Natural killer (NK) cells play an important role in innate immunity, especially in the response to viral infections, such as hepatitis C virus (HCV). Killer cell immunoglobulin-like receptors (KIRs) are the primary receptors of NK cells that mediate innate immunity. KIRs are also involved in acquired immunity, because some KIRs are expressed on the surface of certain subsets of T cells. In this study, the frequency of KIR genes, HLA-C allotypes, and combinations of KIR genes with their HLA-C ligands were evaluated in two different groups of the Korean population: controls and patients with chronic HCV infection. The study population consisted of 147 Korean patients with chronic HCV infection. The frequency of KIR2DS2 in patients with chronic HCV infection was 9.5% which was significantly lower than 19.5% of the control (P < 0.01). However, there were no significant differences in the frequency of other KIR genes, HLA-C allotypes or different combinations of KIR genes with their HLA-C ligands. This study can contribute to the further prospective study with a larger scale, suggesting the assumption that KIR2DS2 might aid in HCV clearance by enhancing both the innate and acquired immune responses of people in Korea.
Adult ; Aged ; Female ; Genes, MHC Class I ; Genotype ; HLA-C Antigens/genetics ; Hepacivirus/immunology ; Hepatitis C, Chronic/*genetics/immunology ; Humans ; Killer Cells, Natural/immunology/virology ; Male ; Middle Aged ; Receptors, KIR/*genetics/immunology ; Republic of Korea ; T-Lymphocyte Subsets/immunology

BACKGROUND: Although the polyproteins of hepatitis C virus(HCV) are processed and formed in nearly equimolar amounts, individual functional proteins have a discrepancy in their time of appearance following HCV infection and eliciting immune response. This study was conducted to compare the reactivity toward regional specific HCV protein in relation to virological characteristics, including HCV genotype and HCV replication. METHODS: Sera from forty-five patients with chronic HCV infection were analyzed through the experiments of the recombinant immunoblot assay(RIBA-2), HCV genotyping and HCV RNA quantitation. RESULTS: The frequencies of seropositivity to C22-3, C33C, C100-3 and 5-1-1 proteins were 91.1+ACU-, 91.1+ACU-, 64.4+ACU- and 53.3+ACU-, respectively, of all the patients, and thus the antibodies to C22-3 and C33C proteins were found more frequently (p +ADw- 0.05). The antibody responses between core or NS3 proteins and NS4 proteins showed more discrepancy in the HCC group than that in the CH group, implying a possibility of oncogenic potential of core or NS3 gene in hepatocarcinogenesis. The detection rate of antibodies to C22-3 and C33C, in accordance with serum HCV RNA levels, was significantly higher in highly viremic patients than that in low viremic patients (p +ADw- 0.05). Antibodies to C22-3, C33C, C100-3 and 5-1-1 were also found more frequently in patients with HCV genotype 1b, compared to those with HCV genotype 2a (p +ADw- 0.05). CONCLUSION: These results suggest that antibody detection of HCV may depend on the virological characteristics of HCV, the levels of HCV replication and HCV genotype and, therefore, HCV RNA detection using RT-PCR technique is essential for confirmatory diagnosis for HCV infection. Furthermore, the HCV core or NS3 Protein may play important role in hepatocarcinogenesis.
Adult ; Aged ; Female ; Genotype ; Hepatitis C Antibodies/blood+ACo- ; Hepatitis C, Chronic/virology ; Hepatitis C, Chronic/immunology+ACo- ; Hepatitis C-Like Viruses/physiology ; Hepatitis C-Like Viruses/genetics ; Human ; Male ; Middle Age ; RNA, Viral/blood ; Viral Core Proteins/immunology+ACo- ; Viral Nonstructural Proteins/immunology+ACo- ; Virus Replication

Alanine Transaminase ; blood ; Genotype ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; immunology ; virology ; Humans ; RNA, Viral ; blood

Adult ; Animals ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Female ; Hepatitis B, Chronic ; immunology ; metabolism ; Humans ; Leukocyte Common Antigens ; biosynthesis ; genetics ; Liver Neoplasms ; immunology ; metabolism ; Male ; Mice ; Mice, Inbred BALB C ; 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

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

OBJECTIVESTo study the effects of HCV genotypes and HLA-DRB alleles on the response of chronic hepatitis C patients to interferon alpha and libavilin.

METHODSGenotypes of HCV in 113 patients with HCV infection treated with interferon alpha and libavilin were investigated. Gene chips were used to analyze the frequency of HLA-DRB alleles in 25 patients of them. The response to interferon alpha and libavilin therapy were discussed.

RESULTSThe response rates in the four HCV types were different, HCV-IV/2b the highest (57.78%), HCV-I/1a and -III/2a lower (46.15% and 47.62%), and HCV-II/1b the lowest (11.76%). The response rate to IFN and libavilin therapy in patients with DRB1*07 positive was higher, while in patients with DRB1*04 positive was lower. Sex, HCV genotypes and HLA-DRB alleles were all related to the response. Female, patients with HCV-IV/2b and HLA-DRB1*07 presented almost complete response, but male, patients with HCV-II/1b and HLA-DRB1*04 usually appeared non-response. DRB1*07 allele and HCV-IV/2b were the closest factors related to the response.

CONCLUSIONSNot only virus but also host playes an important role in the curative effect of anti-virus therapy. It is necessary to view from the angle of host, adjusting the host's immune status to accelerate the clearance of HCV.

Adult ; Alleles ; Antiviral Agents ; therapeutic use ; Drug Therapy, Combination ; Female ; Genotype ; HLA-DR Antigens ; genetics ; HLA-DRB1 Chains ; Hepacivirus ; classification ; genetics ; Hepatitis C, Chronic ; drug therapy ; immunology ; virology ; Humans ; Interferon-alpha ; therapeutic use ; Male ; Middle Aged ; Ribavirin ; therapeutic use

OBJECTIVETo observe the relationship between the amount of HBV DNA in serum/liver tissue and HGV infection in patients with chronic hepatitis B (CH-B) for exploring the effect of HGV infection on hepatitis B virus (HBV) replication of CH-B.

METHODSHGV RNA in serum, HGV nonstructural region 5 (NS5) antigen (HGV Ag) in liver tissue and the amount of HBV DNA in serum, liver tissue were detected for 56 patients with CH-B by reverse transcription-polymerase chain reaction (RT-PCR) assay, peroxidase antiperoxidase (PAP) immunohistochemical method and fluorescence quantitative PCR assay, respectively. Then the relationship between HGV Ag expression in liver tissue and HGV RNA expression in serum was analysed and the amount of HBV DNA in serum and liver tissues from the serum HGV RNA or liver tissue HGV Ag positive patients were compared with those of the serum HGV-RNA or liver tissue HGV Ag negative patients, respectively.

RESULTSTen (17.9%) and eight (14.3%) patients were positive for serum and liver tissues,respectively.HGV RNA expression in serum was closely related to HGV Ag expression in liver tissues, but there was HGV RNA in serum from some of the liver tissues HGV Ag negative patients ?cases of HGV RNA and HGV Ag positive or negative,HGV RNA positive but HGV Ag negative, HGV RNA negative but HGV Ag positive, respectively: 5,43,5,3,(P<0.01). There was no significant difference in the amount of HBV DNA in serum and liver tissues between HGV RNA or HGV Ag positive and negative patients (P>0.05).

CONCLUSIONSHGV infection may not affect HBV replication. Liver is the site of HGV replication, but HGV probably also replicates in extrahepatic tissues. HGV hepatic pathogenicity is probably mild and further studies are still needed.

Adult ; DNA, Viral ; analysis ; blood ; Female ; Flaviviridae Infections ; complications ; virology ; GB virus C ; genetics ; immunology ; pathogenicity ; Hepatitis Antigens ; analysis ; Hepatitis B virus ; genetics ; physiology ; Hepatitis B, Chronic ; complications ; virology ; Hepatitis, Viral, Human ; virology ; Humans ; Liver ; virology ; Male ; RNA, Viral ; blood ; Virus Replication

Peg-interferon and ribavirin has been the standard therapy of chronic hepatitis C for the past 15 years in Korea. However, the treatment paradigm is changing. Direct acting agents (DAAs) are oral pills that can be easily taken. In addition, DAAs are more effective and have less adverse reactions compared to the previously used drugs. Chronic hepatitis C is hard to treat because the virus is error-prone virus. Host immunity is helpless against the hepatitis C virus since it evades the host immunity through various complex mechanisms. There are 6 genotypes. Quasispecies can co-exist even in the same patients. The treatment strategy is based on the combination of the individual drug corresponding to each step of viral replication process. NS5B nucleosides are the most powerful and effective drug available until now. Other drugs with different mechanisms of action can be used to provide synergy. NS5A and NS5B inhibition drugs currently belong to the leading group amongst many DAAs. These drugs will soon be available in Korea. We have to know the merits and adverse drug reactions of the new drug.
Antiviral Agents/*therapeutic use ; Drug Therapy, Combination ; Enzyme Inhibitors/therapeutic use ; Genotype ; Guidelines as Topic ; Hepacivirus/genetics ; Hepatitis C, Chronic/*drug therapy/immunology/virology ; Humans ; Viral Nonstructural Proteins/antagonists & inhibitors/metabolism

OBJECTIVETo investigate the hepatic expression of immunological markers relevant to a cytotoxic response in relation to viral genotype.

METHODSThe frozen liver biopsies were obtained from 28 HF genotyped patients and made the sections stained. The morphometry was used to analyze the major histocompatibility complex class I (MHC-I), CD8, beta(2)-microglobulin (beta(2) -mG), HFE and CD68 in the stained sections. Biopsy data of response to therapy with interferon were available in 18 cases.

RESULTSCD8+ was usually clustered together and localized in portal tracts and sinusoids, and seen to interact with MHC I positive lining cells. MHC-I and beta(2) -mG were expressed mainly in endothelial and Kupffer cells. HFE was expressed in most round and dendritic CD68+ cells. Patients with virus genotype 3a had higher hepatic MHC-I and HFE expression, and a better sustained response to interferon (IFN) therapy than patients without.

CONCLUSIONThe MHC-I expression in the liver of patient with chronic hepatitis C virus infection seems to relate to viral-genotype. The hepatic MHC-I and HFE expression are higher in patients with virus genotype 3a than that in patients with non-3a genotype.

Adult ; Antigens, CD ; metabolism ; Antigens, Differentiation, Myelomonocytic ; metabolism ; Antiviral Agents ; therapeutic use ; Blotting, Western ; CD8 Antigens ; metabolism ; Enzyme-Linked Immunosorbent Assay ; Female ; Genotype ; Hemochromatosis Protein ; Hepacivirus ; drug effects ; genetics ; Hepatitis C, Chronic ; genetics ; metabolism ; virology ; Histocompatibility Antigens Class I ; genetics ; metabolism ; Humans ; Interferons ; therapeutic use ; Liver ; immunology ; metabolism ; virology ; Male ; Membrane Proteins ; genetics ; metabolism ; Middle Aged ; Reverse Transcriptase Polymerase Chain Reaction