Genotype ; Hepacivirus ; genetics ; physiology ; Hepatitis B ; complications ; Hepatitis B virus ; Hepatitis C ; complications ; Humans ; RNA, Viral ; analysis

The pathogenesis of hepatitis B virus （HBV）-associated hepatocellular carcinoma （HCC） is complicated with the crosstalk of multiple factors and the multi-step processes. The main mechanisms underlying the HBV-induced HCC include:①integration of HBV DNA into the host hepatocyte genome to alter gene function at the insertion site，resulting in host genome instability and expression of carcinogenic truncated proteins;②HBV gene mutations at S，C，and X coding regions in the genome;③HBV X gene-encoded HBx protein activates proto-oncogenes and inhibits tumor suppressor genes，leading to the HCC occurrence. In this article，the recent research progress on the molecular mechanism of HBV-induced HCC is comprehensively reviewed，so as to provide insights into the prevention，early prediction and postoperative adjuvant therapy of HCC.
Carcinoma, Hepatocellular ; Hepatitis B/complications* ; Hepatitis B virus/genetics* ; Hepatocytes ; Humans ; Liver Neoplasms

Hepatitis D virus (HDV) infection causes the most severe form of viral hepatitis with rapid progression to cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Although discovered > 40 years ago, little attention has been paid to this pathogen from both scientific and public communities. However, effectively combating hepatitis D requires advanced scientific knowledge and joint efforts from multi-stakeholders. In this review, we emphasized the recent advances in HDV virology, epidemiology, clinical feature, treatment, and prevention. We not only highlighted the remaining challenges but also the opportunities that can move the field forward.
Carcinoma, Hepatocellular/complications* ; Hepatitis B virus ; Hepatitis D/epidemiology* ; Hepatitis Delta Virus/genetics* ; Humans ; Liver Cirrhosis/etiology* ; Liver Neoplasms/complications*

<b>OBJECTIVEb>To assess the association of human leucocyte antigen (HLA)-DRB1 allele with the genetic susceptibility to cirrhosis due to hepatitis B virus(HBV).

<b>METHODSb>One hundred and six patients with cirrhosis due to HBV in Hubei area were investigated for HLA-DRB1 gene by polymerase chain reaction-sequence specific primers technique. The results were compared with those from 108 normal healthy people.

<b>RESULTSb>The frequency of HLA-DRB1*1201/1202 allele was 20.28% in patient group, which was significantly higher than the frequency (6.01%) in control group, the relative risk (RR) being 4.9878 (P<0.01). The frequency of HLA-DRB1*1501/1502 allele was decreased in patient group (patient 6.6%, control 16.67%, RR=0.3043, P<0.05), while the frequencies of other HLA-DRB1 alleles were not significantly different(P>0.05).

<b>CONCLUSIONb>HLA-DRB1*1201/1202 allele may be the susceptibility gene in patients with cirrhosis due to HBV in Hubei Han nationality; HLA-DRB1*1501/1502 allele is a resistant gene in patients with cirrhosis.

Adult ; Female ; Genetic Predisposition to Disease ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepatitis B ; complications ; genetics ; Hepatitis B virus ; genetics ; pathogenicity ; Hepatitis B, Chronic ; complications ; genetics ; Humans ; Liver Cirrhosis ; etiology ; genetics ; Male ; Middle Aged ; Polymorphism, Genetic

<b>OBJECTIVEb>To investigate genotypes of the hepatitis B virus (HBV) and alanine aminotransferase (ALT) levels of HBeAg negative patients with chronic hepatitis B and liver cirrhosis.

<b>METHODSb>HBV serological markers and ALT levels were detected in 62 patients with chronic hepatitis B and 41 cases with liver cirrhosis, using enzyme linked absorbent immunoassays and an enzyme method, respectively. A polymerase chain reaction of S region was used for HBV genotyping.

<b>RESULTSb>Of the 62 patients with chronic hepatitis B, 21 (33.9%) were HBeAg negative, and 41 (66.1%) HBeAg positive. Among 41 cases with liver cirrhosis, 28 (68.3%) were HBeAg negative, and 13 (31.7%) HBeAg positive. Of these 62 patients with chronic hepatitis B, 53 (85.5%) were infected with HBV genotype C, and 9 (14.5%) with genotype B. Thirty-nine (95.1%) of the 41 patients with liver cirrhosis were infected with genotype C, and 2 (4.9%) with genotype B. The proportion of HBeAg negative chronic hepatitis B patients with ALT level > 40 U/L was lower than that of the HBeAg positive group (47.6% and 85.4%, respectively) (P < 0.01). The percentage of ALT levels > 40 U/L of the negative patients with liver cirrhosis was also lower as compared to that of the HBeAg positive patients, but there was no statistical difference between the two groups, because of the small sample size (P > 0.05).

<b>CONCLUSIONb>The proportion of HBeAg negative patients is high in the group of chronic hepatitis B and liver cirrhosis. These patients have relatively low ALT levels, and mainly have HBV genotype C infection.

Alanine Transaminase ; blood ; Female ; Genotype ; Hepatitis B e Antigens ; blood ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; blood ; complications ; virology ; Humans ; Liver Cirrhosis ; blood ; etiology ; virology ; Male

Objective:b> To investigate the demographic characteristics and clinical influencing factors which associates with the occurrence probability of persistent or intermittent hypoviremia (LLV) in patients with chronic hepatitis B (CHB) treated with nucleos(t)ide analogues (NAs). Methods:b> A single-center retrospective analysis was performed on patients with CHB who received outpatient NAs therapy for≥48 ± 2 weeks. According to the serum hepatitis B virus (HBV) DNA load at 48±2 weeks treatment, the study groups were divided into LLV (HBV DNA < 20 IU/ml and < 2 000 IU/ml) and MVR group (sustained virological response, HBV DNA < 20 IU/ml). Demographic characteristics and clinical data at the start of NAs treatment (considered as baseline) were retrospectively collected for both patient groups. The differences in the reduction of HBV DNA load during treatment was compared between the two groups. Correlation and multivariate analysis were further conducted to analyze the associated factors influencing the LLV occurrence. Statistical analysis was performed using the independent samples t-test, c2 test, Spearman analysis, multivariate logistic regression analysis, or area under the receiver operating characteristic curve. Results:b> A total of 509 cases were enrolled, with 189 and 320 in the LLV and MVR groups, respectively. Compared to patients with MVR group at baseline: (1) the demographics characteristics of patients showed that LLV group was younger in age (39.1 years, P = 0.027), had a stronger family history (60.3%, P = 0.001), 61.9% received ETV treatment, and higher proportion of compensated cirrhosis (20.6%, P = 0.025) at baseline; (2) the serum virological characteristics of patients showed that LLV group had higher HBV DNA load, qHBsAg level, qHBeAg level, HBeAg positive rate, and the proportion of genotype C HBV infection but decreased HBV DNA during treatment (P < 0.001) at baseline; (3) the biochemical characteristics of patients showed that LLV group had lower serum ALT levels (P = 0.007) at baseline; (4) the noninvasive fibrosis markers of patients showed that LLV group were characterized by high aspartate aminotransferase platelet ratio index (APRI) (P = 0.02) and FIB-4 (P = 0.027) at baseline. HBV DNA, qHBsAg and qHBeAg were positively correlated with LLV occurrence (r = 0.559, 0.344, 0.435, respectively), while age and HBV DNA reduction were negatively correlated (r = -0.098, -0.876, respectively). Logistic regression analysis showed that ETV treatment history, high HBV DNA load at baseline, high qHBsAg level, high qHBeAg level, HBeAg positive, low ALT and HBV DNA level were independent risk factors for patients with CHB who developed LLV with NAs treatment. Multivariate prediction model had a good predictive value for LLV occurrence [AUC 0.922 (95%CI: 0.897 ~ 0.946)]. Conclusion:b> In this study, 37.1% of CHB patients treated with first-line NAs has LLV. The formation of LLV is influenced by various factors. HBeAg positivity, genotype C HBV infection, high baseline HBV DNA load, high qHBsAg level, high qHBeAg level, high APRI or FIB-4 value, low baseline ALT level, reduced HBV DNA during treatment, concomitant family history, metabolic liver disease history, and age < 40 years old are potential risk factors for developing LLV in patients with CHB during the therapeutic process.
Humans ; Adult ; Hepatitis B, Chronic/complications* ; Retrospective Studies ; Cross-Sectional Studies ; Hepatitis B e Antigens ; DNA, Viral ; Antiviral Agents/therapeutic use* ; Hepatitis B virus/genetics* ; Demography

In China, hepatitis B virus (HBV) infection is the major cause of hepatocellular carcinoma (HCC), which is called HBV-related HCC (HBV-HCC), but the pathogenesis has not been clearly elucidated. Long non-coding RNAs (lncRNAs) have been paid increasing attention to, as an important regulatory molecule involved in many biological processes, as well as a variety of diseases. This study examined lncRNA that might play an important role in HBV-HCC pathogenesis by conducting lncRNA and mRNA profile comparison between HBV-HCC and normal liver tissues. The differentially expressed lncRNA and mRNA profiles between HBV-HCC and normal liver tissues were analyzed by microarrays. The potential protein-encoding gene regulated by lncRNA, and the biological function (gene ontology, pathway analysis) of the target gene were investigated. The results showed that the expression levels of lncRNA and mRNA in HBV-HCC tissues were different from those in normal liver tissues. As compared with normal liver tissue, 837 (4.30%) lncRNAs exhibited more than two-fold change (P<0.05); 325 were up-regulated, and 512 were down-regulated; 991 (5.70%) mRNAs exhibited more than 2-fold change (P<0.05); 733 were up-regulated and 258 were down-regulated in HBV-HCC tissue. Besides, there were 7 lncRNAs with above 10-fold elevation, 6 lncRNAs with above 10-fold decrease, 18 mRNAs with above 10-fold elevation and 11 mRNAs with above 10-fold decrease. 444 (53.05%) lncRNAs had their corresponding mRNAs, some of which were adjacent to lncRNAs. The biological analysis showed that the target gene of differentially expressed lncRNAs took part in the important biological regulatory function. Target gene-related pathway analysis revealed the pathways in carcinoma and mitogen-activated protein kinase (MAPK) signaling pathways significantly changed in the HBV-HCC tissues as compared with normal liver tissues (P<0.05). It was suggested that as compared with normal liver tissues, the expression of lncRNAs in HBV-HCC tissues changed significantly, and lncRNAs played a key role in the pathogenesis of HBV-HCC probably by mainly regulating the carcinoma-related signaling pathway and MAPK signaling pathways.
Carcinoma, Hepatocellular ; complications ; genetics ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; genetics ; Hepatitis B ; complications ; genetics ; Humans ; Liver Neoplasms ; complications ; genetics ; Mutation ; genetics ; RNA, Long Noncoding ; genetics

Occult HBV infection is defined as the presence of HBV DNA in the liver (with or without detectable or undetectable HBV DNA in the serum) of individuals testing negative for HBsAg. Studies on occult HBV infection in hepatitis C patients have reported highly variable prevalence, because the prevalence of occult HBV infection varies depending on the hepatitis B risk factors and methodological approaches. The most reliable diagnostic approach for detecting occult HBV detection is through examination of liver DNA extracts. HCV has been suspected to strongly suppress HBV replication up to the point where it may be directly responsible for occult HBV infection development. However, more data are needed to arrive at a definitive conclusion regarding the role of HCV in inducing occult HBV infection. Occult HBV infection in chronic hepatitis C patients is a complex biological entity with possible relevant clinical implications. Influence of occult HBV infection on the clinical outcomes of chronic hepatitis C may be considered negative. However, recent studies have shown that occult HBV infection could be associated with the development of hepatocellular carcinoma and contribute to the worsening of the course of chronic liver disease over time in chronic hepatitis C patients. Nevertheless, the possible role of occult HBV infection in chronic hepatitis C is still unresolved and no firm conclusion has been made up until now. It still remains unclear how occult HBV infection affects the treatment of chronic hepatitis C. Therefore, in order to resolve current controversies and understand the pathogenic role and clinical impacts of occult HBV infection in chronic hepatitis C patients, well-designed clinical studies are needed.
Carcinoma, Hepatocellular/complications ; DNA, Viral/analysis ; Hepacivirus/genetics ; Hepatitis B/*complications/*diagnosis/drug therapy ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/*complications/*diagnosis/drug therapy ; Humans ; Interferon-alpha/therapeutic use ; Liver/virology ; Liver Neoplasms/complications

Female ; Genetic Predisposition to Disease ; Hepatitis B ; genetics ; Hepatitis B virus ; Humans ; Polymorphism, Genetic ; Pregnancy ; Pregnancy Complications, Infectious ; virology ; Promoter Regions, Genetic ; genetics ; Tumor Necrosis Factor-alpha ; genetics

Many studies have suggested that occult HBV infection has a substantial clinical relevance to hepatocellular carcinoma (HCC). Occult HBV infection is an important risk factor for the development of cirrhosis and HCC in patients without HBsAg. As a matter of fact, occult HBV infection is one of the most common causes of crytogenic HCC in endemic areas of HBV. However, there still are controversial issues about the association between occult HBV infection and HCC according to the underlying liver disease. In alcoholic cirrhosis, occult HBV infection may exert synergistic effect on the development of HCC. However, there is insufficient evidence to relate occult HBV infection to hepatocarcinogenesis in non-alcoholic fatty liver disease. In cryptogenic HCC, occult HBV infection may play a direct role in the development of HCC. In order to elucidate the assocciation between occult HBV infection and HCC, underlying liver disease must be specified and larger number of cases must be included in future studies.
Carcinoma, Hepatocellular/*complications/*diagnosis/epidemiology ; DNA, Viral/analysis ; Hepatitis/complications ; Hepatitis B/*complications/*diagnosis/epidemiology ; Hepatitis B virus/genetics ; Humans ; Liver Cirrhosis, Alcoholic/complications ; Liver Neoplasms/*complications/*diagnosis/epidemiology ; Risk Factors