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Coronavirus disease 2019 is an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 that manifests as a variety of clinical manifestations, including liver damage commonly detected by a hepatocellular pattern from liver function tests. Liver injury is associated with a worse prognosis overall. Conditions associated with the severity of the disease include obesity and cardiometabolic comorbidities, which are also associated with nonalcoholic fatty liver disease (NAFLD). The presence of NAFLD, similarly to obesity, is associated with an unfavourable impact on the coronavirus disease 2019 outcome. Individuals with these conditions could present with liver damage and elevated liver function tests due to direct viral cytotoxicity, systemic inflammation, ischemic or hypoxic liver damage or drug side effects. However, liver damage in the setting of NAFLD could also be attributed to a pre-existing chronic low-grade inflammation associated with surplus and dysfunctional adipose tissue in these individuals. Here we investigate the hypothesis that a pre-existing inflammatory status is exacerbated after severe acute respiratory syndrome coronavirus 2 infection, which embodies a second hit to the underestimated liver damage.

Immoderate caspase-mediated apoptosis in chronic liver injury is a crucial driver of sustained HSC activation and worsening hepatic inflammation as well as fibrosis, with the ultimate outcome of liver cirrhosis and its consequences. Therefore, the inhibition of hepatocyte apoptosis by caspase cascade blockage may be a promising therapeutic strategy to achieve fibrosis regression in chronic liver diseases. Emricasan is a broad-spectrum, liver-targeted caspase inhibitor with a favorable pharmacokinetic profile, characterized by prolonged retention in the liver and low systemic exposure after oral administration. In animal models, emricasan had a clear intrahepatic anti-apoptotic effect with consequent elimination of circulating pro-inflammatory cytokines and favorable impact in liver fibrogenesis and portal pressure. Even though, this intrahepatic drug effect confirmed in human clinical trials, no clear linkage was emerged with portal hypertension, liver function or liver histology in both non-cirrhotic and cirrhotic patients except from a subgroup of patients with high MELD score ( 15) or severe HVPG ( 16 mmHg). As emricasan treatment appeared safe and well-tolerated, irrespective the severity of liver disease, more studies are required to clarify better these subgroups of patients who may benefit most from this drug.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the most common liver disorder worldwide mainly attributed to the epidemic spread of obesity and type 2 diabetes mellitus. Although it is considered a benign disease, NAFLD can progress to non-alcoholic steatohepatitis, liver cirrhosis and hepatocellular carcinoma (HCC). Most data regarding the epidemiology of NAFLD-related HCC are derived from cohort and population studies and show that its incidence is increasing as well as it is likely to emerge as the leading indication for liver transplantation, especially in the Western World. Although cirrhosis constitutes the main risk factor for HCC development, in patients with NAFLD, HCC can arise in the absence of cirrhosis, indicating specific carcinogenic molecular pathways. Since NAFLD as an underlying liver disease for HCC is often underdiagnosed due to lack of sufficient surveillance in this population, NAFLD-HCC patients are at advanced HCC stage at the time of diagnosis making the management of those patients clinically challenging and affecting their prognostic outcomes. In this current review, we summarize the latest literature on the epidemiology, other than liver cirrhosis-pathogenesis, risk factors and prognosis of NAFLD-HCC patients. Finally, we emphasize the prevention of the development of NAFLD-associated HCC and we provide some insight into the open questions and issues regarding the appropriate surveillance policies for those patients.

PURPOSE To evaluate the association between severity of hepatic steatosis/fibrosis with clinical, laboratory, and echocardiographic characteristics, including visceral obesity and type 2 diabetes mellitus (T2DM)-related micro- and macrovascular complications in diabetic patients with non-alcoholic fatty liver disease (NAFLD). METHODS We studied 60 consecutive NAFLD outpatients with T2DM, recording several demographic and clinical characteristics, trunk and visceral fat, cardiac ultrasound, and micro- and macrovascular complications of diabetes mellitus including microalbuminuria, diabetic peripheral neuropathy, peripheral vascular disease, and cardiac autonomic function. Severity of steatosis and fibrosis was evaluated with abdominal ultrasound and liver stiffness measurements, respectively. RESULTS Twenty-three (41%) of the patients had grade 1 steatosis and mean liver stiffness was 7.5 ± 3 kPa. After applying Bonferroni correction for multiple comparisons, ferritin concentration was the only factor significantly different between patients with mild (grade 1) compared to those with moderate/severe (grade 2/3) steatosis and showed good discriminative ability for the presence of moderate/severe steatosis (AUC: 0.74, sensitivity 88%, specificity 48%, PPV 74%, and NPV 72%). In addition, waist circumference was the only factor associated with the presence of significant fibrosis (≥ F2) with very good discriminative ability (AUC: 0.77, sensitivity 89%, specificity 45%, PPV 75%, and NPV 70%). CONCLUSION Specific clinical and laboratory characteristics, which may be determined via widely accessible and noninvasive techniques, were associated with severity of diabetics NAFLD, taking into account echocardiographic characteristics, visceral obesity, and T2DM-related systemic complications.

De novo lipogenesis (DNL) plays an important role in the pathogenesis of hepatic steatosis and also appears to be implicated in hepatic inflammation and fibrosis. Accordingly, the inhibition of acetyl-CoA carboxylase, which catalyzes the rate-limiting step of DNL, might represent a useful approach in the management of patients with nonalcoholic fatty liver disease (NAFLD). Animal studies and preliminary data in patients with NAFLD consistently showed an improvement in steatosis with the use of these agents. However, effects on fibrosis were variable and an increase in plasma triglyceride levels was observed. Therefore, more long-term studies are needed to clarify the role of these agents in NAFLD and to determine their risk/benefit profile.

Background/AimLiver stiffness measurement (LSM) has been predicting liver decompensation and survival in cirrhotics. The aim of our study was to investigate if spleen stiffness measurement (SSM) by 2D-Shear Wave Elastography could predict better the probability of decompensation and mortality, compared to LSM and other parameters.MethodsConsecutive cirrhotic patients were recruited between 1/2017-12/2021. LSM and SSM were performed at baseline and epidemiological, clinical and laboratory data were collected. Clinical events were recorded every 3 months.ResultsTotally, 177 patients were followed for a mean period of 31±18 months. In Cox regression analysis, only SSM was independently associated with the probability of decompensation (HR: 1.063, 95% CI: 1.009-1.120; p=0.021), offering an AUROC of 0.710 (p=0.003) for predicting 1-year liver decompensation (NPV: 81.1% for the cut-off point of 37 kPa). The occurrence of death/liver transplantation was independently associated only with higher SSM (HR: 1.043; 95% CI:1.003-1.084; p=0.034). The AUROC of SSM for predicting 1-year death/liver transplantation was 0.72 (p=0.006), (NPV: 95% for the cut-off of 38.8 kPa). The performance of SSM to predict the 1-year death/liver transplantation increased in high-risk patients (CTP: B/C plus MELD >10 plus LSM >20 kPa) giving an AUROC of 0.80 (pConclusionsSSM was the only factor independently associated with the probability of decompensation and occurrence of death, showing better diagnostic accuracy for the prediction of 1-year decompensation or death compared to LSM and MELD score.

AimsTo estimate all-cause mortality in a cohort of people who inject drugs (PWID) over the period 2018–2022 in the two major cities of Greece (Athens and Thessaloniki).MethodsPWID were recruited from two community-based seek-test-treat programs for HCV and HIV infections in Athens and Thessaloniki. Participants provided information on sociodemographic characteristics, injection practices, social security number, access to harm reduction and treatment. Data on the vital status and date of death were identified from the national HCV treatment registry. All-cause mortality rates (CMR) were estimated as well as age-, gender- and calendar-year standardized mortality ratios (SMR). Determinants of mortality were assessed using a Cox proportional-hazards model.ResultsOf 2,433 PWID, 243 (10.0%) died over a total of 6,649 person-years (PYs) of follow-up. The CMR [95% confidence interval (CI)] was 3.50 (3.08–3.97) deaths per 100 PYs; 3.03 (2.58–3.57) in Athens and 4.56 (3.74–5.57) in Thessaloniki. An increasing trend in CMR was identified over the period 2018–2022 in Athens (p for trend=0.004). The overall SMR (95% CI) was 17.17 (15.14–19.47) per 100 PYs in the combined cohort; 15.10 (12.85–17.75) in Athens and 21.72 (17.78–26.53) in Thessaloniki. The SMR was particularly increased in younger ages, females, those injecting daily, and HIV-infected PWID. Older age, living in Thessaloniki, Greek origin, homelessness, daily injecting drug use, HIV, and HCV infections were independently associated with all-cause mortality.ConclusionAll-cause mortality among PWID in Greece during 2018–2022 is high with the population in Thessaloniki being particularly affected. The increasing trend in mortality in Athens might be the long-term impact of the pandemic on the health of PWID. Preventive programs such as take-home naloxone distribution and community involvement to increase harm reduction, screening, and uptake of antiretroviral and chronic hepatitis C treatment are urgently needed.

Excessive alcohol intake is an established risk factor for chronic liver disease. At the same time, moderate alcohol intake appears to reduce cardiovascular morbidity. Accordingly, recommendations for alcohol intake in patients with nonalcoholic fatty liver disease (NAFLD), who are at increased risk for liver-related and cardiovascular events, are a point of debate. Some studies have shown beneficial effects of alcohol on cardiovascular and overall mortality in this specific subset of patients. Nonetheless, even light alcohol intake appears to aggravate liver disease and increase the risk of hepatocellular cancer. Therefore, patients with nonalcoholic steatohepatitis or advanced fibrosis should be advised against consuming alcohol. On the other hand, only light alcohol consumption (

Coronavirus disease 2019 (COVID-19) is a systemic illness with an increased host inflammatory response that affects multiple extra-pulmonary organs, including the gastrointestinal tract. Abnormalities in liver biochemistry have been observed in a significant proportion of patients with COVID-19 upon admission, and this proportion increases with hospitalization. These abnormalities are typically manifested as elevations in aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, with less frequently detected elevations in the levels of cholestatic enzymes. Elevated aminotransaminase levels have been linked to an increased risk of mortality and complications, indicating the severity of COVID-19 infection. The present study evaluated the prevalence and the baseline factors associated with the development of acute hepatitis (ΑΗ), liver injury (LI) and associated patterns, as well as the presence of abnormalities in the levels of aminotransferases at discharge in the same cohort. For this purpose, 1,304 patients with confirmed COVID-19 infection were enrolled in the study. According to the results obtained, AST levels at baseline were the only independent factor for AH during hospital stay, while AST, alkaline phosphatase and ferritin levels were independent baseline factors for the development of LI. The patients with hepatocellular, compared to those with cholestatic LI, exhibited similar survival rates, as well as similarities in the development of acute kidney injury and the need for oxygen via high-flow nasal cannula and/or mechanical ventilation. In addition, age and ALT were independent risk factors for persistent abnormal values of AST and ALT at discharge.

Nonalcoholic fatty liver disease (NAFLD) has emerged as the predominant cause of chronic liver injury worldwide. Bile acids and their receptors are profoundly implicated in the pathogenesis of NAFLD and its progression to nonalcoholic steatohepatitis and cirrhosis.We conducted extensive literature search using PubMed database, and we summarized the relevant literature. We provided an overview of the fibroblast growth factor 19 (FGF-19)-farnesoid X receptor (FXR) axis and summarized the latest findings derived from animal and human studies concerning the impact of FGF-19 on NAFLD.FGF-19, a nutritionally regulated endocrine post-prandial hormone, governs bile acid metabolism, lipid oxidation, lipogenesis, and energy homeostasis. As no approved medication for NAFLD exists, FGF-19 seems to be a propitious therapeutic opportunity for NAFLD, since its administration was associated with ameliorated results in hepatic steatosis, liver inflammation and fibrosis. Furthermore, promising results have been derived from clinical trials concerning the beneficial efficacy of FGF-19 on histological findings and laboratory parameters of NAFLD. However, we should bear in mind the pleiotropic effects of FGF-19 on various metabolically active tissues along with its potential tumorigenic reservoir. Further clinical research is required to determine the clinical application of FGF-19-based therapies on NAFLD.

Although several liver- and inflammation-based scores to predict the clinical course of patients with coronavirus disease 2019 (COVID-19) have been evaluated, no direct comparison regarding their predictive ability has been performed.1038 patients (608 males, age 63.5 ± 17 years) hospitalized with documented COVID-19 infection to the non-ICU ward, were included retrospectively. Clinical and laboratory characteristics on admission including evaluation of Fibrosis-4 (FIB-4) score and C-Reactive Protein (CRP) to albumin ratio (CAR) were recorded.One hundred and twenty-four patients (11.9%) died during hospitalization after 8 (3-72) days. In multivariate analysis, FIB-4 (hazard ratio, 1.11; 95% confidence interval (CI), 1.034-1.19; P = 0.004), was independently associated with mortality, with very good discriminative ability (area under the receiver operating characteristic curve curve, 0.76). The patients with FIB-4amp;gt;2.67 (n = 377), compared to those with ≤2.67 (n = 661), had worse survival (log-rank 32.6; P amp;lt; 0.001). Twenty-four (6.8%) of 352 patients with possible nonalcoholic fatty liver disease (NAFLD) (defined as Hepatic Steatosis Indexamp;gt;36) died during hospitalization. In multivariate analysis, CAR was an independent risk factor (1) for mortality (hazard ratio, 1.014; 95% CI, 1.002-1.025; P = 0.021), (2) the need for high-flow nasal cannula with or without intubation (hazard ratio, 1.016; 95% CI, 1.004-1.027; P = 0.007) and (3) development of acute kidney injury (hazard ratio, 1.017; 95% CI, 1.006-1.028; P = 0.002). In addition, the patients with possible NAFLD and CARamp;gt;12 (n = 154), compared to those with CAR ≤12 (n = 198), had worse survival (log-rank 5.1; P = 0.024).FIB-4 was an independent factor for mortality with better performance compared to other liver function test- and inflammation-based scores in patients with COVID-19, while CAR was the only score independently associated with the clinical course in COVID-19 patients with possible NAFLD.

The aim of this study is to evaluate the performance of 2D-shear wave elastography (2D-SWE) in patients with nonalcoholic fatty liver disease (NAFLD) and compare it to transient elastography.Over 6 months, 552 patients with NAFLD underwent liver stiffness measurement (LSM) by both 2D-SWE and transient elastography with controlled attenuation parameter (CAP) at the same visit.LSM was not feasible by transient elastography (M/XL probe) in 18 (3.3%) and by 2D-SWE in 26 (4.7%) patients. The median LSM of transient elastography was 5.5 (2.8-75) kPa and of 2D-SWE 6.2 (3.7-46.2) kPa. LSMs by transient elastography and 2D-SWE were correlated regardless of the obesity status (r, 0.774; P0.001; r, 0.774; P0.001; r, 0.75; P0.001 in BMI25, 25-30 and ≥30 kg/m2 respectively), or the degree of liver steatosis (r = 0.63; P0.001 and r = 0.743; P0.001 in mild and moderate/severe steatosis, respectively). According to transient elastography, 88 (15.9%) patients were classified with at least severe fibrosis (≥F3) and 55 (10%) with cirrhosis. By using the 2D-SWE, 85 (15.4%) patients had at least severe fibrosis and 52 (9.4%) cirrhosis. The correlation between the two methods was strong in patients with at least severe fibrosis (r, 0.84; P0.001) or cirrhosis (r, 0.658; P0.001). When transient elastography was used as reference, 2D-SWE showed an excellent accuracy of 98.8 and 99.8% in diagnosing severe fibrosis and cirrhosis, respectively.In NAFLD, 2D-SWE and transient elastography have comparable feasibility and clinical applicability providing LSMs with strong correlation, even in overweight/obese patients, independently of the severity of liver steatosis and fibrosis. Thus, either of the two methods can be effectively used for the assessment of fibrosis in this setting.

The advance in treatment against hepatitis B virus (HBV) infection with the development of nucleos(t)ide analogues (NAs) with high genetic barrier to resistance, including entecavir and tenofovir, has improved clinical outcomes of patients transplanted for HBV infection, by preventing HBV recurrence after liver transplantation (LT) effectively. Currently, after LT, the combination of hepatitis B immunoglobulin (HBIG) and a high-barrier NA is considered as the standard of care for prophylaxis against HBV recurrence. However, because of the high cost of intravenous high-dose HBIG, other routes of HBIG administration, such as intramuscular or subcutaneous, have come to the foreground. In addition, several transplant centres tend to use a NA as monoprophylaxis, following a short post-LT period of HBIG and NA combination. Lately, studies using HBIG-free prophylactic regimens with entecavir or tenofovir have shown promising outcomes in preventing HBV recurrence, mostly regarding patients with undetectable HBV DNA at the time of LT. Although vaccination against HBV has been an attractive prophylactic approach, its efficacy has been controversial. Moreover, further studies are needed regarding long-term outcomes of complete withdrawal anti-HBV prophylaxis. For patients transplanted for HBV/HDV co-infection, combined regimen should be administered for a longer period post-LT. Finally, the use of grafts from hepatitis B core antibody-positive donors is safe for HBV-negative recipients, with the administration of lifelong antiviral prophylaxis.

Hepatocellular carcinoma (HCC) may still develop in chronic hepatitis B (CHB) patients even under effective long-term oral antiviral therapy, but its pathogenesis in the setting of long-standing inhibition of viral replication has not been completely elucidated. We investigated whether species of circulating cell-free DNA (cfDNA) may be involved in the process of hepatocarcinogenesis in treated CHB patients. Serum samples were obtained from HBeAg-negative CHB patients with (HCC cases, n = 37) or without HCC development during the first 5 years of oral antiviral therapy (controls, n = 74). HCC cases and controls were matched 1:2 for age, sex and platelets. Determination of different circulating cfDNA species (before HCC diagnosis in HCC cases) including total cfDNA quantity, levels of Alu repeat DNA and RNase P coding DNA, copies of mitochondrial DNA and levels of 5-methyl-2'-deoxycytidine as an indicator of DNA methylation was performed. HCC cases compared with controls had higher median levels of Alu247 (123 vs 69 genomic equivalent, p = .042) and RNase P coding DNA (68 vs 15 genomic equivalent, p < .001). In contrast, median cfDNA concentration, Alu115 levels, Alu247/Alu115 ratio as an index of DNA integrity and mitochondrial DNA copies did not differ significantly between HCC cases and controls. Receiver operating characteristic curve analysis showed that levels RNase P coding DNA offered good prediction of subsequent HCC development (c-statistic: 0.80, p < .001). In conclusion, serum levels of RNase P coding DNA are increased years before HCC diagnosis and could be potentially helpful in the prediction of the HCC risk in treated HBeAg-negative CHB patients.

Nonalcoholic fatty liver disease (NAFLD) accounts for most cases of chronic liver disease worldwide, with an estimated global prevalence of approximately 25% and ranges from simple steatosis to nonalcoholic steatohepatitis and cirrhosis. NAFLD is strongly connected to metabolic syndrome, and for many years, fatty liver was considered to be an exclusive feature of obese patients. However, recent studies have highlighted the presence of NAFLD in non-obese subjects, with or without increased visceral fat or even in lean subjects without increased waist circumference. "Lean NAFLD" is a relatively new concept and there is significant scientific interest in understanding the differences in pathophysiology, prognosis and management compared with NAFLD in overweight/obese patients. In the present editorial, we discuss the clinical and metabolic profiles and outcomes of lean NAFLD compared with both obese NAFLD and lean healthy individuals from Asian and Western countries. Moreover, we shed light to the challenging topic of management of NAFLD in lean subjects since there are no specific guidelines for this population. Finally, we discuss open questions and issues to be addressed in the future in order to categorize NAFLD patients into lean and non-lean cohorts.

Affecting one fourth of the global population, non-alcoholic fatty liver disease (NAFLD) is the commonest chronic liver disorder. It encompasses the simple liver fat accumulation to more progressive steatosis, inflammation, and fibrosis characterized as non-alcoholic steatohepatitis (NASH) and in some cases cirrhosis and hepatocellular carcinoma. NAFLD regularly coexists with metabolic disorders, such as obesity and mostly type 2 diabetes mellitus (T2DM). A relatively new class of antidiabetic drugs, the sodium glucose co-transporter 2 (SGLT2) inhibitors exert their action by increasing the urinary glucose and calorie excretion leading to ameliorated plasma glucose levels and lower bodyweight. Recently, several animal studies and human clinical trial have emphasized the possible beneficial impact of SGLT2 inhibitors on NAFLD and its progression to NASH. In this present review, we summarize the current literature regarding the efficacy of the aforementioned category of drugs on anthropometric, laboratory, and histological features of patients with NAFLD. Conclusively, as SGLT2 inhibitors seem to be an appealing therapeutic opportunity for NAFLD management, we identify the open issues and questions to be addressed in order to clarify the impact in choosing antidiabetic medication to treat NAFLD patients associated with T2DM.

Background: Nonalcoholic fatty liver disease, particularly in the presence of hepatic fibrosis, is associated with an increased risk of cardiovascular events, including ischemic stroke. However, it is unclear whether hepatic fibrosis is associated with the severity and outcome of acute ischemic stroke. Aim: To evaluate the relationship between hepatic fibrosis and the severity at admission and in-hospital outcome of acute ischemic stroke. Patients and methods: We prospectively studied all patients who were admitted to our department with acute ischemic stroke between September 2010 and February 2018 (n = 1107; 42.1% males, age 79.8 ± 7.2 years). The severity of stroke was assessed at admission with the National Institutes of Health Stroke Scale (NIHSS). Severe stroke was defined as NIHSS ≥ 21. The presence of hepatic fibrosis was evaluated with the Fibrosis-4 index (FIB-4). The outcome was assessed with dependency at discharge (modified Rankin Scale between 2 and 5) and with in-hospital mortality. Results: Patients with severe stroke had a higher FIB-4 index than patients with non-severe stroke (2.7 ± 1.7 and 2.3 ± 1.4, respectively; p < 0.05). Independent risk factors for severe IS were age (relative risk (RR) 1.064, 95% confidence interval (CI) 1.030–1.100, p < 0.001), female sex (RR 1.723, 95% CI 1.100–2.698, p = 0.012), atrial fibrillation (RR 1.869, 95% CI 1.234–2.831, p = 0.002), diastolic blood pressure (DBP) (RR 1.019, 95% CI 1.006–1.033, p = 0.001), and the FIB-4 index (RR 1.130, 95% CI 1.007–1.268, p = 0.022). At discharge, 64.2% of patients were dependent. The FIB-4 index did not differ between patients who were dependent and those who were independent at the time of discharge (2.3 ± 1.5 and 2.1 ± 1.2, respectively; p = 0.061). During hospitalization, 9.8% of patients died. Patients who died during hospitalization had a higher FIB-4 index than those who were discharged (2.9 ± 1.8 and 2.3 ± 1.4, respectively; p < 0.005). Independent risk factors for in-hospital mortality were DBP (RR 1.022, 95% CI 1.010–1.034, p < 0.001), serum glucose levels (RR 1.004, 95% CI 1.001–1.007, p = 0.007), serum triglyceride levels (RR 0.993, 95% CI 0.987–0.999, p = 0.023), NIHSS (RR 1.120, 95% CI 1.092–1.149, p < 0.001), and the FIB-4 index (RR 1.169, 95% CI 1.060–1.289, p = 0.002). Conclusions: Hepatic fibrosis, evaluated with the FIB-4 index, appears to be associated with more severe ischemic stroke and might also represent an independent risk factor for in-hospital mortality in patients admitted with acute ischemic stroke.

Diabetes mellitus (DM) is an independent risk factor for admission to intensive care unit and death in patients with coronavirus disease 2019 (COVID-19). On the other hand, medications used in the management of COVID-19 are potentially associated with increases in blood glucose levels and a higher incidence of infections. Accordingly, care of patients with DM and acute COVID-19 requires careful consideration of both diseases. Hyperglycemia and hypoglycemia are associated with adverse outcomes and therefore frequent measurement of blood glucose levels and a basal-bolus insulin regimen are required in most patients. Regarding the management of COVID-19, dexamethasone increases blood glucose levels and might also increase the risk for infections. On the other hand, limited data suggest that antiviral and immunomodulatory agents used in COVID-19 are not strongly associated with higher incidence of infections in this population. As knowledge evolves in this field, optimization of the management of both DM and COVID-19 will hopefully improve the outcome of these patients.

Hepatitis E virus (HEV) is a common cause of acute hepatitis in developing countries, but it can also take a chronic course especially in immunocompromised patients. Its epidemiology after liver transplantation (LT) is hard to assess and treatment options are still explored. Between 2009 and 2020, literature reporting HEV prevalence and treatment in LT recipients was searched and a synthesis was attempted. Sixteen studies reported HEV prevalence in consecutive LT patients: HEV RNA positivity ranged between 0%-1.4% and 0%-7.7% for Western and Eastern cohorts, respectively. In studies published between 2009-2014 and 2015-2020, HEV RNA positivity ranged between 0.35%-1.3% (all European) and 0%-7.7% (European: 0%-1.4%), respectively. Five studies evaluated HEV prevalence in LT recipients with abnormal liver enzymes: HEV RNA positivity was 2.9% in studies published between 2009 and 2014 and from 3.5% to 20% in studies published between 2015 and 2020. Twenty-seven studies reported HEV treatment in LT recipients: sustained virologic response was achieved in 15% by immunosuppression reduction alone and in 83% of cases by ribavirin regiments. Chronic HEV infection is affecting LT recipients, mostly those with abnormal liver enzymes and in Eastern countries. HEV diagnoses should be based on PCR techniques. Successful treatment can be achieved with ribavirin in most cases.

Abnormalities in aminotransferases are frequently observed in hospitalized COVID-19 patients, but their clinical impact is poorly characterized.A total of 1046 patients hospitalized to the non-intensive care unit ward with documented COVID-19 were included retrospectively. Demographic, clinical and laboratory characteristics on admission and during hospital stay, including the presence of liver injury (LI), defined as aspartate aminotransferase (AST)200 IU/L, were recorded.On admission, 363 (34.7%) and 269 (25.7%) patients had abnormal AST and ALT values (i.e.,40 IU/L), respectively, while during hospitalization 53 (5%) patients fulfilled the criteria for LI. In multivariate logistic regression analysis, AST (odds ratio [OR] 1.023, 95% confidence interval [CI] 1.016-1.029; P0.001), and ferritin (OR 1.01, 95%CI 1.001-1.02; P0.001) were the baseline factors independently associated with the development of LI during hospital stay. One hundred twenty-three (11.7%) patients died during hospitalization. The independent variables associated with mortality were: age (hazard ratio [HR] 1.043, 95%CI 1.029-1.056; P0.001), ferritin (HR 1.1, 95%CI 1.05-1.2; P0.001), platelets (HR 0.996, 95%CI 0.994-0.999; P=0.003), and administration of remdesivir (HR 0.50, 95%CI 0.30-0.85; P=0.009). The patients with abnormal baseline AST (i.e.,40 IU/L), compared to those with normal AST values, had worse outcomes (log rank test: 8.8, P=0.003).Elevated aminotransferases are commonly seen in COVID-19 patients. They possibly reflect disease severity and may be associated with in-hospital mortality.

In recent years, frailty has been increasingly recognized among researchers of distinct medical specialties worldwide. Frailty comprises a complex of multisystemic physiological decline, reduced physiologic reserve, and vulnerability to stressors. Frail people tend to have a shorter lifespan and greater disability, morbidity and mortality. In the field of hepatology, frailty is identified in nearly 50% of patients who have cirrhosis of any cause. The most predominant cause of chronic liver disease is nonalcoholic fatty liver disease (NAFLD), considered as the hepatic manifestation of the metabolic syndrome (MetS). Although it is viewed as a benign disease, it may progress to nonalcoholic steatohepatitis (NASH), characterized by the additional emergence of inflammation and hepatocyte ballooning, with or without fibrosis. During the progression of NAFLD to NASH and liver cirrhosis, NAFLD patients present sarcopenia along with lower skeletal muscle strength and function. Moreover, aging and the increased prevalence of comorbidities further exacerbate their physical performance. The aforementioned features are strongly associated with the frailty phenotype, implying that the latter could be associated with both MetS and NAFLD. Although it is a relatively new topic of research interest, in this review we aim to provide a synopsis of the current literature dealing with the interplay between frailty and MetS, and to shed more light on the association between NAFLD and frailty. Finally, we discuss the potential pathophysiological mechanisms linking the distinct features of MetS and NAFLD with aspects of the frailty phenotype.

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Primary liver cancer is the sixth most common cancer and the fourth leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for 75% of primary liver cancer cases, mostly on the basis of cirrhosis. However, the data and therapeutic options for the treatment of HCC in patients with decompensated cirrhosis are rather limited. This patient category is often considered to be in a terminal stage without the possibility of a specific treatment except liver transplantation, which is restricted by several criteria and liver donor shortages. Systemic treatments may provide a solution for patients with Child Pugh class B or C since they are less invasive. Although most of the existing trials have excluded patients with decompensated cirrhosis, there are increasing data from real-life settings that show acceptable tolerability and satisfying efficacy in terms of response. The data on the administration of locoregional treatments in such patients are also limited, but the overall survival seems to be potentially prolonged when patients are carefully selected, and close adverse event monitoring is applied. The aim of this review is to analyze the existing data regarding the administration of treatments in decompensated patients with HCC, evaluate the effect of therapy on overall survival and highlight the potential risks in terms of tolerability.

Hepatopulmonary syndrome (HPS) and porto-pulmonary hypertension (PoPH) represent relatively common pulmonary vascular complications of advanced liver disease. Despite distinct differences in their pathogenetic background, both clinical states are characterized by impaired arterial oxygenation and limited functional status, and are associated with increased pre-transplantation mortality. Accumulation of ascitic fluid in the pleural cavity, known as hepatic hydrothorax (HH), is another frequent manifestation of decompensated cirrhosis, which may cause severe respiratory dysfunction, depending on the volume of the effusion, the rapidity of its development and its resistance to therapeutic measures. Orthotopic liver transplantation constitutes the only effective treatment able to resolve the pulmonary complications of liver disease. A prioritization policy for liver transplantation has evolved over the past years regarding advanced stages of HPS, yielding favorable outcomes regarding post-transplantation survival and HPS resolution. In contrast, severe PoPH is associated with poor post-transplantation survival. Hence, liver transplantation is recommended only for patients with PoPH and an acceptable reduction in pulmonary pressure values, after receiving PoPH-targeted vasodilating therapy. This review focuses on basic pathogenetic and diagnostic principles and discusses the current therapeutic approaches regarding HPS, PoPH, and HH.

Newly introduced galectin-3 (gal-3) has been associated to impaired renal function. Gal-3 may become prognostic biomarker in hepatic diseases.To investigate the association of gal-3 with prognosis and renal function in patients with stable decompensated cirrhosis.We studied prospectively 100 stable decompensated patients in our Department between 2010 and 2017. We measured gal-3 in serum samples. Patients' renal function was assessed usingSeventy patients (70%) survived and 30 died (n = 16) or underwent LT (n = 14). Twenty nine patients (29%) had normal gal-3, 71 (71%) had ≥11.7 ng/mL; they differed significantly regarding mean "true"-GFR: 90 ± 20 mL/min vs. 76 ± 26 mL/min, p = 0.03 and mean creatinine: 0.83 ± 0.14 mg/dL vs. 0.97 ± 0.4 mg/dL, p = 0.05. Median gal-3 levels were 17.5 ng/mL (range 4.9-76.5 ng/mL); 49 patients with gal-3 ≥17.5 ng/mL had significantly higher MELD score, (15 ± 5 vs. 13 ± 4, p = 0.02) and worse "true" GFR (74 vs. 85 mL/min, p = 0.04). Gal-3 had good performance in predicting "true"-GFR 60 mL/min; AUC: 0.71, 95%CI [0.58-0.85], best cut off value 17.5 ng/mL. Kaplan-Meier analysis, using median gal-3 (17.5 ng/mL) revealed different survival time for our patients (log-rank p = 0.04).Gal-3 proved trustworthy marker of established chronic kidney disease, with predictive ability in stable decompensated cirrhosis. Gal-3 came also a significant factor for our patients' outcome.

Introduction: Red cell distribution width to platelet ratio (RPR) may be a useful marker for the evaluation of liver fibrosis in chronic liver disease (CLD). We sought to investigate its value in fibrosis-related outcomes in a meta-analysis of diagnostic accuracy. Areas covered: We searched MEDLINE (1966-2019), Clinicaltrials.gov (2008-2019), Cochrane Central Register of Controlled Trials (CENTRAL) (1999-2019), Google Scholar (2004-2019) and WHO (International Clinical Trials Register Platform) databases using a structured algorithm. The articles were assessed by Quality Assessment of Diagnostic Accuracy Studies tool (QUADAS-2). In over 1,800 patients for each outcome, pooled sensitivity and specificity for a) significant fibrosis, b) advanced fibrosis and c) cirrhosis were: a) 0.635 and 0.769 with an AUC of 0.747, b) 0.607 and 0.783 with an AUC of 0.773, c) 0.739 and 0.768 with an AUC of 0.818 respectively. Similar results were found for chronic hepatitis B in all outcomes. Subgroup analysis indicated a high specificity for advanced fibrosis detection in primary biliary cirrhosis. Sensitivity analysis did not alter the results. Expert opinion: RPR is a good predictor of fibrosis, especially as severity of chronic liver disease progresses. Future research should elucidate its value in specific etiologies of chronic liver disease.