Closing the Care Gap: Management of Alcohol Use Disorder in Patients with Alcohol-associated Liver Disease.

Alcohol-associated liver disease (ALD)-related morbidity and mortality are rising in the United States. Although effective medications and behavioral interventions are available for the treatment of patients with alcohol use disorder (AUD), patients with ALD are profoundly undertreated for AUD. This article reviews the management of AUD in patients with ALD, with a focus on appropriate screening and diagnosis, management of alcohol withdrawal syndrome, pharmacotherapy for AUD, alcohol biomarkers, and behavioral interventions. Expanding access to AUD treatment is imperative for improving health outcomes in patients with ALD.

Patients With Acute-on-Chronic Liver Failure Have Greater Healthcare Resource Utilization After Liver Transplantation.

BACKGROUND & AIMS: Although liver transplantation (LT) has been demonstrated to provide survival benefit for patients with acute-on-chronic liver failure (ACLF), data are lacking regarding resource utilization for this population after LT. METHODS: We retrospectively reviewed data from 10 centers in North America of patients transplanted between 2018 and 2019. ACLF was identified by using the European Association for the Study of the Liver-Chronic Liver Failure criteria. RESULTS: We studied 318 patients of whom 106 patients (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Healthcare resource utilization after LT was greater among recipients with ACLF compared with patients without ACLF regarding median post-LT length of hospital stay (LOS) (P < .001), length of post-LT dialysis (P < .001), discharge to a rehabilitation center (P < .001), and 30-day readmission rates (P = .042). Multivariable negative binomial regression analysis demonstrated a significantly longer LOS for patients with ACLF-1 (1.9 days; 95% confidence interval [CI], 0.82-7.51), ACLF-2 (6.7 days; 95% CI, 2.5-24.3), and ACLF-3 (19.3 days; 95% CI, 1.2-39.7), compared with recipients without ACLF. Presence of ACLF-3 at LT was also associated with longer length of dialysis after LT (9.7 days; 95% CI, 4.6-48.8) relative to lower grades. Multivariable logistic regression analysis revealed greater likelihood of discharge to a rehabilitation center among recipients with ACLF-1 (odds ratio [OR], 1.79; 95% CI, 1.09-4.54), ACLF-2 (OR, 2.23; 95% CI, 1.12-5.01), and ACLF-3 (OR, 2.23; 95% CI, 1.40-5.73). Development of bacterial infection after LT also predicted LOS (20.9 days; 95% CI, 6.1-38.5) and 30-day readmissions (OR, 1.39; 95% CI, 1.17-2.25). CONCLUSIONS: Patients with ACLF at LT, particularly ACLF-3, have greater post-transplant healthcare resource utilization.

Diagnosis and management of hepatic encephalopathy: A summary for patients.

Content available: Author Interview and Audio Recording.

Risk Factors for Posttransplantation Mortality in Recipients With Grade 3 Acute-on-Chronic Liver Failure: Analysis of a North American Consortium.

Although liver transplantation (LT) yields survival benefit for patients with acute-on-chronic liver failure grade 3 (ACLF-3), knowledge gaps remain regarding risk factors for post-LT mortality. We retrospectively reviewed data from 10 centers in the United States and Canada for patients transplanted between 2018 and 2019 and who required care in the intensive care unit prior to LT. ACLF was identified using the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) criteria. A total of 318 patients were studied, of whom 106 (33.3%) had no ACLF, 61 (19.1%) had ACLF-1, 74 (23.2%) had ACLF-2, and 77 (24.2%) had ACLF-3 at transplantation. Survival probability 1 year after LT was significantly higher in patients without ACLF (94.3%) compared with patients with ACLF (87.3%; P = 0.02), but similar between ACLF-1 (88.5%), ACLF-2 (87.8%), and ACLF-3 (85.7%; P = 0.26). Recipients with ACLF-3 and circulatory failure (n = 29) had similar 1-year post-LT survival (82.3%) compared with patients with ACLF-3 without circulatory failure (89.6%; P = 0.32), including those requiring multiple vasopressors. For patients transplanted with ACLF-3 including respiratory failure (n = 20), there was a trend toward significantly lower post-LT survival (P =  0.07) among those with respiratory failure (74.1%) compared with those without (91.0%). The presence of portal vein thrombosis (PVT) at LT for patients with ACLF-3 (n = 15), however, yielded significantly lower survival (91.9% versus 57.1%; P < 0.001). Multivariable logistic regression analysis revealed that PVT was significantly associated with post-LT mortality within 1 year (odds ratio, 7.3; 95% confidence interval, 1.9-28.3). No correlation was found between survival after LT and the location or extent of PVT, presence of transjugular intrahepatic portosystemic shunt, or anticoagulation. LT in patients with ACLF-3 requiring vasopressors yields excellent 1-year survival. LT should be approached cautiously among candidates with ACLF-3 and PVT.

EGFR transactivates RON to drive oncogenic crosstalk.

Crosstalk between different receptor tyrosine kinases (RTKs) is thought to drive oncogenic signaling and allow therapeutic escape. EGFR and RON are two such RTKs from different subfamilies, which engage in crosstalk through unknown mechanisms. We combined high-resolution imaging with biochemical and mutational studies to ask how EGFR and RON communicate. EGF stimulation promotes EGFR-dependent phosphorylation of RON, but ligand stimulation of RON does not trigger EGFR phosphorylation - arguing that crosstalk is unidirectional. Nanoscale imaging reveals association of EGFR and RON in common plasma membrane microdomains. Two-color single particle tracking captured formation of complexes between RON and EGF-bound EGFR. Our results further show that RON is a substrate for EGFR kinase, and that transactivation of RON requires formation of a signaling competent EGFR dimer. These results support a role for direct EGFR/RON interactions in propagating crosstalk, such that EGF-stimulated EGFR phosphorylates RON to activate RON-directed signaling.

Treatment and Prevention of Acute Hepatitis B Virus.

This article reviews the incidence of acute hepatitis B virus (HBV) infection, its clinical course, strategies to prevent acute HBV infection in susceptible individuals, and the management of patients with acute HBV.

Multidisciplinary Team Management of Hepatocellular Carcinoma Is Standard of Care.

Hepatocellular carcinoma (HCC) is a leading cause of cancer mortality, but unlike other leading causes of cancer death, HCC is increasing in mortality and burden of management. Management of HCC is unique because it usually arises in a diseased liver, which itself may be a driver of mortality. Multidisciplinary teams (MDTs) for the management of complex diseases are becoming more common, but are especially needed in the management of patients with HCC. Liver cancer MDTs are used in most centers providing comprehensive care for patients with HCC, and should be considered the standard of care for these patients.