Alcoholic Etiology, Severity of Liver Disease, and Post-Transplant Adherence Are Correlated with Worse Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) in Liver Transplant Candidates.

Introduction: Psychosocial pre-transplant evaluation in patients undergoing liver transplantation (LT) could help identify those patients at higher risk of pharmacological non-adherence, organ rejection, and mortality. The Stanford Integrated Psychosocial Assessment for Transplantation (SIPAT) is a validated tool for assessing LT candidates' psychosocial well-being. Data on the ability of the SIPAT evaluation to predict post-transplant outcomes are sparse. Material and Methods: clinical and psychosocial data from a sample of 134 candidates for LT were analyzed. Moreover, the association between pre-transplant psychosocial evaluation and post-transplant clinical outcomes, including organ rejection, mortality, and immunosuppressant drug adherence, was calculated. Results: At the pre-transplant evaluation, patients who showed high SIPAT scores (77, 57%) also had more liver disease assessed by model for end-stage liver disease (MELD; F = 5.04; p < 0.05), alcoholic etiology (F = 35.80; p < 0.001), encephalopathy (F = 5.02; p < 0.05), and portal hypertension (F = 7.45; p < 0.01). Of the 51 transplant patients, those who had a high pre-transplant SIPAT score showed lower post-transplant immunosuppressive adherence, linked to more frequent immunological events. Conclusions: Patients with an alcoholic etiology of liver disease and more severe liver dysfunction are likelier to not adhere to medical prescriptions following transplantation. Current data suggests that this specific group of patients could benefit from early psychological pre-habilitation before undergoing liver transplantation.

Multidrug-resistant bacterial infections in the liver transplant setting.

Bacterial infections pose a life-threatening complication in patients with decompensated liver cirrhosis and acute-on-chronic liver failure. An increasing prevalence of infections caused by multidrug-resistant organisms (MDROs) has been observed in these patients, significantly impacting prognosis. A growing body of evidence has identified the most common risk factors for such infections, enabling the development of preventive strategies and therapeutic interventions. MDRO infections may also occur after liver transplantation (most commonly in the early post-operative phase), affecting both graft and patient survival. This review provides an overview of MDRO infections before and after liver transplantation, discussing epidemiological aspects, risk factors, prevention strategies, and novel therapeutic approaches. Furthermore, it examines the implications of MDRO infections in the context of prioritizing liver transplantation for the most severe patients, such as those with acute-on-chronic liver failure.

Liver transplantation for wilson disease: Current knowledge and future perspectives.

Liver transplantation currently represents a therapeutic option for patients Wilson's disease presenting with end-stage liver disease or acute liver failure. Indeed, it has been associated with excellent post-operative survival curves, in view of young age at transplant and absence of recurrence. Attention has shifted over the past decades to a wise expansion of indications for liver transplantation. Evidence has emerged supporting transplantation of carefully selected patients with primarily neuropsychiatric symptoms and compensated cirrhosis. The rationale behind this approach is the potential for surgery to improve copper homeostasis and consequently ameliorate neuropsychiatric symptoms. However, several questions remain unanswered, such as how to establish thresholds for assessing pre-transplant neuropsychiatric impairment, how to standardize preoperative neurological assessments, and how to define post-operative outcomes for patients meeting these specific criteria. Furthermore, a disease-specific approach will be proposed both for the liver transplant evaluation of Wilson's disease candidates and for patient care during the transplant waiting period, highlighting peculiarities of this systemic disease.

Myosteatosis is closely associated with sarcopenia and significantly worse outcomes in patients with cirrhosis.

BACKGROUND & AIMS: Sarcopenia and myosteatosis are common in patients with cirrhosis. This study aimed to determine the prevalence of these muscle changes, their interrelations and their prognostic impact over a 12-month period. METHODS: We conducted a prospective multicentre study involving 433 patients. Sarcopenia and myosteatosis were evaluated using computed tomography scans. The 1-year cumulative incidence of relevant events was assessed by competing risk analysis. We used a Fine-Gray model adjusted for known prognostic factors to evaluate the impact of sarcopenia and myosteatosis on mortality, hospitalization, and liver decompensation. RESULTS: At enrolment, 166 patients presented with isolated myosteatosis, 36 with isolated sarcopenia, 135 with combined sarcopenia and myosteatosis and 96 patients showed no muscle changes. The 1-year cumulative incidence of death in patients with either sarcopenia and myosteatosis (13.8%) or isolated myosteatosis (13.4%) was over twice that of patients without muscle changes (5.2%) or with isolated sarcopenia (5.6%). The adjusted sub-hazard ratio for death in patients with muscle changes was 1.36 (95% CI 0.99-1.86, p = 0.058). The cumulative incidence of hospitalization was significantly higher in patients with combined sarcopenia and myosteatosis than in patients without muscle changes (adjusted sub-hazard ratio 1.18, 95% CI 1.04-1.35). The cumulative incidence of liver decompensation was greater in patients with combined sarcopenia and myosteatosis (p = 0.018) and those with isolated sarcopenia (p = 0.046) than in patients without muscle changes. Lastly, we found a strong correlation of function tests and frailty scores with the presence of muscle changes. CONCLUSIONS: Myosteatosis, whether alone or combined with sarcopenia, is highly prevalent in patients with cirrhosis and is associated with significantly worse outcomes. The prognostic role of sarcopenia should always be evaluated in relation to the presence of myosteatosis. IMPACT AND IMPLICATIONS: This study investigates the prognostic role of muscle changes in patients with cirrhosis. The novelty of this study is its multicentre, prospective nature and the fact that it distinguishes between the impact of individual muscle changes and their combination on prognosis in cirrhosis. This study highlights the prognostic role of myosteatosis, especially when combined with sarcopenia. On the other hand, the relevance of sarcopenia could be mitigated when considered together with myosteatosis. The implication from these findings is that sarcopenia should never be evaluated individually and that myosteatosis may play a dominant role in the prognosis of patients with cirrhosis.

A holistic evaluation of patients with chronic Hepatitis D virus (HDV) infection enrolled in the Italian PITER-B and delta cohort.

BACKGROUND AND AIMS: We aimed to characterize the epidemiologic and comorbidities profiles of patients with chronic Hepatitis D (CHD) followed in clinical practice in Italy and explored their interferon (IFN) eligibility. METHODS: This was a cross-sectional study of the PITER cohort consisting of consecutive HBsAg-positive patients from 59 centers over the period 2019-2023. Multivariable analysis was performed by logistic regression model. RESULTS: Of 5492 HBsAg-positive enrolled patients, 4152 (75.6%) were screened for HDV, 422 (10.2%) were anti-HDV positive. Compared with HBsAg mono-infected, anti-HDV positive patients were more often younger, non-Italians, with a history of drug use, had elevated alanine transaminase (ALT), cirrhosis, or hepatocellular carcinoma (HCC). Compared with Italians, anti-HDV positive non-Italians were younger (42.2% age ≤ 40 years vs. 2.1%; P < 0.001), more often females (males 43.0% vs. 68.6%; P < 0.001) with less frequent cirrhosis and HCC. HDV-RNA was detected in 63.2% of anti-HDV-positive patients, who were more likely to have elevated ALT, cirrhosis, and HCC. Extrahepatic comorbidities were present in 47.4% of anti-HDV positive patients and could affect the eligibility of IFN-containing therapies in at least 53.0% of patients in care. CONCLUSIONS: CHD affects young, foreign-born patients and older Italians, of whom two-thirds had cirrhosis or HCC. Comorbidities were frequent in both Italians and non-Italians and impacted eligibility for IFN.

Evolution of Liver Transplantation Indications: Expanding Horizons.

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.

Trends in liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Primary sclerosing cholangitis is a cholestatic disease with a low prevalence in Italy. Indications for liver transplantation and the time of listing are not stated. AIM: We performed a national survey to investigate the listing criteria, comorbidities, and outcomes. METHODS: In April 2022, we surveyed liver transplantation in primary sclerosing cholangitis nationwide for the last 15 years. RESULTS: From 2007 to 2021, 445 patients were included on waiting lists, and 411 had undergone liver transplants. The median age at transplantation was 46 years (males 63.9%); 262 patients (59%) presented an inflammatory bowel disease. Transplants increased over the years, from 1.8 % in 2007 to 3.0 % in 2021. Cholangitis (51%) and hepatic decompensation (45%) were the main indications for listing. The disease recurred in 81 patients (20%). Patient survival after the first transplant was 94 %, 86% and 84% at one, five, and ten years. Twenty-four died in the first year (50% surgical complications, 25% infections); 33 between one to five years (36% recurrence, 21% cholangiocarcinoma recurrence) and nine after five years (56% de novo cancer, 44% recurrence). CONCLUSIONS: Primary sclerosing cholangitis has been an increasing indication for transplantation in Italy. Cholangitis and decompensation were the main indications for listing. Recurrence and cancer were the leading causes of death.

The role of an integrated referral program for patients with liver disease: A network between hub and spoke centers.

INTRODUCTION: Access to Liver transplantation (LT) can be affected by several barriers, resulting in delayed referral and increased risk of mortality due to complications of the underlying liver disease. AIM: To assess the clinical characteristics and outcomes of patients with acute or chronic liver disease referred using an integrated referral program. MATERIALS AND METHODS: An integrated referral program was developed in 1 October 2017 based on email addresses and a 24/7 telephone availability. All consecutive adult patients with liver disease referred for the first time using this referral program were prospectively collected until 1 October 2021. Characteristics and outcomes of inpatients were compared with a historical cohort of patients referred without using the integrated referral program (1 October 2015-1 October 2017). Patients were further divided according to pre- and post-Covid-19 pandemic. RESULTS: Two hundred eighty-one referred patients were considered. End stage liver disease was the most common underlying condition (79.3%), 50.5% of patients were referred as inpatients and 74.7% were referred for LT evaluation. When inpatient referrals (n = 142) were compared with the historical cohort (n = 86), a significant increase in acute liver injury due to drugs/herbals and supplements was seen (p = 0.01) as well as an increase in End stage liver disease due to alcohol-related liver disease and NASH, although not statistically significant. A significant increase in referrals for evaluation for Trans-jugular intrahepatic portosystemic shunt placement was seen over time (5.6% vs. 1%; p = 0.01) as well as for LT evaluation (84.5% vs. 81%; p = 0.01). Transplant-free survival was similar between the study and control groups (p = 0.3). The Covid-19 pandemic did not affect trends of referrals and patient survival. CONCLUSIONS: The development of an integrated referral program for patients with liver disease can represent the first step to standardize already existing referral networks between hub and spoke centers. Future studies should focus on the timing of referral according to different etiologies to optimize treatment options and outcomes.

Evolution of liver fibrosis in diabetic patients with NAFLD in a follow-up study: Hepatoprotective effects of sodium-glucose co-transporter-2 inhibitors.

BACKGROUND AND AIMS: Patients with non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM) are at high risk of hepatic fibrosis. To prospectively evaluate changes in fibrosis in diabetic patients with NAFLD, predisposing factors and sodium glucose cotransporter 2 inhibitors (SGLT2i) influence. METHODS: 237 T2DM outpatients (mean age 67 ± 9 years, 54% male) were enrolled and re-evaluated after 52 ± 10 months. At baseline and follow-up NAFLD and liver fibrosis (LSM) were detected by ultrasonography and Fibroscan®. RESULTS: During follow-up an increase in LSM (6.0 ± 2.8 vs 5.8 ± 2.7 kPa, p = 0.02) and in the prescription of SGLT2i (20% vs 6%, p<0.001) was registered, despite stability of diabetic control. LSM worsened in 133(56%) subjects, 92 (39%) with worsening >10% from baseline. Patients with worsening versus non worsening of LSM had higher prevalence of increase in BMI during follow-up (45% vs 32%, p = 0.06) and lower SGLT2i prescription (15% vs 27%, p = 0.034). In multivariate analysis use of SGLT2-inhibitors at follow-up reduced the risk of LSM worsening (HR 0.34, 95% CI 0.13-0.88), even when considered>10% from baseline. CONCLUSIONS: A high prevalence of fibrosis progression was observed in diabetic subjects with NAFLD over a nearly 5-years follow up and SGLT2-inhibitors seem to reduce the risk of worsening of liver stiffness.

Toward a more precise prognostic stratification in acute decompensation of cirrhosis: The Padua model 2.0.

BACKGROUND: The clinical course of acutely decompensated cirrhosis (AD) is heterogeneous. Presepsin (PSP) is a plasmatic biomarker that reflects Toll-like receptor activity and systemic inflammation. We conducted a prospective study to: (1) measure PSP in AD and (2) assess whether PSP in AD can predict the development of acute-on-chronic liver failure (ACLF). METHODS: Patients with AD were prospectively recruited at admission and underwent determination of PSP. In study part 1, we compared PSP in AD versus controls (stable decompensated and compensated cirrhosis). In study part 2, we prospectively followed patients with AD for 1 year and evaluated predictors of ACLF. RESULTS: One hundred and seventy three patients with AD were included (median MELD: 18; CLIF-C AD score: 54). Compared with controls, patients with AD had higher levels of PSP (674 ng/L vs. 310 ng/L vs. 157 ng/L; p < 0.001). In patients with AD, Child-Pugh C and acute kidney injury were associated with higher levels of PSP. During the follow-up, 52 patients developed ACLF (median time from recruitment: 66 days). PSP, CLIF-C AD score, and Child-Pugh stage were independently associated with ACLF. A predictive model combining these variables (Padua model 2.0) accurately identified patients at higher risk of ACLF (AUROC 0.864; 95% CI 0.780-0.947; sensitivity 82.9%, specificity 76.7%). In patients at lower risk of ACLF based on a CLIF-C AD <50, a PSP >674 ng/L could discriminate between two groups at significantly different risk of ACLF. Finally, in patients who did not develop ACLF, baseline PSP was significantly higher in those who progressed toward unstable versus stable decompensated cirrhosis. CONCLUSION: The Padua model 2.0 can be used to identify patients with AD at high risk of ACLF. If these results are validated by external cohorts, PSP could become a new biomarker to improve risk stratification in AD.

The non-invasive evaluation of liver involvement in patients with cystic fibrosis: A prospective study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disease (PSVD) has been described as the prominent pathology in liver explants of patients with cystic fibrosis (CF), but data outside the transplant setting are lacking. We aimed to investigate the prevalence of portal hypertension (PH) in CF-associated liver disease (CFLD) and develop an algorithm to classify liver involvement in CF patients. METHODS: This is a cross-sectional study of consecutive paediatric and adult patients in a tertiary centre between 2018 and 2019, who underwent ultrasound, liver (LSM) and spleen stiffness (SSM) measurement. CFLD was defined according to physical examination, liver tests and ultrasound findings. PSVD was likely if there were PH signs in the absence of advanced chronic liver disease (CF-ACLD, LSM <10 kPa). A historical cohort was used to validate the prognostic significance of the new definitions. RESULTS: Fifty (27.5%) patients met CFLD criteria. At least one sign of PH was found in 47 (26%) patients, but most (81%) had LSM <10 kPa and were likely to have PSVD; only 9 (5%) had CF-ACLD. PSVD and CFLD (LSM <10 kPa) co-existed in most (23/36) cases. In the historical cohort (n = 599 patients), likely PSVD and CFLD+PH were independently associated with a 2-fold and 3.5-fold increase in mortality compared to patients without PH, respectively. In 34 patients with SSM, values <21 and >50 kPa accurately diagnosed specific signs of PH. CONCLUSIONS: PSVD is the prevailing cause of PH in CF patients. We developed a new diagnostic algorithm based on clinical and elastosonography criteria to classify liver involvement in patients with CF.

Long-Term Impact of Direct-Acting Antivirals on Liver Fibrosis and Survival in HCV-Infected Liver Transplant Recipients.

(1) Background: Little is known about the long-term impact of sustained virological response (SVR) on fibrosis progression and patient survival in liver transplantation (LT) recipients treated with direct-acting antivirals (DAAs). We investigated liver fibrosis evolution and patient survival in hepatitis C virus (HCV)-infected patients receiving DAAs after LT. (2) Methods: All consecutive HCV-infected patients treated with DAAs after LT between May 2014 and January 2019 were considered. The clinical and virological features were registered at the baseline and during the follow-up. The liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at the baseline and at least 1 year after the end of treatment (EoT). (3) Results: A total of 136 patients were included. The SVR12 was 78% after the first treatment and 96% after retreatment. After the SVR12, biochemical tests improved at the EoT and remained stable throughout the 3-year follow-up. Liver fibrosis improved after the SVR12 (p < 0.001); nearly half of the patients with advanced liver fibrosis experienced an improvement of an F ≤ 2. The factors associated with lower survival in SVR12 patients were the baseline platelet count (p = 0.04) and creatinine level (p = 0.04). (4) Conclusions: The long-term follow-up data demonstrated that SVR12 was associated with an improvement in hepatic function, liver fibrosis, and post-LT survival, regardless of the baseline liver fibrosis. The presence of portal hypertension before the DAAs has an impact on patient survival, even after SVR12.

Validation of the INCREMENT-SOT-CPE score in a large cohort of liver transplant recipients with carbapenem-resistant Enterobacterales infection.

BACKGROUND: Management of infections due to carbapenemase-resistant Enterobacterales (CRE) in solid organ transplant (SOT) recipients remains a difficult challenge. The INCREMENT-SOT-CPE score has been specifically developed from SOT recipients to stratify mortality risk, but an external validation is lacking. METHODS: Multicenter retrospective cohort study of liver transplant (LT) recipients colonized with CRE infection who developed infection after transplant over 7-year period. Primary endpoint was all-cause 30-day mortality from infection onset. A comparison between INCREMENT-SOT-CPE and other selected scores was performed. A two-level mixed effects logistic regression model with random effects for the center was fitted. Performance characteristics at optimal cut-point were calculated. Multivariable Cox regression analysis of risk factors for all-cause 30-day mortality was carried out. RESULTS: Overall, 250 CRE carriers developed infection after LT and were analyzed. The median age was 55 years (interquartile range [IQR]: 46-62) and 157 were males (62.8%). All-cause 30-day mortality was 35.6%. A sequential organ failure assessment (SOFA) score ≥ 11 showed a sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of 69.7%, 76.4%, 62.0%, 82.0%, and 74.0%, respectively. An INCREMENT-SOT-CPE ≥ 11 reported a sensitivity, specificity, PPV, NPV, and accuracy of 73.0%, 62.1%, 51.6%, 80.6% and 66.0%, respectively. At multivariable analysis acute renal failure, prolonged mechanical ventilation, INCREMENT-SOT-CPE score ≥ 11 and SOFA score ≥ 11 were independently associated with all-cause 30-day mortality, while a tigecycline-based targeted regimen was found to be protective. CONCLUSIONS: Both INCREMENT-SOT-CPE ≥ 11 and SOFA ≥ 11 were identified as strong predictors of all-cause 30-day mortality in a large cohort of CRE carriers developing infection after LT.

The interplay between sarcopenia and portal hypertension predicts ascites and mortality in cirrhosis.

BACKGROUND: The role of sarcopenia in predicting decompensation other than hepatic encephalopathy is unclear. We aimed to evaluate the prognostic role of sarcopenia, assessed by computed tomography (CT), in the development of ascites and mortality in patients with advanced chronic liver disease (ACLD) outside the liver transplantation (LT) setting. MATERIAL AND METHODS: We retrospectively evaluated ACLD patients with liver stiffness measurement (LSM) >10 kPa and an available CT scan within 6 months. Sarcopenia was defined as skeletal muscle index (SMI) <50 and <39 cm2/m2, respectively, in men and women. Competing risk regression models were used to assess the variables associated with the main outcomes. RESULTS: 209 patients were included in the final analysis and sarcopenia was present in 134 (64.1%). During a median follow-up of 37 (20-63) months, 52 patients developed ascites, 24 underwent LT, and 30 died. Sarcopenia was found a predictive factor of decompensation with ascites (SHR 2.083, 95%-CI: 1.091-3.978), independently from the features of clinically significant portal hypertension (LSM≥21 kPa or portosystemic shunts). Sarcopenia (SHR: 2.744, 95%-CI: 1.105-6.816) and LSM≥21 kPa (SHR: 3.973, 95%-CI: 1.548-10.197) were independent risk factors for increased mortality. CONCLUSIONS: Sarcopenia and portal hypertension are two major and independent risk factors for decompensation with ascites and mortality in cirrhotic patients outside the LT context.

A Combined Baveno VII and Spleen Stiffness Algorithm to Improve the Noninvasive Diagnosis of Clinically Significant Portal Hypertension in Patients With Compensated Advanced Chronic Liver Disease.

INTRODUCTION: A noninvasive diagnosis of clinically significant portal hypertension (CSPH) has important prognostic and therapeutic implications for patients with compensated advanced chronic liver disease. We aimed to validate and improve the available algorithms for the CSPH diagnosis by evaluating spleen stiffness measurement (SSM) in patients with compensated advanced chronic liver disease. METHODS: This is a retrospective study including patients with liver stiffness measurement (LSM) ≥10 kPa, no previous decompensation, and available measurements of hepatic venous pressure gradient, LSM, and SSM by transient elastography referring to our center in Bologna. The diagnostic algorithms were adequate if negative and positive predictive values were >90% when ruling out and ruling in CSPH, respectively; these models were validated in a cohort from Verona. The 5-year decompensation rate was reported. RESULTS: One hundred fourteen patients were included in the derivation cohort. The Baveno VII diagnostic algorithm (LSM ≤15 kPa + platelet count ≥150 × 10 9 /L to rule out CSPH and LSM >25 kPa to rule in CSPH) was validated; however, 40%-60% of the patients remained in the gray zone. The addition of SSM (40 kPa) to the model significantly reduced the gray zone to 7%-15%, maintaining adequate negative and positive predictive values. The diagnostic algorithms were validated in a cohort of 81 patients from Verona. All first decompensation events occurred in the "rule-in" zone of the model including SSM. DISCUSSION: The addition of SSM significantly improves the clinical applicability of the algorithm based on LSM and platelet count for CSPH diagnosis. Our models can be used to noninvasively identify candidates for nonselective beta-blocker treatment and patients at a high risk of decompensation.

HBV-positive and HIV-positive organs in transplantation: A clinical guide for the hepatologist.

Organ transplantation is a life-saving treatment for patients with end-stage organ disease, a severe condition associated with a high risk of waitlist mortality. It is primarily limited by a shortage of available organs. Maximising available donors can increase access to transplantation. Transplantation from donors positive for HBV and HIV has increased in many countries. However, antiviral therapies need to be readily available for recipients after transplantation to prevent possible reactivation of the virus following the administration of immunosuppressive therapies. Furthermore, the intentional transmission of a virus has practical, ethical, and clinical implications. In this review, we summarise the current research, focusing on grafts from donors positive for the HBV surface antigen, antibodies against the HBV core antigen, and HIV, to help hepatologists and physicians interested in transplantation to select the best antiviral and/or prophylactic regimens for after transplantation.

Nash Up, Virus Down: How the Waiting List Is Changing for Liver Transplantation: A Single Center Experience from Italy.

Background and Objectives: Non-alcoholic steatohepatitis (NASH) has become the leading indication for liver transplantation in many countries, with a growing rate in the Western world. NASH patients are older and share a higher risk of comorbidities and cancer than patients with viral and/or alcoholic etiologies. The aims of this study were to evaluate waiting list (WL) registration and liver transplantation rates in patients with NASH-related cirrhosis at Padua University Hospital in the last fifteen years (1.2006-6.2020) and to compare clinical characteristics and indications for liver transplantation between patients with and without NASH, as well as the WL survival and post-transplant outcome. Materials and Methods: All adult patients with cirrhosis listed for liver transplantation at Padua University Hospital between 1.2006 and 6.2020 were retrospectively collected using a prospectively updated database; patients with NASH-related cirrhosis were divided by indication for liver transplantation (Dec-NASH vs. hepatocellular carcinoma (HCC)-NASH) and compared with patients with other etiologies of liver disease. The outcomes in terms of waiting list survival and post-transplant outcome were assessed. Results: One thousand four hundred and ninety-one adult cirrhotic patients were waitlisted during the study period. NASH patients accounted for 12% of all WL registrations, showing an increasing trend over time (from 2.5% in 2006 to 23% in 2020). In the last five years, NASH was the third, but most rapidly growing, indication for liver transplantation at our center. This trend was confirmed both for patients with decompensated cirrhosis (from 1.8% to 18%) and HCC as leading indication for transplantation (from 4% to 30%). NASH patients were older than non-NASH ones (mean ± SD age 59 ± 9 vs. 56 ± 9 years; p < 0.01), whereas no difference was found in gender or Child-Pugh of the model for end-stage liver disease score at WL registration. A majority (60.9%) of NASH patients underwent liver transplantation, showing 1-, 5- and 10-y post-transplant survivals of 86%, 73% and 60%, respectively. Conclusion: NASH cirrhosis has become a rapidly growing indication for liver transplantation at our center, both for HCC and decompensated disease, with good post-transplant survival.

Future challenges in gastroenterology and hepatology, between innovations and unmet needs: A SIGE Young Editorial Board's perspective.

Gastroenterology, Digestive Endoscopy and Hepatology have faced significant improvements in terms of diagnosis and therapy in the last decades. However, many fields still remain poorly explored, and many questions unanswered. Moreover, basic-science, as well as translational and clinical discoveries, together with technology advancement will determine further steps toward a better, refined care for many gastroenterological disorders in the future. Therefore, the Young Investigators of the Italian Society of Gastroenterology (SIGE) joined together, offering a perspective on major future innovations in some hot clinical topics in Gastroenterology, Endoscopy, and Hepatology, as well as the current pitfalls and the grey zones.

An Essential Guide for Managing Post-Liver Transplant Patients: What Primary Care Physicians Should Know.

With long-term survival after liver transplantation becoming the rule, care for medical problems arising over time in liver-transplanted patients gained increasing importance. The most common causes of death occurring more than 1 year after liver transplantation are unrelated to liver diseases and facilitated by immunosuppressive treatments; examples are malignancies, renal failure, and cardiovascular, metabolic, and infectious diseases. Recipients receive life-long follow-up care at transplant centers, however, the increasing number of liver-transplanted patients is saturating the health care supply that transplant centers have to offer. Primary care physicians are increasingly exposed to liver-transplanted patients, even in the early periods after transplant, and an understanding of the most common risks and complications faced by these patients would enhance their care. This article reviews the long-term care of liver transplant recipients, emphasizing the key internal medicine-related issues that should be known by primary care physicians. A specific section is devoted to implementing strategies to involve these physicians in the long-term follow-up of liver-transplanted patients in close collaboration with transplant hepatologists.