Izzy, Manhal

Background: Hepatorenal syndrome–acute kidney injury (HRS-AKI) is associated with high mortality in cirrhosis. Recent FDA approval of terlipressin and updated clinical guidance have expanded management options, but real-world practice patterns remain unknown. Methods: We conducted a nationwide survey of U.S. hepatology providers regarding HRS-AKI management practices. The 33-question survey assessed provider demographics, vasoconstrictor selection, treatment timing, and adherence to guideline recommendations. Results: Among 162 respondents, most were hepatologists (94%) at academic centers (83%). Only 11% obtained a nephrology consultation at AKI detection, with 44% waiting until worsening renal function. Terlipressin was available at 80% of institutions but more commonly at academic centers (84% vs. 53%, p =0.003). Consistent with guideline recommendations, 77% of providers initiate vasoconstrictors only after completing a trial of volume expansion (if no renal improvement), particularly in academic centers (80% vs. 60% non-academic, p =0.03). Terlipressin (49%) and midodrine/octreotide (44%) were preferred first-line treatments, with providers at academic centers more likely to use midodrine/octreotide (46% vs. 30%, p =0.008). Mean arterial pressure was used by 62% of providers to guide vasoconstrictor dosing. Most providers (73%) discontinued vasoconstrictor treatment after 4 days if no improvement. Conclusions: Significant variations exist between guideline recommendations and real-world HRS-AKI management, especially first-line treatment choice, treatment monitoring, and nephrology consultation. These findings highlight opportunities to improve guideline implementation and identify areas where practice patterns might inform provider education and future guidance updates.

Acute-on-chronic liver failure (ACLF) has been associated with excellent post-liver transplant (LT) outcomes at 1 year; however, the impact of alcohol as ACLF precipitant, specifically alcohol-associated hepatitis (AH), and as etiology of chronic liver disease remains uncertain. This study aimed to assess the effect of alcohol as ACLF precipitant and chronic liver disease etiology (alcohol-associated liver disease vs. non–alcohol-associated liver disease) on posttransplant outcomes. We performed a retrospective study using the Multi-Organ Dysfunction and Evaluation for LT Consortium database and included 640 patients with ACLF who underwent LT across 15 transplant centers in North America. The primary outcome was 1-year posttransplant survival. We used logistic regression and Cox proportional hazards to compare posttransplant survival, mortality risk, and health care utilization, adjusting for age, ACLF grade, comorbid diabetes mellitus, chronic kidney disease, and HCC. The median follow-up from LT was 2.8 years (P25–P75, 2.2–5.5 y) for patients with AH-ACLF (n=42) and 3.1 years (P25–P75, 1.6–4.9 y) for patients without AH (n=598). No significant difference was observed in 1-year survival after LT in patients with AH-ACLF versus those without AH ( p =0.36). Patients with AH had significantly higher health care utilization evidenced by greater length of stay (28.5 vs. 19.0 d, p =0.004; adjusted linear estimate 16.89, 95% CI: 7.66–26.11, p <0.001), higher rates of rehabilitation placement (71.4% vs. 41.8%, p =0.002; adjusted odds ratio: 4.13, 95% CI: 2.04–8.89, p <0.001), and non-ambulatory status (39.0% vs. 21.0%, p =0.005; adjusted odds ratio: 4.54, 95% CI: 1.90–10.79, p <0.001). Compared with other etiologies, alcohol-associated liver disease was not associated with differences in 1-year mortality, mortality risk over time, or health care utilization, after excluding patients with AH as ACLF precipitant. While there were no differences in 1-year survival, AH-ACLF was associated with higher health care resource utilization compared with other ACLF precipitants. LT centers should ensure adequate resources are allocated for the management of these patients.

ABSTRACT Introduction Although liver transplantation (LT) rates have increased globally, the demand for organs still exceeds the supply. This review highlights cultures with significant influences on organ donation and LT. Methods We performed a literature search for articles related to cultures, ethnologies, philosophies, policies, religions, socio‐economic factors, and other influences affecting organ donation in LT around the world. Results There are astonishing similarities between different cultures. In Africa, Asia, and Europe, people often view the postmortem bodies as sacred and believe that their bodies are gifts from “God” or ancestors. To respect the gift of life, to have a chance in reincarnation, or to enjoy life after death, many believe that their bodily sanctity must be preserved. In Asia, Europe, and Latin America, there is a general reluctance to speak about death. Religions also play an important role in people's views on organ donation. Different regions around the world have similar challenges to organ donation, such as misconceptions about organ trafficking, political and economic instability, and a lack of governmental or religious support. Conclusion Addressing the complexities of organ donation and LT requires a multifaceted approach. Culturally sensitive education tailored to diverse communities can dispel myths and misconceptions surrounding organ donation. Fostering partnerships between healthcare providers, religious leaders, community organizations, and policymakers can further facilitate open dialogues and promote organ donation as a noble act to save lives. Social Media Similar cultures around the world post challenges for organ donation. Organizations should foster partnerships between healthcare providers, politicians, and religious leaders to promote donation.

Goals: Our aim was to perform a national survey of provider attitudes, practices, and knowledge regarding weight loss and MASLD medications in patients with MASLD. Background: While weight loss is a cornerstone in the management of metabolic dysfunction-associated steatotic liver disease (MASLD), FDA-approved medications for weight loss remain underutilized. Results: We conducted a survey before resmetirom approval of hepatology and gastroenterology providers practicing in 44 states. Surveys were sent to 747 providers with 304 complete responses (41%), of whom 260 (86%) work at a liver transplant center. While nearly all respondents (96%) believed that weight loss medications could benefit patients with MASLD, 77% have never/rarely prescribed them due to low comfort (81%). Among weight loss medication prescribers, glucagon-like peptide-1 (GLP-1) receptor agonists were preferred (66%). In contrast, 63% had prescribed off-label medications for MASLD in the past 12 months, most commonly vitamin E (30%) and GLP-1 receptor agonists (25%). The top reported barriers to prescribing weight loss medications were lack of training/unfamiliarity, cost/insurance coverage, and side-effects, which may be explained by low formal obesity education and lack of knowledge (only 33% of FDA-approved medications for weight loss were correctly identified by >50% of providers). Overall, there was reasonable provider-reported adherence to the 2023 AASLD practice guidance for MASLD. Conclusions: This nationwide survey of hepatology and gastroenterology providers before resmetirom demonstrates that while off-label prescribing for MASLD was common, weight loss medication prescription rates remain very low due to low comfort possibly from insufficient education despite strong beliefs that they can benefit patients with MASLD.

Hepatorenal syndrome-acute kidney injury (HRS-AKI) is associated with significant morbidity and mortality. While liver transplantation is the definitive treatment, continuous terlipressin infusion for HRS-AKI may provide benefit and, as such, was assessed in a population composed of candidates for liver transplant (LT). Fifty hospitalized LT-eligible patients with HRS-AKI received a single bolus followed by continuous terlipressin infusion. Acute-on-chronic liver failure grade 3, serum creatinine (SCr)>5.0 mg/dL, or Model for End-Stage Liver Disease (MELD) ≥35 were exclusions. Fifty hospitalized patients who received midodrine and octreotide or norepinephrine for HRS-AKI served as a historical comparator cohort. Complete response (CR) was defined as a ≥30% decrease in SCr with end-of-treatment (EOT) SCr≤1.5, partial response as a ≥30% decrease in SCr with EOT SCr>1.5, and nonresponse as a <30% decrease in SCr. CR rate was significantly higher in the terlipressin cohort compared to the historical cohort (64% vs. 16%, p<0.001). Survival, while numerically higher in those who received terlipressin, was statistically similar (D30: 94% vs. 82%, p=0.12; D90: 78% vs. 68%, p=0.37). Renal replacement therapy (RRT) was more common among terlipressin NR than CR and PR (70% vs. 3% vs. 13%, p < 0.001). EOT MELD and SCr were significantly lower within terlipressin cohort (MELD: 19 vs. 25, SCr: 1.4 vs. 2.1 mg/dL, p<0.001). Sixteen of 40 terlipressin-treated patients received LT-alone (terlipressin CR in 10/16). One patient on terlipressin had a hypoxic respiratory failure that responded to diuretics; one possibly had drug-related rash. With continuous terlipressin infusion, a CR rate of 64% was observed with a favorable safety profile. Terlipressin use was associated with lower EOT MELD and SCr than the historical midodrine and octreotide/norepinephrine cohort; LT-alone was accomplished in a high proportion of complete terlipressin responders.

Cardiovascular disease (CVD) is a leading complication after liver transplantation and has a significant impact on patients’ outcomes posttransplant. The major risk factors for post–liver transplant CVD are age, preexisting CVD, nonalcoholic fatty liver disease, chronic kidney disease, and metabolic syndrome. This review explores the contemporary strategies and approaches to minimizing cardiometabolic disease burden in liver transplant recipients. We highlight areas for potential intervention to reduce the mortality of patients with metabolic syndrome and CVD after liver transplantation.

Post‐transplant diabetes mellitus (PTDM) is a significant contributor to morbidity and mortality in liver transplant recipients (LTRs). With concurrent comorbidities and use of various immunosuppression medications, identifying a safe and personalized regimen for management of PTDM is needed. There are many comorbidities associated with the post‐transplant course including chronic kidney disease, cardiovascular disease, allograft steatosis, obesity, and de novo malignancy. Emerging data suggest that available diabetes medications may carry beneficial or, in some cases, harmful effects in the setting of these co‐existing conditions. Sodium‐glucose co‐transporter 2 inhibitors and glucagon‐like peptide 1 receptor agonists have shown the most promising beneficial results. Although there is a deficiency of LTR‐specific data, they appear to be generally safe. Effects of other medications are varied. Metformin may reduce the risk of malignancy. Pioglitazone may be harmful in patients combatting obesity or heart failure. Insulin may exacerbate obesity and increase the risk of developing malignancy. This review thoroughly discusses the roles of these extra‐glycemic effects and safety considerations in LTRs. Through weighing the risks and benefits, we conclude that alternatives to insulin should be strongly considered, when feasible, for personalized long‐term management based on risk factors and co‐morbidities.

AbstractBackground & AimsGlycogenic hepatopathy (GH) in type 1 diabetes‐mellitus (T1DM) is characterized by hepatomegaly and perturbations of liver chemistries (LC) that have not been well studied. Furthermore, misdiagnosis with other hepatic complications of T1DM, such as nonalcoholic fatty liver disease, has been described. We perform a systematic review of biopsy‐proven GH reports in T1DM patients to identify LC patterns.MethodsA systematic review identified reports of biopsy‐proven GH in patients with T1DM. We excluded GH with other liver diseases, Mauriac syndrome, or GH without T1DM. Two reviewers screened and extracted studies and assessed their methodological quality. LC elevation magnitude, AST‐to‐ALT ratio, R‐ratio to designate hepatocellular, cholestatic or mixed pattern of hepatic injury, and evolution of transaminases after glycemic control were analyzed.ResultsA total of 192 patients were included, with median age of 20 years, 73% adults, 66% females, median duration of T1DM before diagnosis 10 years, median adult body mass index 21 kg/m2, median HbA1c 12%, at least one episode of diabetic ketoacidosis 70%, and hepatomegaly 92%. ALT and AST showed moderate‐to‐severe elevation in 78% and 76%, respectively, AST/ALT >1 in 71% and hepatocellular to mixed pattern of hepatic injury in 81%. Transaminase improvement with glycemic control was the rule, regardless of other factors in multilinear regression analysis.ConclusionGH tends to have AST‐predominant elevation with a median of 13 times the upper normal limit and R‐ratio >2, which may distinguish it from other etiologies of AST‐predominant LC elevation, and in the appropriate clinical context, may obviate invasive tests.