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Background The COVID-19 pandemic significantly compromised screening, laboratory controls, clinical surveillance and treatment of chronic hepatitis patients and worsened their outcome, as evidenced by its significant correlation with advanced cirrhosis, liver decompensation and mortality. Results This pandemic significantly impaired also the sector of liver transplantation, whose wards, operating rooms, outpatients' facilities, and healthcare personnel have been dedicated to patients with COVID-19. In addition, screening and treatment for HBV infection have been delayed or suspended in in most countries, with an increased risk of viral reactivation. Similar delay or suspension have also occurred for universal hepatitis B vaccination programs in many countries. Likewise, COVID-19 pandemic has made unreachable the goal of elimination of HCV infection as a worldwide public-health issue predicted for 2030 by the WHO. Conclusion This review article demonstrates how COVID-19 pandemic is causing serious damage to the sector of liver disease, which has quickly lost the beneficial effects of years of study, research, and clinical and technological application, as well as considerable financial investments.

AIM to assess vitamin E efficacy, defined as its ability to induce hepatitis B e antigen (HBeAg) seroconversion, in children with HBeAg-positive persistent hepatitis. METHODS In July 2016, we extracted articles published in MEDLINE and the Cochrane Library using the following search terms: "chronic hepatitis B", "children", "childhood", "therapy", "treatment", "vitamin E", "tocopherols", "tocotrienols". Only randomized controlled trials (RCTs) published in English language were collected. RESULTS Three RCTs met inclusion criteria and were considered in the present meta-analysis. Overall, 23/122 children in the treatment group underwent HBeAg seroconversion vs 3/74 in the control group (OR = 3.96, 95%CI: 1.18-13.25, p = 0.025). CONCLUSION Although our meta-analysis has several limits, including the very small number of available studies and enrolled children with HBeAg positivity-related hepatitis, it suggests that vitamin E use may enhance the probability to induce HBeAg seroconversion in these patients. Further well designed and adequately sized trials are required to confirm or deny these very preliminary results.

Background and Aims: Tenofovir disoproxil fumarate (TDF) is recommended for chronic hepatitis B (CHB) treatment, but it may induce kidney dysfunction whose management is not yet known. This Italian, multicentre, retrospective study aimed to assess the efficacy and safety of switching to entecavir (ETV) patients who developed TDF-associated glomerular and/or tubular dysfunction. Methods: A total of 103 TDF-treated patients were included as follows: age 64years, 83% male, 49% cirrhotics, 98% with undetectable HBV DNA, 47% with previous lamivudine resistance (LMV-R) and 71% previously treated with adefovir. Twenty-nine (28%) were switched to ETV because estimated glomerular filtration rate (eGFR MDRD ) was

The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). Some cellular microRNAs are emerging as important regulators of virus-host interaction, indirectly or directly modulating HBV replication and pathogenesis. miR-125a binds the viral transcript encoding the surface antigen and interferes with its expression, thus inhibiting viral replication. Intriguingly, liver miR-125a expression has been found increased in patients with high levels of hepatic HBV-DNA. The present study investigates the mechanism by which liver exposure to HBV induces the expression of miR-125a. The analyses were first performed on liver biopsies from HBV patients, showing that the expression of the viral transactivator X protein (HBx) paralleled the increase of miR-125a expression. Then, transfection of HCC cell lines with an HBx-expressing vector showed a substantial increase of miR-125a expression. Overall, the available data depict a self-inhibitory feedback loop in which HBV, through HBx, increases the expression of miR-125a, that in turn interferes with expression of HBV surface antigen, thus repressing viral replication. © 2014 Elsevier Inc. All rights reserved. The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). Some cellular microRNAs are emerging as important regulators of virus-host interaction, indirectly or directly modulating HBV replication and pathogenesis. miR-125a binds the viral transcript encoding the surface antigen and interferes with its expression, thus inhibiting viral replication. Intriguingly, liver miR-125a expression has been found increased in patients with high levels of hepatic HBV-DNA. The present study investigates the mechanism by which liver exposure to HBV induces the expression of miR-125a. The analyses were first performed on liver biopsies from HBV patients, showing that the expression of the viral transactivator X protein (HBx) paralleled the increase of miR-125a expression. Then, transfection of HCC cell lines with an HBx-expressing vector showed a substantial increase of miR-125a expression. Overall, the available data depict a self-inhibitory feedback loop in which HBV, through HBx, increases the expression of miR-125a, that in turn interferes with expression of HBV surface antigen, thus repressing viral replication. © 2014 Elsevier Inc. All rights reserved.

SummarySome studies suggest that patients with hepatitis C virus (HCV) infection have an increased risk of deep venous thrombosis (DVT) and pulmonary embolism (PE). Unfortunately, available data on this association are contrasting. A systematic review and meta-analysis of literature studies was performed to evaluate the risk of venous thromboembolism (VTE) associated with HCV. Studies reporting on VTE risk associated with HCV were systematically searched in the PubMed, Web of Science, Scopus and EMBASE databases. Six studies (10 data-sets) showed a significantly increased VTE risk in 100,364 HCV patients as compared with 8,471,176 uninfected controls (odds ratio [OR]: 1.900; 95 % confidence interval [CI]: 1.406, 2.570; pSupplementary Material to this article is available online at www.thrombosis-online.com.

Background Anti-phospholipid antibodies positivity is associated with several clinical conditions, including infectious diseases. Aims We performed a meta-analysis evaluating the association of hepatitis B and C with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications. Methods Studies evaluating the association of viral hepatitis with anti-cardiolipin, anti-β 2 glycoprotein-I and lupus anticoagulant antibodies and anti-phospholipid antibody-related thrombotic events were systematically searched. Results 20 studies (2319 cases, 1901 controls) were included. The analyses showed that viral hepatitis is associated with the presence of anti-cardiolipin and anti-β 2 glycoprotein-I antibodies. The association with anticardiolipin antibodies was confirmed in both hepatitis B (OR 11.22, 95% CI: 6.68–18.84) and hepatitis C (OR 11.26, 95% CI: 6.82–18.59). Similarly, compared to controls, anti-β 2 glycoprotein-I antibodies were found more frequently in hepatitis B (OR 14.07, 95% CI: 3.06–64.66) and hepatitis C (OR 5.64, 95% CI: 1.69–18.77). Moreover, 11 studies (257 cases, 1079 controls) showed a higher prevalence of venous and/or arterial thrombosis in patients with hepatitis and anti-cardiolipin antibody positivity compared hepatitis alone (OR 3.29, 95% CI: 1.79–6.07). This result was consistently confirmed in hepatitis C (OR 3.64, 95% CI: 1.78–7.46) but not in hepatitis B. Conclusions Viral hepatitis is significantly associated with anti-phospholipid antibody positivity and with anti-phospholipid antibody-related thrombotic complications.

Historically, only 10% of hepatocellular cancer (HCC) patients are diagnosed with early stage, potentially curable disease. We prospectively screened chronic hepatitis virus-infected patients to determine 1) the proportion diagnosed with potentially curable HCC, and 2) survival following curative therapy. The study included 5670 chronic hepatitis B (1,077, 19.0%), C (4,196, 74.0%), or both (397, 7.0%)-infected patients enrolled in a prospective screening program. Screening was every 6 months with serum alpha-fetoprotein (AFP) measurement and ultrasonography. Curative treatments included liver transplantation, resection, RFA, and/or ethanol injection. HCC was diagnosed in 464 (8.2%) patients. Of 1006 cirrhotic patients, 462 (45.9%) developed HCC. Curative treatment was possible in 319 (68.7%). The 2- and 5-year overall survival rates in the curative treatment group were 65% and 28%, respectively, compared to 10% and 0% in the advanced disease group (p < 0.001). Prospective screening of patients at high risk to develop HCC increases the proportion diagnosed with potentially curable disease. This may result in an increase of the number of long-term survivors. A screening strategy should focus on those patients with chronic hepatitis B or C virus infection that has progressed to cirrhosis since more than 40% of these patients will develop HCC.

Molecular assays are instrumental in the clinical management of viral hepatitis. During the past years, a wide variety of molecular assays have been developed and implemented. This considerably improved the understanding of the natural history and pathogenesis of Hepatitis B virus (HBV), Hepatitis C virus (HCV) or Hepatitis delta virus (HDV) hepatitis, but also caused uncertainties in the selection of the most appropriate assays for clinical requirements. Indeed, a rational choice and application of these assays requires adequate knowledge of the performance of the single test. Moreover, the choice of the most accurate assay for patients' needs and physicians' objectives, needs to be oriented to specific contexts, such as diagnosis, management or treatment. In the past, a hurdle in the routine use of assays for hepatitis viruses nucleic acid quantification was represented by the availability of only "home brew" methods which lacked standardization. Major improvement in addressing the use of molecular assays for viral hepatitis has been derived from recent standardization procedures that allowed a comparison between different tests after results were given as International Units. In addition, it should be reminded that, before getting into the market, molecular assays should be approved by European regulation authorities and validated using internationally recognized standards. A subsequent clinical validation should address the diagnostic accuracy of the assay. These proceedings have the aim of identifying which molecular tests, among those currently available, meet clinical requirements for each specific application.

Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation.

Objective: To examine the efficacy of interferon therapy of hepatitis C in liver transplant recipients, to determine the effect of interferon on allograft rejection rates, and to examine the effect of the primary immunosuppressive agent (FK-506/cyclosporin) on the above. Design: A non-randomized consecutive patient treatment study. Patients: Fifty-two liver allograft recipients with hepatitis C virus (HCV) associated liver disease. All 52 patients had abnormal serum alanine aminotransferase (ALT) levels and in all, a liver biopsy confirmed the finding of post-transplant viral hepatitis.Interventions: All patients were treated with interferon at a dose of 5 million units three times weekly, administered subcutaneously for 6 months. Main outcome measures: Normalization of serum ALT levels was defined as a full response. A 50% reduction in serum ALT levels without normalization was defined as a partial response. Results: No difference in entry ALT levels or white blood cell counts was evident for the two groups based in the type of immunosuppression used, either cyclosporin or FK-506. Similarly, no difference in the response rate to interferon was observed based on the type of immunosuppression used. Improvement in ALT levels was not accompanied by a concomitant improvement in hepatic histology. Overall, Knodell scores for histology deteriorated in two-thirds of the patients despite interferon treatment. Conclusions: The use of interferon in liver transplant recipients reduces serum ALT levels but has little effect, if any, on hepatic allograft histopathology. In most patients, histology worsens despite interferon therapy. No difference in interferon response rates were observed between liver allograft recipients receiving either cyclosporin or FK-506.