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Background: Transjugular intrahepatic portosystemic shunt (TIPSS) is highly effective for treatment of variceal bleeding; however, factors contributing to rebleeding complications remain unclear., Aims: In this study, we aim to determine risk factors for recurrent portal hypertensive gastrointestinal bleeding following TIPSS., Methods: Utilising the Advancing Liver Therapeutic Approaches multicentre database, we retrospectively identified adult patients who underwent TIPSS for secondary prophylaxis of variceal bleeding and had a gastrointestinal rebleeding event within 1 year. We developed multivariable logistic regression models to identify clinical/procedural characteristics associated with rebleeding., Results: We identified 476 patients, predominately middle-aged (mean age 57), male (62%) and White (65%), with mean MELD-Na 16. 16% (n = 77) had a rebleeding event; these patients were more likely to be male (p = 0.016), with higher serum creatinine (p = 0.005), MELD-Na (p = 0.0002), portal hypertensive gastropathy on pre-TIPSS upper endoscopy (p = 0.000) and with higher incidence of TIPSS revision (p = 0.000). There were no significant differences in type of TIPSS endoprosthesis, concurrent embolotherapy, and post-TIPSS pressure gradients between those who experienced rebleeding and those who did not. After adjusting for TIPSS revision, multivariable analysis revealed MELD-Na and presence of portal hypertensive gastropathy on pre-TIPSS endoscopy were independently associated with rebleeding., Conclusions: In this retrospective analysis of a multicentre, nationally representative database, we found that apart from TIPSS-related factors, high MELD-Na and portal hypertensive gastropathy on pre-TIPSS endoscopy were independent predictors of rebleeding within 1 year following TIPSS. These variables may be used to identify high-risk patients who may require additional monitoring following TIPSS., (© 2024 John Wiley & Sons Ltd.)

Introduction: One of the primary goals of the Liver Cirrhosis Network (LCN) is to develop a cohort study to better understand and predict the risk of hepatic decompensation and other clinical and patient-reported outcomes among patients with Child A cirrhosis., Methods: The LCN consists of a Scientific Data Coordinating Center and 10 clinical centers whose investigators populate multiple committees. The LCN Definitions and Measurements Committee developed preliminary definitions of cirrhosis and its complications by literature review, expert opinion, and reviewing definition documents developed by other organizations. The Cohort Committee developed the study protocol with the input of the steering committee., Results: The LCN developed a prospective cohort study to describe and predict the rates of incident clinical events pertaining to first decompensation and patient-reported outcomes. The LCN developed a pragmatic definition of compensated cirrhosis incorporating clinical, laboratory, imaging, and histological criteria. Definitions of incident and recompensated ascites, overt hepatic encephalopathy, variceal hemorrhage, bleeding because of portal gastropathy, and hepatocellular carcinoma were also codified., Discussion: The LCN Cohort Study design will inform the natural history of cirrhosis in contemporary patients with compensated cirrhosis. The LCN Definitions and Measures Committee developed criteria for the definition of cirrhosis to standardize entry into this multicenter cohort study and standardized criteria for liver-related outcome measures. This effort has produced definitions intended to be both sensitive and specific as well as easily operationalized by study staff such that outcomes critical to the LCN cohort are identified and reported in an accurate and generalizable fashion., Registration: NCT05740358., (Copyright © 2024 by The American College of Gastroenterology.)

Portal hypertension leads to the formation of portosystemic collaterals that divert portal blood to the systemic circulation and bypass the liver, resulting in multiple severe complications. Portal hypertension has classically been diagnosed using invasive methods to calculate the hepatic venous pressure gradient. There has been a recent evolution in portal hypertension pathology emphasizing dynamic changes and integrated pathophysiology, as well as concurrent changes in medical management. There is now a focus on using less-invasive approaches to diagnose portal hypertension and novel treatments that target the various components of evolving portal hypertension pathophysiology. This article details the latest techniques in diagnosing and treating portal hypertension that are becoming cornerstones of portal hypertension management., (Copyright © 2023, Gastro-Hep Communications, Inc.)

Purpose: To evaluate recovery of platelet count after transjugular intrahepatic portosystemic shunt (TIPS) creation and patient factors predicting platelet recovery after TIPS creation., Materials and Methods: Adults with cirrhosis who underwent TIPS creation at 9 U.S. hospitals from 2010 to 2015 were included in this retrospective analysis. Change in platelets from before TIPS to 4 months after TIPS creation was characterized. Logistic regression was used to assess factors associated with top quartile percentage platelet increase after TIPS. Subgroup analyses were performed among patients with a pre-TIPS platelet count of ≤50 ×10 9 /L., Results: A total of 601 patients were included. The median absolute change in platelets was 1 × 10 9 /L (-26 × 10 9 /L to 25 × 10 9 /L). Patients with top quartile percent platelet increase experienced ≥32% platelet increase. In multivariable analysis, pre-TIPS platelet counts (odds ratio [OR], 0.97 per 10 9 /L; 95% CI, 0.97-0.98), age (OR, 1.24 per 5 years; 95% CI, 1.10-1.39), and pre-TIPS model for end-stage liver disease (MELD) scores (OR, 1.06 per point; 95% CI, 1.02-1.09) were associated with top quartile (≥32%) platelet increase. Ninety-four (16%) patients had a platelet count of ≤50 × 10 9 /L before TIPS. The median absolute platelet change was 14 × 10 9 /L (2 × 10 9 /L to 34 × 10 9 /L). Fifty-four percent of patients in this subgroup were in the top quartile for platelet increase. In multivariable logistic regression, age (OR, 1.50 per 5 years; 95% CI, 1.11-2.02) was the only factor associated with top quartile platelet increase in this subgroup., Conclusions: TIPS creation did not result in significant platelet increase, except among patients with a platelet count of ≤50 × 10 9 /L before TIPS. Lower pre-TIPS platelet counts, older age, and higher pre-TIPS MELD scores were associated with top quartile (≥32%) platelet increase in the entire cohort, whereas only older age was associated with this outcome in the patient subset with a pre-TIPS platelet count of ≤50 × 10 9 /L., (Copyright © 2023. Published by Elsevier Inc.)

Liver transplantation (LT), the only cure for end-stage liver disease, is a lifesaving, costly, and limited resource. LT recipients (LTRs) are aging with an increasing burden of medical comorbidities. Patient and graft survival rates exceed 70% at 5 years; however, patient-centered health outcomes beyond survival have received relatively little attention. LTRs must have strong self-management skills to navigate health systems, adhere to clinical monitoring, and take complex, multidrug regimens. All of these tasks require formidable cognitive abilities for active learning and problem solving. Yet, LTRs are at higher risk for impaired cognition as a result of the high prevalence of pretransplant hepatic encephalopathy, multiple chronic conditions, alcohol use, physical frailty, sarcopenia, and older age. Cognitive impairment after transplant may persist and has been causally linked to poor self-management skills, worse physical function, and inferior health outcomes in other health care settings, yet its impact after LT is largely unknown. There is a need to study potentially modifiable, posttransplant targets including caregiver support, physical activity, sleep, and treatment adherence to inform future health system responses to promote the long-term health and well-being of LTRs. Prospective, longitudinal data collection that encompasses key sociodemographic, cognitive-behavioral, psychosocial, and medical factors is needed to improve risk prediction and better inform patient and caregiver expectations. Interventions with proactive monitoring, reducing medical complexity, and improved care coordination can be tailored to optimize posttransplant care. We propose a research agenda focused on understudied, potentially modifiable risk factors to improve the long-term health of LTRs. Our conceptual model accounts for cognitive function, caregiver and patient self-management skills, health behaviors, and patient-centered outcomes beyond mortality. We propose actionable health-system, patient, and caregiver-directed interventions to fill knowledge gaps and improve outcomes., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

Simultaneous liver-kidney transplantation (SLKT) is increasingly common in the United States. However, little is known about the renal-related outcomes following SLKT, which are essential to maximize the health of these allografts. We examined the factors impacting renal function following SLKT. This is an observational multicenter cohort study from the US Multicenter SLKT Consortium consisting of recipients of SLKT aged ≥18 years of transplantations performed between February 2002 and June 2017 at 6 large US centers in 6 different United Network for Organ Sharing regions. The primary outcome was incident post-SLKT stage 4-5 chronic kidney disease (CKD) defined as <30 mL/minute/1.73 m 2 or listing for kidney transplant. The median age of the recipients (n = 570) was 58 years (interquartile range, 51-64 years), and 37% were women, 76% were White, 33% had hepatitis C virus infection, 20% had nonalcoholic steatohepatitis (NASH), and 23% had alcohol-related liver disease; 68% developed ≥ stage 3 CKD at the end of follow-up. The 1-year, 3-year, and 5-year incidence rates of post-SLKT stage 4-5 CKD were 10%, 12%, and 16%, respectively. Pre-SLKT diabetes mellitus (hazard ratio [HR], 1.45; 95% CI, 1.00-2.15), NASH (HR, 1.58; 95% CI, 1.01-2.45), and delayed kidney graft function (HR, 1.72; 95% CI, 1.10-2.71) were the recipient factors independently associated with high risk, whereas the use of tacrolimus (HR, 0.44; 95% CI, 0.22-0.89) reduced the risk. Women (β = -6.22 ± 2.16 mL/minute/1.73 m 2 ; P = 0.004), NASH (β = -7.27 ± 3.27 mL/minute/1.73 m 2 ; P = 0.027), and delayed kidney graft function (β = -7.25 ± 2.26 mL/minute/1.73 m 2 ; P = 0.007) were independently associated with low estimated glomerular filtration rate at last follow-up. Stage 4-5 CKD is common after SLKT. There remains an unmet need for personalized renal protective strategies, specifically stratified by sex, diabetes mellitus, and liver disease, to preserve renal function among SLKT recipients., (Copyright © 2021 by the American Association for the Study of Liver Diseases.)

The liver transplantation (LT) population is aging, with the need for transplant being driven by the growing prevalence of nonalcoholic steatohepatitis (NASH). Older LT recipients with NASH may be at an increased risk for adverse outcomes after LT. Our objective is to characterize outcomes in these recipients in a large multicenter cohort. All primary LT recipients ≥65 years from 2010 to 2016 at 13 centers in the Re-Evaluating Age Limits in Transplantation (REALT) consortium were included. Of 1023 LT recipients, 226 (22.1%) were over 70 years old, and 207 (20.2%) had NASH. Compared with other LT recipients, NASH recipients were older (68.0 versus 67.3 years), more likely to be female (47.3% versus 32.8%), White (78.3% versus 68.0%), Hispanic (12.1% versus 9.2%), and had higher Model for End-Stage Liver Disease-sodium (21 versus 18) at LT (P < 0.05 for all). Specific cardiac risk factors including diabetes with or without chronic complications (69.6%), hypertension (66.3%), hyperlipidemia (46.3%), coronary artery disease (36.7%), and moderate-to-severe renal disease (44.4%) were highly prevalent among NASH LT recipients. Graft survival among NASH patients was 90.3% at 1 year and 82.4% at 3 years compared with 88.9% at 1 year and 80.4% at 3 years for non-NASH patients (log-rank P = 0.58 and P = 0.59, respectively). Within 1 year after LT, the incidence of graft rejection (17.4%), biliary strictures (20.9%), and solid organ cancers (4.9%) were comparable. Rates of cardiovascular (CV) complications, renal failure, and infection were also similar in both groups. We observed similar posttransplant morbidity and mortality outcomes for NASH and non-NASH LT recipients. Certain CV risk factors were more prevalent in this population, although posttransplant outcomes within 1 year including CV events and renal failure were similar to non-NASH LT recipients., (Copyright © 2020 by the American Association for the Study of Liver Diseases.)

Background & Aims: Fontan surgery for single ventricle congenital heart disease leads to Fontan-associated liver disease (FALD). Typical laboratory tests, imaging, and histopathology cannot predict clinical severity in FALD. HepQuant SHUNT is a proprietary serum test of hepatic function and physiology that has not yet been evaluated in FALD., Methods: Fourteen adult FALD patients at a single urban tertiary care center who underwent a Fontan procedure in childhood received HepQuant SHUNT testing between September 2015 and April 2018. The HepQuant SHUNT disease severity index (DSI) assesses global liver function and physiology from systemic and portal hepatic filtration rates (HFRs, clearances adjusted for body mass) of orally and intravenously administered cholates labeled with deuterium or 13C. The SHUNT parameter of the test measures portal systemic shunting from the ratio of Systemic HFR to Portal HFR. Chart review included laboratory tests, imaging, and clinical findings. Data from FALD patients were compared with data from healthy controls., Results: The average DSI and SHUNT values for the FALD patients were 17.5% and 36.1%, respectively, compared to 9.2% and 24.1%, respectively, for controls. Twelve (85.7%) FALD patients had a DSI >15 (upper limit of normal). Seven (50.0%) FALD patients had SHUNT values >30% (upper limit of normal), while three FALD patients (21.4%) had SHUNT values >49%. One FALD patient with preoperative SHUNT of 69%, who underwent a combined heart-liver transplant, had confirmed cirrhotic morphology within the liver explant., Conclusions: This pilot study demonstrated that most FALD patients had hepatic impairment detected by abnormal DSI, with a smaller number having markedly elevated SHUNT values >49% suggesting intrinsic liver disease. The HepQuant SHUNT test may be useful in detecting and quantifying liver disease severity in FALD patients., (© 2019 Wiley Periodicals, Inc.)

Background: Nonalcoholic steatohepatitis (NASH) is a leading indication for liver transplantation (LT). We hypothesized that weight gain after LT may be exacerbated by reduced metabolic rates due to the LT procedure, particularly during exercise. We aimed to compare resting and exercise energy expenditure between patients transplanted for NASH and nontransplant nonalcoholic fatty liver disease (NAFLD) subjects., Methods: NASH LT recipients (>1-year post, n = 14) and NAFLD controls (n = 13) underwent analysis of body composition, resting energy expenditure (REE), and exercise energy expenditure (VO 2max ), the latter using a ramped-Bruce protocol assessed by expired gas analysis and peak heart rate., Results: Participants were mean 61.5 ± 7.9 years, 48.1% men, and 66.7% white. Baseline comorbidities were similar between groups. Among men, mean REE adjusted for total (17.7 vs 18.8, P = 0.87) and lean body mass (23.5 vs 26.9, P = 0.26), as well as VO 2 (20.1 vs 23.9, P = 0.29), was lower in NASH LT recipients compared with NAFLD controls, respectively, although not statistically significant. However, female NASH LT recipients had significantly lower mean REE than NAFLD controls when adjusted for total (14.2 vs 18.9, P = 0.01) and lean body mass (19.3 vs 26.5, P = 0.002), as well as significantly lower VO 2max (14.4 vs 20.6, P = 0.017)., Conclusions: NASH LT recipients, particularly women, have lower REE and exercise energy expenditure compared with nontransplant NAFLD patients. More aggressive diet and exercise programs for post-LT NASH recipients to account for reduced resting and exercise metabolic rates may attenuate weight gain in this vulnerable population., Competing Interests: The authors declare no conflicts of interest.

Objectives: Young women with hyperandrogenism have high risk of metabolic co-morbidities, including increased risk of nonalcoholic fatty liver disease (NAFLD). Whether testosterone (the predominant androgen) is associated with NAFLD independent of metabolic co-factors is unclear. Additionally, whether testosterone confers increased risk of NAFLD in women without hyperandrogenism is unknown., Methods: Among women in the prospective population-based multicenter Coronary Artery Risk Development in Young Adults (CARDIA) study, we assessed whether free testosterone levels measured at Year 2 (1987-1988) were associated with prevalent NAFLD at Year 25 (2010-2011) (n=1052). NAFLD was defined using noncontrast abdominal CT scan with liver attenuation≤40 Hounsfield units after excluding other causes of hepatic fat. The association of free testosterone with prevalent NAFLD was assessed by logistic regression., Results: Increasing quintiles of free testosterone were associated with prevalent NAFLD at Year 25 (adjusted odds ratio (AOR) 1.25, 95% confidence interval (CI) 1.04-1.50, P=0.015), independent of insulin resistance, body mass index, waist circumference, and serum lipids. Importantly, the association persisted among n=955 women without androgen excess (AOR 1.27, 95% CI 1.05-1.53, P=0.016). Visceral adipose tissue (VAT) volume partially mediated the association of free testosterone with NAFLD (mediating effect 41.0%, 95% CI 22-119%)., Conclusions: Increasing free testosterone is associated with prevalent NAFLD in middle age, even in women without androgen excess. Visceral adiposity appears to play an important role in the relationship between testosterone and NAFLD in women. Testosterone may provide a potential novel target for NAFLD therapeutics, and future studies in pre-menopausal women should consider the importance of testosterone as a risk factor for NAFLD.