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.

Although sex-based disparities in the liver transplantation (LT) setting have been acknowledged for several years, particularly by studies conducted in the USA, data from European countries are scarce. We conducted a nationwide, retrospective, observational study on candidates identified for LT in Italy between January 2017 and December 2021 using national registry data with follow-up until June 2023. The primary aim was to assess sex-based differences in LT access, analyzing delisting, retransplantation, and mortality rates. Patients were monitored from waitlist admission to transplant, removal, or death, with competing risks modeled (Fine and Gray) multivariable analysis. Survival outcomes were evaluated using Kaplan–Meier estimates, time-dependent Cox models, and stratified log-rank tests. In total, 7,563 patients were included in the analysis, 5,575 (73.7%) of whom were men. Men had higher 1- and 2-year probabilities of undergoing LT compared with women for both liver cirrhosis (subdistribution hazard ratio [sHR] 1.13, 95% CI 1.02–1.26, p = 0.02 and sHR 1.12, 95% CI 1.01–1.24, p = 0.03, respectively) and hepatocellular carcinoma (HCC) (sHR 1.20, 95% CI 1.07–1.36, p = 0.003 and sHR 1.21, 95% CI 1.08–1.35, p = 0.001, respectively). The wait list (WL) dropout rate in men did not differ significantly to that for women (12.6% vs. 13.9%, p = 0.14) except when the indication to LT was HCC (10.6% vs. 14.2%, p = 0.035). In addition, men had a lower wait list (WL) mortality rate compared with women (7.0% vs. 8.5%, p = 0.04). Post-LT survival rates were similar for both sexes. In this large Italian cohort, female standard allocation patients appeared to be at a disadvantage compared with men, because they received LT less frequently, but with similar post-LT outcomes. Although sex-based disparities in the LT setting have been acknowledged for several years, particularly in studies conducted in the USA, few data are available in Europe. Our study provides an exhaustive overview regarding the disadvantage facing women outside the USA in accessing LT. By detailing these differences, it provides solid arguments for developing equitable health policy. Given that these differences are affected by the national scenario, having local data is crucial for defining possible targeted actions.

Background and Objective: Drug-induced liver injury (DILI) is increasingly becoming a cause of acute hepatitis. The study evaluated the role of liver-specific microRNAs (miRNAs) and keratin-18 (K-18) markers M30 (apoptosis) and M65 (necrosis) as biomarkers of acute hepatitis. Methods: Sixty-eight patients were sub-grouped as DILI, HBV- and alcohol-related acute hepatitis. Five healthy controls were included. The expression of plasma miR-21-5p, miR-34a-5p and miR-122-5p was evaluated by RT-qPCR analysis using healthy volunteers as reference. M30 and M65 were determined with ELISA kits. Results: All markers were significantly higher in the acute liver disease patients compared to controls. In DILI, miRNA levels positively correlated with M30, M65 and ALT. miR-122-5p had the highest AUC of 0.73, sensitivity of 76.2 and specificity of 72.2 in identifying DILI from other groups. Patients with hepatocellular-pattern DILI showed higher miR-122-5p and miR-21-5p compared to patients with cholestatic or mixed pattern. A new score to discriminate DILI versus other causes of acute hepatitis was developed using the identified risk factors as follows: 0.012 × miR-34a-5p + 0.012 × miR-122-5p − 0.001 × M30 + 2.642 × 1 (if mixed pattern) + 0.014 × 1 (if hepatocellular pattern) + 1.887. The AUC of the score was 0.86, with a sensitivity and specificity of 81%, better than the values of the single markers. Conclusions: Liver-specific miRNAs and K-18 could be promising serum biomarkers of DILI, especially when used in combination.

Alcohol-related hepatitis (AH) is a clinical syndrome characterized by recent-onset jaundice in the context of alcohol consumption. In patients with severe AH “unresponsive” to steroid therapy, mortality rates exceed 70% within six months. According to European and American guidelines, liver transplantation (LT) may be considered in highly selected patients who do not respond to medical therapy. The aim of this narrative review is to summarize current knowledge from medical therapy to liver transplantation in acute alcohol-related hepatitis. Due to the impossibility to guarantee six-month abstinence, LT for AH is controversial. Principal concerns are related to organ scarcity in the subset of stigma of “alcohol use disorder” (AUD) and the risk of relapse to alcohol use after LT. Return to alcohol use after LT is a complex issue that cannot be assessed as a yes/no variable with heterogeneous results among studies. In conclusion, present data indicate that well-selected patients have excellent outcomes, with survival rates of up to 100% at 24 and 36 months after LT. Behavioral therapy, ongoing psychological support, and strong family support seem essential to improve long-term outcomes after LT and reduce the risk in relapse of alcohol use.

The impact of body composition abnormalities and clinical outcomes in patients with cirrhosis is well established. Abdominal computed tomography (CT) evaluation is the technique that is better evaluated; however, agreements are not well known. Fifty patients were randomly selected from two centers, and two observers independently evaluated their CT. The cross-sectional muscle area (CSMA), skeletal muscle index (SMI), muscle attenuation (MA), visceral adipose tissue area (VAT), visceral adipose tissue index (VATI), subcutaneous adipose tissue area (SAT), and subcutaneous adipose tissue area (SATI) were analyzed using SliceOmatic©V.5.0 (Magog, Canada), and Synapse 3D, Fujifilm. The interobserver and intersoftware intra-class correlation coefficients (ICCs) were highly equivalent for CSMA, SMI, MA, VAT, VATI, SAT, and SATI (Range 0.984-0.999, P < 0.001), and excellent Pearson's correlation coefficients were found for all comparisons (Range 0.970-0.998). Using different software programs to evaluate body composition in patients with cirrhosis showed excellent agreement for measuring muscle mass and adipose depots.