Hepatitis B Virus Related Liver Cirrhosis Research Articles

Clinical value of plasma scaffold protein SEC16A in evaluating hepatitis B-related liver cirrhosis and hepatocellular carcinoma

Objective: To investigate the clinical value of plasma scaffold protein SEC16A level and related models in the diagnosis of hepatitis B virus-related liver cirrhosis (HBV-LC) and hepatocellular carcinoma (HBV-HCC). Methods: Patients with HBV-LC and HBV-HCC and a healthy control group diagnosed by clinical, laboratory examination, imaging, and liver histopathology at the Third Hospital of Hebei Medical University between June 2017 and October 2021 were selected. Plasma SEC16A level was detected using an enzyme-linked immunosorbent assay (ELISA). Serum alpha-fetoprotein (AFP) was detected using an electrochemiluminescence instrument. SPSS 26.0 and MedCalc 15.0 statistical software were used to analyze the relationship between plasma SEC16A levels and the occurrence and development of liver cirrhosis and liver cancer. A sequential logistic regression model was used to analyze relevant factors. SEC16A was established through a joint diagnostic model. Receiver operating characteristic curve was used to evaluate the clinical efficacy of the model for liver cirrhosis and hepatocellular carcinoma diagnosis. Pearson correlation analysis was used to identify the influencing factors of novel diagnostic biomarkers. Results: A total of 60 cases of healthy controls, 60 cases of HBV-LC, and 52 cases of HBV-HCC were included. The average levels of plasma SEC16A were (7.41 ± 1.66) ng/ml, (10.26 ± 1.86) ng/ml, (12.79 ± 1.49) ng /ml, respectively, with P < 0.001. The sensitivity and specificity of SEC16A in the diagnosis of liver cirrhosis and hepatocellular carcinoma were 69.44% and 71.05%, and 89.36% and 88.89%, respectively. SEC16A, age, and AFP were independent risk factors for the occurrence of HBV-LC and HCC. SAA diagnostic cut-off values, sensitivity, and specificity were 26.21 and 31.46, 77.78% and 81.58%, and 87.23% and 97.22%, respectively. The sensitivity and specificity for HBV-HCC early diagnosis were 80.95% and 97.22%, respectively. Pearson correlation analysis showed that AFP level was positively correlated with alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), and γ-glutamyltransferase (GGT) with P < 0.01, while the serum SEC16A level was only slightly positively correlated with ALT and AST in the liver cirrhosis group (r = 0.268 and 0.260, respectively, P < 0.05). Conclusion: Plasma SEC16A can be used as a diagnostic marker for hepatitis B-related liver cirrhosis and hepatocellular carcinoma. SEC16A, combined with age and the AFP diagnostic model with SAA, can significantly improve the rate of HBV-LC and HBV-HCC early diagnosis. Additionally, its application is helpful for the diagnosis and differential diagnosis of the progression of HBV-related diseases.

Prevalence of HBV and its Associated Risks Factors among Patients Accessing Care at a Secondary Health Facility in Ekiti State, Southwest, Nigeria

Viral hepatitis is a serious disease of the liver that can have grim prognosis in the absence of early and appropriate medical intervention. Globally, an estimated two billion people are reported to have been infected with hepatitis B virus (HBV) and out of this, more than 350 million are said to have chronic(long term) liver infection. The likelihood that Hepatitis B Virus infection will become chronic depends upon the age at which a person becomes infected. Young children who become infected with HBV are most likely to develop chronic infection. About 25% of adults who become chronically infected during childhood die from HBV related liver cancer or cirrhosis. According to WHO ranking of hepatitis prevalence, ≤ 1.9%, 2-7.9% and ≥ 8% are low, moderate and high prevalence respectively. Hepatitis is endemic in Ekiti State, there is therefore the need to know its prevalence in the major cities of Ekiti State. Since Ikere-Ekiti is the second major city of Ekiti State, therefore this study set out to know the prevalence of HBV-caused hepatitis in Ikere-Ekiti and its associated factors,. One hundred participants were enrolled- at the State specialist Hospital, Ikere-Ekiti- into the study after obtaining their informed consent. Consecutive sampling was used. Thirty-three (33%) of the subjects were males while 67 (67%) were females. Thirty-seven (37%) , 30 (30%) and 33 (33%) respectively fell were in the ≤26 years, 27-36 and ≥37 age-brackets. Fifty-two (52 %) were singles while 48 (48%) were married. Ninety-three (93%) were Christians while 7 (%) were Muslims. Structured self-administered questionnaires were served on the subjects. Five millilitres of blood were collected from each subject using venepuncture method. The samples were screened for the presence or otherwise of antibodies to HBsAg using a rapid test kit that worked on the principle of immunochromatography. An overall prevalence of 8% was discovered. Five (5%) of the positive subjects were males while 3 (%) were females (p=0.064). Half (50%) of the positive subjects were within the ≤26 years age-bracket, the 27-36 age-bracket had the least number of positive subjects (p=0.512). Two out of the positive subjects had a history of blood transfusion (p=0.748), one had history of surgery (p=0.580). The imports and implications of these are here discussed. Since viral hepatitis is vaccine-preventable and herd immunity can only be achieved when the vast majority of a society acquires immunity against a particular infectious disease, the government is advised to strive to vaccinate at least 70% of the populace against viral hepatitis- a disease which is endemic, not only in Ekiti State, but in many parts of Nigeria.

Identification of miR-4793-3p as a potential biomarker for bacterial infection in patients with hepatitis B virus-related liver cirrhosis: A pilot study.

Hepatitis B virus-related liver cirrhosis (HBV-LC) is susceptible to bacterial infections, which could lead to adverse prognosis in patients. MicroRNAs (miRs/miRNAs) are easily detected in peripheral blood and are involved in multiple liver diseases. The present pilot study aimed to investigate differentially expressed (DE) miRNAs in the serum of patients with HBV-LC and bacterial infection, and to identify potential biomarkers. The first batch of clinical samples was collected, including four patients with HBV-LC and infection, four patients with HBV-LC without infection, four patients with chronic hepatitis B (CHB) and four healthy controls. miRNA expression was analyzed by Affymetrix GeneChip miRNA 4.0 Array. A total of 385 DE miRNAs (upregulated, 160; downregulated, 225) were detected in patients with HBV-LC and infection compared with patients with HBV-LC without infection. miR-4793-3p was significantly upregulated in patients with HBV-LC and infection compared with its levels in the other three groups: HBV-LC without infection [log-transformed fold change (logFC)=7.96; P=0.0458), CHB (logFC=34.53; P=0.0003) and healthy controls (logFC=3.34; P=0.0219)]. Reverse transcription-quantitative PCR (RT-qPCR) was performed to validate miR-4793-3p expression in another batch of clinical samples. RT-qPCR showed that miR-4793-3p was highly expressed in patients with HBV-LC and infection compared with its levels in patients with HBV-LC without infection (P<0.05). The non-parametric random forest regression model was built to access the diagnostic value of miR-4793-3p, and the receiver operating characteristic curve demonstrated that the area under the curve was 92.2%. Target gene analysis with bioinformatics tools and Gene Expression Omnibus data (GSE46955) showed that miR-4793-3p could participate in the TGF-β signaling pathway. Functional experiments revealed that overexpressed miR-4793-3p could impair TGF-β function by downregulating Gremlin-1. The present pilot study suggests that miR-4793-3p could be a feasible indicator for bacterial infection in patients with HBV-LC, and it would be valuable for further research.

Is Budd–Chiari Syndrome Associated to Alcoholic Related Liver Cirrhosis

Introduction and aim: The Budd-Chiari Syndrome (BCS) is redefined as hepatic vein outflow tract obstruction with a very low incidence. We aim to analyze the etiology and clinical character of BCS in Hebei area of North China.Material and methods: The diagnosis of BCS and alcoholic related liver cirrhosis (Alcohol-LC) are according to the guidelines of American Association for the Study of Liver Diseases (AASLD), while the diagnosis of hepatitis B virus related liver cirrhosis (HBV-LC) is according to the guidelines of European Association for the Study of the Liver (EASL). BCS patients including inferior vena cava block (IVC), hepatic vein block (HV) and inferior vena cava combining with hepatic vein block (IVC/HV) are involved in this analysis.Results: The subtype’s distributions of this disease are more frequent for IVC patients compared with HV and IVC/ HV patients. The subsequent analysis shows that the incidence of BCS is more predisposed to Alcohol-LC than HBV-LC (p &lt; 0.001).Conclusion: BCS seem to be associated with Alcohol-LC compared with that of HBV-LC.

Characteristics of Recipients With 10 or More Years of Allograft Survival in Deceased Donor Kidney Transplantation

BackgroundThe development of immunosuppressants improved the short-term outcomes of deceased donor kidney transplantation (DDKT), but the long-term survival rate was not improved. MethodsThe study included 127 patients who received first-time kidneys from deceased donors at Keimyung University Dongsan hospital between October 1994 and June 2007. We analyzed the clinical features of recipients with long-term allograft survival. ResultsThe mean follow-up period was 163 months. Among the 127 recipients, 53 (41.7%) maintained allograft survival for more than 10 years (AS group), 58 (45.7%) lost allograft function (AL group), and 16 (12.6%) were lost to follow-up. The 5- and 10-year allograft survival rates were 84.7% and 65.5%. The 5- and 10-year patient survival rates were 95.9% and 92.5%. The patient survival rate was significantly higher in the AS group than in the AL group. In the AS group, the use of basiliximab and mycophenolate mofetil (MMF) were significantly higher, and the number of HLA-DR mismatches and the incidence of rejection and infection were significantly lower. In multivariate Cox proportional hazards analysis, the use of MMF reduced the risk of allograft loss (hazard ratio [HR], 0.361; 95% confidence interval [CI], 0.172–0.757; P = .007). On the other hand, the incidence of rejection, hepatitis B virus-related liver cirrhosis (HBV-LC), and viral infection were independent risk factors for allograft loss (HR, 5.327; 95% CI, 2.813–10.090; P < .001; HR, 5.862; 95% CI, 1.891–18.168; P = .002; HR, 2.614; 95% CI, 1.355–5.043; P = .004, respectively). ConclusionFor long-term survival of allograft kidney in DDKT, it is important to use appropriate immunosuppressants including MMF and prevent complications such as rejection, HBV-LC, and viral infection.

Mo1023 The Single Nucleotide Polymorphism in the Vitamin D Pathway DHCR7 Gene and Pre-Treatment HBV-DNA Strongly Predict HBeAg Loss in HBeAg-Positive Chronic Hepatitis B Patients Treated With Pegylated Interferon: Multicenter Study

Aim: Clinical outcome after hepatitis B virus (HBV) exposure vary extremely from spontaneous clearance to chronic hepatitis B and often progresses to liver cirrhosis and hepatocellular carcinoma. Host genetic factor plays an important role in the regulation of immune response. The study was designed to investigate whether (HLA) class II DQA1 and DQB1 gene polymorphism are associated with chronic hepatitis B infection and whether it leads to the development of HBV related liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in north Indian population. Methods: We have assessed the DQA1 and DQB1 allele polymorphism in 187 HBV related liver diseases which included (73 chronic hepatitis B, 84 LC, and 30 HCC patients) and 109 controls who had spontaneously recovered from HBV infection by using polymerase chain reaction amplification with sequence specific primers (PCR-SSP). Results: The data suggest that DQA1*0101/2/4 (OR=2.78; P=0.003), DQA1*0103 (OR= 2.64; P=0.0007) and DQB1*0302/3 (OR=2.15; P=0.01) were associated with protection from chronic HBV infection, while DQB1*0402 (OR=0.25; P=0.001) conferred susceptibility to chronic HBV infection, respectively. It was also observed that DQB1*0601 (OR=3.73; P=0.006) conferred protective effect from developing Liver Cirrhosis, similarly DQB1*0302/ 3 (OR=5.53; P=0.05) and DQB1*0402 (OR=0.00; P=0.0001) conferred protective effect from progressing to HCC. Though, DQA1*0601 and DQB1*0503 showed some susceptible effect on chronic HBV infection, these association were no longer significant after Bonferroni correction (P=0.23, P=0.59). Conclusion: The results suggest that various subtypes of HLA-DQA1 and DQB1 does influence the HBV clearance and development of chronic HBV infections in north Indian population.

Elevated TGF-β1/IL-31 Pathway Is Associated with the Disease Severity of Hepatitis B Virus-Related Liver Cirrhosis.

The proinflammatory cytokines transforming growth factor beta 1 (TGF-β1) and interleukin (IL)-31 have been implicated in tissue injury. However, whether TGF-β1/IL-31 are stimulated and elevated in response to liver injury that leads to fibrogenesis in hepatitis B virus-related liver cirrhosis (HBV-LC) remains unclear. To investigate the association between TGF-β1/IL-31 and stages of chronic HBV infection, serum TGF-β1, IL-9, IL-10,IL-17, IL-22, IL-23, IL-31, IL-33, and IL-35 were determined among patients with chronic hepatitis B (CHB; n=19), HBV-LC (n=20), and a normal control population (NC; n=18). Disease severity in patients with HBV-LC was assessed using model for end-stage liver disease (MELD) scores. Serum TGF-β1 and IL-31 levels were strongly positively linked in all subjects, and both correlated positively with IL-22, IL-33, and IL-17. TGF-β1 and IL-31 levels in the blood were both significantly higher in CHB and HBV-LC patients than in NC subjects. Elevated serum TGF-β1 and IL-31 levels were positively associated with albumin, alpha-fetoprotein, creatinine, white blood cell count, and platelet levels. Serum TGF-β1 and IL-31 were markedly higher in HBV-LC patients who did not have esophageal varices, and IL-31 had the highest sensitivity and specificity (90.9% and 66.7%, respectively) for indicating the absence of this complication. In summary, TGF-β1 and IL-31 were linked to progression from CHB to LC, and correlated well with the severity of HBV-LC. These findings suggest possible roles of the TGF-β1/IL-31 pathway in the pathogenesis of liver fibrosis during chronic HBV infection.

Effects of nucleos(t)ide analogues initial treatment on virology and complications in hepatitis B virus related decompensated liver cirrhosis: a multicenter, prospective and observational study

Objective To evaluate the effects of nucleos(t)ide analogues initial treatment on virology and complications in hepatitis B virus (HBV) related decompensated liver cirrhosis. Methods From May 2012 to October 2013, a total of 209 patients with HBV related decompensated liver cirrhosis of 18 hospitals in China were enrolled. According to antiviral medicine taken by them, they were divided into entecavir (ETV) group (n=161), lamivudine (LAM) monotherapy or combined with adefovir (ADV) group (n=48, LAM 22 cases, LAM+ ADV 26 cases). During the 12-month follow-up period, Child-Pugh scores, the level of HBV DNA and complications of liver cirrhosis were documented every three months, the safety evaluation was also carried out. The t-test or chi-square test was performed for statistical analysis. Results In ETV group, before treatment and 12 months after treatment, Child-Pugh scores were 7.91±2.05 and 5.75±1.72, respectively, and the latter was lower than the former (t=10.130, P 0.05). The undetectable rates of HBV DNA gradually increased along with the treatment period. After 12 months treatment, the undetectable rate of HBV DNA of ETV group was 91.0%(61/67), and that of LAM alone or combined with ADV group was 87.5% (35/40), there was no significant difference between the two groups (P>0.05). Before treatment and 12 months after treatment, the incidences of ascites were 59.4% (82/138) and 15.0% (12/80) in ETV group, the latter was lower than the former (χ2=40.740, P 0.05). There was no significant difference in serum urea nitrogen, serum creatinine and estimated glomerular filtration rates between the two groups before treatment and at different time points after treatment (all P>0.05). Conclusion The efficacy and safety of ETV and LAM alone or combined with ADV are similar in patients with HBV related decompensated liver cirrhosis, however, the long-term efficacy should be identified by further clinical observation. Key words: Liver cirrhosis; Hepatitis B virus; Entecavir; Complications

Gut flora and gut-derived endotoxin in minimal hepatic encephalopathy

To investigate the relationship of gut flora and gut-derived endotoxin with minimal hepatic encephalopathy (MHE). Patients with hepatitis B virus-related liver cirrhosis (HBV-LC) were screened for MHE using the number connect test-A (NCT-A) and digital symbol test (DST) and divided into the following groups: HBV-LC with (+) MHE (n = 26) and HBV-liver cirrhosis without (-) MHE (n = 25); in addition, one healthy immediate family member of each patient in the HBV-LC + MHE group was enrolled as a control. Each participant provided fecal and blood samples. PCR amplification and 454 pyrosequencing were used to detect bacterial 16S rRNA in feces. Turbidimetric Limulus amebocyte lysate assay was used to detect level of endotoxin in serum. The significance of inter-group differences was assessed by one-way ANOVA or Student's t-test. The three groups showed different distributions of gut flora. The differences in the microbial communities' members and distributions were related to disease or health status, but not to the patient's genetic makeup or diet. In particular, the HBV-LC + MHE patients showed significantly lower amounts of different bacterial species and abundance of these species than the other two (non-MHE) groups (P less than 0.05). The healthy control family members had a richer diversity of gut flora than their counterparts with HBV-LC + MHE (P less than 0.05). The HBV-LV + MHE patients also had higher serum levels of endotoxin. Development of minimal hepatic encephalopathy in patients with HBV-LC may be related to a gut flora disorder or higher levels of endotoxin in serum.

English

OBJECTIVE: To establish the relationship between biochemical, serological and viral replication indices in an individual with incidentally detected asymptomatic HBsAg positive. METHOD: This cross-sectional study was undertaken on 73 asymptomatic HBsAg positive individuals between January 2010 and December 2011. They were divided into 5 groups on the basis of HBeAg status, ALT levels, and HBV DNA levels. RESULTS: There was statistically significant difference in HBV DNA levels and ALT between HBeAg positive and negative; and in ALT levels between cases in Group C and E and that between Groups C & D. There were significant difference in DNA levels between group D & group E and that between group C & group E. HBV DNA levels Co- related significantly with grade (r = 0.48, p 40 IU/ml) and those with normal ALT(<40 IU/ml). CONCLUSION: ALT and AST had a strong correlation with HBV DNA level. INTRODUCTION: Hepatitis B Virus (HBV) infection and its sequel are serious public health problems worldwide. Around 2 billion people are infected by hepatitis B virus (HBV) worldwide of which 400 million persons suffer chronic infection with HBV. 1 HBV infection is usually clinically in apparent. Approximately, 5-10% of infected adults develop chronic liver disease of varying severity. More than 90% of infants infected during the first year of life and 30-50% children infected between 1-4 yrs of age develop chronic infection. The risk of death from HBV related liver cancer and cirrhosis is approximately 25% in persons who become chronically infected during child hood.2, 3 15-40% of carriers will develop serious complications during lifetime like cirrhosis, decompensated liver disease or HCC. 1 75% of carriers are present in Asia. India has the second largest pool of HBsAg carriers after China. AIMS AND OBJECTIVES: This study was undertaken to establish the relationship between biochemical, serological, viral replication indices in an individual with incidentally detected asymptomatic HBsAg positive.

Which patients respond best to hepatitis B vaccination after a hepatitis B virus-related liver transplantation?

BackgroundA combination of hepatitis B immunoglobulin and nucleos(t)ide analogues is the current standard of care for controlling hepatitis B recurrence after orthotopic liver transplantation (OLT). However, frequent immunoglobulin treatment is expensive and inconvenient. This study investigated the efficacy of hepatitis B virus (HBV) vaccination in preventing the recurrence of hepatitis B after living donor OLT.MethodsTwenty-seven patients who had undergone living donor OLT participated in the study; five had acute HBV infected liver failure (ALF-OLT) and 22 had HBV related liver cirrhosis (LC-OLT). Hepatitis B surface antigen (HBsAg)-containing vaccine was administered to them for at least 1 year after transplantation and continued once monthly for up to 36 months post-OLT. Patients who had anti-HBs antibody titers above 100 mIU/mL for a minimum of 6 months without immunoglobulin administration were defined as good responders; the others were defined as poor responders. Interferon-γ enzyme-linked immunospot assays against HBs and HBc antigens were used to assay cellular immune responses.ResultsAll five of the ALF-OLT patients had good responses after a median of four (range 2.5–5) vaccinations. Nine of the 22 LC-OLT patients had good responses after a median of 19 (range 11.5–30) vaccinations. Among the LC-OLT group, those with livers donated by relatively higher-aged, marital and high-titer anti-HBs antibody donors were good responders. LC-OLT patients classed as good responders showed interferon-γ responses comparable to those of the ALF-OLT patients.ConclusionsThe ALF-OLT and LC-OLT patients who received livers from relatively higher-aged, marital, high-titer anti-HBs antibody donors were the best candidates for HBV vaccine administration. Boosting donors before transplantation may facilitate later vaccine response of the recipients.

Decrease in Size of Non-Treated Lesions after Cryoablation for Hepatocellular Carcinoma

We present the case of one 58-year-old man with advancd hepatocellular carcinoma and hepatitis-B virus-related liver cirrhosis who received hepatic cryoablation. Magnetic resonance imaging (MRI) showed multiple liver tumors and the diameter of the largest tumor was more than 10cm. The patient received 2 percutaneous cryoablations in December 2009 and January 2010. Ten months later, MRI showed that not only the treated areas underwent necrosis but also the non-treated area decreased. The a-fetoprotein (AFP) level and the frequency of circulated regulatory T cell (Treg) before treatment were 13,800ng/mL and 15.6%, respectively. Following the cryoablations they dropped to 436ng/mL and 7.6%, respectively, 10 months later. The patient remains in good condition until now.

A cis-acting regulatory variation of the estrogen receptor α (ESR1) gene is associated with hepatitis B virus-related liver cirrhosis

The hepatic fibrogenesis and sexual dimorphism of hepatitis B virus-related liver cirrhosis (HBV-LC) are related to estrogen and its receptors. Abnormal expression of estrogen receptor α (ESR1) is implicated in the development of cirrhosis in both animal models and humans. Here, we examine whether the ESR1 polymorphisms are related to HBV-LC risk among chronic HBV carriers, and we investigate the functional significance of positively associated polymorphisms. A total of 2,404 unrelated Chinese HBV carriers were recruited to conduct the two-stage designed case-control study. Two ESR1 haplotype tagging polymorphisms, c.30T>C (rs2077647) and c.453-397T>C (rs2234693), were genotyped in 1,285 patients with HBV-LC and in 1,119 asymptomatic HBV carriers. We observed a significantly increased susceptibility to HBV-LC associated with the c.30C allele (P = 4.2 × 10(-8) ), c.453-397C allele (P = 2.0 × 10(-8) ), and [c.30C; c.453-397C] haplotype (Dominant model, P = 8.85 × 10(-10) , odds ratio = 1.50, 95% CI 1.32∼1.71) compared with the T alleles and (c.30T; c.453-397T) haplotype of c.30T>C and c.453-397T>C polymorphisms, respectively. Functional analyses were conducted to verify the biological functions of the associated genetic variations and showed that the c.453-397T>C polymorphism is a novel c.453-397C allele-specific and c-myb-dependent enhancer-like cis-acting regulatory variation and could be part of the genetic variations underlying the susceptibility of individuals to HBV-LC.

Seroprevalence of anti-HAV among patients with chronic viral liver disease

To investigate the current seroprevalence of hepatitis A virus (HAV) antibodies in patients with chronic viral liver disease in Korea. We also tried to identify the factors affecting the prevalence of HAV antibodies. We performed an analysis of the clinical records of 986 patients (mean age: 49 ± 9 years, 714 males/272 females) with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection who had undergone HAV antibody testing between January 2008 and December 2009. The overall prevalence of IgG anti-HAV was 86.61% (854/986) in patients with chronic liver disease and was 88.13% (869/986) in age- and gender-matched patients from the Center for Health Promotion. The anti-HAV prevalence was 80.04% (405/506) in patients with chronic hepatitis B, 86.96% (20/23) in patients with chronic hepatitis C, 93.78% (422/450) in patients with HBV related liver cirrhosis, and 100% (7/7) in patients with HCV related liver cirrhosis. The anti-HAV prevalence according to the decade of age was as follows: 20s (6.67%), 30s (50.86%), 40s (92.29%), 50s (97.77%), and 60s (100%). The anti-HAV prevalence was significantly higher in patients older than 40 years compared with that in patients younger than 40 years of age. Multivariable analysis showed that age ≥ 40 years, female gender and metropolitan cities as the place of residence were independent risk factors for IgG anti-HAV seropositivity. Most Korean patients with chronic liver disease and who are above 40 years of age have already been exposed to hepatitis A virus.

Matrix Metalloproteinase (MMP)-3 Polymorphism in Patients with HBV Related Chronic Liver Disease

A common and important problem in patients with chronic hepatitis B is the progression of liver fibrosis. Matrix metalloproteinases (MMPs) play an important role in the progression of liver fibrosis. Our aim of this study was to examine the association of MMP-3 polymorphism with liver cirrhosis in Korean patients with chronic hepatitis B. Genomic DNA was extracted from 127 patients with chronic hepatitis B (CHB), 92 patients with hepatitis B virus (HBV)-related liver cirrhosis (HBV-LC), and 146 healthy subjects. MMP-3 polymorphism was determined by polymerase-chain reaction-based assays, and the association with the progression of liver cirrhosis was investigated. With regard to MMP-3 polymorphism, there was no statistical difference in genotype distributions among the three groups. However, the peripheral platelet count of the 5A carriers was significantly lower than that of the 6A homozygotes in the HBV-LV group (85.0 +/- 36.9 vs. 109.8 +/- 47.0 x 10(9)/l; P = 0.02). With MMP-3 promoter polymorphism (rs3025058), a lower peripheral blood platelet count, which was related to advanced liver cirrhosis, was observed in 5A carriers. Therefore, more studies of MMP-3 gene polymorphism with larger populations should be conducted to further understand its role in the progression of liver cirrhosis.

Influence of viral load and genotype in the progression of Hepatitis B‐associated liver cirrhosis to hepatocellular carcinoma

Hepatitis B virus (HBV) is an important factor in the development of hepatocellular carcinoma (HCC). We studied the influence of HBV viral load on HCC occurrence in HBV related liver cirrhosis (LC). Ninety-one LC patients were followed up over a period of 7 years. Twenty three patients received Interferon (IFN) therapy. In 7 years, 23 patients developed HCC. Of them twenty-two (95.6%) were of genotype C. HBV DNA was found to be the only significant variable associated with HCC occurrence on both univariate (P = 0.029) and multivariate analysis (odds ratio 2.33; P < 0.033). The cumulative survival at 5 years was 83% and the annual rate of hepatitis B surface antigen clearance was 0.9 %. All of 17 HCC patients observed over a period of 5 years or more belonged to the continuously high HBV DNA group (annual average >3.7 log copies/ml) and all but one belonged to the continuously high alanine aminotransferase group (annual average >40 IU/l). Patients with genotype C and a continuously high HBV DNA for 5 years or more are at a high-risk group for HCC development. Maintaining continuously low HBV DNA for 3 years or more with anti-viral therapy, may be useful in preventing or delaying HCC occurrence.