Chronic hepatitis B (CHB) is a widespread infectious disease with unfavorable outcomes and life-threatening consequences for patients, in spite of modern vaccination and antiviral treatment modalities. Cutting-edge experimental approaches have demonstrated key pathways that involve cross-talk between viral particles and host immune cells. All events, including penetration of hepatitis B virus (HBV) particles into host cells, establishing persistence, and chronization of CHB infection, and possibility of complete elimination of HBV particles are controlled by the immune system. Researchers have paid special attention to the replication capacity of HBV in host cells, which is associated with cellular changes that reflect presentation of viral antigens and variability of HBV antigen features. In addition, specific HBV proteins have an immune-modulating ability to initiate molecular mechanisms that "avoid" control by the immune system. The relationship between immunological shifts and chronic infection stages has been intensively studied since it was recognized that the immune system is a direct participant in the recurrent (cyclic) nature of CHB. Understanding the wide diversity of molecular pathways and the crosstalk between innate and adaptive immune system components will provide fresh insight into CHB immune pathogenesis and the possibilities of developing new treatment strategies for this disease.

To examine the clinical features and risk factors for adverse outcomes in chronic hepatitis B (CHB) superimposed with hepatitis E virus (HEV).

Hepatitis B virus (HBV) infection causes oxidative stress (OS) and alters mitochondria in experimental models. Our goal was to investigate whether HBV might alter liver mitochondria also in humans, and the resulting mitochondrial stress might account for the progression of fibrosis in chronic hepatitis B (CHB).

Sporadic hepatitis E is an emerging indigenous disease in Europe induced by genotype 3 of the virus. While the disease takes an acute self-limited course in immunocompetent individuals, under immunocompromised conditions chronic hepatitis E might develop. The histology of chronic hepatitis E has not been described in detail systematically.

Since it is currently not possible to eradicate hepatitis B virus (HBV) infection with existing treatments, research continues to uncover new therapeutic strategies. HBV core protein, encoded by the HBV core gene (HBC), intervenes in both structural and functional processes, and is a key protein in the HBV life cycle. For this reason, both the protein and the gene could be valuable targets for new therapeutic and diagnostic strategies. Moreover, alterations in the protein sequence could serve as potential markers of disease progression.

Hepatitis C virus (HCV) envelope glycoprotein co-evolution was studied in 14 genotype 1-infected and treatment-naive subjects, including 7 with mild and 7 with severe liver disease. Cassettes encoding the envelope 1 gene (E1) and hypervariable region (HVR1) of the envelope 2 gene were isolated at 38 different time points over 81 follow-up years. There were no significant differences in age, gender, alcohol use, or viral load between the mild and severe disease groups. Virus from subjects with severe disease had significantly slower evolution in HVR1, and significant divergent evolution of E1 quasispecies, characterized by a preponderance of synonymous mutations, compared to virus from subjects with mild disease. Phylogenetic comparisons indicated higher similarity between amino acid sequences of the E1 and HVR1 regions with mild disease versus severe disease (r=0.44 versus r=0.17, respectively; P=0.01). In summary, HCV envelope quasispecies co-evolution differs during mild versus severe disease.

Although the role of autophagy has been implicated in several forms of chronic hepatitis, it is still not fully understood. Active autophagy eliminates damaged molecules and organelles (such as mitochondria) by lysosomal degradation. In the present study, we aimed to examine and compare autophagy activity in chronic hepatitis C (CHC) and autoimmune hepatitis (AIH) by detecting the expression of autophagy (LC3 and p62) and mitochondrium-related (TOMM20) proteins, as well as the levels of selected microRNAs (miR-101, -155, -204 and - 224) known to be involved in the regulation of autophagy. In addition, the expression levels were related to pathohistological parameters. Liver biopsy samples, including 45 CHC and 18 AIH cases, were immunohistochemically stained for LC3, p62 and TOMM20 and the expression of miRNAs was determined using real-time PCR. We found elevated LC3 and p62 in AIH samples as compared with CHC ones, indicating an activated autophagy that is impaired in AIH as no degradation of p62 seemed to occur. Moreover, p62 showed strong correlation with necroinflammatory grades in the AIH group. The observed elevated levels of TOMM20 and p62 suggest a less efficient elimination of damaged mitochondria in AIH as opposed to CHC, in which autophagy seems to have a more active function. The level of miR-101 was increased in case of CHC as compared with AIH, however, miR-155, -204 and 224 resulted in no expressional. Furthermore, miR-224 level correlated with steatosis and miR-155 expression with fibrosis stage in CHC. In conclusion, dissimilar autophagic activity was observed in CHC and AIH, suggesting a close association between impaired autophagy and severity of necroinflammation. This impairment may not be regulated by the analyzed miRNAs. Nevertheless, miR-224 and - 155 seem to be associated with CHC progression.

Data concerning the prevalence of hepatitis B virus (HBV) occult infection (OBI) varies greatly in the different studies according to the sensitivity and specificity of the diagnostic approaches and the HBV prevalence in the different populations examined. The clinical implications of OBI are still debated. While the impact of OBI in HBV transmission as well as in HBV reactivation under immunosuppression are well established, the role of OBI in liver disease and hepatocellular carcinoma (HCC) development are still not definitively elucidated. It has been hypothesized that OBI might contribute to worsening the liver disease course when other causes of liver damage co-exist. Furthermore, much evidence suggests a role of OBI in the hepato-carcinogenesis processes through both indirect and direct oncogenic mechanisms that might favour HCC development. Data on the OBI clinical implications mainly come from studies performed in patients with hepatitis C virus (HCV) infection. However, HCV prevalence has dramatically fallen in the past years also because of the advent of specific and highly effective direct acting antivirals, with a consequent abrupt change of the worldwide scenario of chronic liver disease. Information about OBI prevalence and possible clinical impact in non-HCV-related liver disease are fragmentary, and the objective of this review is to critically summarize the available data in this field.

No abstract available

HBV-X protein is associated with the pathogenesis of HBV related diseases, specially in hepatocellular carcinomas of chronic patients. Genetic variability of the X gene includes genotypic specific variations and mutations emerging during chronic infection. Its coding sequence overlaps important regions for virus replication, including the basal core promoter. Differences in the X gene may have implications in biological functions of the protein and thus, affect the evolution of the disease. There are controversial results about the consequences of mutations in this region and their relationship with pathogenesis. The purpose of this work was to describe the diversity of HBV-X gene in chronic hepatitis patients infected with different genotypes, according to liver disease.

Background: The liver-specific microRNA-122 (miR-122) has been demonstrated as a powerful and promising biomarker of hepatic diseases. However, the researches on the accuracy of miR122 detection in chronic viral hepatitis have been inconsistent, leading us to conduct this meta-analysis to systematically summarize the diagnostic value of circulating miR-122 in patients with hepatitis B virus (HBV) and/or hepatitis C virus (HCV)-associated chronic viral hepatitis.Methods: A comprehensive literature search (updated to January 30, 2019) in PubMed, Cochrane library, EMBASE, CNKI, Wanfang, and CQVIP databases was performed to identify eligible studies. The sensitivity (SEN), specificity (SPE), positive and negative likelihood ratios (PLR and NLR), diagnostic odds ratio (DOR), and area under the curve (AUC) were pooled to explore the diagnostic performance of circulating miR-122. Subgroup and threshold effect analysis were further carried out to explore the heterogeneity.Results: Overall, 15 studies were finally included in this meta-analysis according to the exclusion and inclusion criteria. The pooled estimates indicated a moderately high diagnostic accuracy for circulating miR-122, with a sensitivity of 0.92 [95% confidence interval (CI), 0.86-0.95], a specificity of 0.84 (95% CI, 0.78-0.89), a PLR of 5.7 (95% CI, 4.7-8.1), a NLR of 0.1 (95% CI, 0.06-0.18), a DOR of 57 (95% CI 25-129), and an AUC of 0.93 (95% CI, 0.91-0.95). The subgroup analysis demonstrated that diagnostic accuracy was better for HCV-associated chronic viral hepatitis patients and non-Chinese compared with other subgroups. In addition, we found that serum might be a more promising matrix for detecting the expression of miR-122 than plasma.Conclusions: Our results demonstrated that circulating miR-122 have a relatively high diagnostic value for chronic viral hepatitis detection, especially in the patients with HCV-associated chronic viral hepatitis. However, further large cohort studies are still required to confirm our findings.

The hepatitis B virus (HBV) is one of the leading causes of acute, chronic and occult hepatitis (OBI) representing a serious public health threat. Cytokines are known to be important chemical mediators that regulate the differentiation, proliferation and function of immune cells. Accumulating evidence indicate that the inadequate immune responses are responsible for HBV persistency. The aim of this study were to investigate the cytokines IFN-γ, TNF-α, IL-2, IL-4, IL-6, IL-10 and IL-17A in patients with OBI and verify if there is an association between the levels of these cytokines with the determination of clinical courses during HBV occult infection.

The aim of this study was to determine the correlation between vaccine therapy and appearance of mutations in hepatitis B surface antigen (HBsAg)-positive chronic hepatitis B virus (HBV) patients.

The aim of the study was to explore the diagnostic value of T2 mapping in an experimental rat model of chronic liver disease. Chronic hepatitis was induced in Sprague-Dawley male rats (n=88) by intraperitoneal and abdominal subcutaneous injection of carbon tetrachloride in olive oil. The normal control rats (n=12) were similarly injected with the same dose of normal saline. All rats were randomly selected and subjected to T2-weighted/spectral adiabatic inversion recovery and multiple gradient- and spin-echo sequence. After scanning, rats were sacrificed immediately and livers removed for staining with hematoxylin and eosin, as well as Masson's trichrome, to determine the pathological stage of hepatic fibrosis, necroinflammatory activity and steatosis. The T2 values were measured and associated with histopathological findings. The T2 values were significantly associated with hepatic fibrosis (P<0.05), but not with hepatitis (P>0.05) or steatosis (P>0.05). By partial correlation analysis, a significant positive correlation was observed between the T2 values and stages of liver fibrosis (r=0.820; P<0.05). T2 values increased with progressive hepatic fibrosis. The differences between T2 values and stages of liver fibrosis were statistically significant. Statistically significant differences were observed between different stages of liver fibrosis (P<0.05), with an area under the curve value of 0.944 for predicting stage F1 or greater, 0.942 for stage F2 or greater, 0.958 for stage F3 or greater, and 0.948 for F4. Thus, the T2 value is one of the quantitative indices of imaging and accurately reflects the stages of liver fibrosis.

The clinical relevance of single nucleotide polymorphisms (SNPs) near the IL28B gene is controversial in patients with hepatitis B virus (HBV) infection. This study aimed to investigate the role of viral and host factors, including IL28B genotypes, in the natural course of chronic hepatitis B (CHB).

Previous reports show conflicting results regarding hepatitis B virus (HBV) vaccine efficacy in Hepatitis C virus (HCV)-infected individuals.

Background: The main objective of this study was to analyse the spread of hepatitis C virus (HCV) genotype in patients with chronic liver disease; commenting on the molecular characterization of HCV and gender and age in Varna, Bulgaria. Across Europe and the world, HCV is a significant economic concern and public health crisis. Defined by genotype variations, HCV is the leading cause of chronic liver disease, liver related morbidity, and mortality worldwide. Active examination for asymptomatic patients is essential, initiating early treatment aimed at the specific HCV genotype, effective outcomes, and reducing transmission and mortality in Bulgaria. Methods and materials: Nucleic acid extraction and amplification were performed with commercially available test kits on 115 patients blood samples collected from March 2018 to October 2018. Male (n = 58) (50.43%, 95% CI = 41.29%-59.57%) and female (n = 57) (49.57%, 95% CI = 41.29%-59.57%) samples were equally distributed (mean age = 51.4 years; SD = ±16.5 years; range = 17-87 years old). Results: Genotype 1b predominated (73%, 95% CI = 64.89%-81.11%), followed by high prevalence of 1a (13.9%, 95% CI = 7.58%-20.22%) and 3 genotypes (11.3%, 95% CI = 5.51%-17.09%). Genotypes 2 and 4 were equally the least prevalent (0.9%, 95% CI = -0.83%-2.63%). In genotype 1b, 60.7% were women and 39.3% were men; in genotype 1a, 25% were women and 75% were men; and in genotype 3, only 7.7% were women and 92.3% were men. Males were most prevalent in genotypes 1a (75%) and 3 (92.3%), while women were most prevalent in genotype 1b (60.7%). Conclusions: HCV genotype lb is the predominant variant within the epidemiological pattern of HCV genotypes in patients with chronic liver diseases in North Eastern Bulgaria.

The hepatitis E virus (HEV) was initially thought to exclusively cause acute hepatitis. However, the first diagnosis of chronic hepatitis E in transplant recipients in 2008 profoundly changed our understanding of this pathogen. We have now begun to understand that specific HEV genotypes can cause chronic infection in certain immunocompromised populations. Over the past decade, dedicated clinical and experimental research has substantiated knowledge on the epidemiology, transmission routes, pathophysiological mechanisms, diagnosis, clinical features and treatment of chronic HEV infection. Nevertheless, many gaps and major challenges remain, particularly regarding the translation of knowledge into disease prevention and improvement of clinical outcomes. This article aims to highlight the latest developments in the understanding and management of chronic hepatitis E. More importantly, we attempt to identify major knowledge gaps and discuss strategies for further advancing both research and patient care.

Hepatitis E virus (HEV) genotypes 3 and 4 (HEV-3, HEV-4) infections are an emerging public health issue in industrialized countries. HEV-3 and -4 are usually self-limiting but can progress to chronic hepatitis E in immunocompromised individuals. The molecular mechanisms involved in persistent infections are poorly understood. Micro RNAs (miRNAs) can regulate viral pathogenesis and can serve as novel disease biomarkers. We aimed to explore the modulation of serum miRNAs in patients with acute (AHE) and chronic (CHE) hepatitis E. Both AHE- and CHE-patients exhibited high viral loads (median 3.23E + 05 IU/mL and 2.11E + 06 IU/mL, respectively) with HEV-3c being the predominant HEV-genotype. Expression analysis of liver-specific serum miRNAs was performed using real-time PCR. miR-99a-5p, miR-122-5p, and miR-125b-5p were upregulated in AHE (4.70-5.28 fold) and CHE patients (2.28-6.34 fold), compared to HEV-negative controls. Notably, miR-192-5p was increased 2.57 fold while miR-125b-5p was decreased 0.35 fold in CHE but not in AHE patients. Furthermore, decreased miR-122-5p expression significantly correlates with reduced liver transaminases in CHE patients. To our knowledge, this marks the first investigation concerning the regulation of circulating liver-specific miRNAs in acute and chronic HEV infections. We found that miR-125b-5p, miR-192-5p, and miR-99a-5p may prove useful in the diagnosis of chronic hepatitis E.

No abstract available