BACKGROUND/AIMS: HBcAg is the most immunogenic HBV component and anti-Bc usually persists irrespective of ongoing liver disease or clearance of the virus in human. Therefore anti-Bc is considered as the most sensitive and occasionally the only marker of the HBV infection. Nevertheless, there are a few HBsAg carrier with persistent negative anti-Bc. The epitope which responds to HBcAg is recently defined in HLA A2 from acute viral hepatitis patient due to HBV. So we studied the clinical and laboratory features and nucleotide sequence of HBcAg corresponding to HLA A2 in the HBsAg carrier with persistent negative anti-Bc. METHODS: The subject of these study consists of eight HBsAg chronic carriers with persistent negative anti-Bc. We followed up the clinical features and serological markers of HBV infection and determined the amount of humoral immunoglobulin, HBV DNA and HBcAg when we performed the HLA class I typing and sequencing analysis of core of HBV. Control cases were selected from 3 HLA A2 heterozygote cases with chronic HBsAg carriers with anti-Bc. RESULTS: All subjects had the HBsAg persistently and good health conditions with normal ranges of aminotransferase and humoral immunoglobulin. One of them was converted to anti-Bc-ositive during follow-p period. The level of HBV DNA in serum was higher than 1.2 pg/mL in 7 of 8 chronic HBV carriers. There was a trend of differences between chronic anti-Bc negative carriers and converted one case to anti-Bc positive in the serum of HBcAg and HBV DNA(p=0.06). But strong positive correlation was observed between the amount of HBcAg and HBV DNA in sera. The core portion of HBV was amplified in 4 of 6 HLA A2 heterozygotes by single PCR. When sequenced the PCR products of the above 4 chronic anti-Bc negative HBV carriers and 3 control cases directly, there were no significant difference in the nucleotide and amino acid sequence at the HBcAg epitope which corresopond to class 1 HLA A2. CONCLUSIONS: Our results show that persistent anti-Bc negative chronic HBV carriers may be caused by large amounts of HBV DNA and HBcAg in their sera and not by variants of HBV. These suggested that active viral replication was going on, but are undetectable by the available commercial tests due to binding with excessive amount of HBcAg in the HBV carriers with persistent negative anti-Bc.
Amino Acid Sequence ; Base Sequence* ; DNA ; Hepatitis ; Hepatitis B Core Antigens* ; Hepatitis B Surface Antigens ; Hepatitis B, Chronic* ; Hepatitis, Chronic* ; Heterozygote* ; Humans ; Immunoglobulins ; Liver Diseases ; Polymerase Chain Reaction ; Reference Values

Benign tumors of the extrahepatic bile duct are rare. They occur mostly in the common bile duct. Among them, papillomas and adenomas are most common. We experienced a case of villous adenomas in the common bile duct and also in the cystic duct. The ultrasound and the CT scan of the abdomen revealed markedly dilated common bile duct, subtle filling defect, and irregular mass narrowing the lumen of the common bile duct. The cholangiogram demonstrated movable, feathery, and marginated papillary mass with tumors, a broad base, and biopsy of this mass was done through the PTBD. The biopsy specimen showed villous adenoma. Even though it was diagnosed as benign, cholecystectomy and excision with Roux-en-Y hepaticojejunostomy was performed because of the high incidence of recurrences and malignant potential.
Abdomen ; Adenoma ; Adenoma, Villous* ; Bile Ducts, Extrahepatic ; Biopsy ; Cholecystectomy ; Common Bile Duct* ; Cystic Duct* ; Incidence ; Papilloma ; Recurrence ; Tomography, X-Ray Computed ; Ultrasonography

BACKGROUND/AIMS: The hepatitis B virus (HBV) genome contains binding sites for hepatocyte nuclear factors (HNF) 3 and 4 in the core domain of enhancer 1 (Enh1), and mutations in this domain have a strong impact on virus replication. We aimed to identify frequent base-mutation sites in the core domain of Enh1 and to examine the impact of these mutations on viral replication. METHODS: We studied virological characteristics and genetic sequences in 387 patients with chronic hepatitis B. We evaluated functional differences associated with specific mutations within the core domain of Enh1. RESULTS: Mutations in the core domain were found with significant frequency in C1126 (122/387 [31.5%], the binding site for HNF3) and in C1134 (106/387 [27.4%], the binding site for HNF4). A single mutation at nt 1126 (C1126) was identified in 17/123 (13.8%), and 105/123 (85.4%) had double mutations (C1126/1134). The level of HBV DNA (log10 copies/mL) was lower in single mutants (C1126, 5.81+/-1.25) than in wild (6.80+/-1.65) and double mutants (C1126/1134, 6.81+/-1.54). Similarly, the relative luciferase activity of C1126 and C1126/C1134 was 0.18 and 1.12 times that of the wild-type virus, respectively. CONCLUSIONS: Mutations in the HNF3 binding site inhibit viral replication, whereas mutations at the HNF4 binding site restore viral replication.
Binding Sites ; DNA ; Genome ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Hepatocyte Nuclear Factors ; Humans ; Luciferases ; Virus Replication ; Viruses

BACKGROUND: Hepatitis B virus (HBV) is major source of chronic liver disease in Korea. However this virus might have different nucleotide sequence according to races, different region, etc. Recently the novel method that allows sensitive amplification with dramatically decreased mis-incorporation has developed. We determined to get the major form of HBV nucleotide sequence from whole sequencing data of 26 Korean HBV carriers. METHODS: HBV DNA were collected from 26 Korean chronic HBV carriers. We used the novel PCR with pfu for the amplification of HBV DNA, and specific primers were made with combination sequence bases of non-HBV part and HBV parts which were located head and tail in the virion. Then whole length of HBV were directly sequenced and analysed. RESULT: HBV DNA was consisted of 3215 bases in 20 cases of 26 Korean chronic HBV carriers. And the remainder had smaller or larger number due to deletion, insertion or both in pre-S2 and S gene. They were 99.03% homology of their nucleotide sequence and belong to genotype C. The variability of nucleotide sequence was significantly higher in the singly coding region (SCR) than doubly coding region (DCR), and also high in pre-S1 and pre-S2 gene among the DCR. Hot-spots were more frequently found in the SCR, pre-S1 and pre-S2 gene. CONCLUSION: In Korean chronic HBV carriers, HBV is consisted of 3215 nucleotides, and belongs to genotype C. And it might exist one genotype with the variability in Korea.
Base Sequence* ; Clinical Coding ; Continental Population Groups ; DNA ; Genome* ; Genotype* ; Head ; Hepatitis B virus* ; Hepatitis B* ; Hepatitis* ; Humans ; Korea ; Liver Diseases ; Nucleotides ; Polymerase Chain Reaction ; Polymerization* ; Polymers* ; Virion

BACKGROUND/AIMS: Few reports have described the association between mutations in the entire X gene of the hepatitis B virus (HBV) and the clinical status of HBV-infected patients. We studied the association between HBV X gene mutations and the disease status of patients infected with HBV genotype C. METHODS: Mutations in the HBV X genes of 194 patients were determined by direct sequencing. The subject population consisted of patients with chronic hepatitis (n=60), liver cirrhosis (n=65), and hepatocellular carcinoma (HCC) (n=69). The sequencing results of these 3 groups were compared. RESULTS: Each of the mutations G1386M, C1485T, C1653T, T1753V, A1762T, and G1764A was significantly associated with the patient's clinical status. The T1753V (p<0.001) and A1762T/G1764A (p<0.001) mutations were found more frequently in Hepatitis B e antigen (HBeAg)-negative than in HBeAg-positive patients. Specific X gene mutations (G1386M, C1653T, and A1762T/G1764A) were more prevalent in patients with liver cirrhosis and HCC than in chronic hepatitis patients (p<0.005 for all). In addition, the T1753V (p<0.001) and C1485T (p<0.001) mutations were significantly more prevalent in HCC patients than in chronic hepatitis patients. Only the prevalence of the T1753V mutation increased as the HBV infection progressed from liver cirrhosis to HCC (p=0.023). CONCLUSIONS: Our findings show a difference in the pattern of X gene mutations that were associated with the clinical status of patients with chronic HBV infection.
Carcinoma, Hepatocellular ; Fibrosis ; Genotype ; Hepatitis ; Hepatitis B ; Hepatitis B virus ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Liver Cirrhosis ; Liver Diseases ; Prevalence

The authors assessed the efficacy and antiviral resistance of 48-week clevudine therapy versus lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B. In this retrospective study, a total of 116 HBeAg positive patients, who received 30 mg of clevudine once daily (n=53) or 100 mg of lamivudine once daily (n=63) for 48 weeks, were included. At week 48, clevudine therapy produced a significantly greater mean reductions in serum HBV DNA levels from baseline than lamivudine therapy (-5.2 vs. -4.2 log(10)IU/mL; P=0.005). Furthermore, a significantly higher proportion of patients on clevudine achieved negative serum HBV DNA by PCR (<13 IU/mL) at week 48 (60.4% vs. 38.1%; P=0.025). The incidence of virologic breakthrough in the clevudine group was significantly lower than in the lamivudine group (9.4% vs. 25.4%; P=0.031). However, rates of alanine aminotransferase normalization and HBeAg loss or seroconversion were similar in the two groups (83.0% vs. 81.0%, 11.3% vs. 11.1%; P=0.813, 1.000, respectively). In conclusion, clevudine is more potent for viral suppression and lower for antiviral resistance at week 48 than lamivudine in treatment of naive patients with HBeAg positive chronic hepatitis B.
Adult ; Antiviral Agents/administration & dosage ; Arabinofuranosyluracil/administration & dosage/*analogs & derivatives ; Drug Resistance, Viral ; Female ; Hepatitis B e Antigens/*blood ; Hepatitis B, Chronic/diagnosis/*drug therapy/*immunology ; Humans ; Lamivudine/*administration & dosage ; Male ; Treatment Outcome

Congenital hepatic fibrosis (CHF) is an autosomal recessive disease, presenting principally in children or young adults with portal hypertension, and infrequently associated with cholangitis. It is associated with renal malformation and Caroli's disease. The diagnosis of CHF is usually confirmed by its typical histological features. Cholangitis is a severe and frequently fatal complication. We report a 22-year-old man with congenital hepatic fibrosis who showed the cholangitis without radiological features of cystic dilatation or stone of intrahepatic ducts.
Acute Disease ; Adult ; Cholangitis/*complications/diagnosis ; Humans ; Liver Cirrhosis/*complications/*congenital/diagnosis ; Male

Eosinophilic cholecystitis is a rare, poorly understood inflammatory condition of the gall bladder. It is characterized by transmural inflammation of the gallbladder wall in which more than 90% of the white cells are eosinophils. The etiology of eosinophilic cholecystitis remains obscure, although suggested causes include allergies, parasites, eosinophilic enteritis, and local reaction to gall stones. We report the case of a 66-year-old man who had eosinophilic cholecystitis associated with gall stones.
Aged ; Cholecystitis ; Enteritis ; Eosinophilia ; Eosinophils ; Gallbladder ; Gallstones ; Gastritis ; Humans ; Hypersensitivity ; Inflammation ; Parasites ; Urinary Bladder

Extrahepatic metastasis of hepatocellular carcinoma (HCC) is occasionally seen in the lung, bone, adrenal gland, and lymph nodes. It is well known that HCC sometimes invades the biliary system. Since there is no peritoneum between the gallbladder and the liver fossa, a gallbladder cancer easily invades the liver; however, HCC seldom invades the gallbladder because it rarely destroys the muscle layer or the collagen fibers of the gallbladder wall. Routes of gallbladder metastasis of HCC include direct invasion, extension to the biliary system, and invasion of the adjacent hepatic vascular system. Some cases of gallbladder metastasis of HCC without direct invasion have been reported. We report here a case of HCC that directly invaded the gallbladder, and that resembled gallbladder carcinoma invading the liver.
Adult ; Carcinoma, Hepatocellular/*diagnosis/pathology/ultrasonography ; Diagnosis, Differential ; Gallbladder Neoplasms/diagnosis/*secondary ; Humans ; Liver Neoplasms/*diagnosis/pathology/ultrasonography ; Male ; Neoplasm Invasiveness ; Tomography, X-Ray Computed

BACKGROUND/AIMS: Hepatitis B virus (HBV) was classified into 8 genotypes by a sequence divergence in the entire genome designated from A to H. HBV genotypes have distinct geographic distributions. Recently, HBV genotypes have been partially found as influencing the clinical manifestation of chronic liver disease in hosts. In Korea, the distribution of HBV genotypes remains unclear. The aim of this study was to evaluate the prevalence of the HBV genotype on Jeju Island. METHODS: Hepatitis B virus genotypes were evaluated among 107 hepatitis B carriers residing on Jeju Island. We used single PCR and multiplex-PCR assay with genotype-specific primer pairs for HBV genotypes A-F for the genotyping. RESULTS: 1. Fifty nine samples (55%) were positive for HBV DNA. The positivity was different according to the pattern of HBeAg/ anti-HBe expression, as -/-; 2/3 (66.7%), -/+; 30/73 (30%), +/-; 24/28 (85.7%) and +/+; 3/3 (100%). 2. In the single primer set of genotype-specific PCR, 59 samples (100%) were detected as genotype C and 2 (3%) were also detected as genotype A and B. 3. In multiplex-PCR, 58 samples (98%) were detected as genotype C and only one (2%) as a mixed pattern of genotype B and C. 4. When the PCR products were amplified with universal sense and genotype specific anti-sense from one genotype A, one B, and 2 C, all were included in genotype C. CONCLUSIONS: These results suggest that on Jeju Island, almost all HBV genotypes are C.
Adolescent ; Adult ; Aged ; Child ; English Abstract ; Female ; Hepatitis B virus/classification/*genetics ; Humans ; Korea ; Male ; Middle Aged