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Clinically significant portal hypertension (CSPH) in patients with advanced chronic liver disease (ACLD) is high-risk condition for liver-related events (LRE). According with BAVENO VII, non-invasive tests (NIT) should be preferred to rule in or out for CSPH to avoid endoscopy. The novel score HVPG-3Parameters gave a prediction of HVPG showing good accuracy in CSPH prediction. Aim is to evaluate the ability of HVPG-3P in PH and LRE prediction. A retrospective study was conducted in two different Italian centers: University of Naples and University of Marche. In 10 years, consecutive compensated-ACLD patients who underwent upper-GI endoscopy for PH assessment were enrolled. NIT (FIB-4,ANTICIPATE,PLT/spleen-diameter ratio and HVPG-3P) were calculated. During the follow-up any LRE were recorded. Two-hundred and ninety-one ACLD subjects (with no differences between centers) were recruited (62.1% males, mean age 60 years). Mean LSM was 23.6±11.7kPa; HVPG-3P was 13.3±2.0mmHg, ANTICIPATE was 1.0±1.6, FIB-4 was 5.0±3.2, platelets/spleen-diameter ratio was 906.5±568.2. One-hundred and forty-two (48,9%) subjects showed PH endoscopic signs. They had higher LSM (26.6±12.4vs20.8±10.3kPa, p=0.00002), HVPG-3P (14.2±1.6vs12.4±2.0mmHg, p<0.001), ANTICIPATE (1.66±1.4vs0.31±1.5, p<0.001), FIB-4 (5.87±3.28vs4.13±2.84, p=0.001) and lower platelets/spleen-diameter ratio (652.4±323.6vs1148.6±641.8, p<0.0001) compared to subjects without PH endoscopic signs. During a median follow-up of 41.5months (IQR 17.8-74.0) LRE occurred in a median of 18.9months (IQR 7.5-37) in 126/291 (43.2%). Patients who experienced LRE showed higher LSM (26.0±12.3 vs21.9±11.0kPa, p=0.003), HVPG-3P (14.1±1.7vs12.6±2.0mmHg, p<0.0001), ANTICIPATE (1.54±1.57vs0.55±1.56, p<0.0001), FIB-4 (6.02±3.36vs4.19±2.79, p<0.0001) and lower platelets/spleen-diameter ratio (694.9±385.7vs1068.0±630.0, p<0.0001). The HVPG-3P seems to have a good performance in PH and LRE prediction (considering the results from Random Forest model: MDA 4.52 and 6.55, higher than the majority of variables). HVPG-3P is a simple tool for non-invasive prediction of PH and could be used to stratify the risk of LRE in patients with ACLD. However, this score needs to be validated in larger cohorts. [ABSTRACT FROM AUTHOR]

The efficacy of systemic therapy for unresectable advanced hepatocellular carcinoma (aHCC) has not been proven in patients with Child-Pugh (C-P) B cirrhosis. Nevertheless, in real-world these patients are treated with tyrosine-kinase inhibitors (TKIs) since their toxicity is similar to that observed in C-P A patients and, off-label, with Metronomic Capecitabine (MC) in patients not amenable to TKIs. This study aimed to compare Sorafenib and MC's outcomes versus best supportive care (BSC) in C-P B-HCC patients. Between 2008 and 2020, among 774 consecutive C-P B patients with aHCC not amenable/responding to locoregional treatments extracted from the ITA.LI.CA database, 410 underwent Sorafenib, 62 MC, and 302 BSC. The propensity score matching method was used to correct the baseline unbalanced prognostic factors, with a 1:1 allocation of Sorafenib vs BSC, MC vs BSC, and Sorafenib vs MC patients, and Kaplan-Meier method and Log-rank test were used to define overall survival (OS) and differences. in the unmatched population median OS (95% CI) was 9.9 (8.3-11.4) months in Sorafenib, 8.0 (0.4-15.7) months in MC, and 3.9 (3.1-4.8) months in BSC-treated patients (p<0.001 for Sorafenib vs BSC and for MC vs BSC; p=0.812 for Sorafenib vs MC). In Sorafenib vs BSC-matched patients (135 couples) median OS was 7.3 (4.8-9.7) vs 3.9 (2.6-5.2) months (p<0.001). Independent predictors of survival were ECOG-Performance Status >1 [HR: 1.61 (1.22-2.13)], tumour size [HR: 1.04 (1.01-1.07)] macrovascular invasion [HR: 1.48 (1.12-1.96)], AFP >400 ng/mL [HR: 1.52 (1.14-2.04)], treatment-naïve [HR: 1.54 (1.15-2.07)] and Sorafenib [HR: 0.51 (0.38-0.68)]. In MC vs BSC matched patients (40 couples) median OS was 9.0 (0.2-17.8) vs 3.0 (2.2-3.8) months (p<0.001). In Sorafenib vs MC-matched patients (55 couples) the median OS did not differ (p=0.283). C-P B patients with aHCC undergoing BSC have poor survival. Both Sorafenib and MC treatment improve their prognosis. [ABSTRACT FROM AUTHOR]

In Italy, the spread of the COVID-19 pandemic has stressed the entire healthcare system and required a huge re-organization of many Divisions, including those of Gastroenterology. to assess the impact of COVID-19 pandemic on Gastroenterology Divisions across Italy. All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. Data of 121 hospitals from all 20 Italian regions were analyzed. Overall, 10.7% Gastroenterology Divisions have been converted to Covid Units. Outpatients consultations, endoscopic and ultrasound procedures were limited to urgencies and oncology indications in 85.1%, 96.2% and 72.2% of Units, respectively, and 46.7% of them suspended the screening for colorectal cancer. Moreover, 72.2% of the staff received a training for use of personal protective equipment, although 45.5% did not have sufficient devices for adequate replacement. Overall, 132 healthcare workers in 41 Gastroenterology Divisions were found to be infected. This is the first study to evaluate, at a country level, the impact of COVID-19 outbreak on Gastroenterology Divisions. Substantial changes of practice and reduction of procedures have been recorded in the entire country. The long-term impact of such modifications is difficult to estimate but potentially very risky for many digestive diseases. [ABSTRACT FROM AUTHOR]

In Italy, the prevalence of HDV infection in HBsAg carriers is about 9.9% (6.4% in Italian natives and 26.4% in immigrants). However, the actual prevalence is probably underestimated because the anti-HDV test is not performed routinely in all HBsAg carriers. The HDV causes a rapidly progressive liver disease and as new antiviral therapies are coming, it is fundamental to known the exact HDV prevalence. The aim of this study was to assess the real HDV prevalence in the AOU Federico II. From April 2021 to July 2022, reflex test for the detection of total HDV antibodies was performed in all HBsAg positive subjects observed at AOU Federico II. Demographic, clinical and laboratory data were collected. Liver fibrosis was evaluated with FIB-4. Sera were evaluated with ADVIA Centaur HBsAgII Qualitative, Liaison Murex HBsAg Quantitative and Liaison Murex Total Anti-HDV Qualitative. Of 365 HBsAg carriers, 46 (12.6%) resulted positive for total anti-HDV. The majority of them (89.2%) were Italian natives and only 5 (10.8%) of them were immigrants. Twenty-one (45.6%) were males with a median age of 62.2 years. Thirty-five (76%) patients were already aware of HBV/HDV coinfection. HDV-RNA was performed in 18 (39.1%) subjects and resulted detectable in 15 (83.3%) of them, with a median HDV-RNA level of 84.300 [25th – 75th percentiles: 1.685-547.796] IU/ml. Twenty (43.5%) anti-HDV positive subjects had advanced liver fibrosis. Our data showed that the HDV prevalence is higher than expected, demonstrating that the reflex test in HBsAg carriers could be a useful approach to identify the real prevalence of HDV infection. Moreover, the HDV-RNA is performed only in the minority of the anti-HDV positive subjects. In this setting, due to the forthcoming approval of specific anti-HDV drugs, a reflex test for HDV-RNA should be implemented to identify viremic patients needing antiviral treatment. [ABSTRACT FROM AUTHOR]

Emerging reports suggest a relationship between thyroid hormones (TH) signalling pathways and liver diseases, including hepatocellular carcinoma (HCC). Although it has been proven that the expression of deiodinases type 1 and 3 (D1-3) changes during induced liver injury, their role is still poorly understood in hepatocarcinogenesis. We aimed to evaluate the role of deiodinases and their regulation in liver carcinogenesis. This is a proof of knowledge introductory to an ongoing monocentric prospective study. We enrolled 19 patients underwent liver surgery for HCC (10 cases) or for other non-neoplastic liver diseases in non-cirrhotic context (9 controls). We evaluated genes and protein expression of the main TH metabolism factors (D1, Monocarboxylate transporter-MCT8, Thyroid receptors-TR alpha and beta and Kruppel-like factor-KLF-9), with RT-PCR and Western blot analysis in HCC, cirrhotic tissue and healthy liver samples. RT -PCR analysis showed a progressive statistically significant decrease of D1 (p=0.004), MCT-8 (p=0.001) and TRα (p=0.02) mRNA expression from healthy liver to HCC. The expression of KLF9, involved in cell differentiation and proliferation, decreased accordingly (p=0.03). Western Blot analysis showed a decreased expression of D1 protein in all cirrhotic samples (p=0.01), while D3 increased in 50% of HCC (p=0.02). Among HCC patients, D3 expression was associated with more severe liver stiffness (32 kPa, IQR:23.47-35.5, p=0.002) and high BMI (p=0.004). A statistically significant overall survival (OS) difference between D3 positive and D3 negative HCC patients was observed (log rank p=0.003), with a median OS of 17.9 (IQR:15.5-18.7) months for D3 positive vs 41.3 (IQR:35.1-43.8) months in D3 negative. Furthermore, a shorter Progression Free Survival and an increased recurrence rate was observed in D3 positive patients, even if not statistically significant. These preliminary data showed that D3 expression could define a more severe phenotype of HCC and it could be used in clinical practice as negative prognostic biomarker. [ABSTRACT FROM AUTHOR]

Several studies showed that patients with liver cirrhosis have an immune dysregulation leading to poor immunological response to vaccination. However, in literature there are few data about the response to SARS-CoV-2 vaccination in patients with chronic liver disease (CLD). Aims of the study are (is) the evaluation of safety and immunogenicity of booster dose in patients with CLD. From September 2021 to April 2022, all consecutive outpatients with CLD who completed the primary vaccination course and the booster dose for anti-SARS-CoV-2 vaccination were enrolled. Blood samples were collected 12-16 weeks after second dose and after booster dose. Collected samples were analyzed for detecting anti-Spike protein IgG using LIAISON TrimericS IgG chemiluminescent assay (Diasorin, Italy). We enrolled 340 patients (187 Males, mean age:64.32±17.34years). Stratified by the presence of cirrhosis, 249 had CLD and 91 were cirrhotic whose 57 (62.24%) had portal hypertension. At the end of the primary vaccination course, 60 patients (17.65%) did not develop a protective antibody titer, with no statistically significant differences between the two groups (19.7% in cirrhotic vs 16.8% in non-cirrhotic; p=0.076). The majority of them (53/60 patients; 88.3%) developed a protective titer after booster dose, without differences between cirrhotics and non-cirrhotics (p=0.089). At multivariate analysis, factors associated with a higher humoral response after booster dose were young age (p=0.0098); porto-sinusoidal vascular disorder (p=0.005), none or a single comorbidity rather than two or more (p=0.05) and Spikevax booster dose compared with Comirnaty (p=0.001). Moreover, the antibody titer is inversely related to age (p=0.000). In a large cohort of patients with CLD booster dose of anti-Sars-CoV-2 vaccine has an excellent immunogenicity and leads to an adequate antibody response even in those who had not produced a protective titer after the primary vaccination course. Cirrhosis is not associated with a reduced humoral response. [ABSTRACT FROM AUTHOR]

Abstract: Background: Hepatitis C virus (HCV) infection is often clinically silent in haemodialysed (HD) patients and their immune response may modulate liver damage in HCV infection. IL-10 and TGF-β1 could play a role in this setting as, IL-10 down-regulates hepatic fibrosis, while TGF-β1 is a pro-fibrotic cytokine. Aim: To evaluate the role of IL-10 and TGF-β1 in HD/HCV+ patients. Patients: 71 HD/HCV+ patients (58 with normal [HD/HCV-N] and 13 with high serum transaminases [HD/HCV-H]), 40 non-uremic patients with chronic hepatitis C (HCV+), 56 HD anti-HCV− patients and 20 healthy volunteers (H). Methods: IL-10 and TGF-β1 serum levels were assessed using ELISA tests. Liver histology was assessed by Ishak''s score. Results: IL-10 serum levels were significantly higher in HD patients, both HCV+ (3.7±0.4pg/ml; p <0.01) and HCV− (3.8±0.8pg/ml; p <0.05) than in non-uremic HCV patients (2.3±0.4pg/ml). Among the HD/HCV+ patients, IL-10 serum levels were similar in HD/HCV-N and in HD/HCV-H patients. Among the HD/HCV+ patients, IL-10 serum levels were similar in those with moderate histological damage compared to those with mild damage. TGF-β1 serum levels were significantly lower in HD patients, both HCV+ (4.6±0.9ng/ml) and HCV− (6.0±0.9ng/ml) than in non-uremic HCV+ patients (8.1±1.1ng/ml; p <0.001 and p <0.01, respectively), but similar to the values found in H (5.3±0.9ng/ml; p =n.s.). No correlation was seen between IL-10 and TGF-β1 serum levels in any of the groups considered. Conclusions: Patients on haemodialysis treatment to have high levels of IL-10, which remain high even when patients are anti-HCV+, whereas the opposite is true of TGF-β1. The cytokine pattern observed in HD patients is compatible with the hypothesis explaining the relatively benign evolution of HCV-related liver disease in HD patients, and has a pathophysiological role. [Copyright &y& Elsevier]

Abstract: A persistent increase in non-virus non-alcohol related aminostransferase levels can have multiple causes, which differ in terms of prevalence and clinical importance. In the general population, the most frequent cause is non-alcoholic hepatic steatosis, which can evolve into steato-hepatitis and cirrhosis. The treatment for steatosis and non-alcoholic steato-hepatitis consists of modifying lifestyles, whereas the effectiveness of drug treatment remains to be determined. Other much less frequent (yet not rare) causes of persistent non-virus non-alcohol related elevations in aminotransferase levels are celiac disease and hemochromatosis, whereas autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, and alpha-1-anti-trypsin deficit are rare. Given that some of these conditions are susceptible to treatment, early diagnosis is important. No epidemiological data are available for evaluating the prevalence of elevated aminotransferase levels correlated with the toxicity of drugs or other xenobiotics, including herbal products. The present document, created by a panel of experts based on a systematic review of scientific evidence, is mainly geared towards physicians working in General Medicine and Transfusion Centres, who generally represent the first contact of persons with elevated aminotransferase levels. The document includes suggestions for diagnosing causes of persistent non-virus non-alcohol related increases in aminotransferase levels, considering the frequency and response to treatment. The conditions requiring specialized visits are also indicated. [Copyright &y& Elsevier]