < 0.001). There was a significant interaction between infection category and ACLF grade on the outcome of 90-day mortality (p < 0.001). Conclusions: The impact of infection on short-term mortality in ACLF varies depending on the source of infection. This has relevance for ACLF prognostication and challenges previous notions that bacterial infection invariably worsens prognosis among all patients with ACLF. [ABSTRACT FROM AUTHOR]

Background: Alcoholic hepatitis (AH) is a clinically diagnosed syndrome with high short-term mortality for which liver transplantation may be curative. A lack of validated algorithms to identify AH hospitalizations has hindered clinical epidemiology research. Methods: This was a retrospective cohort study of patients with cirrhosis using Veterans Health Administration (VHA) data from 2008 to 2015. We randomly sampled hospitalizations based upon abnormal liver tests and administrative codes for acute hepatitis or alcohol-associated liver disease (ALD). Hospitalizations were manually adjudicated for AH per society guidelines. A priori algorithms were evaluated to compute positive predicted value (PPV) and positive likelihood ratio (LR+), and were tested in an external University of Pennsylvania Health System (UPHS) cohort. Results: Of 368 hospitalizations, 142 (38.6%) were adjudicated as AH. AH patients were younger (55 vs. 58 years, p < 0.001), less likely to have prior cirrhosis decompensation (57% vs. 73.9%, p < 0.001), and had higher AST-to-ALT ratios (median 2.9 vs. 1.9 mg/dL, p < 0.001) and higher bilirubin levels (median 2.9 vs. 1.9 mg/dL, p < 0.001). Algorithms combining clinical laboratory criteria (AST > 85 U/L but < 450 U/L, AST-to-ALT ratio > 2, total bilirubin > 5 mg/dL) and administrative coding criteria yielded the highest PPV (96.4%, 95% CI 87.7–99.6) and the highest LR+ (43.0, 95% CI 10.6–173.5). Several algorithms demonstrated 100% PPV for definite AH in the UPHS external cohort. Conclusion: We have identified algorithms for AH hospitalizations with excellent PPV and LR+. These high-specificity algorithms may be used in VHA datasets to identify patients with high likelihood of AH, but should not be used to study AH incidence. [ABSTRACT FROM AUTHOR]

Background: The Freiburg index of post-TIPS survival (FIPS) score was recently demonstrated to improve prediction of post-TIPS mortality relative to existing standards. As this score was derived from a German cohort over an extended time period, it is unclear if performance will translate well to other settings. This study aimed to externally validate the FIPS score in a large Veterans Affairs (VA) cohort over two separate eras of TIPS-related care. Methods: This was a retrospective cohort study of patients with cirrhosis who underwent TIPS placement in the VA from 2008 to 2020. Cox regression models for post-TIPS survival were constructed using FIPS, MELD, MELD-Na, or CTP scores as predictors. Discrimination (Harrell's C) and calibration (joint tests of calibration curve slope and intercept) were evaluated for each score. A stratified analysis was performed for time periods between 2008–2013 and 2014–2020. Results: The cohort of 1,274 patients was 97.3% male with mean age 60.9 years and mean MELD-Na 14. The FIPS score demonstrated the highest overall discrimination versus MELD, MELD-Na, and CTP (0.634 vs. 0.585, 0.626, 0.612, respectively). However, in the modern treatment era (2014–2020), the FIPS score performed similarly to MELD-Na. Additionally, the FIPS score demonstrated poor calibration at one-month and six-month post-TIPS timepoints (joint p = 0.04 and 0.004, respectively). MELD, MELD-Na, and CTP were well-calibrated at each timepoint (each joint p > 0.05). Conclusion: The FIPS score performed similarly to MELD-Na in the modern TIPS treatment era and demonstrated regions of poor calibration. Future models derived with contemporary data may improve prediction of post-TIPS mortality. [ABSTRACT FROM AUTHOR]

Background: Little is known about use of specialty care among patients admitted with cirrhosis complications. Aims: We sought to characterize the use and impact of gastroenterology/hepatology (GI/HEP) consultations in hospitalized patients with cirrhosis. We studied two national cohorts—the Veterans Affairs Costs and Outcomes in Liver Disease (VOCAL) and a nationally representative database of commercially insured patients (Optum Clinformatics™ DataMart). Methods: Cirrhosis-related admissions were classified by ICD9/10 codes for ascites, hepatic encephalopathy, alcohol-associated hepatitis, spontaneous bacterial peritonitis, or infection related. We included 20,287/222,166 index admissions from VOCAL/Optum from 2010 to 2016. Propensity-matched analyses were conducted to balance clinical characteristics. Mortality and readmission were evaluated using competing risk regression (subhazard ratios, sHR), and length of stay (LOS) was assessed using negative binomial regression. Results: GI/HEP consultations were completed among 37% and 42% patients in VOCAL and Optum, respectively. In propensity-matched analyses for VOCAL, GI/HEP consultation was associated with adjusted estimates of increased LOS (1.55 + 1.03 additional days), 90-day mortality (sHR 1.23, 95% CI 1.14–1.36), and lower 30-day readmissions (sHR 0.82, 95% CI 0.75–0.89). In Optum, inpatient consultation was associated with higher LOS (1.13 + 1.01 additional days), higher 90-day mortality (sHR 1.57, 95% CI 1.43–1.72), and higher 30-day readmission risk (sHR 1.04, 95% CI 1.02–1.05). Post-discharge primary and specialty care was higher among admissions receiving GI/HEP consultation in both cohorts. Conclusions: Use of GI/HEP consultation for cirrhosis-related admissions was low. Patients who received consultation had higher disease severity, and consultation was not associated with lower mortality but was associated with lower 30-day readmissions in the VA cohort only. [ABSTRACT FROM AUTHOR]

Background: The Food and Drug Administration requested withdrawal of ranitidine formulations, due to a potentially carcinogenic contaminant, N-nitrosodimethylamine. Aims: We evaluate whether ranitidine use is associated with gastric cancer. Methods: This is a retrospective multicenter, nationwide cohort study within the Veterans Health Administration, among patients with Helicobacter pylori (HP) prescribed long-term acid suppression with either: (1) ranitidine, (2) other histamine type 2 receptor blocker (H2RB), or (3) proton pump inhibitor (PPI)) between May 1, 1998, and December 31, 2018. Covariates included race, ethnicity, smoking, age, HP treatment, HP eradication. Primary outcome was non-proximal gastric adenocarcinomas, using multivariable Cox proportional hazards analysis. Results: We identified 279,505 patients with HP prescribed long-term acid suppression (median 53.4 years; 92.9% male). Compared to ranitidine, non-ranitidine H2RB users were more likely to develop cancer (HR 1.83, 95%CI 1.36–2.48); PPI users had no significant difference in future cancer risk (HR 0.92, 95% CI 0.82–1.04), p < 0.001. Demographics associated with future cancer included increasing age (HR 1.18, 95% CI 1.15–1.20, p < 0.001), Hispanic/Latino ethnicity (HR 1.46, 95% CI 1.21–1.75, p < 0.001), Black race (HR 1.89, 95% CI 1.68–2.14) or Asian race (HR 2.03, 95% CI 1.17–3.52), p < 0.001, and gender (female gender HR 0.64, 95% CI 0.48–0.85, p = 0.02). Smoking was associated with future cancer (HR 1.38, 95% CI 1.23–1.54, p < 0.001). Secondary analysis demonstrated decreased cancer risk in those with confirmed HP eradication (HR 0.24, 95% CI 0.14–0.40). No association between ranitidine and increased gastric cancer was found. Conclusion: There is no demonstrable association between ranitidine use and future gastric cancer among individuals with HP on long-term acid suppression. [ABSTRACT FROM AUTHOR]

Background: Accuracy of glomerular filtration rate estimating (eGFR) equations has significant implications in cirrhosis, potentially guiding simultaneous liver kidney allocation and drug dosing. Most equations adjust for Black race, partially accounted for by reported differences in muscle mass by race. Patients with cirrhosis, however, are prone to sarcopenia which may mitigate such differences. We evaluated the association between baseline eGFR and incident acute kidney injury (AKI) in patients with cirrhosis with and without race adjustment. Methods: We conducted a retrospective national cohort study of veterans with cirrhosis. Baseline eGFR was calculated using multiple eGFR equations including Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI), both with and without race adjustment. Poisson regression was used to investigate the association between baseline eGFR and incident AKI events per International Club of Ascites criteria. Results: We identified 72,267 patients with cirrhosis, who were 97.3% male, 57.8% white, and 19.7% Black. Over median follow-up 2.78 years (interquartile range 1.22–5.16), lower baseline eGFR by CKD-EPI was significantly associated with higher rates of AKI in adjusted models. For all equations this association was minimally impacted when race adjustment was removed. For example, removal of race adjustment from CKD-EPI resulted in a 0.1% increase in the association between lower eGFR and higher rate of AKI events per 15 mL/min/1.73 m2 change (p < 0.001). Conclusions: Race adjustment in eGFR equations did not enhance AKI risk estimation in patients with cirrhosis. Further study is warranted to assess the impacts of removing race from eGFR equations on clinical outcomes and policy. [ABSTRACT FROM AUTHOR]

In future trial design and in clinical practice, patients with CTP C cirrhosis or total bilirubin >= 3 mg/dl should not be initiated on statins and if already taking should discontinue therapy. Two CTP C patients developed myonecrosis in this study; it was only patients with CTP C cirrhosis in the Bleeding Prevention With Simvastatin (BLEPS) trial that developed rhabdomyolysis [[6]]. [Extracted from the article]