<b>Objective:b> To investigate the effects of hepatitis B virus (HBV) genotype and mutations on the development of hepatocellular carcinoma (HCC) and to establish a new qualified HCC risk scores. <b>Methods:b> A cohort study enrolling patients with chronic HBV infection was conducted. HBV genotypes were identified by nested multiplex PCR. HBV mutations in the basic core promoter region and PreS region were sequenced after PCR amplification. Scores on risk factors were set based on nomogram. <b>Results:b> Totally, 1 525 patients were followed-up in this research. A total of 1 110 patients infected with genotype C were followed-up for 8.52 (Q(R): 5.36-11.68) years on average, of whom the incidence of HCC was 11.93/1 000 person-years. In genotype C HBV infected patients, male gender, aged 40 years and over, and four DNA mutations (T1674CG, A1762T/G1764A, A3120T, and A2962G) can increase the risk of HCC (P<0.05); interferon therapy can reduce the risk of HCC (P<0.05). A new HCC predicting model was established according to the results. After validation, the predicted disease-free survival rate was consistent with the real one. <b>Conclusions:b> Hepatitis B virus genotypes and mutations were closely associated with HCC. The new risk scoring system can well predict HCC occurrence in genotype C HBV infected patients.
Adult ; Aged ; Carcinoma, Hepatocellular/virology* ; China/epidemiology* ; Cohort Studies ; DNA, Viral/genetics* ; Female ; Genotype ; Hepatitis B virus/genetics* ; Hepatitis B, Chronic/complications* ; Humans ; Liver Neoplasms/virology* ; Male ; Middle Aged ; Mutation ; Predictive Value of Tests ; Risk Factors ; Sensitivity and Specificity

BACKGROUND/AIMS: This study aimed to clarify the effect of obesity on the development of hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients receiving antiviral treatment. METHODS: This study applied a retrospective analysis to a historical cohort in Bundang Jesaeng Hospital. In total, 102 CHB patients were treated with entecavir as an initial treatment for CHB and checked for obesity using a body composition analyzer. Hepatic steatosis was measured semiquantitatively using Hamaguchi’s scoring system in ultrasonography. Risk factors for the development of HCC were analyzed, including obesity-related factors (body mass index [BMI], waist circumference [WC], waist-to-hip ratio [WHR], visceral fat area [VFA], and hepatic steatosis). RESULTS: The median follow-up duration of the patients was 45.2 months (interquartile range: 36.0-58.3 months). The cumulative incidence rates of HCC at 1 year, 3 years, and 5 years were 0%, 5.3%, and 9.0%, respectively. Univariable analysis revealed that the risk factors for HCC development were a platelet count of <120,000 /mm² (hazard ratio [HR]=5.21, P=0.031), HBeAg negativity (HR=5.61, P=0.039), and liver cirrhosis (HR=10.26, P=0.031). Multivariable analysis showed that the significant risk factor for HCC development was liver cirrhosis (HR=9.07, P=0.042). However, none of the obesity-related risk factors were significantly associated with HCC: BMI ≥25 kg/m² (HR=0.90, P=0.894), WC ≥90 cm (HR=1.10, P=0.912), WHR ≥0.9 (HR=1.94, P=0.386), VFA ≥100 cm² (HR=1.69, P=0.495), and hepatic steatosis (HR=0.57, P=0.602). CONCLUSION: HCC development is associated with liver cirrhosis but not obesity-related factors in CHB patients receiving entecavir.
Adult ; Antiviral Agents/*therapeutic use ; Body Mass Index ; Carcinoma, Hepatocellular/epidemiology/*etiology ; Cohort Studies ; DNA, Viral/blood ; Female ; Guanine/*analogs & derivatives/therapeutic use ; Hepatitis B virus/genetics/isolation & purification ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Incidence ; Liver Cirrhosis/complications ; Liver Neoplasms/epidemiology/*etiology ; Male ; Middle Aged ; Obesity/*complications ; Proportional Hazards Models ; Retrospective Studies ; Risk Factors ; Viral Load

<b>OBJECTIVEb>To analyze the development of liver damage and reactivation of hepatitis B virus (HBV) during the treatment of extremely severe burn injury in HBsAg positive patients, in order to provide reference for prevention and treatment of liver damage in patients with HBV infection after extremely severe burn.

<b>METHODSb>Medical records of 54 HBsAg positive patients after extremely severe burn injury admitted from January 2004 to December 2014 were retrospectively analyzed. Development of liver damage and HBV reactivation of these patients during the treatment were analyzed according to the classification of their gender, results of hepatitis B e antigen (HBeAg) and HBV DNA examinations on admission, and development of sepsis in the process of treatment. Data were processed with chi-square test.

<b>RESULTSb>(1) The incidence of liver damage in the process of treatment of these patients was 85.2% (46/54). Among all the patients, the proportion of liver damage was 35/38 in male, which was significantly higher than that in female (11/16, χ² = 4.867, P<0.05). Liver damage was found in all of 26 patients who were HBeAg positive on admission, 34 patients who were HBV DNA positive on admission, and 36 patients who developed sepsis in the process of treatment; the proportions were significantly higher than those in patients who were HBeAg negative on admission (20/28), patients who were HBV DNA negative on admission (12/20), and patients who did not develop sepsis in the process of treatment (10/18), with χ² values respectively 11.801, 18.384, and 20.574, P values below 0.01. (2) The incidence of HBV reactivation in these patients was 29.6% (16/54). Among all the patients, the proportion of HBV reactivation was 13/38 in male and 3/16 in female, with no statistically significant difference between them (χ² = 0.656, P>0.05). The proportions of HBV reactivation in patients who were HBeAg positive on admission, patients who were HBV DNA positive on admission, and patients who developed sepsis in the process of treatment were respectively 13/26, 16/34, and 15/36, and they were significantly higher than those in patients who were HBeAg negative on admission (3/28), patients who were HBV DNA negative on admission (0/20), and patients who did not develop sepsis in the process of treatment (1/18), with χ² values respectively 9.979, 18.615, and 5.873, P<0.05 or P<0.01.

<b>CONCLUSIONSb>Patients who are HBsAg positive, HBeAg positive, HBV DNA positive on admission, and develop sepsis in the process of treatment of extremely severe burn injury are more likely to develop liver damage and HBV reactivation. It is necessary to dynamically monitor the changes in HBV DNA and liver function, in order to identity the reactivation of virus.

Alanine Transaminase ; blood ; Burns ; complications ; drug therapy ; Chemical and Drug Induced Liver Injury ; DNA, Viral ; Female ; Hepatitis Antibodies ; blood ; Hepatitis B ; drug therapy ; epidemiology ; virology ; Hepatitis B Surface Antigens ; blood ; immunology ; Hepatitis B virus ; drug effects ; immunology ; isolation & purification ; Hepatitis B, Chronic ; blood ; pathology ; virology ; Humans ; Incidence ; Liver ; pathology ; Male ; Retrospective Studies

BACKGROUND/AIMS: This study assessed the antiviral efficacy and safety of tenofovir disoproxil fumarate (TDF) for up to 12 months in Korean treatment-naive chronic hepatitis B (CHB) patients. METHODS: A total of 411 treatment-naive CHB patients who had been treated with TDF for at least 3 months (median 5.6) were consecutively enrolled. Clinical, biochemical, virological parameters and treatment adherence were routinely assessed every 3 months. RESULTS: The median age was 51.3 years, 63.0% of the patients were male, 49.6% were HBeAg (+), and 210 patients had liver cirrhosis. The median baseline HBV DNA was 5.98 (SD 1.68) log10 IU/mL. Among the patients completing week 48, 83.3% had a complete virologic response (CVR, <12 IU/mL by HBV PCR assay), and 88.2% had normalized levels of alanine aminotransferase (ALT). The cumulative probabilities of CVR at 3, 6, 9 and 12 months were 22.8%, 53.1%, 69.3% and 85.0%. During the follow-up period, 9.8% patients achieved HBeAg loss and 7.8% patients achieved HBeAg seroconversion. There was no virological breakthrough after initiating TDF. The most common TDF-related adverse event was gastrointestinal upset, and three patients discontinued TDF therapy. However, no serious life-threatening side effect was noted. CONCLUSIONS: In a clinical practice setting, TDF was safe and highly effective when administered for 12 months to Korean treatment-naive CHB patients.
Adenine/adverse effects/*analogs & derivatives/therapeutic use ; Adult ; Aged ; Aged, 80 and over ; Alanine Transaminase/blood ; Antiviral Agents/adverse effects/*therapeutic use ; Cohort Studies ; DNA, Viral/blood ; Female ; Gastrointestinal Diseases/epidemiology/etiology ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/complications/*drug therapy/virology ; Humans ; Liver Cirrhosis/etiology ; Male ; Middle Aged ; Organophosphonates/adverse effects/*therapeutic use ; Republic of Korea ; Retrospective Studies ; Treatment Outcome ; Young Adult

BACKGROUND/AIMS: The prevalence of occult HBV infection depends on the prevalence of HBV infection in the general population. Hemodialysis patients are at increased risk for HBV infection. The aim of this study was to determine the prevalence of occult HBV infection in hemodialysis patients. METHODS: Total of 98 patients undergoing hemodialysis in CHA Bundang Medical Center (Seongnam, Korea) were included. Liver function tests and analysis of HBsAg, anti-HBs, anti-HBc and anti-HCV were performed. HBV DNA testing was conducted by using two specific quantitative methods. RESULTS: HBsAg was detected in 4 of 98 patients (4.1%), and they were excluded. Among 94 patients with HBsAg negative and anti-HCV negative, one (1.1%) patient with the TaqMan PCR test and 3 (3.2%) patients with the COBAS Amplicor HBV test were positive for HBV DNA. One patient was positive in both methods. Two patients were positive for both anti-HBs and anti-HBc and one patient was negative for both anti-HBs and anti-HBc. CONCLUSIONS: The present study showed the prevalence of occult HBV infection in HBsAg negative and anti-HCV negative patients on hemodialysis at our center was 3.2%. Because there is possibility of HBV transmission in HBsAg negative patients on hemodialysis, more attention should be given to prevent HBV transmission.
Adult ; Aged ; Aged, 80 and over ; Antibodies/blood ; DNA, Viral/analysis ; Feces/*virology ; Female ; Hepatitis B/complications/*epidemiology/transmission ; Hepatitis B Core Antigens/immunology ; Hepatitis B virus/genetics/immunology ; Hepatitis C Antibodies/blood ; Humans ; Kidney Failure, Chronic/*complications/diagnosis ; Male ; Middle Aged ; Polymerase Chain Reaction ; Prevalence ; Renal Dialysis ; Risk Factors

BACKGROUND/AIMS: Lamivudine (LAM) plus adefovir (ADV) combination therapy has been accepted as one of the best treatments for LAM-resistant chronic hepatitis B (CHB). The aim of this study was to determine the efficacy of this combination therapy in hepatocellular carcinoma (HCC) patients. METHODS: The medical records of CHB patients who developed LAM resistance and were treated with LAM plus ADV combination therapy for more than 6 months were reviewed. Their virological response (VR; undetectable HBV DNA) and biochemical response (BR; alanine aminotransferase normalization) were evaluated, and the findings of HCC and non-HCC patients were compared. RESULTS: The data from 104 patients (19 with HCC and 85 without HCC) were analyzed. The VR rates did not differ significantly between the HCC and non-HCC groups: 33.3% vs. 55.6% at 12 months (P=0.119), 58.3% vs. 67.2% at 24 months (P=0.742), 50% vs. 69.8% at 36 months (P=0.280), and 66.7% vs. 71.0% at 48 months (P=1.000). The BR rates also did not differ significantly between the groups: 55.6% vs. 84.0% at 12 months (P=0.021), 58.3% vs. 83.8% at 24 months (P=0.057), 70.0% vs. 77.8% at 36 months (P=0.687), and 66.7% vs. 80.6% at 48 months (P=0.591). CONCLUSIONS: The efficacy of LAM plus ADV combination therapy is comparable in HCC and non-HCC patients.
Adenine/*analogs & derivatives/therapeutic use ; Adult ; Antiviral Agents/*therapeutic use ; Carcinoma, Hepatocellular/*diagnosis/epidemiology/etiology ; DNA, Viral/analysis ; Drug Administration Schedule ; Drug Resistance, Viral ; Drug Therapy, Combination ; Genotype ; Hepatitis B virus/genetics ; Hepatitis B, Chronic/*drug therapy/virology ; Humans ; Incidence ; Lamivudine/*therapeutic use ; Liver Cirrhosis/diagnosis/epidemiology/etiology ; Liver Neoplasms/*diagnosis/epidemiology/etiology ; Middle Aged ; Organophosphonates/*therapeutic use ; Retrospective Studies ; Treatment Outcome

<b>OBJECTIVEb>To investigate drug resistance, genotype and serotype of hepatitis B virus (HBV) in nucleos(t)ide analogue (NA) naive patients with chronic hepatitis B (CHB).

<b>METHODSb>Full-length reverse transcriptase region of HBV DNA was amplified by semi-nested polymerase chain reaction from 97 NA-naive CHB patients, and the PCR product was sequenced, and analyzed to screen 11 classical antiviral drug resistance mutation sites and to identify HBV genotypes, subgenotypes and serotypes.

<b>RESULTSb>Wild-type sequences were found at all of the 11 classical antiviral drug resistance mutation sites from all samples. The patients were infected with either genotype B (36.1%, 35/97) or C (63.9%, 62/97) HBV. The former were all belonged to subgenotype B2 strain; while the latter were divided further into subgenotype C2 (91.9%, 57/62), subgenotype C1 (6.5%, 4/62) and unknown subgenotype (1.6%, 1/62). The 71.9% (23/32) of HBV genotype B patients were born in southern China, while 81.6% (40/49) of HBV genotype C patients were from northern China, showing a clear geographic distribution (Chi-square test = 23.19, Probability value less than 0.01). Of 97 CHB patients, 59 (60.8%) were serotype adr associated with genotype C, while 37 (38.1%) were adw related to genotype B (subgenotype B2) (Chi-square test = 87.83, P less than 0.01).

<b>CONCLUSIONb>The wild-type HBV strains prevail in NA-naive CHB patients, whose HBV genotypes, subgenotypes and serotypes are associated with their places of birth.

Adult ; Antiviral Agents ; therapeutic use ; Base Sequence ; DNA, Viral ; blood ; genetics ; Drug Resistance, Viral ; genetics ; Female ; Genetic Variation ; Genotype ; Hepatitis B virus ; classification ; genetics ; Hepatitis B, Chronic ; drug therapy ; epidemiology ; virology ; Humans ; Male ; Middle Aged ; Nucleotides ; therapeutic use ; Polymerase Chain Reaction ; methods ; Sequence Analysis, DNA ; Serotyping ; Young Adult

<b>OBJECTIVESb>To investigate the prevalence of hepatitis B virus (HBV) genotypes and the association with hepatocellular carcinoma (HCC) or basal core promoter (BCP) mutation in Qidong, China.

<b>METHODSb>The whole genome of HBV or X gene sequences were obtained from serum samples of HBV infected patients by using PCR and direct sequencing methods. Phylogenetic tree was constructed to determine the genotypes or subgenotypes of HBV.

<b>RESULTSb>According to the phylogenetic tree constructed from full-length sequence of HBV, genotype C2 was predominant in Qidong area. It was prevalent in 44 out of the 48 cases (91.7%), whereas genotype B2 only existed in 4 cases (8.3%). No other genotypes or recombinant types were found in Qidong patients. The result of genotyping based on X gene sequence confirmed the above observation. In a total of 182 samples, 169 (92.9%) showed genotype C2 and 10 (5.5%) showed genotype B2. There were 3 (1.6%) patients showed a coinfection with C2 and B2. The infection rate of genotype C in Qidong was significantly higher than that in neighboring city Shanghai (chi(2) = 12.252, P less than 0.01). There was no significant difference of genotype distribution between HCC and chronic hepatitis groups (P is more than 0.05). The frequency of T1762/A1764 double mutation in genotype C2 (70.3%) was significantly higher than that in genotype B2 (30.8%, P less than 0.05). The other two types of point mutation which also occurred in BCP, i.e. T1766 and A1768, were only seen in genotype C2.

<b>CONCLUSIONb>(1) Genotype C2 is the predominant genotype in Qidong, China. (2) There is no association between genotype C and HCC in Qidong. (3) Genotype C has a higher prevalence of BCP mutation than genotype B.

Adolescent ; Adult ; Aged ; Carcinoma, Hepatocellular ; epidemiology ; virology ; Child ; Child, Preschool ; China ; epidemiology ; DNA, Viral ; genetics ; Female ; Genotype ; Hepatitis B virus ; genetics ; Hepatitis B, Chronic ; virology ; Humans ; Liver Neoplasms ; epidemiology ; virology ; Male ; Middle Aged ; Mutation ; Prevalence ; Viral Core Proteins ; genetics ; Young Adult

Adult ; Aged ; Aged, 80 and over ; China ; epidemiology ; Diabetes Mellitus ; epidemiology ; etiology ; Fatty Liver ; complications ; Female ; Glucose Metabolism Disorders ; epidemiology ; etiology ; Hepatitis B, Chronic ; complications ; virology ; Hepatitis C ; complications ; virology ; Humans ; Liver ; metabolism ; pathology ; Liver Cirrhosis ; epidemiology ; etiology ; Liver Cirrhosis, Alcoholic ; epidemiology ; etiology ; Male ; Middle Aged ; Odds Ratio ; Retrospective Studies

<b>OBJECTIVEb>To explore clinical and pathological features of chronic hepatitis B (CHB) with hepatic steatosis.

<b>METHODSb>Retrospective analysis of hepatic steatosis in patients with liver biopsy-proven CHB between January 2005 and June 2008. Detailed clinical, laboratory and pathological data of CHB patients with steatosis were compared with those in sex-, age- matched CHB patients without steatosis. Patients co-infected hepatitis C virus or HIV or suffering from liver diseases of other causes were excluded.

<b>RESULTSb>Histological hepatic steatosis was found in 33.4% of the 1263 CHB patients. The prevalence of steatosis was increased with time in the study period (20.3%, 28.2%, 32.6%, 65.4%, in trend analysis, P values less than 0.05). Body mass index, fasting plasma glucose, serum triglyceride and total cholesterol level in CHB patients with hepatic steatosis (n = 114) were significantly higher than those in 113 patients without steatosis (t values were 6.811, 2.733, 3.063, 2.340, respectively, P values less than 0.01 or 0.05). Compared to patients without steatosis, serum hepatitis B virus DNA titer in patients with steatosis was significantly lower (x2 = 6.154, P less than 0.05) and reduced sharply with the increased degree of hepatic steatosis (x2 = 4.941, P less than 0.05). There were no differences in liver biochemical test (t values were 0.744, 1.390, -0.029, -1.175, 1.393, respectively, P values more than 0.05), hepatic inflammation grade and fibrosis stage between CHB patients with and without steatosis (x2 = 1.434, 0.106, respectively, P more than 0.05), and these parameters were not associated with different degree of hepatic steatosis (x2 = 2.447, 2.911, respectively, P more than 0.05).

<b>CONCLUSIONSb>Hepatic steatosis is common in patients with CHB, and is related to metabolic disorders. Hepatic steatosis does not affect the severity of CHB. The reverse association of hepatitis B virus titer with the degree of hepatic steatosis needs further investigation.

Alanine Transaminase ; blood ; Biomarkers ; blood ; Body Mass Index ; Cholesterol ; blood ; DNA, Viral ; blood ; Fatty Liver ; epidemiology ; etiology ; pathology ; Female ; Hepatitis B virus ; Hepatitis B, Chronic ; complications ; pathology ; virology ; Humans ; Liver ; pathology ; virology ; Liver Cirrhosis ; epidemiology ; etiology ; pathology ; Male ; Obesity ; complications ; Retrospective Studies ; Risk Factors ; Severity of Illness Index