entecavir and Inflammation

Hepatitis B (HBV) is a DNA virus, which cannot be eradicated completely from the organism by treatment, only its replication can be suppressed to low levels. The pathogenesis of liver damage due to HBV is immune mediated, the infected hepatocytes represent the target structures of immune reaction. In individuals who spontaneously achieved the state of inactive carriage of the virus or even achieved HBsAg negativity, we deal only with immune control of viral replication. Chemotherapy or immunosuppressive treatment disrupt the immune control of HBV infection, the virus replication substantially increases and hepatitis B reactivates. HBV reactivation manifests as further flareup of chronic inflammation with rapid progression of liver cirrhosis or even as a fulminant hepatitis with liver failure. The risk of reactivation increases with degree of induced immunosuppression, the highest risk is associated with corticosteroid and rituximab therapy. HBV reactivation threatens patients during solid tumours treatment as well as haemato oncological malignancies, patients treated with immunosuppressive and bio-logical therapies for systemic inflammatory diseases and inflammatory bowel diseases, as well as patients on maintenance haemodialysis, after kidney transplantation and patients with HBV/ HIV co infection. HBV reactivation increases both morbidity and mortality in listed groups of patients. The patients threatened by HBV reactivation can be identified easily based on HBV serological markers assessment. Preemptive therapy with nucleos(t)ide analogues significantly reduces the risk of HBV reactivation, the effect of longterm antiviral therapy is described in detail in kidney transplant recipients in whom the 3rd generation antivirals (entecavir and tenofovir) completely obviate the negative impact of HBV on longterm survival. In oncological patients who are treated for a determined time period, we can use lamivudine, which is not suitable for longterm treatment due to high risk of resistance emergence.

Topics: Adenine; Antibodies, Monoclonal, Murine-Derived; Antineoplastic Agents; Antiviral Agents; Biomarkers; Guanine; Hepatitis B Surface Antigens; Hepatitis B virus; Hepatitis B, Chronic; Humans; Immunocompromised Host; Immunosuppressive Agents; Inflammation; Lamivudine; Organophosphonates; Rituximab; Tenofovir; Virus Activation

Objective Patients with acute hepatitis B sometimes develop acute liver failure (ALF), which has a poor prognosis. The efficacy of nucleoside analogue (NA) monotherapy for ALF due to transient hepatitis B virus infection (HBV-ALF) remains controversial. Further investigations are necessary in nations with a shortage of donor livers for liver transplantation. In the present study, we aimed to clarify the efficacy of combination therapy with corticosteroid (CS) and NA in the treatment HBV-ALF. Patients We examined the clinical and biochemical features of 19 patients with HBV-ALF who were treated in the early stage of the disease between 2000 and 2015. Results Fourteen patients received CS and NA (CS + NA group) and 5 received NA monotherapy (NA group). Eleven patients (58%) survived and 8 (42%) died. The survival rates in the CS + NA and NA groups were 64% and 40%, respectively (p=0.60). The mean alanine aminotransferase (ALT) levels declined significantly at week 2 in both groups. The mean PT activities improved significantly at weeks 1 and 2 in the CS + NA group (p<0.05) but not in the NA group. None of the surviving patients developed persistent infection. Conclusion Combination therapy with CS and NA induces the rapid resolution of inflammation leading to a rapid recovery of the liver function. When it is administered at a sufficiently early stage, it would have a survival benefit and prevent persistent infection in HBV-ALF.

Topics: Adult; Alanine Transaminase; Antiviral Agents; Drug Therapy, Combination; Female; Glucocorticoids; Guanine; Hepatitis B; Hepatitis B virus; Humans; Inflammation; Lamivudine; Liver Failure, Acute; Male; Methylprednisolone; Middle Aged; Prednisolone; Retrospective Studies; Survival Rate; Time-to-Treatment

The aims of this study were to determine the changes in serum histologic surrogate markers and to identify the serum markers predicting treatment response in patients with chronic hepatitis B (CHB) during entecavir treatment.. Sixty CHB patients who received entecavir for 12 months were included. We assessed serum markers of liver fibrosis and/or inflammation at baseline and after 12 months of entecavir treatment.. The procollagen III N-terminal peptide (PIIINP) and TIMP1, MMP2, hyaluronic acid and cytokeratin 18 fragment levels were significantly decreased and the haptoglobin level was significantly increased from baseline after entecavir treatment. Multivariate analysis identified PIIINP (P=0.028) and the initial virologic response (P=0.019) as independent predictors of HBeAg loss.. During entecavir treatment, most serum markers of liver fibrosis and inflammation improved in patients with CHB. The PIIINP level at baseline and the initial virologic response are independent predictors of HBeAg loss.

Topics: Adult; Antiviral Agents; Biomarkers; Female; Fibrosis; Guanine; Hepatitis B; Hepatitis B e Antigens; Hepatitis B virus; Humans; Hyaluronic Acid; Inflammation; Keratin-18; Male; Matrix Metalloproteinase 2; Middle Aged; Peptide Fragments; Procollagen; Retrospective Studies; Tissue Inhibitor of Metalloproteinase-1