Introduction Sarcoidosis is a systemic granulomatous disease involving the liver in about 10-20% of cases. In absence of high-quality data on the management of hepatic sarcoidosis (HS), it is still experienced-based. Aim To collect and analyze data on the Italian real-world experience in HS management. Methods, Results Thirty-six AISF-affiliated hepatologic centers received questionnaires, thirty-three of them reported managing 78 patients with HS. Eighteen centers subsequently transmitted demographic and clinical data belonging to 11 Italian regions. Statistical analyses were performed with R Studio. 55 patients were included, median age at diagnosis was 52(44.8-57.3).Female patients were 33 (60%) and 45 (82%) patients were Caucasian.Most patients (45%) reported systemic symptoms (asthenia, fever) and a cholestatic pattern of liver enzymes elevation (Table1). Males had a significantly higher level of GGT (p 0.02) and bilirubin (p<0.01) at presentation. Figure1 shows radiological findings. In coexistence with HS, mainly pulmonary (43%) and lymphatic (36%) involvement were reported. Patients with only HS were 6 (10.9%).Clinically-significant-portal-hypertension (CSPH) at diagnosis was detected in 8(14.5%) patients according to LSM≥25Kpa or varices, only one of them had histological cirrhosis. BMI was significantly higher in patients with CSPH(p 0.01). Twenty-six patients were treated with first-line steroid therapy (48%), 11(20%) patients with steroid+ ursodeoxycholic-acid (UDCA), 6(11%) patients with UDCA only, 11 (20%) with combination of different agents, including anti-metabolites. Median alkaline-phosphatase (ALP) decrease was 56,3% in 12 months, independently from the medical treatment used (p>0.09). Seventeen (31%) patients received treatment adjustment with a second line agent. None of the patients underwent liver transplantation or developed hepatocellular carcinoma. One patient died during follow-up owing to liver-related complications. Conclusion HS is a rare entity with a heterogeneus clinical presentation and management. HS has an intrinsic risk of CSPH not only explained by the presence of cirrhosis, that is higher in patients with higher BMI; these findings need further investigations. Drug choice doesn't have an impact on ALP decrease, but UDCA are associated to a better GPT-reduction. A multicentric, prospective, national cohort study is eeded to further study this disease.

Hepatitis B virus (HBV) is a major health problem worldwide, with approximatively 240 million people living with a chronic HBV infection. HBV chronic infection remains the major cause of hepatocellular carcinoma worldwide, with more than half of HCC patients being chronic HBV carriers, even if underlying mechanisms of tumorigenesis are not totally understood. HBV-related HCC can be prevented by reducing the exposure to HBV by vaccination or by treatment of CHB infection. Current treatment of CHB are Peg-IFN alpha and oral NUCs. Treating HBV infection, either with IFN or NUCs, substantially reduces the risk of HCC development, even if antiviral therapy fails to completely eliminate HCC risk. Among treated patients, cirrhosis, HBeAg negative at baseline and failure to remain in virological remission were associated with an increased risk of HCC. The reduction of the risk of developing HCC during antiviral therapy is largely dependent upon the maintenance of virological remission, since viral load is found to be the most important factor leading to cirrhosis and its complications, including liver cancer development. The question whether Peg-IFN-alpha is superior to NUCs and whether there is a superior agent among NUCs is still controversial. Several studies demonstrated that antiviral therapy with NUCs could reduce the risk of HCC recurrence after curative treatment of HBV-related HCC.

Hepatocellular carcinoma (HCC) represents the sixth most commonly diagnosed cancer and the fourth leading cause of cancer-related death worldwide. HCC occurs predominantly in patients with underlying chronic liver disease and cirrhosis, and it presents a poor prognosis in advanced stage. Since its approval, for the following 10 years, sorafenib remained the only systemic agent with proven clinical efficacy for patients with advanced HCC. Recently, more drugs have been studied and several advances in first‑line and second‑line treatment options should yield significant improvements in survival. Lenvatinib, another tyrosine‑kinase inhibitor, was found to be non-inferior to sorafenib in terms of overall survival (OS), with significantly better progression-free survival and objective response rate (ORR). The tyrosinekinase inhibitors, regorafenib and cabozantinib, were shown to significantly improve survival in the second‑line setting after sorafenib failure. Ramucirumab, a VEGF inhibitor, can also improve survival in the second‑line setting among patients with AFP≥400 ng/dL. Moreover, good efficacy was seen in phase I/II trials of immune checkpoint inhibitors as monotherapy. Ongoing trials are evaluating combination immune checkpoint inhibitor and tyrosine‑kinase inhibitors or VEGF inhibitors for increasing overall survival in this patient population with advanced HCC.

Malnutrition and sarcopenia have a high prevalence in cirrhotic patients. Frailty generally overlaps with malnutrition and sarcopenia in cirrhosis, leading to increased morbidity and mortality. Rapid nutritional screening assessment should be performed in all patients with cirrhosis, and more specific tests for sarcopenia should be performed in those at high risk. The pathogenesis of malnutrition in cirrhosis is complex and multifactorial and it is not just due to reduction in protein and calorie intake. Nutritional management in malnourished patients with cirrhosis should be undertaken by a multidisciplinary team to achieve adequate protein/calorie intake. While the role of branched-chained amino acids remains somewhat contentious in achieving a global benefit of decreasing mortality- and liver-related events, these latter and vitamin supplements, are recommended for those with advanced liver disease. Novel strategies to reverse sarcopenia such as hormone supplementation, long-term ammonia-lowering agents and myostatin antagonists, are currently under investigation. Malnutrition, sarcopenia and frailty are unique, inter-related and multidimensional problems in cirrhosis which require special attention, prompt assessment and appropriate management as they significantly impact morbidity and mortality.

Background and Aims: Hepatitis C virus (HCV) infection is associated with faster liver fibrosis progression and higher mortality in solid organ transplant (SOT) recipients compared to the non-transplanted population. Excellent safety and efficacy of direct acting antivirals (DAAs) after SOT were reported worldwide. Our aim was to evaluate long-term impact of viral eradication on fibrosis progression and patient survival after SOT. Methods: All consecutive HCV-infected patients treated with DAAs after SOT in a single transplant center between 08-2014 and 01-2019, included in the Veneto-NAVIGATORE platform or treated within the Compassionate Use Program, were considered. Clinical and virological features were registered at baseline, during treatment and up to 3-years after end of treatment (EoT). Liver fibrosis was assessed by liver biopsy and/or transient elastography (TE) at baseline and during the follow-up. Results: 110 patients treated with DAAs after SOT (liver = 93, kidney = 14, heart = 1, heart-kidney = 1, liver-kidney = 1) were included. 55% (n = 61) showed F3-F4 liver fibrosis at baseline. Median follow-up after DAAs was 47 months (IQR 31-54). Sustained virological response rate (SVR12) was 80% and 96% after retreatment. Patients with SVR12 showed a significant improvement in bilirubin (p< 0.001), ALT (p< 0.001) and platelet count (p = 0.006) from baseline to SVR48. During the follow-up liver fibrosis measured by TE and APRI improved in patients who achieved SVR12 (p< 0.001, p< 0.001); this result was confirmed in cirrhotic patients (p = 0.001, p< 0.001). Patient survival at 12, 24 and 36 months after DAAs was 96%, 91% and 86%, respectively. Patients with F3-4 pre-treatment fibrosis who achieved SVR had similar survival to those with F0-2 (p = 0.087). Patients with F3-4 pre-treatment fibrosis who relapsed showed lower survival compared to other groups (p < 0.001). Conclusions: Long-term follow-up data demonstrated that DAAs-induced HCV eradication after SOT was associated with improved hepatic function, liver fibrosis and post-SOT survival, even in patients with F3-4 pre-treatment fibrosis.

Introduction: An adequate referral system for patients with liver cirrhosis, acute liver injury (ALI) or acute liver failure (ALF) and potential indication to liver transplantation (LT) is crucial to guarantee a rapid diagnostic and therapeutic management. Aim: to develop a referral system for patients with potential indication to LT and to assess clinical characteristics and outcomes of referred patients.

Background De novo metabolic syndrome (MS) is a frequent complication after liver transplantation (LT). The aim of this prospective study is to identify potential risk factors longitudinally associated to post-LT de novo MS. Patients without pre-LT MS who underwent LT between April 2013 and October 2017 were prospectively included. Metabolic variables were collected at LT and at 6, 12, and 24 months post-LT. Results Sixty-three patients fulfilled the inclusion criteria (76% male, mean age 53.6 +/- 9.5 years). The prevalence of de novo MS was 46%, 43%, and 49% at 6, 12, and 24 months after LT, respectively. Among other MS components, the prevalence of type 2 diabetes, hypertension and hypertriglyceridemia significantly increased after LT. Considering the baseline characteristics at the adjusted analysis, alcoholic liver disease (OR 4.17, 95%CI 1.20-14.51; p = .03) and hypertension pre-LT (OR 11.3, 95% CI 1.49-85.46; p = .02) were confirmed as independent risk factors of post-LT de novo MS. In the time-varying analysis, only eGFR (OR .97, 95% CI .97-.98; p < .0001) was found associated with post-LT de novo MS. Conclusions De novo MS frequently occurs shortly after LT, affecting nearly half of patients at 24 months post-LT. Lifestyle modifications should be recommended starting early post-LT, particularly for patients with established risk factors.

Portal hypertension is a clinical syndrome characterized by an increase in the portal pressure gradient, defined as the gradient between the portal vein at the site downstream of the site of obstruction and the inferior vena cava. The most frequent cause of portal hypertension is cirrhosis. In patients with cirrhosis, portal hypertension is the main driver of cirrhosis progression and development of hepatic decompensation (ascites, variceal hemorrhage and hepatic encephalopathy), which defines the transition from compensated to decompensated stage. In decompensated patients, treatments aim at lowering the risk of death by preventing further decompensation and/or development of acute-on-chronic liver failure. Decompensated patients often pose a complex challenge which typically requires a multidisciplinary approach. The aims of the present review were to discuss the current knowledge regarding interventional treatments for patients with portal hypertension complications as well as to highlight useful information to aid hepatologists in their clinical practice. Specifically, we discussed the indications and contraindications of transjugular intra-hepatic portosystemic shunt and for the treatment of gastro-esophageal variceal hemorrhage in patients with decompensated cirrhosis (first section); we reviewed the use of interventional treatments in patients with hepatic vein obstruction (Budd-Chiari Syndrome) and in those with portal vein thrombosis (second section); and we briefly comment on the most frequent applications of selective splenic embolization in patients with and without underlying cirrhosis (third section).

Introduction: Acute alcoholic hepatitis (AAH) is characterized by high mortality rates mainly due to the development of infections.

Introduction: Infections are the main complications in patients with severe acute alcoholic hepatitis (AAH), being associated with a 2 month mortality rate of 50%. In these patients the identification of predictive factors of mortality is mandatory to set an effective antibiotic therapy and to assess the need of intensive care.

Diagnosis of severe hepatitis C recurrence is based on analytical and histological criteria but there is little information about their correlation. To assess the accuracy of laboratory criteria for the diagnosis of fibrosing cholestatic hepatitis (FCH). Retrospective analysis of prospectively collected data form HCV positive patients who underwent liver transplantation (LT) between 2000 and 2014 in two European university hospitals. Patients were classified according to laboratory criteria such as FCH, cholestatic hepatitis (CH) and non-cholestatic acute hepatitis (NCAH). Histological characteristics were also evaluated. Seventy patients with acute HCV recurrence within the first year after LT with an available liver biopsy were included in the study. Most patients were male (70%) with a median age of 58 years (50–64) and infected with genotype 1b (71.4%). Median time from LT to diagnosis of recurrence was 2.96 months (2.1–5.3). Thirty-nine patients were classified as FCH, 21 as CH and 10 as NCAH. Marked hepatocyte ballooning and ductular reaction were associated with the presence of FCH with an OR of 4.66 (p = 0.047) and 20.58 (p = 0.025), respectively. Considering liver biopsy as the gold standard, the sensitivity, specificity, positive and negative predictive values of the analytical criteria were 0.8, 0.5, 0.3 and 0.9, respectively. However, correlation between histological and analytical criteria was poor (k = 0.033). Analytical criteria may be used to rule out the presence of FCH, but a biopsy is mandatory to confirm the diagnosis. Ductular reaction and hepatocyte ballooning were independent predictors of FCH. El diagnóstico de la recurrencia grave de la hepatitis C se basa en criterios histológicos y analíticos. Sin embargo, existe poca información respecto su correlación. Evaluar la precisión de los criterios analíticos el diagnóstico de la hepatitis colestásica fibrosante (HCF). Análisis retrospectivo de pacientes con una recidiva grave precoz del virus de la hepatitis C (VHC) tras el trasplante hepático (TH) en 2 hospitales universitarios europeos entre 2000-2014. Los pacientes se clasificaron según criterios analíticos en HCF, hepatitis colestásica (HC) y hepatitis aguda no colestásica (HANC). Las características histológicas también fueron evaluadas. Se incluyeron 70 pacientes que desarrollaron una recurrencia grave del VHC en el primer año tras TH con una biopsia hepática disponible. La mayoría eran varones (70%) con mediana de edad de 58 años (50-64) y genotipo 1b (71,4%). La mediana de tiempo desde el TH hasta el diagnóstico de la recurrencia fue de 2,96 meses (2,1-5,3). Treinta y nueve pacientes fueron clasificados como HCF, 21 como HC y 10 como HANC. La balonización intensa y reacción ductular se asociaron con HCF con una OR de 4,66 (p = 0,047) y 20,58 (p = 0,025), respectivamente. Considerando la biopsia hepática como gold standard, la sensibilidad, especificidad y valores predictivos positivo y negativo de los criterios analíticos fueron 0,8, 0,5, 0,3 y 0,9, respectivamente. Sin embargo, la correlación entre ambos fue escasa (k = 0,033). Los criterios analíticos podrían utilizarse para descartar la presencia de HCF, pero la biopsia sigue siendo obligatoria para el diagnóstico. La reacción ductular y la balonización son predictores de HCF.

Hepatoma Research is an open access journal and focuses on all topics related to hepatoma. The following articles are especially welcome: pathogenesis, clinical examination and early diagnosis of hepatoma, complications of hepatoma, and their preventions and treatments, etc.

Background: Acute alcoholic hepatitis (AAH) is a clinical syndrome characterized by high mortality rates. There is increasing evidence that early liver transplantation (LT), performed within strict and standardized protocols, can improve survival.