Disparities in steatosis prevalence in the United States by Race or Ethnicity according to the 2023 criteria.

INTRODUCTION: The 2023 nomenclature defined criteria for steatotic liver disease (SLD), including metabolic dysfunction-associated SLD (MASLD), alcohol-associated liver disease (ALD), and the overlapping MASLD/ALD (MetALD). We aimed to assess racial and ethnic disparities in the SLD prevalence among United States (US) adults based on this new nomenclature. METHODS: We undertook a cross-sectional study employing the 2017-2018 National Health and Nutrition Examination Survey (NHANES) database. We identified SLD according to a controlled attenuation parameter ≥288 dB/m, liver stiffness ≥7.2 kPa, or elevated aminotransferase levels. Alcohol use thresholds were established according to the updated SLD definition. We estimated prevalences using the complex design of the NHANES survey. Multivariable logistic regressions with complex design weights were employed. RESULTS: A total of 5532 individuals are included. The mean age is 45.4 years, and 50.9% are women. The adjusted estimated prevalence of MASLD is 42.4% (95% CI: 41.1-43.8%), MetALD 1.7% (95% CI: 1.3-2.0%), and ALD 0.6% (95% CI: 0.3-0.8%). Hispanics exhibit a higher prevalence of SLD, but there are no significant differences in advanced fibrosis prevalence due to SLD among racial/ethnic groups. In MASLD, men, individuals aged 40-64 and ≥65 years, Hispanics, those with health insurance, higher BMI, diabetes, hypertension, hypertriglyceridemia, and low high-density lipoprotein (HDL) cholesterol or use of lipid-lowering agents are independently associated with a higher risk, while Blacks have the lowest risk. In MetALD, men and higher BMI are independently associated with a higher risk of MetALD in adjusted multivariable analysis. In ALD, the adjusted multivariable analysis shows that only health insurance is independently associated with a lower ALD risk. CONCLUSIONS: MASLD prevalence is high in the US, especially in men, older individuals, and Hispanics. MetALD and ALD prevalence was substantial but could be underestimated.

This study aims to estimate the prevalence of different types of fatty liver disease, in which excess fat occurs in the liver. A particular type of fatty liver disease that is not caused by excess alcohol consumption affects 42.4% of adults in the USA, with men, older adults, and Hispanics being more likely to have this form of liver disease. People with health insurance are less likely to have liver disease caused by excess alcohol consumption. These results highlight the importance of targeted prevention efforts in people with a higher risk of developing liver disease. Future public health strategies should focus on reducing risk factors and providing equitable healthcare access.

Racial and ethnic disparities in the natural history of alcohol-associated liver disease in the United States.

BACKGROUND: Outcomes in alcohol-associated liver disease (ALD) are influenced by several race and ethnic factors, yet its natural history across the continuum of patients in different stages of the disease is unknown. METHODS: We conducted a retrospective cohort study of U.S. adults from 2011 to 2018, using three nationally representative databases to examine potential disparities in relevant outcomes among racial and ethnic groups. Our analysis included logistic and linear regressions, along with competing risk analysis. RESULTS: Black individuals had the highest daily alcohol consumption (12.6 g/day) while Hispanic participants had the largest prevalence of heavy episodic drinking (33.5%). In a multivariable-adjusted model, Hispanic and Asian participants were independently associated with a higher ALD prevalence compared to Non-Hispanic White interviewees (OR: 1.4, 95% CI: 1.1-1.8 and OR: 1.5 95% CI:1.1-2.0, respectively), while Blacks participants had a lower ALD prevalence (OR: .7 95% CI: .6-.9), and a lower risk of mortality during hospitalization due to ALD (OR: .83 95% CI: .73-.94). Finally, a multivariate competing-risk analysis showed that Hispanic ethnicity had a decreased probability of liver transplantation if waitlisted for ALD (SHR: .7, 95% CI: .6-.8) along with female Asian population (HR: .40, 95% CI: .26-.62). CONCLUSIONS: After accounting for key social and biological health determinants, the Hispanic population showed an increased risk of ALD prevalence, even with lower alcohol consumption. Additionally, Hispanic and Asian female patients had reduced access to liver transplantation compared to other enlisted patients.

Acute kidney injury in severe alcohol-associated hepatitis treated with anakinra plus zinc or prednisone.

BACKGROUND AND AIMS: In a recent trial, patients with severe alcohol-associated hepatitis treated with anakinra plus zinc (A+Z) had lower survival and higher acute kidney injury (AKI) rates versus prednisone (PRED). We characterize the clinical factors and potential mechanisms associated with AKI development in that trial. APPROACH AND RESULTS: Data from 147 participants in a multicenter randomized clinical trial (74 A+Z, 73 PRED) were analyzed. AKI, AKI phenotypes, and kidney injury biomarkers were compared between participants who did/did not develop AKI in the 2 treatment arms. Multivariable competing risk analyses were performed to identify baseline risk factors for incident AKI, with death treated as a competing event. Risk factors considered were age, sex, mean arterial pressure, white blood cell count, albumin, MELD, ascites, HE, and treatment arm. At baseline, no participants had AKI; 33% (n=49) developed AKI during follow-up. AKI incidence was higher in A+Z than in PRED (45% [n=33] versus 22% [n=16], p =0.001). AKI phenotypes were similar between the 2 treatment arms ( p =0.361), but peak AKI severity was greater in A+Z than PRED (stage 3 n=21 [63.6%] vs. n=8 [50.0%], p =0.035). At baseline, urine-neutrophil-gelatinase-associated lipocalin levels were similar between participants who developed AKI in both treatment arms ( p =0.319). However, day 7 and 14 urine-neutrophil-gelatinase-associated lipocalin levels were significantly elevated in participants treated with A+Z who developed AKI versus participants treated with PRED who developed AKI ( p =0.002 and 0.032, respectively). On multivariable competing risk analysis, only A+Z was independently associated with incident AKI (subdistribution hazard ratio 2.35, p =0.005). CONCLUSIONS: AKI occurred more frequently and was more severe in participants treated with A+Z. A+Z-treated participants with AKI had higher urine-neutrophil-gelatinase-associated lipocalin, suggesting that A+Z maybe nephrotoxic in patients with severe alcohol-associated hepatitis.

Psychiatric disorders in patients with hepatocellular carcinoma: A large US cohort of commercially insured individuals.

BACKGROUND/AIMS: Patients with hepatocellular cancer (HCC) are vulnerable to psychological distress given a new cancer diagnosis superimposed on pre-existing chronic liver disease. We aimed to characterise the psychiatric burden in HCC, risk factors for incident diagnosis and treatment patterns over time. METHODS: Using IQVIA PharMetrics® Plus for Academics-a nationally representative claims database of the commercially insured US population-we identified psychiatric diagnoses and treatment among patients with newly diagnosed HCC. Multivariable logistic regression modelling identified factors associated with psychiatric diagnosis and treatment. RESULTS: Of 11,609 patients with HCC, 2166 (18.6%) had a psychiatric diagnosis after cancer diagnosis with depression (58.3%) and anxiety (53.0%) being most common. Women (aOR 1.33, 95% CI [1.19-1.49]), pre-existing psychiatric diagnoses (aOR 9.12 [8.08-10.3]) and HCC treatment type (transplant: aOR 2.15 [1.66-2.77]; locoregional therapies: aOR 1.74 [1.52-1.99]; hospice: aOR 2.43 [1.79-3.29]) were significantly associated with psychiatric diagnosis. Female sex, ascites, higher comorbidity and treatment type were associated with incident psychiatric diagnosis. Pharmacotherapy was used in 1392 (64.3%) patients with a psychiatric diagnosis, with antidepressants (46.2%) and anxiolytics (32.8%) being most common. Psychiatric diagnoses increased from 14.8% in 2006-2009 to 21.1% in 2018-2021 (p < 0.001). In almost 20% of patients with pre-existing psychiatric conditions, therapy was discontinued after HCC diagnosis. CONCLUSIONS: Nearly 2 of 10 patients with HCC were diagnosed with a psychiatric condition after cancer diagnosis with unique sociodemographic and clinical risk factors identified. This highlights a risk for increased psychological burden in need of early evaluation and treatment among patients with newly diagnosed HCC.

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.

Brief alcohol interventions are underutilized in persons with nonalcohol-associated chronic liver diseases.

BACKGROUND: Brief alcohol interventions use patient-provider communication to promote alcohol cessation. We characterized the receipt of this intervention in chronic liver disease (CLD). METHODS: We surveyed patients with CLD for weekly drinking patterns and examined associations with patient-provider communication receipt. RESULTS: Among 840 participants, 82.1% and 56.5% reported ≥1 standard drink weekly and excessive alcohol consumption, respectively. Patient-provider communication was lower in noncirrhotic (adjusted odds ratio:0.34, 95% CI: 0.22-0.54) and nonalcohol-associated CLD (adjusted odds ratio: 0.22, 95% CI: 0.15-0.34) among individuals drinking ≥1 standard drink weekly, and similarly in noncirrhotic CLD (adjusted odds ratio: 0.45, 95% CI: 0.21-0.95) among those with excessive drinking. CONCLUSIONS: Brief alcohol interventions are underutilized in noncirrhotic and nonalcohol-associated CLD.

Association between bridging therapy and posttransplant outcomes in patients with HCC within Milan criteria: A systematic review and meta-analysis.

Liver transplantation is the curative therapy of choice for patients with early-stage HCC. Locoregional therapies are often employed as a bridge to reduce the risk of waitlist dropout; however, their association with posttransplant outcomes is unclear. We conducted a systematic review using Ovid MEDLINE and EMBASE to identify studies published between database inception and August 2, 2023, which reported posttransplant recurrence-free survival and overall survival among patients transplanted for HCC within Milan criteria, stratified by receipt of bridging therapy. Pooled HRs were calculated for each outcome using the DerSimonian and Laird method for a random-effects model. We identified 38 studies, including 19,671 patients who received and 20,148 patients who did not receive bridging therapy. Bridging therapy was not associated with significant differences in recurrence-free survival (pooled HR: 0.91, 95% CI: 0.77-1.08; I2 =39%) or overall survival (pooled HR: 1.09, 95% CI: 0.95-1.24; I2 =47%). Results were relatively consistent across subgroups, including geographic location and study period. Studies were discordant regarding the differential strength of association by pretreatment tumor burden and pathologic response, but potential benefits of locoregional therapy were mitigated in those who received 3 or more treatments. Adverse events were reported in a minority of studies, but when reported occurred in 6%-15% of the patients. Few studies reported loss to follow-up and most had a risk of residual confounding. Bridging therapy is not associated with improvements in posttransplant recurrence-free or overall survival among patients with HCC within Milan criteria. The risk-benefit ratio of bridging therapy likely differs based on the risk of waitlist dropout.

Racial and ethnic disparities in alcohol-associated liver disease in the United States: A systematic review and meta-analysis.

BACKGROUND: Alcohol-associated liver disease (ALD), encompassing alcohol-associated hepatitis and alcohol-associated cirrhosis, is rising in the United States. Racial and ethnic disparities are evident within ALD; however, the precise nature of these disparities is poorly defined. METHODS: We conducted a search of the PubMed/MEDLINE and EMBASE databases to identify studies published from inception through September 2023 that reported ALD incidence, prevalence, and mortality within the United States, stratified by race and ethnicity. We calculated pooled prevalence and incidence by race and ethnicity, including risk ratios and ORs for ALD pooled prevalence and alcohol-associated hepatitis/alcohol-associated cirrhosis pooled proportions, and OR for ALD mortality using the DerSimonian and Laird method for random-effect models. RESULTS: We identified 25 relevant studies (16 for quantitative meta-analysis), comprising 76,867,544 patients. ALD prevalence was highest in Hispanic (4.5%), followed by White (3.1%) and Black (1.4%) individuals. Pooled risk ratios of ALD prevalence were 1.64 (95% CI: 1.12-2.39) for Hispanic and 0.59 (95% CI: 0.35-0.87) for Black compared to White individuals. Mortality among those with ALD did not significantly differ between White and Hispanic (OR: 1.54, 95% CI: 0.9-2.5; I2=0%), Black (OR: 1.2, 95% CI: 0.8-1.6; I2=0%), or Native American (OR: 2.41, 95% CI: 0.9-2.9) individuals, while there was a significant difference between White and Asian (OR: 0.1; 95% CI: 0.03-0.5) individuals. Most data were cross-sectional and assessed to be of poor or fair quality. CONCLUSIONS: Differences were observed in ALD epidemiology, including higher prevalence among Hispanic and lower prevalence among Black individuals, although there were smaller differences in ALD mortality. Differences in ALD prevalence and prognosis remain poorly defined based on existing data, highlighting a need for higher-quality epidemiological studies in this area.

Early Graft Failure After Living-Donor Liver Transplant.

BACKGROUND: Living-donor liver transplantation (LDLT) has been increasing in the USA. While data exist on longer-term patient and graft outcomes, a contemporary analysis of short-term outcomes is needed. AIM: Evaluate short-term (30-day) graft failure rates and identify predictors associated with these outcomes. METHODS: Adult (≥ 18) LDLT recipients from 01/2004 to 12/2021 were analyzed from the United States Scientific Registry of Transplant Recipients. Graft status at 30 days was assessed with graft failure defined as retransplantation or death. Comparison of continuous and categorical variables was performed and a multivariable logistic regression was used to identify risk factors of early graft failure. RESULTS: During the study period, 4544 LDLTs were performed with a graft failure rate of 3.4% (155) at 30 days. Grafts from male donors (aOR: 0.63, CI 0.44-0.89), right lobe grafts (aOR: 0.40, CI 0.27-0.61), recipients aged > 60 years (aOR: 0.52, CI 0.32-0.86), and higher recipient albumin (aOR: 0.73, CI 0.57-0.93) were associated with superior early graft outcomes, whereas Asian recipient race (vs. White; aOR: 3.75, CI 1.98-7.10) and a history of recipient PVT (aOR: 2.7, CI 1.52-4.78) were associated with inferior outcomes. LDLTs performed during the most recent 2016-2021 period (compared to 2004-2009 and 2010-2015) resulted in significantly superior outcomes (aOR: 0.45, p < 0.001). CONCLUSION: Our study demonstrates that while short-term adult LDLT graft failure is uncommon, there are opportunities for optimizing outcomes by prioritizing right lobe donation, improving candidate nutritional status, and careful pre-transplant risk assessment of candidates with known PVT. Notably, a period effect exists whereby increased LDLT experience in the most recent era correlated with improved outcomes.

Increasing practice and acceptable outcomes of high-MELD living donor liver transplantation in the USA.

Recent deceased-donor allocation changes in the United States may have increased high-Model for End-Stage Liver Disease (MELD) living donor liver transplantation (LDLT); however, outcomes in these patients remain poorly defined. We aimed to examine the impact of the MELD score on LDLT outcomes. Using UNOS data (January 1, 2010-December 31, 2021), LDLT recipients were identified and stratified into low-MELD (<15), intermediate-MELD (15-24), and high-MELD (≥25) groups. We compared outcomes between MELD-stratified LDLT groups and between MELD-stratified LDLT and donation after brain death liver transplantation recipients. We used Kaplan-Meier analysis to compare graft survival rates and multivariable Cox proportional hazards modeling to identify factors associated with graft outcomes. Of 3558 LDLTs, 1605 (45.1%) were low-MELD, 1616 (45.4%) intermediate-MELD, and 337 (9.5%) high-MELD. Over the study period, the annual number of LDLTs increased from 282 to 569, and the proportion of high-MELD LDLTs increased from 3.9% to 7.7%. Graft survival was significantly higher in low-MELD versus high-MELD LDLT recipients (adjusted HR = 1.36, 95% CI: 1.03-1.79); however, 5-year survival exceeded 70.0% in both groups. We observed no significant difference in graft survival between high-MELD LDLT and high-MELD donation after brain death liver transplantation recipients (adjusted HR: 1.25, 95% CI:0.99-1.58), with a 5-year survival of 71.5% and 77.3%, respectively. Low LDLT center volume (<3 LDLTs/year) and recipient life support requirement were both associated with inferior graft outcomes among high-MELD LDLT recipients. While higher MELD scores confer graft failure risk in LDLT, high-MELD LDLT outcomes are acceptable with similar outcomes to MELD-stratified donation after brain death liver transplantation recipients. Future practice guidance should consider the expansion of LDLT recommendations to high-MELD recipients in centers with expertise to help reduce donor shortage.

Hepatocellular Carcinoma Surveillance Patterns and Outcomes in Patients With Cirrhosis.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) surveillance is associated with improved early detection and reduced mortality, although practice patterns and effectiveness vary in clinical practice. We aimed to characterize HCC surveillance patterns in a large, diverse cohort of patients with HCC. METHODS: We conducted a retrospective cohort study of patients diagnosed with HCC between January 2008 and December 2022 at 2 large US health systems. We recorded imaging receipt in the year before HCC diagnosis: ultrasound plus α-fetoprotein (AFP), ultrasound alone, multiphasic contrast-enhanced computed tomography (CT)/magnetic resonance imaging (MRI), and no liver imaging. We used multivariable logistic and Cox regression analysis to compare early tumor detection, curative treatment receipt, and overall survival between surveillance strategies. RESULTS: Among 2028 patients with HCC (46.7% Barcelona Clinic Liver Cancer stage A), 703 (34.7%) had ultrasound plus AFP, 293 (14.5%) had ultrasound alone, 326 (16.1%) had multiphasic CT/MRI, and 706 (34.8%) had no imaging in the year before HCC diagnosis. Over the study period, proportions without imaging were stable, whereas use of CT/MRI increased. Compared with no imaging, CT/MRI and ultrasound plus AFP, but not ultrasound alone, were associated with early stage HCC detection and curative treatment. Compared with ultrasound alone, CT/MRI and ultrasound plus AFP were associated with increased early stage detection. CONCLUSIONS: HCC surveillance patterns vary in clinical practice and are associated with differing clinical outcomes. While awaiting data to determine if CT or MRI surveillance can be performed in a cost-effective manner in selected patients, AFP has a complementary role to ultrasound-based surveillance, supporting its adoption in practice guidelines.

Association between public health policies on alcohol and worldwide cancer, liver disease and cardiovascular disease outcomes.

BACKGROUND & AIMS: The long-term impact of alcohol-related public health policies (PHPs) on disease burden is unclear. We aimed to assess the association between alcohol-related PHPs and alcohol-related health consequences. METHODS: We conducted an ecological multi-national study including 169 countries. We collected data on alcohol-related PHPs from the WHO Global Information System of Alcohol and Health 2010. Data on alcohol-related health consequences between 2010-2019 were obtained from the Global Burden of Disease database. We classified PHPs into five items, including criteria for low, moderate, and strong PHP establishment. We estimated an alcohol preparedness index (API) using multiple correspondence analysis (0 lowest and 100 highest establishment). We estimated an incidence rate ratio (IRR) for outcomes according to API using adjusted multilevel generalized linear models with a Poisson family distribution. RESULTS: The median API in the 169 countries was 54 [IQR 34.9-76.8]. The API was inversely associated with alcohol use disorder (AUD) prevalence (IRR 0.13; 95% CI 0.03-0.60; p = 0.010), alcohol-associated liver disease (ALD) mortality (IRR 0.14; 95% CI 0.03-0.79; p = 0.025), mortality due to neoplasms (IRR 0.09; 95% CI 0.02-0.40; p = 0.002), alcohol-attributable hepatocellular carcinoma (HCC) (IRR 0.13; 95% CI 0.02-0.65; p = 0.014), and cardiovascular diseases (IRR 0.09; 95% CI 0.02-0.41; p = 0.002). The highest associations were observed in the Americas, Africa, and Europe. These associations became stronger over time, and AUD prevalence was significantly lower after 2 years, while ALD mortality and alcohol-attributable HCC incidence decreased after 4 and 8 years from baseline API assessment, respectively (p <0.05). CONCLUSIONS: The API is a valuable instrument to quantify the robustness of alcohol-related PHP establishment. Lower AUD prevalence and lower mortality related to ALD, neoplasms, alcohol-attributable HCC, and cardiovascular diseases were observed in countries with a higher API. Our results encourage the development and strengthening of alcohol-related policies worldwide. IMPACT AND IMPLICATIONS: We first developed an alcohol preparedness index, an instrument to assess the existence of alcohol-related public policies for each country. We then evaluated the long-term association of the country's alcohol preparedness index in 2010 with the burden of chronic liver disease, hepatocellular carcinoma, other neoplasms, and cardiovascular disease. The strengthening of alcohol-related public health policies could impact long-term mortality rates from cardiovascular disease, neoplasms, and liver disease. These conditions are the main contributors to the global burden of disease related to alcohol use. Over time, this association has not only persisted but also grown stronger. Our results expand the preliminary evidence regarding the importance of public health policies in controlling alcohol-related health consequences.

Racial and Ethnic Disparities in Liver Transplantation for Alcohol-associated Liver Diseases in the United States.

BACKGROUND: Emerging data suggest disparities exist in liver transplantation (LT) for alcohol-associated liver disease (ALD). As the incidence of ALD increases, we aimed to characterize recent trends in ALD LT frequency and outcomes, including racial and ethnic disparities. METHODS: Using United Network for Organ Sharing/Organ Procurement and Transplantation Network data (2015 through 2021), we evaluated LT frequency, waitlist mortality, and graft survival among US adults with ALD (alcohol-associated hepatitis [AH] and alcohol-associated cirrhosis [AAC]) stratified by race and ethnicity. We used adjusted competing-risk regression analysis to evaluate waitlist outcomes, Kaplan-Meier analysis to illustrate graft survival, and Cox proportional hazards modeling to identify factors associated with graft survival. RESULTS: There were 1211 AH and 26 526 AAC new LT waitlist additions, with 970 AH and 15 522 AAC LTs performed. Compared with non-Hispanic White patients (NHWs) with AAC, higher hazards of waitlist death were observed for Hispanic (subdistribution hazard ratio [SHR] = 1.23, 95% confidence interval [CI]: 1.16-1.32), Asian (SHR = 1.22, 95% CI:1. 01-1.47), and American Indian/Alaskan Native (SHR = 1.42, 95% CI: 1.15-1.76) candidates. Similarly, significantly higher graft failures were observed in non-Hispanic Black (HR = 1.32, 95% CI: 1.09-1.61) and American Indian/Alaskan Native (HR = 1.65, 95% CI: 1.15-2.38) patients with AAC than NHWs. We did not observe differences in waitlist or post-LT outcomes by race or ethnicity in AH, although analyses were limited by small subgroups. CONCLUSIONS: Significant racial and ethnic disparities exist for ALD LT frequency and outcomes in the United States. Compared with NHWs, racial and ethnic minorities with AAC experience increased risk of waitlist mortality and graft failure. Efforts are needed to identify determinants for LT disparities in ALD that can inform intervention strategies.

Bifidobacteria metabolize lactulose to optimize gut metabolites and prevent systemic infection in patients with liver disease.

Progression of chronic liver disease is precipitated by hepatocyte loss, inflammation and fibrosis. This process results in the loss of critical hepatic functions, increasing morbidity and the risk of infection. Medical interventions that treat complications of hepatic failure, including antibiotic administration for systemic infections and lactulose treatment for hepatic encephalopathy, can impact gut microbiome composition and metabolite production. Here, using shotgun metagenomic sequencing and targeted metabolomic analyses on 847 faecal samples from 262 patients with acute or chronic liver disease, we demonstrate that patients hospitalized for liver disease have reduced microbiome diversity and a paucity of bioactive metabolites, including short-chain fatty acids and bile acid derivatives, that impact immune defences and epithelial barrier integrity. We find that patients treated with the orally administered but non-absorbable disaccharide lactulose have increased densities of intestinal bifidobacteria and reduced incidence of systemic infections and mortality. Bifidobacteria metabolize lactulose, produce high concentrations of acetate and acidify the gut lumen in humans and mice, which, in combination, can reduce the growth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus faecium in vitro. Our studies suggest that lactulose and bifidobacteria serve as a synbiotic to reduce rates of infection in patients with severe liver disease.

Comparing High- and Low-Model for End-Stage Liver Disease Living-Donor Liver Transplantation to Determine Clinical Efficacy: A Systematic Review and Meta-Analysis (CHALICE Study).

INTRODUCTION: Various studies have demonstrated that low-Model for End-Stage Liver Disease (MELD) living-donor liver transplant (LDLT) recipients have better outcomes with improved patient survival than deceased-donor liver transplantation (DDLT) recipients. LDLT recipients gain the most from being transplanted at MELD <25-30; however, some existing data have outlined that LDLT may provide equivalent outcomes in high-MELD and low-MELD patients, although the term "high" MELD is arbitrarily defined in the literature and various cut-off scores are outlined between 20 and 30, although most commonly, the dividing threshold is 25. The aim of this meta-analysis was to compare LDLT in high-MELD with that in low-MELD recipients to determine patient survival and graft survival, as well as perioperative and postoperative complications. METHODS: Following PROSPERO registration CRD-42021261501, a systematic database search was conducted for the published literature between 1990 and 2021 and yielded a total of 10 studies with 2183 LT recipients; 490 were HM-LDLT recipients and 1693 were LM-LDLT recipients. RESULTS: Both groups had comparable mortality at 1, 3 and 5 years post-transplant (5-year HR 1.19; 95% CI 0.79-1.79; p-value 0.40) and graft survival (HR 1.08; 95% CI 0.72, 1.63; p-value 0.71). No differences were observed in the rates of major morbidity, hepatic artery thrombosis, biliary complications, intra-abdominal bleeding, wound infection and rejection; however, the HM-LDLT group had higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. CONCLUSIONS: The high-MELD LDLT group had similar patient and graft survival and morbidities to the low-MELD LDLT group, despite being at higher risk for pulmonary infection, abdominal fluid collection and prolonged ICU stay. The data, primarily sourced from high-volume Asian centers, underscore the feasibility of living donations for liver allografts in high-MELD patients. Given the rising demand for liver allografts, it is sensible to incorporate these insights into U.S. transplant practices.

Biliary atresia and liver transplantation in the United States: A contemporary analysis.

BACKGROUND: Biliary atresia (BA) remains the number one indication for paediatric liver transplantation (LT) worldwide but is an uncommon indication for older LT recipients. The impact of recent donor allocation changes, pervasive organ shortage and evolving LT practices on the BA LT population is unknown. METHODS: We identified patients who underwent LT between January 2010 and December 2021 using the UNOS database. We compared clinical outcomes between patients with BA and those with non-BA cholestatic liver disease. Groups were stratified by age, <12 years (allocated via PELD system) and ≥12 years (allocated via MELD system). Waitlist outcomes were compared using competing-risk regression analysis, graft survival rates were compared using Kaplan-Meier time-to-event analysis and Cox proportional hazards modelling provided adjusted estimates. RESULTS: There were 2754 BA LT waitlist additions and 2206 BA LTs (1937 <12 years [younger], 269 ≥12 years [older]). There were no differences in waitlist mortality between BA and non-BA cholestatic patients. Among BA LT recipients, there were 441 (20.0%) living-donor liver transplantations (LDLT) and 611 (27.7%) split deceased-donor LTs. Five-year graft survival was significantly higher among BA versus non-BA cholestatic patients in the older group (88.3% vs. 79.5%, p < .01) but not younger group (89.3% vs. 89.5%). Among BA LT recipients, improved graft outcomes were associated with LDLT (vs. split LT: HR: 2, 95% CI: 1.03-3.91) and higher transplant volume (volume >100 vs. <40 BA LTs: HR: 3.41, 95% CI: 1.87-6.2). CONCLUSION: Liver transplant outcomes among BA patients are excellent, with LDLT and higher transplant centre volume associated with optimal graft outcomes.

Mortality and Morbidity Among Adult Liver Retransplant Recipients.

BACKGROUND: Liver transplantation (LT) is life-saving procedure for patients with end-stage liver failure with up to 20% of patients suffering graft failure following primary transplantation. Retransplantation (ReLT) remains the only definitive treatment for irreversible graft failure. AIMS: We aimed to explore the postoperative outcomes following liver ReLT. METHODS: Patients who had received a liver transplant between 2003 and 2016 were retrospectively identified using the Scientific Registry of Transplant Recipients (SRTRs). Patients were stratified based on previous liver transplant history. The primary outcomes of this study were 5-year postoperative mortality, morbidity, and length of hospital stay following LT. RESULTS: 60,554 (96%) recipients were first LT recipients and 2524 (4%) were ReLT recipients. Compared with first LT, ReLT recipients had significantly higher rates of mortality (OR 1.93, 95%CI 1.76-2.12), overall morbidity (OR 1.80, 95%CI 1.65-1.96), and prolonged length of stay (OR 1.66, 95%CI 1.52-1.81) on multivariate analysis. Morbidity including cardiovascular (CVD) complications (OR 1.32, 95%CI 1.08-1.60), graft failure (OR 2.18, 95%CI 1.84-2.57), infection (OR 2.13, 95%CI 1.82-2.50), and hemorrhage (OR 2.67, 95%CI 2.00-3.61) were significantly greater in ReLT recipients. Compared to first LT, ReLT patients had a significant increase in overall 5-year mortality (p < 0.001), 5-year mortality due to CVD complications (p < 0.001), infection (p = 0.009), but not graft failure (p = 0.3543). CONCLUSION: ReLT is associated with higher rates of 5-year mortality, overall morbidity, CVD morbidity, infection, and graft failure. Higher 5-year mortality in ReLT is due to CVD and infections. These results could be used in preoperative patient assessment and prognostic counseling for ReLT.

Treatment of Mental Health in Patients With Chronic Liver Disease.

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