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.

Transplant selection simulation: Liver transplantation for alcohol-associated hepatitis.

Liver transplantation (LT) for alcohol-associated hepatitis (AH) remains controversial due to concerns about candidate selection subjectivity, post-LT alcohol relapse, and the potential exacerbation of LT disparities. Our aim was to design, perform, and examine the results of a simulated selection of candidates for LT for AH. Medical histories, psychosocial profiles and scores, and outcomes of 4 simulation candidates were presented and discussed at 2 multidisciplinary societal conferences with real-time polling of participant responses. Candidate psychosocial profiles represented a wide spectrum of alcohol relapse risk. The predictive accuracy of four psychosocial scores, Dallas consensus criteria, sustained alcohol use post-LT, Stanford Integrated Psychosocial Assessment for Transplant, and QuickTrans, were assessed. Overall, 68 providers, mostly academic transplant hepatologists, participated in the simulation. Using a democratic process of selection, a significant majority from both simulations voted to accept the lowest psychosocial risk candidate for LT (72% and 85%) and decline the highest risk candidate (78% and 90%). For the 2 borderline-risk candidates, a narrower majority voted to decline (56% and 65%; 64% and 82%). Two out of 4 patients had post-LT relapse. Predictive accuracies of Dallas, Stanford Integrated Psychosocial Assessment for Transplant, and Quicktrans scores were 50%, while sustained alcohol use post-LT was 25%. The majority of voting outcomes were concordant with post-LT relapse in 3 out of 4 patients. When defining "success" in LT for AH, providers prioritized allograft health and quality of life rather than strict abstinence. In this simulation of LT for AH using a democratic process of selection, we demonstrate its potential as a learning model to evaluate the accuracy of psychosocial scores in predicting post-LT relapse and the concordance of majority voting with post-LT outcomes. Provider definitions of "success" in LT for AH have shifted toward patient-centered outcomes.

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.

A phase II, randomized, open-label, 52-week study of seladelpar in patients with primary biliary cholangitis.

BACKGROUND & AIMS: We examined the efficacy and safety of seladelpar, a selective peroxisome proliferator-activated receptor-delta agonist, in adults with primary biliary cholangitis (PBC) at risk of disease progression (alkaline phosphatase [ALP] ≥1.67xupper limit of normal [ULN]) who were receiving or intolerant to ursodeoxycholic acid. METHODS: In this 52-week, phase II, dose-ranging, open-label study, patients were randomized (1:1) to seladelpar 5 mg/day (n = 53) or 10 mg/day (n = 55) or assigned to 2 mg/day (n = 11; United Kingdom sites after interim analysis) for 12 weeks. Doses could then be uptitrated to 10 mg/day. The primary efficacy endpoint was ALP change from baseline to Week 8. RESULTS: Mean baseline ALP was 300, 345, and 295 U/L in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Twenty-one percent of patients had cirrhosis, 71% had pruritus. At Week 8, mean ± standard error ALP reductions from baseline were 26 ± 2.8%, 33 ± 2.6%, and 41 ± 1.8% in the 2 mg (n = 11), 5 mg (n = 49), and 10 mg (n = 52) cohorts (all p ≤0.005), respectively. Responses were maintained or improved at Week 52, after dose escalation in 91% and 80% of the 2 mg and 5 mg cohorts, respectively. At Week 52, composite response (ALP <1.67xULN, ≥15% ALP decrease, and normal total bilirubin) rates were 64%, 53%, and 67%, and ALP normalization rates were 9%, 13%, and 33% in the 2 mg, 5 mg, and 10 mg cohorts, respectively. Pruritus visual analog scale score was decreased in the 5 mg and 10 mg cohorts. There were no treatment-related serious adverse events, and 4 patients discontinued due to adverse events. CONCLUSIONS: Seladelpar demonstrated robust, dose-dependent, clinically significant, and durable improvements in biochemical markers of cholestasis and inflammation in patients with PBC at risk of disease progression. Seladelpar appeared safe and well tolerated and was not associated with any increase in pruritus. GOV NUMBER: NCT02955602 CLINICALTRIALSREGISTER. EU NUMBER: 2016-002996-91 LAY SUMMARY: Current treatment options for patients living with primary biliary cholangitis (PBC) are not optimal due to inadequate effectiveness or undesirable side effects. Patients with PBC who took seladelpar, a new treatment being developed for PBC, at increasing doses (2, 5, or 10 mg/day) for 1 year had clinically significant, dose-dependent improvements in key liver tests. Treatment appeared safe and was not associated with any worsening in patient self-reported itch scores.

Risk factors and outcomes associated with recurrent autoimmune hepatitis following liver transplantation.

BACKGROUND & AIMS: Autoimmune hepatitis can recur after liver transplantation (LT), though the impact of recurrence on patient and graft survival has not been well characterized. We evaluated a large, international, multicenter cohort to identify the probability and risk factors associated with recurrent AIH and the association between recurrent disease and patient and graft survival. METHODS: We included 736 patients (77% female, mean age 42±1 years) with AIH who underwent LT from January 1987 through June 2020, among 33 centers in North America, South America, Europe and Asia. Clinical data before and after LT, biochemical data within the first 12 months after LT, and immunosuppression after LT were analyzed to identify patients at higher risk of AIH recurrence based on histological diagnosis. RESULTS: AIH recurred in 20% of patients after 5 years and 31% after 10 years. Age at LT ≤42 years (hazard ratio [HR] 3.15; 95% CI 1.22-8.16; p = 0.02), use of mycophenolate mofetil post-LT (HR 3.06; 95% CI 1.39-6.73; p = 0.005), donor and recipient sex mismatch (HR 2.57; 95% CI 1.39-4.76; p = 0.003) and high IgG pre-LT (HR 1.04; 95% CI 1.01-1.06; p = 0.004) were associated with higher risk of AIH recurrence after adjusting for other confounders. In multivariate Cox regression, recurrent AIH (as a time-dependent covariate) was significantly associated with graft loss (HR 10.79, 95% CI 5.37-21.66, p <0.001) and death (HR 2.53, 95% CI 1.48-4.33, p = 0.001). CONCLUSION: Recurrence of AIH following transplant is frequent and is associated with younger age at LT, use of mycophenolate mofetil post-LT, sex mismatch and high IgG pre-LT. We demonstrate an association between disease recurrence and impaired graft and overall survival in patients with AIH, highlighting the importance of ongoing efforts to better characterize, prevent and treat recurrent AIH. LAY SUMMARY: Recurrent autoimmune hepatitis following liver transplant is frequent and is associated with some recipient features and the type of immunosuppressive medications use. Recurrent autoimmune hepatitis negatively affects outcomes after liver transplantation. Thus, improved measures are required to prevent and treat this condition.

Tenofovir Alafenamide Attenuates Effects of Diabetes and Body Mass on Serum Alanine Aminotransferase Activities in Patients With Chronic Hepatitis B.

Persistent serum alanine aminotransferase (ALT) elevation in nucleotide/nucleoside analogue (NA)-treated patients with chronic hepatitis B (CHB) has been associated with unfavorable long-term outcomes.1 It has been consistently shown that a higher proportion of patients receiving tenofovir alafenamide (TAF) achieve normal ALT in comparison with recipients of tenofovir disoproxil fumarate,2-5 the mechanism for which remains unknown.2.

Targeted Electronic Patient Portal Messaging Increases Hepatitis C Virus Screening in Primary Care: a Randomized Study.

IMPORTANCE: Electronic health record (EHR) tools such as direct-to-patient messaging and automated lab orders are effective at improving uptake of preventive health measures. It is unknown if patient engagement in primary care impacts efficacy of such messaging. OBJECTIVE: To determine whether more engaged patients, defined as those who have an upcoming visit scheduled, are more likely to respond to a direct-to-patient message with an automated lab order for hepatitis C virus (HCV) screening. DESIGN: Randomized trial PARTICIPANTS: One thousand six hundred randomly selected Stanford Primary Care patients, 800 with an upcoming visit within 6 months and 800 without, born between 1945 and 1965 who were due for HCV screening. Each group was randomly divided into cohorts of 400 subjects each. Subjects were followed for 1 year. INTERVENTION: One 400 subject cohort in each group received a direct-to-patient message through the EHR portal with HCV antibody lab order. MAIN OUTCOME AND MEASURE: The EHR was queried on a monthly basis for 6 months after the intervention to monitor which subjects completed HCV screening. For any subjects screened positive for HCV, follow-up through the cascade of HCV care was monitored, and if needed, scheduled by the study team. KEY RESULTS: Of 1600 subjects, 538 (34%) completed HCV screening. In the stratum without an upcoming appointment, 18% in the control group completed screening compared to 26% in intervention group (p<0.01). Similarly, in the stratum with an upcoming appointment, 34% in the control group completed screening compared to 58% in the intervention group (p<0.01). CONCLUSION: Direct-to-patient messaging coupled with automated lab orders improved HCV screening rates compared to standard of care, particularly in more engaged patients. Including this intervention in primary care can maximize screening with each visit, which is particularly valuable in times when physical throughput in the healthcare system may be low.

Clinical characteristics and outcomes in those with primary extrahepatic malignancy and malignant ascites.

BACKGROUND: Malignancy-related ascites accounts for approximately 10% of causes of ascites. Our AIM was to characterize the ascites fluid and correlate clinical outcomes in those with extrahepatic malignancy and ascites. METHODS: 241 subjects with extrahepatic solid tumors and ascites were reviewed from 1/1/2000 to 12/31/2019, 119 without liver metastasis and 122 with liver metastasis. RESULTS: Ascites fluid consistent with peritoneal carcinomatosis (PC) was most common, 150/241 (62%), followed by fluid reflecting the presence of portal hypertension (PH), 69/241 (29%). 22/241 (9%) had low SAAG and low ascites fluid total protein, with evidence of PC on cytology and or imaging in 20/22. Lung cancer was the most common malignancy in subjects with ascites due to PC at 36/150 (24%), pancreatic cancer was the most common in subjects with ascites with features of PH at 16/69 (23%). Chemotherapy or immunotherapy alone was the most common management approach. Significantly higher 5-year, 3-year and 1-year mortality rate were noted in subjects with evidence of PC on cytology/imaging versus subjects with no evidence of PC, and in subjects with liver metastasis compared to subjects without liver metastasis. Subjects with pancreatic cancer and evidence of PC on cytology/imaging had higher 1 and 5-year mortality rates compared to subjects without PC. CONCLUSIONS: Ascites in solid tumor malignancy is most commonly due to PC. We also observed ascites fluid with characteristics of PH in 29% of subjects. Higher mortality rates in subjects with peritoneal carcinomatosis and liver metastasis were noted. These findings may help inform prognosis and treatment strategies.

Provider Attitudes and Practices for Alcohol Screening, Treatment, and Education in Patients With Liver Disease: A Survey From the American Association for the Study of Liver Diseases Alcohol-Associated Liver Disease Special Interest Group.

BACKGROUND & AIMS: While abstinence-promoting behavioral and pharmacotherapies are part of the therapeutic foundation for alcohol use disorder (AUD) and alcohol-associated liver disease (ALD), these therapies, along with alcohol screening and education, are often underutilized. Our aim was to examine provider attitudes and practices for alcohol screening, treatment and education in patients with liver disease. METHODS: We conducted a survey of primarily (89%) hepatology and gastroenterology providers within (80%) and outside the United States (20%). Surveys were sent to 921 providers with 408 complete responses (44%), of whom 343 (80%) work in a tertiary liver transplant center. RESULTS: While alcohol screening rates in liver disease patients was nearly universal, less than half of providers reported practicing with integrated addiction providers, using alcohol biomarkers and screening tools. Safe alcohol use by liver disease patients was felt to exist by 40% of providers. While 60% of providers reported referring AUD patients for behavioral therapy, 71% never prescribed AUD pharmacotherapy due to low comfort (84%). Most providers (77%) reported low addiction education and 90% desired more during GI/hepatology fellowship training. Amongst prescribers, baclofen was preferred, but with gaps in pharmacotherapy knowledge. Overall, there was low adherence to the 2019 AASLD practice guidance for ALD, although higher in hepatologists and experienced providers. CONCLUSIONS: While our survey of hepatology and gastroenterology providers demonstrated higher rates of alcohol screening and referrals for behavioral therapy, we found low rates of prescribing AUD pharmacotherapy due to knowledge gaps from insufficient education. Further studies are needed to assess interventions to improve provider alignment with best practices for treating patients with AUD and ALD.

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.

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.

Improved posttransplant mortality after share 35 for liver transplantation.

The Share 35 policy was implemented in June 2013 to improve equity in access to liver transplantation (LT) between patients with fulminant liver failure and those with cirrhosis and severe hepatic decompensation. The aim of this study was to assess post-LT outcomes after Share 35. Relevant donor, procurement, and recipient data were extracted from the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. All adult deceased donor LTs from January 1, 2010, to March 31, 2016, were included in the analysis. One-year patient survival before and after Share 35 was assessed by multivariable Cox proportional hazards analysis, with adjustment for variables known to affect graft survival. Of 34,975 adult LT recipients, 16,472 (47.1%) were transplanted after the implementation of Share 35, of whom 4,599 (27.9%) had a Model for End-Stage Liver Disease (MELD) score ≥35. One-year patient survival improved from 83.9% to 88.4% after Share 35 (P < 0.01) for patients with MELD ≥35. There was no significant impact on survival of patients with MELD <35 (P = 0.69). Quality of donor organs, as measured by a donor risk index without the regional share component, improved for patients with MELD ≥35 (P < 0.01) and worsened for patients with lower MELD (P < 0.01). In multivariable Cox regression analysis, Share 35 was associated with improved 1-year patient survival (hazard ratio, 0.69; 95% confidence interval, 0.60-0.80) in recipients with MELD ≥35. CONCLUSION: Share 35 has had a positive impact on survival after transplantation in patients with MELD ≥35, without a reciprocal detriment in patients with lower acuity; this was in part a result of more favorable donor-recipient matching. (Hepatology 2018;67:273-281).

Early Liver Transplantation is a Viable Treatment Option in Severe Acute Alcoholic Hepatitis.

Liver transplantation is lifesaving for patients with severe acute alcoholic hepatitis (SAH) with preliminary data demonstrating favorable early post-transplant outcomes. Using the United Network for Organ Sharing database, we demonstrate that liver transplantation for SAH in the USA has steadily increased and is associated with similar 1- and 3-year post-transplant survival as well as comparable 30-day waitlist mortality to acute liver failure due to drug-induced liver injury.

A Real-World Evaluation of Repeat Paracentesis-guided Management of Spontaneous Bacterial Peritonitis.

BACKGROUND: Spontaneous bacterial peritonitis (SBP) is a common infection in cirrhosis associated with high mortality. More than 20% of patients with SBP do not respond to initial antibiotics. Guidelines differ in recommendations to repeat paracentesis (retap) to confirm antibiotic efficacy. We aim to evaluate the effect of retap-guided management of SBP on antibiotic escalation and 30-day transplant-free survival. MATERIALS AND METHODS: Retrospective cohort study of cirrhotic patients with SBP admitted to a single transplant center from 2010 to 2014. Patients were divided into 2 groups: retap-guided management versus no retap. Prevalence of initial antibiotic treatment failure, defined as <25% decrease in ascitic polymorphonuclear cells, and factors associated with treatment failure, antibiotic escalation and 30-day transplant-free survival were evaluated. RESULTS: Out of 210 patients, 146 (age 58, 74% male, mean model for end-stage liver disease score, 25) had retap and treatment failure was noted in 28 (22%). Gram-positive bacteria accounted for 44% of all positive cultures and third-generation cepahalosporin resistance was noted in 23%. Thirty-day transplant-free survival was 72% and 62% in retap and control groups, respectively (P=0.07). Treatment failure independently doubled the 30-day mortality rate (hazard ratio: 2.15, 1.03 to 4.50, P=0.04). After adjusting for age, model for end-stage liver disease and nosocomial infection, retap-guided management was not associated with improved survival (P=0.34). CONCLUSIONS: The prevalence of initial treatment failure is high (22%) in patients with SBP and doubles the 30-day mortality risk, supporting recommendations to retap all patients with SBP.

Hepatic artery and biliary complications in liver transplant recipients undergoing pretransplant transarterial chemoembolization.

Liver transplantation (LT) is the treatment of choice for patients with cirrhosis and hepatocellular carcinoma (HCC) not amenable to resection. Locoregional therapies for HCC are often used to reduce tumor burden, bridge patients to LT, and down-stage HCC so that patients are eligible for LT. We hypothesized that prior endovascular antitumor therapy may increase the risk of hepatic artery (HA) and biliary complications after LT. The aim of this study was to compare HA and biliary complications in LT recipients with HCC who received transarterial chemoembolization (TACE) before LT with complications in LT recipients with HCC who did not receive TACE before LT. This was a retrospective cohort study of HCC patients at two transplant centers. The prevalence of HA complications (HA thrombosis, stenosis, or pseudoaneurysm) and biliary complications (nonanastomotic stricture, bile leak, and diffuse injury) were compared between patients treated with or without TACE. There were 456 HCC patients with a median age of 61 years (77% were male, and 63% had hepatitis C virus), and 328 (72%) received TACE before LT. The overall prevalence of HA complications was 4.7% in the no-TACE group and 7.9% in the TACE group (P = 0.22). All HA stenosis complications (n = 14) occurred in the TACE group (P = 0.018 versus the no-TACE group). An older donor age and a lower albumin level significantly increased the odds of HA complications. There was a nonstatistically significant increased odds of HA complications in the TACE group versus the no-TACE group according to an adjusted analysis (odds ratio = 2.02, 95% confidence interval = 0.79-5.16, P = 0.14). The overall prevalence of biliary complications was 16.4% in the no-TACE group and 19.8% in the TACE group (P = 0.40). In conclusion, a lower pre-LT albumin level and an older donor age were significantly associated with higher odds of HA complications after LT. TACE was not associated with higher odds of overall HA complications but was associated with a higher prevalence of HA stenosis. Further studies are warranted to confirm the HA stenosis findings and elucidate the pathogenesis.

Alcohol Use in Liver Transplant Recipients With Alcohol-related Liver Disease: A Comparative Assessment of Relapse Prediction Models.

BACKGROUND: The selection of liver transplant (LT) candidates with alcohol-related liver disease (ALD) is influenced by the risk of alcohol relapse (AR), yet the ability to predict AR is limited. We evaluate psychosocial factors associated with post-LT AR and compare the performance of high-risk alcoholism risk (HRAR), sustained alcohol use post-LT (SALT), and the Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) scores in predicting relapse. METHODS: A retrospective analysis of ALD patients undergoing LT from 2015 to 2021 at a single US transplant center was performed. Risk factors associated with post-LT AR were evaluated and test characteristics of 3 prediction models were compared. RESULTS: Of 219 ALD LT recipients, 23 (11%) had AR during a median study follow-up of 37.5 mo. On multivariate analysis, comorbid psychiatric illness (odds ratio 5.22) and continued alcohol use after advice from a health care provider (odds ratio 3.8) were found to be significantly associated with post-LT AR. On sensitivity analysis, SIPAT of 30 was optimal on discriminating between ALD LT recipients with and without post-LT AR. SIPAT outperformed both the HRAR and SALT scores (c-statistic 0.67 versus 0.59 and 0.62, respectively) in identifying post-LT AR. However, all scores had poor positive predictive value (<25%). CONCLUSIONS: AR after LT is associated with comorbid psychiatric illness and lack of heeding health care provider advice to abstain from alcohol. Although SIPAT outperformed the HRAR and SALT scores in predicting AR, all are poor predictors. The current tools to predict post-LT AR should not be used to exclude LT candidacy.