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

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

BACKGROUND/AIMS: Alcohol and the hepatitis B virus (HBV) exert synergistic effects in hepatocelluar carcinogenesis. We aimed to elucidate the clinical significance of the antibody to hepatitis B core antigen (anti-HBc) and occult HBV infection on the development of hepatocellular carcinoma (HCC) in patients with alcoholic liver cirrhosis (LC). METHODS: Patients with alcoholic LC alone (n=193) or combined with HCC (n=36), who did not have HBsAg or antibody to hepatitis C virus were enrolled. Clinical data and laboratory data including anti-HBc were investigated at enrollment. The polymerase chain reaction was applied to HBV DNA using sera of patients with HCC or LC after age and sex matching. RESULTS: Patients with HCC were older (60+/-11 years vs. 53+/-10 years, mean+/-SD, P<0.001), more likely to be male (100% vs. 89%, P=0.03), and had a higher positive rate of anti-HBc (91.2% vs. 77.3%, P=0.067), and a higher alcohol intake (739+/-448 kg vs. 603+/-409 kg, P=0.076) than those with LC. Age was the only significant risk factor for HCC revealed by multiple logistic regression analysis (odds ratio, 1.056; P=0.003). The positive rate of anti-HBc and alcohol intake did not differ in age- and sex-matched subjects between the LC (n=32) and HCC (n=31) groups. However, the detection rate of serum HBV DNA was higher in the HCC group (48.4%) than in the LC group (0%, P<0.001). CONCLUSIONS: Anti-HBc positivity is not a risk factor for HCC. However, occult HBV infection may be a risk factor for HCC in patients with alcoholic LC.
Adult ; Aged ; Antibodies, Viral/blood ; Carcinoma, Hepatocellular/diagnosis/epidemiology/*etiology ; DNA, Viral/analysis ; Female ; Hepatitis B/*complications/diagnosis ; Hepatitis B Core Antigens/*immunology ; Hepatitis B Surface Antigens/immunology ; Hepatitis B virus/genetics/immunology/isolation & purification ; Hepatitis C/complications/diagnosis ; Humans ; Liver Cirrhosis, Alcoholic/*complications/diagnosis/epidemiology ; Liver Neoplasms/diagnosis/epidemiology/*etiology ; Male ; Middle Aged ; Risk Factors

Hepatocellular carcinoma (HCC) is associated with hepatitis B virus (HBV) as an etiologic agent in 80% of cases, and is the major cause of death among HBV carriers. Family history of HCC is a known risk factor for the development of HCC among chronically HBV infected patients; therefore, genetic factors are likely to modify the risk of HCC. However, the genetic factors that determine progression to HCC remain mostly to be recovered. It is estimated that there are millions of single nucleotide polymorphisms (SNPs) within human genome and they are likely to explain much of the genetic diversity of individuals. In this review, the natural history of HBV infection and host genetic factors related to HCC, study design and target gene selection for the detection of SNPs related to the occurrence of HCC were discussed. Also, several SNPs or haplotypes, which were reportedly associated with increased or reduced risk of HCC occurrence in patients with chronic HBV infection, were reviewed. Especially, recent studies in Korea, one of the HBV endemic areas, were discussed. Screening of these polymorphisms might be useful in clinical practice to stratify the lower or higher risk group for HCC and might modify the design of HCC surveillance programs in patients with chronic HBV infection, if further genetic susceptibilities are identified. The ongoing studies of the distributions and functions of the implicated allele polymorphisms will not only provide insight into the pathogenesis of HCC, but may also provide a novel rationale for new methods of diagnosis and therapeutic strategies.
Biological Markers ; Carcinoma, Hepatocellular/diagnosis/*epidemiology/*genetics ; Genetic Predisposition to Disease ; Hepatitis B, Chronic/*complications/diagnosis/epidemiology ; Humans ; Liver Neoplasms/diagnosis/*epidemiology/*genetics ; *Polymorphism, Single Nucleotide

BACKGROUND/AIMS: Most cases of hepatitis B virus (HBV) are transmitted vertically in endemic areas of HBV. The positivity of serum HBeAg/HBV DNA in pregnant women is associated with vaccine failure. Recently, a national program for HBV vaccines free of charge in neonates born to HBsAg-positive pregnant women is being performed. The aim of this study was to investigate the positivity of serological markers of HBV in pregnant women in Jeju, which is an island separated from the Korean peninsula and a promising cohort to evaluate the effect of a prevention program of HBV infection. In addition, we investigated the geographic differences in the prevalence of HBV infection because it has been reported that the prevalence of HBV has been high in this area previously. METHODS: Between January 2001 and December 2002, all women who gave delivery were studied retrospectively. Women between the ages of thirty and forty, who received health screening at the Asan Medical Center health promotion center in Seoul, were analyzed as controls. RESULTS: During the study period, 1,030 pregnant women (30.8 +/- 4.3 years) and 7,270 controls (33.1 +/- 5.0 years) were enrolled. The positivity of HBsAg was high in Jeju compared with that of Seoul (6.4% vs. 4.9%) (P=0.036). The positivity of HBeAg/HBV DNA was 31.8% (21/66) in HBsAg-positive pregnant women. The positivity of anti-HBs was low in Jeju compared with that of Seoul (54.5% vs. 68.8%) (P<0.001). CONCLUSIONS: The positivity of HBsAg was found to be high in pregnant women in Jeju. Intensive supervision for HBV infection in pregnant women should be given in this area.
Adult ; DNA, Viral/blood ; English Abstract ; Female ; Hepatitis B/diagnosis/*epidemiology ; Hepatitis B Surface Antigens/blood ; Hepatitis B e Antigens/blood ; Hepatitis B virus/genetics/isolation & purification ; Humans ; Korea/epidemiology ; Pregnancy ; Pregnancy Complications, Infectious/diagnosis/*epidemiology ; Seroepidemiologic Studies ; Serologic Tests

Although glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder worldwide, it has rarely been reported among Korean. The patient was previously healthy 39 yr old male who showed severe hemolytic anemia and acute renal failure accompanied by hyperbilirubinemia after hepatitis A infection. The additional studies for differential diagnosis of hemolytic anemia showed a moderate deficiency of G6PD enzyme. Because hepatitis A infection in patient with G6PD deficiency present much more severe clinical symptoms, G6PD enzyme should be examined in patients with triggering factors of hemolysis such as hepatitis A infection.
Adult ; Diagnosis, Differential ; Glucosephosphate Dehydrogenase/genetics ; Glucosephosphate Dehydrogenase Deficiency/*complications/diagnosis ; *Hemolysis ; Hepatitis A/*complications/diagnosis ; Hepatitis A Virus, Human/isolation & purification ; Humans ; Hyperbilirubinemia/etiology ; Kidney Failure, Acute/*diagnosis/etiology ; Male

OBJECTIVETo study the relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B.

METHODSOne hundred and fifty-seven patients with chronic hepatitis B were included in the study, 49 patients among them were diagnosed as early cirrhosis by liver biopsy. Serum HBV DNA levels were determined using fluorescent quantitative PCR, and serum hepatic fibrosis markers including hyaluronic acid (HA), laminin (LN), amino terminal propeptide of type III precollagen (P III P) and type IV collagen (IV-C) were determined by radioimmunity assay. The relationship between serum HBV DNA levels and hepatic fibrosis markers were analyzed. Serum HBV DNA levels and hepatic fibrosis markers of 49 patients with early cirrhosis were compared with those of 108 non-cirrhotic patients.

RESULTSThere was no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in chronic hepatitis B (P>0.05). Patients with early cirrhosis had much higher hepatic fibrosis markers together with lower HBV DNA levels than non-cirrhotic patients (P<0.05).

CONCLUSIONSThere were no significant relationship between serum HBV DNA levels and hepatic fibrosis markers in patients with chronic hepatitis B.

Adult ; Biomarkers ; analysis ; DNA, Viral ; blood ; Female ; Hepatitis B virus ; genetics ; isolation & purification ; Hepatitis B, Chronic ; complications ; virology ; Humans ; Liver Cirrhosis ; diagnosis ; virology ; Male ; Middle Aged

BACKGROUND/AIMS: We investigated the frequency of occult hepatitis B virus (HBV) infection in anti-hepatitis C virus (HCV)-positive individuals and the effects of occult HBV infection on the severity of liver disease. METHODS: Seventy-one hepatitis B virus surface-antigen (HBsAg)-negative patients were divided according to their HBV serological status into groups A (anti-HBc positive, anti-HBs negative; n=18), B (anti-HBc positive, anti-HBs positive; n=34), and C (anti-HBc negative, anti-HBs positive/negative; n=19), and by anti-HCV positivity (anti-HCV positive; n=32 vs. anti-HCV negative; n=39). Liver biopsy samples were taken, and HBV DNA was quantified by real-time PCR. RESULTS: Intrahepatic HBV DNA was detected in 32.4% (23/71) of the entire cohort, and HBV DNA levels were invariably low in the different groups. Occult HBV infection was detected more frequently in the anti-HBc-positive patients. Intrahepatic HBV DNA was detected in 28.1% (9/32) of the anti-HCV-positive and 35.9% (14/39) of the anti-HCV-negative subjects. The HCV genotype did not affect the detection rate of intrahepatic HBV DNA. In anti-HCV-positive cases, occult HBV infection did not affect liver disease severity. CONCLUSIONS: Low levels of intrahepatic HBV DNA were detected frequently in both HBsAg-negative and anti-HCV-positive cases. However, the frequency of occult HBV infection was not affected by the presence of hepatitis C, and occult HBV infection did not have a significant effect on the disease severity of hepatitis C.
Adult ; Aged ; Cohort Studies ; DNA, Viral/analysis ; Female ; Genotype ; Hepatitis B/*complications/*diagnosis ; Hepatitis B Core Antigens/blood/immunology ; Hepatitis B Surface Antigens/blood/immunology ; Hepatitis B virus/*genetics ; Hepatitis C, Chronic/*complications/genetics/*pathology ; Humans ; Liver/virology ; Male ; Middle Aged ; Polymerase Chain Reaction ; Severity of Illness Index

Hepatitis C virus (HCV) is one of the main viral causes of hepatocellular carcinoma (HCC) and is associated with lymphoproliferative disorder such as non-Hodgkin's lymphoma (NHL). However, there are only few case reports on concomitantly induced NHL and HCC by HCV. Herein, we report a case of synchronous NHL and HCC in a patient with chronic hepatitis C which was unexpectedly diagnosed during liver transplantation surgery. This case suggests that although intrahepatic lymph node enlargements are often considered as reactive or metastatic lymphadenopathy in chronic hepatitis C patients with HCC, NHL should also be considered as a differential diagnosis.
Antineoplastic Agents/therapeutic use ; Carcinoma, Hepatocellular/complications/*diagnosis/radiotherapy ; Drug Therapy, Combination ; Embolization, Therapeutic ; Fluorodeoxyglucose F18 ; Gadolinium DTPA ; Genotype ; Hepatitis B virus/genetics ; Hepatitis C, Chronic/complications/*diagnosis/*virology ; Humans ; Liver Neoplasms/complications/*diagnosis/radiotherapy ; Lymph Nodes/pathology ; Lymphoma, Non-Hodgkin/complications/*diagnosis/drug therapy ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Positron-Emission Tomography ; Tomography, X-Ray Computed

A 37-year-old male presented with fever and jaundice was diagnosed as hepatitis A complicated with progressive cholestasis and severe autoimmune hemolytic anemia. He was treated with high-dose prednisolone (1.5 mg/kg), and eventually recovered. His initial serum contained genotype IA hepatitis A virus (HAV), which was subsequently replaced by genotype IIIA HAV. Moreover, at the time of development of hemolytic anemia, he became positive for immunoglobulin M (IgM) anti-hepatitis E virus (HEV). We detected HAV antigens in the liver biopsy specimen, while we detected neither HEV antigen in the liver nor HEV RNA in his serum. This is the first report of hepatitis A coinfected with two different genotypes manifesting with autoimmune hemolytic anemia, prolonged cholestasis, and false-positive IgM anti-HEV.
Adult ; Anemia, Hemolytic, Autoimmune/*diagnosis/drug therapy/etiology ; Anti-Inflammatory Agents/therapeutic use ; Cholestasis/*diagnosis/drug therapy/pathology ; Coinfection/*diagnosis ; Genotype ; Hepatitis A/complications/*diagnosis/genetics ; Hepatitis E/complications/*diagnosis/genetics ; Humans ; Immunoglobulin M/blood ; Liver/pathology/virology ; Male ; Prednisolone/therapeutic use ; RNA, Viral/blood