Legionnaires\' disease is an atypical pneumonia caused by Legionella pneumophila. Legionella species are found in freshwater sources and are transmitted through inhalation of contaminated aerosols. Patients commonly present with fever, chills, and cough. However, in immunosuppressed patients or severe cases, the disease can lead to multiorgan failure. In recent years, the incidence of Legionnaires\' disease has drastically increased and unfortunately is commonly underdiagnosed. Gold-standard diagnosis is made through sputum cultures; however, urine Legionella antigen remains the most common test used for diagnosis. Goal-directed care includes antibiotics and supportive care. This case highlights a rare and unique presentation of Legionnaires\' disease presenting with an elevated 2:1 aspartate aminotransferase to alanine transaminase pattern, typically seen with alcoholic hepatitis.

Liver transplantation (LT) has significantly transformed the prognosis of patients with end-stage liver disease and hepatocellular carcinoma (HCC). The traditional epidemiology of liver diseases has undergone a remarkable shift in indications for LT, marked by a decline in viral hepatitis and an increase in metabolic dysfunction-associated steatotic liver disease (MASLD), along with expanded indications for HCC. Recent advancements in surgical techniques, organ preservation and post-transplant patients\' management have opened new possibilities for LT. Conditions that were historically considered absolute contraindications have emerged as potential new indications, demonstrating promising results in terms of patient survival. While these expanding indications provide newfound hope, the ethical dilemma of organ scarcity persists. Addressing this requires careful consideration and international collaboration to ensure equitable access to LT. Multidisciplinary approaches and ongoing research efforts are crucial to navigate the evolving landscape of LT. This review aims to offer a current overview of the primary emerging indications for LT, focusing on acute-on-chronic liver failure (ACLF), acute alcoholic hepatitis (AH), intrahepatic and perihilar cholangiocarcinoma (i- and p-CCA), colorectal liver metastasis (CRLM), and neuroendocrine tumor (NET) liver metastases.

Zieve\'s syndrome is an underdiagnosed condition characterized by the triad of jaundice, hemolytic anemia, and hyperlipidemia in the setting of chronic alcohol use. It may be accompanied by acute alcoholic hepatitis. The distinction between the coexistence of acute alcoholic hepatitis with Zieve\'s syndrome and Zieve\'s syndrome in isolation is crucial, given the different treatments and prognoses in these situations. A 35-year-old woman presented with complaints of abdominal discomfort, nausea, and vomiting in the previous week. She was a heavy drinker with resultant cirrhosis, splenomegaly, and esophageal varices. An ancillary test showed hemolytic anemia, moderately elevated transaminases, hyperbilirubinemia, and coagulopathy. A negative direct Coombs test established the anemia as non-immune, supporting the diagnosis of Zieve\'s syndrome despite the absence of hyperlipidemia. Maddrey\'s discriminant function score was 92 points, so she was treated with supportive measures, as well as corticosteroids in the setting of acute alcoholic hepatitis. The patient showed a favorable clinical and analytical evolution and was discharged home one month following admission with her hemoglobin levels stabilized. Previous literature focused on the distinction between Zieve\'s syndrome and acute alcoholic hepatitis but they may coexist.

GCSF may improve the prognosis of severe liver disease by promoting liver regeneration and immune restoration. Our Aim was to investigate its controversial efficacy in decompensated cirrhosis, acute alcoholic hepatitis (AAH), or acute-on-chronic liver failure (ACLF) through meta-analysis.
Meta-analysis of proportions (random effect model) including 19 RCTs (1287 patients from 16 Asian and 3 European studies including 487 ACLF, 231 AAH and 569 cirrhotic patients) evaluating survival at day-28, day-90, 6 months, one year, and/or occurrence of sepsis as major outcomes.
In patients with decompensated cirrhosis, G-CSF administration was associated with a reduction in the weight-adjusted risk of mortality of 9% at day-90 (OR=0.33; 95%CI: 0.18-0.58; p = 0.0002), 16% at 6 months (OR=0.31; 95%CI: 0.15-0.62; p = 0.0009), 26% at one year (OR=0.21; 95%CI:0.12-0.38, p<0.0001) and a weight-adjusted 28% risk reduction for sepsis (OR=0.28; 95%CI: 0.16-0.49; p<0.0001). Only Asian studies were positive. In AAH, G-CSF was associated with an 18% reduction in weight-adjusted mortality risk at day-28 (OR=0.31; 95%CI:0.11-0.83, p = 0.021), 32% at day-90 (OR=0.20; 95%CI:0.09-0.46, p<0.0001) and a weight-adjusted 42% risk reduction for sepsis (OR=0.17; 95%CI: 0.08-0.38; p<0.0001). Only Asian studies, in which corticosteroids were not given systematically in case of severe AAH, were positive. In patients with ACLF, the results on mortality at day-28 were heterogeneous, and GCSF had no beneficial effect on sepsis or survival at day-90.
G-CSF may be effective in patients with decompensated cirrhosis or AAH by reducing the occurrence of sepsis and mortality. Further meta-analyses of individual data, or new, powerful and methodologically flawless therapeutic trials, are warranted to confirm these results, which harbor wide divergences between Asian and European RCTs.

Alcoholic liver disease (ALD) is a common pathology in clinical practice and is clinically diverse. Acute alcoholic hepatitis is an acute inflammation of the liver with or without underlying cholestasis and steatosis. In this case, we are presenting a 36-year-old male with a past medical history of alcohol use disorder who presented with two weeks of right upper quadrant abdominal pain and jaundice. However, direct/conjugated hyperbilirubinemia with relatively low aminotransferases in labs prompted investigation for obstructive and autoimmune hepatic pathologies. Unrevealing investigations prompted consideration of acute alcoholic hepatitis with cholestasis and a course of oral corticosteroids that gradually improved the patient\'s clinical symptoms and liver function test. This case helps to remind clinicians that although ALD is usually associated with indirect/unconjugated hyperbilirubinemia and elevated aminotransferases, presentation of ALD with mainly direct/conjugated hyperbilirubinemia with relatively low aminotransferases is a possibility. Although imaging tests should be pursued to rule out obstructive etiologies, invasive tests and liver biopsies are not indicated in typical clinical settings.

Anomalies of the inferior vena cava (IVC) are an uncommon finding in the general population. A wide range of IVC anomalies has been described in the literature, the majority of which lack clinical significance. Agenesis of the IVC (AIVC) is a rare anomaly of the IVC in the general population. This anomaly may involve either complete agenesis of the IVC or agenesis of a segment of the IVC. Agenesis of the suprarenal segment is the most commonly occurring variant, while agenesis of the infrarenal and hepatic segments is less common. Here we report a case of agenesis of the intrahepatic segment of the IVC.

UNASSIGNED: Severe acute alcoholic hepatitis (AAH) has an extremely poor prognosis with a high short term mortality rate. As a result, many centers, including our own, have allowed transplant patients to be listed for transplantation prior to achieving 6-months of sobriety. Several scoring systems, designed to target patients with a minimal period of sobriety, have been proposed to identify patients with alcohol use disorder (AUD), who would be predisposed to relapse after liver transplantation. We investigated whether these scoring systems corroborated the results of the non-structured selection criteria used by our center regarding decision to list for transplant.
UNASSIGNED: We conducted a retrospective case-control study of 11 patients who underwent early liver transplantation for AAH matched with 11 controls who were declined secondary to low insight into AUD. Blinded raters confirmed the severity of the diagnosis of DSM-5 and scored the patients on a variety of structured psychometric scales used to predict alcohol relapse. These included the High Risk for Alcohol Relapse Scale (HRAR), Stanford Integrated Psychosocial Assessment Tool (SIPAT), Alcohol Relapse Risk Assessment (ARRA), Hopkins Psychosocial Scale (HPSS), Michigan Alcoholism Prognosis Score (MAPS), Alcohol Use Disorders Identification Test -Consumption (AUDIT-C), and Sustained Alcohol Use Post-Liver Transplant (SALT) scales. All patients who underwent transplantation were followed for harmful and non-harmful drinking until the end of the study period.
UNASSIGNED: The transplant recipients had significantly favorable MAPS, HRAR, SIPAT, ARRA, and HPSS scores with cutoffs that matched their previous research. The SALT and AUDIT-C scores were not predictive of our selection of patients for transplantation. Despite an expedited evaluation and no significant period of sobriety, our case cohort had a 30% relapse to harmful drinking after an average of 6.6 years (5-8.5 years) of follow-up.
UNASSIGNED: Despite the rapid assessment and the short to no period of sobriety, the patient cohort demonstrated a 30% relapse to harmful drinking, consistent with the 20% to 30% relapse to drinking rate reported after liver transplantation for all forms of alcoholic liver disease. Average scores from MAPS, HRAR, SIPAT, ARRA, and HPSS corroborated our current stratification procedures, with lower mean risk scores found in the transplanted group.
UNASSIGNED: Patients with AUD and severe AAH who obtain new insight into their disease and posses other favorable psychosocial factors have low rates of AUD relapse post-liver-transplantation. The psychosocial selection criteria for patients with alcoholic hepatitis in our institution are consistent with 4 of the 5 scoring systems investigated in their prediction of sobriety post-transplant.

BACKGROUND: Alcohol-associated liver disease is the leading cause of liver transplantation in the western world. For these patients we calculated life expectancies both at time of transplant and several years later, stratified by key risk factors, and determined if survival has improved in recent years.
METHODS: Data on 14 962 patients with alcohol-associated liver disease who underwent liver transplantation in the MELD era (2002-2018) from the United States Organ Procurement and Transplantation Network database were analyzed using the Cox proportional hazards regression model and life table methods.
RESULTS: Demographic and past medical history factors related to survival were patient age, presence of diabetes or severe hepatic encephalopathy, and length of hospital stay. Survival improved over the study period, at roughly 3% per calendar year during the first 5 years posttransplant and 1% per year thereafter.
CONCLUSIONS: Life expectancy in transplanted patients with alcohol-associated liver disease was much reduced from normal, and varied according to age, medical risk factors, and functional status. Survival improved modestly over the study period. Information on patient longevity can be helpful in making treatment decisions.

A 69-year-old man was admitted to Hanawa Kousei Hospital with acute hepatitis attributed to alcohol consumption. His condition improved with conservative treatment. Computed tomography (CT) showed localized thickening of the colonic wall at the splenic flexure;carcinoembryonic antigen level was slightly elevated to 9.7 ng/mL. Colonoscopy (CS) showed an ulcerative lesion in the colonic splenic flexure. Ischemic colitis (IC) and type 4 colon cancer were suspected, but biopsy was not confirmatory. Malignancy could not be ruled out by contrast-enhanced CT;repeat CS showed circumferential stenosis of the colonic splenic flexure. Ischemic colitis was suspected based on changes between the first and second CS. Biopsy histopathology led us to diagnose stricture-type IC. Constipation, but not intestinal obstruction, occurred. Conservative treatment improved the stenosis. Excessive alcohol consumption may lead to IC;imaging studies may be useful to distinguish IC from colon cancer. Since most cases of ischemic colitis can be improved with conservative treatment, patients with stricture-type ischemic colitis may also be treated without surgery early on, with follow-up that includes careful, periodic imaging.

Impaired immune responses and increased susceptibility to infection characterize acute inflammatory conditions such as pancreatitis and alcoholic hepatitis and are major causes of morbidity and mortality. However, the mechanisms that drive this apparent immune paresis remain poorly understood. Monocytes mediate host responses to damage and pathogens in health and disease, and three subsets of monocytes have been defined based on CD14 and CD16 expression. We sought to determine the changes in monocyte subsets in acute pancreatitis (AP) and acute alcoholic hepatitis (AAH), together with functional consequences and mechanisms that underlie this change. Peripheral blood mononuclear cells (PBMCs) from patients with AP or AAH were compared with healthy controls. Monocyte subsets were defined by HLA-DR, CD14, and CD16 expression. Changes in surface and intracellular protein expression and phosphorylation were determined by flow cytometry. Phenotype and function were assessed following stimulation with lipopolysaccharide (LPS) or other agonists in the presence of specific inhibitors of TNFα and a disintegrin and metalloproteinase 17 (ADAM17). Patients with AP and AAH had reduced CD14++CD16+ intermediate monocytes compared to controls. Reduction of intermediate monocytes was recapitulated ex vivo by stimulating healthy control PBMCs with Toll-like receptor (TLR) agonists LPS, flagellin or polyinosilic:polycytidylic acid (poly I:C). Stimulation caused shedding of CD14 and CD16, which could be reversed using the ADAM17 inhibitor, TMI005 but not direct inhibitors of TNFα, a known ADAM17-target. Culturing PBMCs from healthy controls resulted in expansion of intermediate monocytes, which did not occur when LPS was in the culture medium. Cultured intermediate monocytes showed reduced expression of CX3CR1, CCR2, TLR4, and TLR5. We found reduced migratory responses, intracellular signaling and pro-inflammatory cytokine production, and increased expression of IL-10. Stimulation with TLR agonists results in ADAM17-mediated shedding of phenotypic markers from CD16+ monocytes, leading to apparent \"loss\" of intermediate monocytes. Reduction in CD14++CD16- monocytes and increased CD14++CD16+ is associated with altered responses in functional assays ex vivo. Patients with AP and AAH had reduced proportions of CD14++CD16+ monocytes and reduced phosphorylation of NFκB and IL-6 production in response to bacterial LPS. Together, these processes may contribute to the susceptibility to infection observed in AP and AAH.