Clinical Course of Chronic Hepatitis C Virus Infection Is Not Influenced by Concurrent Hepatitis G Virus Infection

To determine the effects of hepatitis G virus(HGV) infection on chronic hepatitis C virus infection(HCV) and to evaluate HGV response to interferon, weinvestigated HGV RNA by polymerase chain reaction in 247 Japanese patients with chronic HCVinfection (166 men and 81 women; 124 had chronichepatitis and 26 cirrhosis, and 97 hepatocellularcarcinoma). HGV RNA was detectable in 22 (8.9%)patients, among whom 21 were men: this male predominance wasstatistically significant (P < 0.01). There were nodifferences in age, aminotransferase level, stage ofliver disease, HCV RNA level by competitive polymerase chain reaction, genotype, or interferonresponse to HCV RNA between patients with HCV infectionalone or with HCV/HGV coinfection. Sustained eliminationof HGV RNA was found in 28.6% of the 14 treated patients with HCV/HGV coinfection. In the 14 treatedpatients, sustained elimination of both viruses was seenin two, HCV alone was eliminated in two, and HGV alonewas eliminated in two. Aminotransferase level improvement by interferon treatment wasassociated with clearance of HCV, but not of HGV. Thus,HGV infection had no apparent effects on HCV infection,and the sensitivity of HGV to interferon is comparable to but independent of HCV.     

GB Virus C/Hepatitis G Virus Infections in Traumatologic Outpatients, Chronic Non-A-E Hepatitis and Extrahepatic Malignancies

Summary GB virus C/hepatitis G virus (GBV-C/HGV) is a recently discovered flavivirus of still unknown pathogenic relevance. We examined traumatologic outpatients to determine GBV-C/HGV viremia for further epidemiological studies, as blood donors hitherto used as controls represent healthy individuals without risk factors. Anti-GBV-C/HGV antibodies were detectable in 13.2% (95% confidence interval [CI] 9.3–18.2) and GBV-C/HGV RNA was detectable in 4.5% (95% CI 2.4–8.2) of the outpatients. In chronic non-A-E hepatitis patients GBV-C/HGV viremia was detectable at a significantly higher level of 16.1% (95% CI 6.1–:34.5), while the prevalence of anti-GBV-C/HGV antibodies was 12.9% (95% CI 4.2–30.8). The rate of GBV-C/HGV viremia in patients with malignant diseases (different types of tumors, blood recipients were excluded) was 12.5% (95% CI 8.4– 18.1), a significant elevation compared to traumatologic outpatients. The seroprevalence in the tumor group was 22.1% (95% CI 16.7–28.6), also significantly elevated. Thus, there are two messages. Firstly, testing for GBV-C/HGV may be a useful extension of the diagnostic procedure of viral hepatitis. Secondly, common risk factors or etiologic relations of GBV-C/HGV and extrahepatic malignancies should be discussed. Received: March 29, 1999 · Revision accepted: November 22, 1999     

Correlation Between Relative Number of Circulating Low-Density Hepatitis C Virus Particles and Disease Activity in Patients with Chronic Hepatitis C

Hepatitis C virus (HCV) circulates as particleshaving differing buoyant densities. Changes in therelative proportions of virus particles of differentdensities were examined in 19 patients with chronic hepatitis C: 6 without (group A) and 13 with(group B) abnormal serum alanine aminotransferase (ALT)levels. High- and low-density virus particles wereseparated by differential flotation centrifugation. The numbers of high-density particlesconsistently exceeded that of low-density particles inall patients in group A, whereas the titers of bothtypes of particles were the same at least once in 7 of10 patients sampled at two time points in group B.The ALT level significantly increased, <2 monthslater (P < 0.05) when the titers of both types ofparticles were the same in patients in group B. Thus, we found a correlation between the relativenumbers of circulating low-density HCV particles anddisease activity in chronic hepatitis Cpatients.     

Hepatitis G Virus Infection Among Liver Graft Recipients: Anatomoclinical Correlations

Hepatitis G virus (HGV) causes persistent infection in man, but its disease association is controversial. We studied the HGV disease association in 25 liver transplantation (LT) recipients without evidence of hepatitis B and C infection. HGV RNA was tested by semiquantitative RT-PCR in serial serum samples and its presence was correlated with the biochemical and histological evidence of liver damage. The overall prevalence of HGV infection in this population was 9/25 (36%), one patient being HGV RNA positive since before LT, while the other eight apparently acquired de novo infections after LT. In five cases, appearance of HGV was followed by biochemical and histological evidence of liver damage: the liver biopsy showed acute rejection in two cases, acute cholangitis in two, and acute hepatitis in one. At the end of follow-up, histological evidence of chronic hepatitis was found in one HGV-positive patient but also in three HGV-negative patients, whereas the only patient with acute hepatitis at the time HGV RNA was first detected in serum developed an intralobular gigantocellular granuloma. In conclusion, HGV infection after LT may be seldom associated with acute and chronic liver damage, but comparable histological features can be observed also among HGV-negative controls.     

G Virus in the General Population and in Patients on Hemodialysis

To determine the routes of transmission ofhepatitis G virus (HGV) and the relationship between HGVand hepatitis C virus (HCV) infections, we tested forHGV RNA by polymerase chain reaction and antibody to HCV (anti-HCV) in 494 hemodialysis patients,638 inhabitants of two HCV endemic areas, and in 400blood donors in Japan. HGV RNA was detected in 6.9% ofhemodialysis patients, in 1.4% of inhabitants, and in 0.8% of donors, and anti-HCV wasdetected in 39.3%, 12.4%, and 1.8%, respectively. Of HGVRNA-positive hemodialysis patients, and HGV RNA-positiveinhabitants, 64.7% and 11.1%, respectively, had been given blood transfusions. Theprevalences of HGV RNA and anti-HCV significantlyincreased with the duration of hemodialysis. Of all HGVRNA positives, 74.4% were coinfected with HCV andsubjects with HGV RNA alone had normal liver function.In conclusion, HGV is transmitted by blood transfusionand within the hemodialysis unit itself. HGV does notseem to injure hepatocytes.     

Viral and Host Factors in Determining Response of Relapsers with Chronic Hepatitis C to Retreatment with Interferon

In chronic hepatitis C the rate of relapse afteran end-of-treatment response to interferon may exceed50%. The usefulness of retreatment of relapsers withinterferon in obtaining a complete sustained response and the role of clinical, virological andimmunological features in determining long-term efficacyof retreatment are unclear. We aimed to assess theefficacy of interferon retreatment in obtaining acomplete sustained response, to evaluate whetherincreasing the dose may enhance responsiveness, and toidentify possible predictors of sustained response. Weenrolled 42 patients with biopsy-proven chronichepatitis C without cirrhosis who had previouslyresponded to a six-month course ofInterferon-_2b (total dose: group A, 22patients, 234 MU; group B, 20 patients, 468 MU) and thenrelapsed. All, except one, were HCV-RNA negative at the end of first cycle ofinterferon; most (31/42, 74%) were infected by HCV 1b.Subjects were randomly allocated to receive anothercycle of interferon either at the original dose (group A₁: 234 MU, 11 patients; groupB 468 MU, 10 patient) or twice the original dose (groupA₂: 468 MU, 11 patients; group B : 936 MU, 10patients). At the end of the second cycle of interferon,24 subjects (57%) had normal ALT and were HCV-RNAnegative, and 16 (39%) had normal ALT, but were HCV-RNApositive. A complete sustained response was obtained ineight patients (19%), at a similar rate in all treatment groups. Complete sustainedresponders were different from the other patients interms of age (35.9 ± 10.4 vs 44.1 ± 8.8,P = 0.027), rate of infection with non-1b HCV (6/8 vs5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428median copies/ml, P = 0.037) and serum levels of90K/MAC-2 BP (5.76 ± 3.01 vs 10.25 ± 5.16units/ml, P = 0.02), an N-glycoprotein implicated incellular defense functions. Multivariate logistic analysisvalidated age and HCV genotype as independent predictorsof CSR. Among noncirrhotic relapsers who received atotal interferon dose 234 MU in the first cycle,retreatment usually induced end-of-treatment response. Acomplete sustained response was obtained in only one ofevery five subjects. Increasing the dose of interferonabove that of the first cycle did not enhance the rate of sustained response. In conclusionwe might assert that young subjects infected by non-1bHCV and with low levels of HCV-RNA and of 90K/MAC-2 BPare the best candidates for retreatment.     

GB Virus C/Hepatitis G Virus Envelope Glycoprotein E2: Computational Molecular Features and Immunoinformatics Study

Introduction:

GB virus C (GBV-C) or hepatitis G virus (HGV) is an enveloped, RNA positive-stranded flavivirus-like particle. E2 envelope protein of GBV-C plays an important role in virus entry into the cytosol, genotyping and as a marker for diagnosing GBV-C infections. Also, there is discussion on relations between E2 protein and gp41 protein of HIV. The purposes of our study are to multi aspect molecular evaluation of GB virus C E2 protein from its characteristics, mutations, structures and antigenicity which would help to new directions for future researches.

Evidence Acquisition:

Briefly, steps followed here were; retrieving reference sequences of E2 protein, entropy plot evaluation for finding the mutational /conservative regions, analyzing potential Glycosylation, Phosphorylation and Palmitoylation sites, prediction of primary, secondary and tertiary structures, then amino acid distributions and transmembrane topology, prediction of T and B cell epitopes, and finally visualization of epitopes and variations regions in 3D structure.

Results:

Based on the entropy plot, 3 hypervariable regions (HVR) observed along E2 protein located in residues 133-135, 256-260 and 279-281. Analyzing primary structure of protein sequence revealed basic nature, instability, and low hydrophilicity of this protein. Transmembrane topology prediction showed that residues 257-270 presented outside, while residues 234- 256 and 271-293 were transmembrane regions. Just one N-glycosylation site, 5 potential phosphorylated peptides and two palmitoylation were found. Secondary structure revealed that this protein has 6 α-helix, 12 β-strand 17 Coil structures. Prediction of T-cell epitopes based on HLA-A*02:01 showed that epitope NH3-LLLDFVFVL-COOH is the best antigen icepitope. Comparative analysis for consensus B-cell epitopes regarding transmembrane topology, based on physico-chemical and machine learning approaches revealed that residue 231- 296 (NH2- EARLVPLILLLLWWWVNQLAVLGLPAVEAAVAGEVFAGPALSWCLGLPVVSMILGLANLVLYFRWL-COOH) is most effective and probable B cell epitope for E2 protein.

Conclusions:

The comprehensive analysis of a protein with important roles has never been easy, and in case of E2 envelope glycoprotein of HGV, there is no much data on its molecular and immunological features, clinical significance and its pathogenic potential in hepatitis or any other GBV-C related diseases. So, results of the present study may explain some structural, physiological and immunological functions of this protein in GBV-C, as well as designing new diagnostic kits and besides, help to better understandingE2 protein characteristic and other members of Flavivirus family, especially HCV.     

Clinical Significance of Hepatitis GB Virus C Infection in Alcoholic Liver Disease

Recently, hepatitis GB virus C (HGBV-C) has been recovered from patients with non-A-E hepatitis. However, it has been unclear whether HGBV-C may be related to the development of alcoholic liver disease (ALD) or not. In this study, we determined HGBV-C RNA in sera from alcoholic patients without markers for hepatitis C and B viruses to evaluate the role of HGBV-C in ALD. Serum samples were obtained from 68 patients with ALD and 40 nonalcoholic patients with chronic type C liver disease. HGBV-C RNA was detected in only 3 of 68 (4.4%) patients with ALD, in 2 of 27 patients with hepatic fibrosis, and in 1 of 5 patients with chronic hepatitis. There was no HGBV-C RNA in sera from patients with fatty liver, alcoholic hepatitis, or cirrhosis. Serum levels of AST, ALT, and γ-glutamyltranspeptidase in alcoholic patients with, as well as without, HGBV-C RNA decreased to normal levels after abstinence. In addition, an inflammatory change was not observed in liver biopsy specimens obtained from two HGBV-C-positive patients with alcoholic hepatic fibrosis. Our results clearly suggest that the prevalence of HGBV-C infection in patients with ALD is rare and that HGBV-C may not play an important role in the development of liver disease in alcoholics.     

Diversity of Nucleotide Sequences in Hypervariable Region 1 of Hepatitis C Virus in Japanese Patients with Chronic Hepatitis C of Unknown Mode of Transmission

We evaluated the sequence diversity of thehypervariable region 1 (HVR1) of hepatitis C virus (HCV)in HCV-infected patients in whom the mode oftransmission is unknown. The sequence diversity of HVR1in 26 Japanese patients with chronic HCV infectionof unknown mode of transmission (UT) was compared with17 patients with chronic posttransfusion hepatitis C inwhom only a single HCV infection had occurred (PH), and with 18 patients with hemophilia withchronic HCV infection who might have been multiplyinfected with HCV (HE). The diversity of HVR1 wasevaluated by direct sequencing after PCR amplification of HVR1. The sequence diversity of HVR1 was10.1 ± 7.7% in UT, 2.7 ± 2.8% in PH, and14.6 ± 6.9% in HE. The diversity of the patientswith unknown transmission was greater than that of theposttransfusion hepatitis patients, and in some patients it wassimilar to that of multitransfused hemophiliac patients(UT vs PH, P = 0.0004; UT vs HE, P = 0.04; and HE vs PH,P < 0.0001). Multiple infections with HCV could have occurred frequently in patientswith chronic HCV infection in whom the mode oftransmission was unknown, which increased the sequencediversity of HVR1 of these patients.     

Portohepatic Gradient and Portal Hemodynamics in Patients with Cirrhosis Due to Hepatitis C Virus Infection

We evaluated the agreement between wedgedhepatic vein pressure (WHVP), portal vein pressure(PVP), and its relationship with portal hemodynamics in21 patients with HCVrelated cirrhosis with esophageal varices. Direct measurements of theportohepatic gradient (HVPG) were obtained byultrasound-guided fine needle puncture of the righthepatic and the portal veins. In five cases PVP was6.4-10.4 mm Hg higher than WHVP. In 12 cases measurements weresimilar (WHVP-PVP 3 mm Hg). In the remaining fourcases WHVP was 3.6-9.6 mm Hg higher than PVP. WHVP andPVP agreement was not related to HVPG mean value,Child-Pugh score, or grading of esophageal varices. Bycontrast, the difference between WHVP and PVP wasinversely related to the portal flow velocity (P =0.053) and directly related to the portal vascularresistance (P = 0.02). Whereas the portal branches werevisualized in patients with WHVP lower or similar toPVP, a predominant left portosystemic collateral flowwas observed in patients with WHVP > PVP. Our data point out that, in patients with cirrhosis dueto hepatitis C virus infection, discrepant HVPG valuesreflect true hemodynamic differences.     

No Significant Changes in Levels of Hepatitis C Virus (HCV) RNA by HCV Infection Competitive Polymerase Chain Reaction in Blood Samples from Patients with Chronic

To determine if levels of hepatitis C virus(HCV) RNA change over a several-year period, wequantified the amount of HCV RNA by competitivepolymerase chain reaction. The population studiedincluded 44 residents of a rural area with chronic HCVinfection, 39 had chronic hepatitis C and 37 werepatients on hemodialysis. All these Japanese patientshad HCV RNA of genotype II. Blood samples were collected once a year from 1992 to 1995. From 1993 to1995 between the groups, there was no significantdifference in change of HCV RNA levels of 44 residentswith chronic HCV infection, with and without liverdysfunction, nor was there any change in the 31 hemodialysispatients from 1992 to 1995. The HCV RNA levels in the 25with chronic hepatitis who did not respond tointerferon-alpha during 1992-1993 returned topretreatment levels after the cessation of interferontreatment. In two of six hemodialysis patients who wereinfected with HCV during this observation period, HCVRNA was eliminated within one year, and the remaining four became HCV carriers. HCV RNA levels in thelatter rose rapidly after infection and were sustainedat a high level throughout the study period. Thus, HCVRNA level did not change remarkably during a three-year period, a finding which supportsthat it does not correlate with deterioration of liverdamage and aging of HCV carriers.     

Lower Hepatitis G Virus Infection Prevalence Compared to Hepatitis B and C Virus Infection Prevalences

To more accurately determine the seroprevalence of hepatitis G virus (HGV) infection, we surveyed antibody to HGV (anti-E2) by enzyme-linked immunosorbent assay (ELISA) and HGV RNA by nested polymerase chain reaction (PCR) in 298 residents of a hepatitis C virus (HCV)-endemic area of Japan and in 225 hemodialysis patients. We then compared these findings with known HCV and hepatitis B virus (HBV) infection prevalences. Anti-E2 and HGV RNA prevalences were 32 (10.7%) and 5 (1.7%) in the residents and 24 (10.7%) and 10 (4.4%) in the hemodialysis patients, respectively. Anti-E2 and HGV RNA concurrence was found in two of the hemodialysis patients. Total HGV marker (anti-E2 and/or HGV RNA) prevalences [37 (12.4%) in residents and 32 (14.2%) in hemodialysis patients], were significantly lower than the prevalences of antibody to HCV (anti-HCV) by ELISA [59 (19.8%) and 96 (42.7%)], and antibody to hepatitis B core antigen (anti-HBc) by radioimmunoassay (RIA) [87 (29.2%) and 101 (44.9%)] (P < 0.05). The anti-HCV prevalence in subjects with total HGV marker was significantly higher than in those without total HGV marker. There was no significant difference in anti-HBc prevalence between those with and without total HGV marker. The viremic rate was highest in HCV infection (HCV RNA by PCR/anti-HCV) (83.2%), with HGV infection (HGV RNA/total HGV marker) (21.7%) intermediate, and HBV infection (hepatitis B surface antigen by RIA/anti-HBc) (5.3%) lowest (P < 0.05). These findings indicate that HGV infection was less endemic than HCV and HBV. HGV was eliminated naturally more frequently than HCV infection and less frequently than HBV infection.     

Prevalence of Mutations in Core Promoter/Precore Region in Japanese Patients with Chronic Hepatitis B Virus Infection

We examined the frequency and significance ofmutations in the core promoter and precore region in 103Japanese patients with chronic hepatitis B virus (HBV)infection. HBV DNAs from the patients' sera were amplified by polymerase chain reaction andwere directly sequenced. A double mutation(T¹⁷⁶² A¹⁷⁶⁴) in the core promoterwas frequently observed in the patients regardless ofHBeAg status except for asymptomatic carriers with HBeAg. Furthermore,a mutation at nucleotide 1753 from T to C or G wasfrequently found in anti-HBe positive patients and wasoften accompanied by the double mutation. TheA¹⁸⁹⁶ mutation was found in only about onefourth of the patients with anti-HBe. These data suggestthat the patients with chronic liver diseases frequentlyhad a double mutation regardless of HBeAg status and a mutation at nucleotide 1753 might beassociated with HBeAg-negative chronic hepatitis B virusinfection.     

GB Virus C infection in Patients With HIV/Hepatitis C Virus Coinfection: Improvement of the Liver Function in Chronic Hepatitis C

Background:

Previous studies in patients with hepatitis C virus (HCV)/HIV coinfection have shown that the presence of GBV-C is associated with significantly less compensated and decompensated cirrhosis, and an improvement in cirrhosis-free survival.

Objectives:

This study aimed to describe the effect of GBV-C in patients with chronic hepatitis C and HIV coinfection.

Patients and Methods:

We retrospectively studied 105 injecting drug users with chronic hepatitis C and HIV coinfection and 72 patients with chronic HCV mono-infections. Plasma samples were tested for GBV-C RNA with primers to the 5’untranslated region gene. HIV and HCV viral load, CD4⁺ and CD8⁺ cell count, and the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were tested in all patients.

Results:

GBV-C RNA was identified in 34 (32.38%) of the patients with HIV/HCV coinfection, and in 24 (33.33%) of the patients with HCV mono-infection. GBV-C infection was associated with significantly lower ALT and AST levels in patients with chronic hepatitis C and HIV coinfection, but not in those HCV mono-infections. The presence of GBV-C infection was not correlated with CD4⁺ and CD8⁺ cell count, gender, age, HIV load, HCV load, and HCV genotype.

Conclusions:

This study found that GBV-C infection has a high frequency among injecting drug users with HIV/HCV coinfection and HCV mono-infection in Yunnan, China. In patients with chronic hepatitis C and HIV coinfection, GBV-C RNA was associated with significantly lower ALT and AST levels, suggesting a beneficial effect of GBV-C infection on chronic hepatitis C.     

Comparison of HCV RNA Levels by Branched DNA Probe Assay and by Competitive Polymerase Chain Reaction to Predict Effectiveness of Interferon Treatment for Patients with Chronic Hepatitis C Virus

To compare hepatitis C virus (HCV) RNA levelsdetermined by branched DNA probe assay and bycompetitive polymerase chain reaction (PCR) aspredictive markers of the response to interferon fortreatment of patients with chronic HCV infection, westudied data on 140 patients treated for six months withnatural interferon-alpha. Serum samples were tested forHCV RNA by PCR. HCV RNA was grouped into four genotypes by PCR with type-specific primers,and HCV RNA level was measured by branched DNA probeassay and by competitive PCR. HCV RNA was detected inall patients prior to initiation of the treatment. A complete response, sustained elimination ofHCV RNA, occurred in 51 patients (36.4%). With multiplelogistic regression analysis assessment, when usingcompetitive PCR, a low level of HCV RNA (P < 0.0001), younger age (P = 0.0054) and genotype 2a and 2b(P < 0.0158) were significant predictive markers fora complete response to interferon treatment. When usingbranched DNA probe assay, a low level of HCV RNA (P < 0.0001) and age (P = 0.0089) werepredictive markers, but genotype was not. The branchedDNA probe assay had a narrower linear range forquantitation of HCV RNA level than competitive PCR. In conclusion, HCV RNA level determined bybranched DNA probe assay proved to be useful forprediction of effects of interferon and it is costeffective as a marker of complete response to interferontreatment for patients with chronic HCVinfection.     

Interaction of Alcohol and Hepatitis C Virus Infection on Severity of Liver Disease

Chronic alcoholics have a high prevalence ofhepatitis C virus (HCV) infection. The present study wascarried out to examine the association between HCVinfection and alcohol abuse, and the influence of these factors on the severity of liver disease.Patients with history of heavy alcohol abuse (80 gof ethanol per day for 5 years) were analyzed withrespect to the amount of alcohol use, clinical evidence of liver disease, and laboratory tests. Onehundred ninety-nine patients, 137 HCV positive and 62HCV negative were included in the study. HCV-infectedsubjects had liver disease for a longer duration (P < 0.0001) and had higher incidence ofsymptoms of hepatic decompensation in the past comparedto uninfected alcoholics. Several differences were notedbetween the two groups at the time of presentation to the hospital. Alcoholics with HCV infectionhad lower daily alcohol consumption (P < 0.001), wereabstinent for a longer duration (P < 0.02) and hadlower lifetime use of ethanol (P < 0.005) compared to HCV-negative subjects. Assessmentof liver tests showed greater derangement in uninfectedalcoholics compared to HCV-positive subjects. Thepresent study shows that HCV-infected chronic alcoholics have lower alcohol consumption and, perhaps asa consequence, have less severe liver disease comparedto HCV-negative individuals. These findings suggest thatin chronic alcoholics, despite the presence of HCV infection, the severity of liver damageis related to the amount of alcoholconsumption.     

Hepatitis G and C Viruses Respond to Interferon-α with Different Virologic Kinetics

The aim of this work was to specify the timecourse of response to interferon (IFN) of hepatitis Gvirus (HGV) and hepatitis C virus (HCV) in coinfectedindividuals. A group of 33 patients, undergoing 12 months of IFN therapy for chronic hepatitis C,was screened for the presence of both HGV and HCV RNAsto select seven coinfected patients. Spontaneousrecovery from HGV infection was excluded through the detection of antibodies to the envelope-2protein of HGV and HCV isolates were genotyped. Withinthree months of treatment, we found that HGV RNA wastransiently cleared in 6/7 patients, but the rate of long-term favorable response was very low(1/7). In addition, considering the same individualsseparately, it was shown that HGV and HCV responded toIFN with different kinetics in 5/7 patients. Takentogether, these results underscore the importance of thevirological basis of the resistance to IFNtreatment.     

Serum Soluble Interleukin-2 Receptor Levels Before and During Interferon Treatment in Patients with Chronic Hepatitis B Virus Infection

To determine the role of serum solubleinterleukin-2 receptor (sIL-2R) in chronic hepatitis Bvirus (HBV) infection, the level of serum sIL-2R wasmeasured in sera of 105 patients with chronic HBVinfection and in 21 healthy controls, using enzyme-linkedimmunosorbent assay. Serum sIL-2R levels weresignificantly higher in chronic HBV-infected patientswith chronic hepatitis (508 ± 310 units/ml) andliver cirrhosis (543 ± 283 units/ml) than inhealthy controls (331 ± 106 units/ml, P <0.05). Moreover, serum sIL-2R levels were significantlyhigher in patients with chronic hepatitis or livercirrhosis than in asymptomatic HBV carriers (341 ±150 units/ml, P < 0.01). There was no difference inserum sIL-2R levels between asymptomatic HBV carriersand healthy controls or between patients with chronic hepatitis and liver cirrhosis. A significantrelationship was found between serum sIL-2R and ALTlevels (P < 0.05) in patients with chronic HBVinfection, although there was no correlation betweensIL-2R and HBV DNA levels. Serum sIL-2R levels in mostpatients decreased to the same level as asymptomatic HBVcarriers and healthy controls at 48 weeks after the endof treatment, and serum ALT and HBV DNA levels were decreased to within the normal range at 96weeks. Thus, serum sIL-2R levels indicate the degree ofliver damage among patients with chronic HBV infection.The serum sIL-2R levels one year after interferon administration may be a useful marker ofdetermined at the effectiveness by thistreatment.