The impact of right atrial pressure on outcomes in patients undergoing TIPS, an ALTA group study.

BACKGROUND AND AIMS: Single-center studies in patients undergoing TIPS suggest that elevated right atrial pressure (RAP) may influence survival. We assessed the impact of pre-TIPS RAP on outcomes using the Advancing Liver Therapeutic Approaches (ALTA) database. APPROACH AND RESULTS: Total 883 patients in ALTA multicenter TIPS database from 2010 to 2015 from 9 centers with measured pre-TIPS RAP were included. Primary outcome was mortality. Secondary outcomes were 48-hour post-TIPS complications, post-TIPS portal hypertension complications, and post-TIPS inpatient admission for heart failure. Adjusted Cox Proportional hazards and competing risk model with liver transplant as a competing risk were used to assess RAP association with mortality. Restricted cubic splines were used to model nonlinear relationship. Logistic regression was used to assess RAP association with secondary outcomes.Pre-TIPS RAP was independently associated with overall mortality (subdistribution HR: 1.04 per mm Hg, 95% CI, 1.01, 1.08, p =0.009) and composite 48-hour complications. RAP was a predictor of TIPS dysfunction with increased odds of post-90-day paracentesis in outpatient TIPS, hospital admissions for renal dysfunction, and heart failure. Pre-TIPS RAP was positively associated with model for end-stage liver disease, body mass index, Native American and Black race, and lower platelets. CONCLUSIONS: Pre-TIPS RAP is an independent risk factor for overall mortality after TIPS insertion. Higher pre-TIPS RAP increased the odds of early complications and overall portal hypertensive complications as potential mechanisms for the mortality impact.

Change in Platelet Count after Transjugular Intrahepatic Portosystemic Shunt Creation: An Advancing Liver Therapeutic Approaches (ALTA) Group Study.

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 ×109/L. RESULTS: A total of 601 patients were included. The median absolute change in platelets was 1 × 109/L (-26 × 109/L to 25 × 109/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 109/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 × 109/L before TIPS. The median absolute platelet change was 14 × 109/L (2 × 109/L to 34 × 109/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 × 109/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 × 109/L.

Outcomes After TIPS for Ascites and Variceal Bleeding in a Contemporary Era-An ALTA Group Study.

INTRODUCTION: Advances in transjugular intrahepatic portosystemic shunt (TIPS) technology have led to expanded use. We sought to characterize contemporary outcomes of TIPS by common indications. METHODS: This was a multicenter, retrospective cohort study using data from the Advancing Liver Therapeutic Approaches study group among adults with cirrhosis who underwent TIPS for ascites/hepatic hydrothorax (ascites/HH) or variceal bleeding (2010-2015). Adjusted competing risk analysis was used to assess post-TIPS mortality or liver transplantation (LT). RESULTS: Among 1,129 TIPS recipients, 58% received TIPS for ascites/HH and 42% for variceal bleeding. In patients who underwent TIPS for ascites/HH, the subdistribution hazard ratio (sHR) for death was similar across all Model for End-Stage Liver Disease Sodium (MELD-Na) categories with an increasing sHR with rising MELD-Na. In patients with TIPS for variceal bleeding, MELD-Na ≥20 was associated with increased hazard for death, whereas MELD-Na ≥22 was associated with LT. In a multivariate analysis, serum creatinine was most significantly associated with death (sHR 1.2 per mg/dL, 95% confidence interval [CI] 1.04-1.4 and 1.37, 95% CI 1.08-1.73 in ascites/HH and variceal bleeding, respectively). Bilirubin and international normalized ratio were most associated with LT in ascites/HH (sHR 1.23, 95% CI 1.15-1.3; sHR 2.99, 95% CI 1.76-5.1, respectively) compared with only bilirubin in variceal bleeding (sHR 1.06, 95% CI 1.00-1.13). DISCUSSION: MELD-Na has differing relationships with patient outcomes dependent on TIPS indication. These data provide new insights into contemporary predictors of outcomes after TIPS.

Nonalcoholic Fatty Liver Disease and Diabetes Mellitus Are Associated With Post-Transjugular Intrahepatic Portosystemic Shunt Renal Dysfunction: An Advancing Liver Therapeutic Approaches Group Study.

Transjugular intrahepatic portosystemic shunt (TIPS) is an effective intervention for portal hypertensive complications, but its effect on renal function is not well characterized. Here we describe renal function and characteristics associated with renal dysfunction at 30 days post-TIPS. Adults with cirrhosis who underwent TIPS at 9 hospitals in the United States from 2010 to 2015 were included. We defined "post-TIPS renal dysfunction" as a change in estimated glomerular filtration rate (ΔeGFR) ≤-15 and eGFR ≤ 60 mL/min/1.73 m2 or new renal replacement therapy (RRT) at day 30. We identified the characteristics associated with post-TIPS renal dysfunction by logistic regression and evaluated survival using adjusted competing risk regressions. Of the 673 patients, the median age was 57 years, 38% of the patients were female, 26% had diabetes mellitus, and the median MELD-Na was 17. After 30 days post-TIPS, 66 (10%) had renal dysfunction, of which 23 (35%) required new RRT. Patients with post-TIPS renal dysfunction, compared with those with stable renal function, were more likely to have nonalcoholic fatty liver disease (NAFLD; 33% versus 17%; P = 0.01) and comorbid diabetes mellitus (42% versus 24%; P = 0.001). Multivariate logistic regressions showed NAFLD (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.00-4.17; P = 0.05), serum sodium (Na; OR, 1.06 per mEq/L; 95% CI, 1.01-1.12; P = 0.03), and diabetes mellitus (OR, 2.04; 95% CI, 1.16-3.61; P = 0.01) were associated with post-TIPS renal dysfunction. Competing risk regressions showed that those with post-TIPS renal dysfunction were at a higher subhazard of death (subhazard ratio, 1.74; 95% CI, 1.18-2.56; P = 0.01). In this large, multicenter cohort, we found NAFLD, diabetes mellitus, and baseline Na associated with post-TIPS renal dysfunction. This study suggests that patients with NAFLD and diabetes mellitus undergoing TIPS evaluation may require additional attention to cardiac and renal comorbidities before proceeding with the procedure.

Novel treatments for alcoholic hepatitis.

PURPOSE OF REVIEW: The current article aims to review the latest literature on updates in therapeutics for alcohol-associated liver disease (ALD), integration of treatment of alcohol use disorder (AUD) into the management of ALD, and the role of liver transplantation for alcoholic hepatitis. RECENT FINDINGS: ALD has recently become the most common indication for liver transplantation due to the increasing prevalence of AUD and the paucity of therapeutic options. There is broad consensus on the importance of early identification of AUD and the incorporation of its treatment in the management of ALD. New targets for treatment of alcoholic hepatitis include the gut-liver axis, anti-inflammatory drugs, antioxidants, and drugs with hepatic regenerative potential. Fecal transplantation in particular has had favorable outcomes at 1 year. n-Acetylcysteine in addition to corticosteroids, granulocyte colony stimulating factor, and IL-22 have also shown improved short-term outcomes. A number of other therapies are being studied in clinical trials and their results are anxiously awaited. SUMMARY: In summary, there are several promising therapeutic options under clinical investigation for the treatment of alcoholic hepatitis and ALD; however, alcohol abstinence is key. In the absence of other effective therapies, liver transplantation for ALD remains a life-saving treatment with excellent patient and graft survival.

Outcomes of Liver Transplantation Among Older Recipients With Nonalcoholic Steatohepatitis in a Large Multicenter US Cohort: the Re-Evaluating Age Limits in Transplantation Consortium.

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.

Statin Use is Protective Against Hepatocellular Carcinoma in Patients With Nonalcoholic Fatty Liver Disease: A Case-control Study.

BACKGROUND AND GOAL: The incidence of nonalcoholic fatty liver disease (NAFLD)-associated hepatocellular carcinoma (HCC) is rising. We aimed to characterize risk factors for NAFLD-HCC development. METHODS: We performed a retrospective case-control study of HCC cases from a cohort of NAFLD patients who underwent at least 2 computed tomography scans. NAFLD-HCC cases confirmed on contrast imaging and/or biopsy were included. Controls were NAFLD patients without HCC matched by sex and age. Clinical variables were assessed. Visceral adipose tissue and subcutaneous adipose tissue were measured by computed tomography at 2 timepoints: before HCC diagnosis and at diagnosis. RESULTS: We identified 102 subjects [34 HCC cases, 68 controls, 65% (n=66) males, mean age: 69 y] from 2002 to 2016. Cirrhosis was present in 91%. In multivariate analysis, statin use was protective against HCC [odds ratio (OR)=0.20, 95% confidence interval (CI): 0.07-0.60, P=0.004], while hypertension was a risk factor for HCC (OR=5.80, 95% CI: 2.01-16.75, P=0.001). In multivariate analysis, visceral adipose tissue in males was higher before HCC diagnosis and declined by HCC diagnosis in 86%, which was a significant difference compared with controls (OR=2.78, 95% CI: 1.10-7.44, P=0.04). CONCLUSIONS: In a cohort of NAFLD-HCC patients, statin use was protective against HCC, while hypertension conferred an increased risk. Visceral adiposity at baseline was not a risk factor, but was higher in male patients before HCC development, declining in the majority by HCC diagnosis.

Designing clinical trials to address alcohol use and alcohol-associated liver disease: an expert panel Consensus Statement.

Most patients with alcohol-associated liver disease (ALD) engage in heavy drinking defined as 4 or more drinks per day (56 g) or 8 (112 g) or more drinks per week for women and 5 or more drinks per day (70 g) or 15 (210 g) or more drinks per week for men. Although abstinence from alcohol after diagnosis of ALD improves life expectancy and reduces the risk of decompensation of liver disease, few studies have evaluated whether treatment of alcohol use disorders will reduce progression of liver disease and improve liver-related outcomes. In November 2021, the National Institute of Alcohol Abuse and Alcoholism commissioned a task force that included hepatologists, addiction medicine specialists, statisticians, clinical trialists and members of regulatory agencies to develop recommendations for the design and conduct of clinical trials to evaluate the effect of alcohol use, particularly treatment to reduce or eliminate alcohol use in patients with ALD. The task force conducted extensive reviews of relevant literature on alcohol use disorders and ALD. Findings were presented at one in-person meeting and discussed over the next 16 months to develop the final recommendations. As few clinical trials directly address this topic, the 28 recommendations approved by all members of the task force represent a consensus of expert opinions.

Testing a Digital Health App for Patients With Alcohol-Associated Liver Disease: Mixed Methods Usability Study.

BACKGROUND: Alcohol-associated liver disease (ALD) is increasingly common and associated with serious and costly health consequences. Cessation of drinking can improve ALD morbidity and mortality; however, support for cessation is not routinely offered to those diagnosed with ALD, and continued drinking or resumption of drinking after diagnosis is common. Mobile health (mHealth) has the potential to offer convenient and scalable support for alcohol cessation to those diagnosed with ALD, but mHealth interventions for alcohol cessation have not been designed for or evaluated in a population with ALD. OBJECTIVE: This study aims to understand how individuals with ALD would perceive and use an mHealth tool for alcohol cessation and to gather their perspectives on potential refinements to the tool that would allow it to better meet their needs. METHODS: We interviewed 11 individuals who attended clinic visits related to their ALD to elicit their needs related to support for alcohol cessation and views on how mHealth could be applied. After completing initial interviews (pre), participants were provided with access to an mHealth app designed for alcohol cessation, which they used for 1 month. Afterward, they were interviewed again (post) to give feedback on their experiences, including aspects of the app that met their needs and potential refinements. We applied a mixed methods approach, including a qualitative analysis to identify major themes from the interview transcripts and descriptive analyses of use of the app over 1 month. RESULTS: First, we found that a diagnosis of ALD is perceived as a motivator to quit drinking but that patients had difficulty processing the overwhelming amount of information about ALD they received and finding resources for cessation of alcohol use. Second, we found that the app was perceived as usable and useful for supporting drinking recovery, with patients responding favorably to the self-tracking and motivational components of the app. Finally, patients identified areas in which the app could be adapted to meet the needs of patients with ALD, such as providing information on the medical implications of an ALD diagnosis and how to care for their liver as well as connecting individuals with ALD to one another via a peer-to-peer support forum. Rates of app use were high and sustained across the entire study, with participants using the app a little more than half the days during the study on average and with 100% (11/11) of participants logging in each week. CONCLUSIONS: Our results highlight the need for convenient access to resources for alcohol cessation after ALD diagnosis and support the potential of an mHealth approach to integrate recovery support into care for ALD. Our findings also highlight the ways the alcohol cessation app should be modified to address ALD-specific concerns.

Internet Published Policies Regarding Liver Transplant Eligibility and Substance Use in United States Transplant Centers.

Liver transplant centers in the United States retain great autonomy in determining eligibility criteria for a liver transplant. This study aims to define the availability and content of liver transplant centers' publicly available Internet policies regarding eligibility criteria for liver transplant. Three trained undergraduate students performed a structured pilot-tested assessment of official websites of the United Network for Organ Sharing-registered liver transplant centers. All 141 liver transplant centers had an accessible website. Some account of eligibility criteria was provided by 53% of centers, while 32% of centers discussed substance use. Only 17% discussed their policy regarding alcohol use in candidates with underlying alcohol use disorder, and only 2% stipulated that 6 months of abstinence was required. While exclusion based on substance use or age was discussed infrequently, insurance coverage requirements, the need for social support, and the need for adherence to medical care were mentioned in 21%, 37%, and 23% of centers, respectively. Conclusion: In 2018, half of liver transplant centers provided some information on their official websites regarding eligibility criteria for liver transplant. Detailed information regarding substance use disorders and social health requirements was rare. The Internet is infrequently used by liver transplant centers as a means to publicly share information regarding selection criteria.

A case of syphilitic hepatitis in an HIV-infected patient.

While the incidence of syphilis has been persistently on the rise in the United States, hepatitis as a complication of early syphilis is relatively uncommon. We present a case of a 51-year-old homosexual, HIV-positive man who presented with acute cholestatic hepatitis with a predominantly elevated alkaline phosphatase. After laboratory studies and imaging were unrevealing, a liver biopsy was performed that showed expanded portal tracts with a predominantly lymphoplasmacytic infiltrate and prominent bile ductular proliferation with periductal neutrophils. Testing revealed a positive rapid plasma reagin, and a subsequent Warthin-Starry stain of the liver tissue demonstrated the presence of scattered spirochetes, confirmed as Treponema pallidum spirochetes on immunohistochemistry testing. These findings confirmed a diagnosis of syphilitic hepatitis. With therapy, symptoms and liver enzymes rapidly normalized. Given the persistent rise in syphilis incidence along with the morbidity and mortality associated with a missed diagnosis, keen suspicion, early identification, and treatment are crucial.