Kumiko Ueno

Human lymphoblastoid interferon treatment for patients with hepatitis C virus-related cirrhosis

To evaluate the efficacy and safety of human lymphoblastoid interferon treatment (interferon alfa) for patients with compensated cirrhosis caused by hepatitis C virus (HCV) infection, we randomly assigned 82 cirrhotic patients with chronic HCV infection (44 men, 38 women; mean age, 58.6 years) to two groups: 41 patients were treated with interferon alfa (480 million U over 6 months), and the other patients received no drug treatment. HCV RNA genotypes were determined by polymerase chain reaction (PCR) testing using type-specific primers. HCV RNA levels were measured by competitive PCR testing. No untreated patients eliminated HCV RNA from the serum or had a decrease in the level of alanine aminotransferase to normal during the observation period. Of the 34 patients who completed interferon alfa treatment, 6 (17.6%) who were considered complete responders eliminated HCV RNA from the serum by the end of treatment and sustained this elimination throughout a 6-month follow-up period. Complete responders constituted 6 (46.2%) of 13 patients with HCV RNA levels < or = 10(5) copies/50 microL, but none of the 21 patients with levels > 10(5) copies/50 microL were complete responders. Two (7.1%) of 28 patients with genotype 1b infection and 4 (66.7%) of 6 with genotype 2a were complete responders. Five patients withdrew because of interferon alfa-induced side effects (1 for thrombocytopenia, 3 for severe general malaise, and 1 for impotence), and 2 withdrew after being diagnosed with hepatocellular carcinoma. Hepatic failure did not occur in any treated patient in the present study. These findings indicate that interferon alfa treatment is useful for compensated cirrhosis caused by HCV infection if the HCV RNA levels are low and the infection is of genotype 2a.

Effectiveness of Interferon Treatment for Patients with Chronic Hepatitis C Virus Infection and Normal Aminotransferase Levels

To determine the effects of interferon treatment, we studied 77 Japanese patients with hepatitis C virus (HCV) infection and normal alanine aminotransferase (ALT). Of 77 patients, 37 were given natural interferon-α for 24 weeks, and 40 not given interferon acted as controls. Serum samples were tested for HCV RNA and genotypes by polymerase chain reaction (PCR). HCV RNA levels were measured by competitive PCR. Of 37 treated patients, 11 (29.7%) had sustained elimination throughout a six-month follow-up, while HCV RNA was not eliminated in any untreated patients. At 24 months, the number of patients with elevated ALT was not significantly different between treated (13.5%) and untreated patients (15%). Interferon eliminates HCV RNA in patients with normal ALT without severe side effects. The natural history of HCV infection should be clarified so that the interferon treatment regimen can be tailored to the needs of each patient.

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.

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.

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). The re 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.

Immunochromatography AssayによるHBs抗体の検出-PHA法との比較

A new immunochromatography assay (Dainascreen Ausab Dainabot) has been recently introduced for the detection of the presence of antibody to HBsAg. To evaluate the feasibility of using the Dainascreen Ausab, we carried out comparison tests with this method and PHA. In the test of 439 sera from HB vaccinees, inhabitants in Iki Island, Nagasaki Pref., patients with autoimmune diseases and with acute hepatitis B, 154 (31.2%) were positive by Dainascreen Ausab, 145 (29.4%) were positive by PHA and 145 (29.4%) were positive by both Dainascreen Ausab and PHA. Nine (1.8%) were positive by only Dainascreen and there were none positive by only PHA. A good correlation was observed between the titer of the antibody by this method and IMx. The anti-HBs assay by this method was able to be completed within 15 minutes and the procedure was very simple. The results indicate that the sensitivity of Dainascreen is superior to PHA and that it is easy to use.