Seiji Noguchi

Routes of Transimission of Hepatitis C Virus in an Endemic Rural Area of Japan Molecular Epidemiologic Study of Hepatitis C Virus Infection

We conducted an epidemiological study to investigate the routes of transmission of hepatitis C virus (HCV) infection in an area endemic for HCV. Subjects were the 857 adult inhabitants of K area, Japan. The prevalence of antibody to HCV (anti-HCV) was 26.3%. The HCV genotype 1b was the most prevalent (89.3%) among the anti-HCV positive subjects. Molecular evolutionary analysis, based on the nucleotide sequences of the HCV core region from 23 participants with type 1b, showed that the isolates were distributed into more than 1 group. Multivariate regression analysis demonstrated that an age over 40 years, a history of blood transfusion, the presence of antibody to hepatitis B core antigen (anti-HBc), or a history of surgery were each independently associated with the presence of anti-HCV. No significant differences in the presence of anti-HCV prevalence were observed between the wives of men positive for anti-HCV (33.3%) and age-matched women (36.4%), or between the husbands of women positive for anti-HCV ...

Higher elimination rate of hepatitis C virus among women

SUMMARY. The mortality rate from liver disease in H town of the Fukuoka prefecture in Japan is significantly higher in men than in women. To clarify the gender‐related difference, we evaluated subjects with hepatitis B virus (HBV) and hepatitis C virus (HCV) infection in the S area of this town. A total of 824 adults participated in this study, 332 men and 492 women. The incidence of positivity for hepatitis B surface antigen (HBsAg) in serum did not differ significantly between the subjects in the S area (1.9%) and Japanese blood donors (1.5%); however, the incidence of positivity for serum antibody to hepatitis C virus (HCVAb) in the subjects (31.8%) greatly exceeded that in Japanese blood donors (1.3%). The rate of positivity for HCVAb did not differ significantly between men (28.3%) and women (34.1%), but the proportion of serum HCV RNA‐positive to HCVAb‐positive subjects was significantly higher in men (78.2% in men vs 67.3% in women). The incidence of elevated serum alanine aminotransferase (ALT) in subjects positive for serum HCV RNA was also significantly higher in men (77.0% in men vs 55.8% in women). These results suggest that a more frequent elimination of HCV from serum in women may explain the observed lower mortality from liver disease.

SERO-EPIDEMIOLOGIC STUDY OF HEPATITIS C VIRUS INFECTION IN FUKUOKA, JAPAN

Abstract: We conducted an epidemiological study of 509 residents of H town, Fukuoka, Japan, to investigate the high mortality rate from liver disease. Antibodies to hepatitis C virus (HCV) (anti-HCV) were detected in 120 residents (23.6%); HCV RNA in 91 (17.9%), and hepatitis B surface antigen (HBsAg) in 13 (2.6%). Multivariate logistic regression analyses showed that presence of anti-HCV, male gender, and history of liver disease were associated with the presence of liver dysfunction, and that age of more than 40 years and a particular district were associated with the presence of anti-HCV. HCV RNA was more frequently detected in anti-HCV-positive men than women (41, or 85.4% versus 50, or 69.4%) (P < 0.05). The incidence of liver dysfunction was significantly higher in HCV RNA-positive men than women (32, or 66.7% versus 22, or 30.6%) (P < 0.05). These findings suggest that: (1) HCV was correlated with the high mortality rate from liver diseases, (2) there were district-related differences in the incidence of HCV, and (3) the lower frequency of elimination of HCV from men may explain why they showed a high mortality from liver disease.

Inflammatory myopathy associated with hepatitis C virus infection: a report of four cases

Abstract Four patients with inflammatory myopathy positive for anti-hepatitis C virus are described. One male and three females are included in this report. Mean age of the four patients was 50 years (range 42–60 years). They were referred to our hospital with muscle weakness or myalgia. Active hepatitis C virus infection was confirmed by the detection of hepatitis C virus RNA with the polymerase chain reaction method in sera of these patients. Serum muscle enzymes, such as creatine kinase, lactate dehydrogenase, aspartate aminotransferase, and aldolase were elevated. Inflammation in the muscle tissue was demonstrated in the muscle biopsy specimens from these patients. The patients received prednisolone and symptoms and elevated muscle enzymes were improved. It is suggested that hepatitis C virus might be one of the possible etiologic factors responsible for inflammatory myopathy.

Lack of detection of hepatitis C virus replicative intermediate in abdominal lymph nodes

Abstract Deep abdominal lymph node enlargement has been detected by ultrasound examination in patients with hepatitis C virus (HCV) infection. To clarify the potential for extrahepatic existence and/or replication of HCV in such abdominal lymph node, positive- and negative-strand HCV RNA were investigated in abdominal lymph node mononuclear cells (MNC) as well as in the serum of patients with HCV. The study population consisted of eight hepatocellular carcinoma (HCC) patients positive for antibody to HCV (anti-HCV). Lymph nodes of hepatoduodenal ligament were resected at surgery for HCC. Both HCV RNA strands were examined using highly strand-specific r Tth reverse transcription-polymerase chain reaction (r Tth RT-PCR) followed by Southern blotting analysis. Positive-strand HCV RNA was detected in three (37.5%) abdominal lymph node MNC and in seven (87.5%) serum samples. Negative-strand HCV RNA was not detected in abdominal lymph node MNC, while it was observed in two (25%) serum samples. Histologically, the lymph nodes taken from subjects showed reactive follicular hyperplasia with or without the presence of HCV RNA. These observations suggest that HCV is located in the abdominal lymph nodes, but does not replicate within them. Negative-strand HCV RNA detected in serum samples may have been due to contamination with circulating HCV RNA from hepatocytes.

Intraspousal transmission of GB virus C/hepatitis G virus in an hepatitis C virus hyperendemic area in Japan

ObjectiveAn immunoassay for antibodies against an hepatitis G virus (HGV) protein (anti-E2) was recently developed that might serve as a useful marker for diagnosing recovery from HGV infection.MethodsWe investigated the intraspousal transmission of GB virus C/hepatitis G virus (GBV-C/HGV) using both reverse transcription hemipolymerase chain reaction (RT-hemi-PCR for the 5′ untranslated region) and a recently developed anti-E2.ResultsThirty-two GBV-C/HGV-infected index subjects were selected from an hepatitis C virus hyperendemic area in Japan. Of the 32 subjects, seven (6.4%) were GBV-C/HGV RNA-positive, 24 (21.8%) were anti-E2-positive, and one (0.9%) was both GBV-C/HGV RNA- and anti-E2-positive. Among the 32 spouses of these subjects, GBV-C/HGV RNA, anti-E2, and both GBV-C/HGV RNA and anti-E2 positivity were detected in 0, 6, (18.8%), and one (3.1%) spouses, respectively (the total prevalence of GBV-C/HGV was 7 spouses [21.9%]). Thus, the intraspousal transmission of GBV-C/HGV was undeniable in these seven couples. The respective positive rates of 175 sex- and age-matched controls were 7 (4.0%), 26 (14.9%), and 0 (the total prevalence of GBV-C/HGV was 34 [19.4%]). No significant difference in positive rates was observed between the subjects/spouses and the controls. Five spouses among the seven couples who were positive for any of GBV-C/HGV markers had parenteral risk factors such as blood transfusion, acupuncture, and major surgery.ConclusionsBased on these observations, we cannot draw a definitive conclusion that intraspousal transmission of GBV-C/HGV had occurred among these seven couples.

Transmission routes and clinical courses in sporadic acute hepatitis C

Summary. Between March 1994 and March 1996 we studied transmission routes and clinical courses in eight patients with sporadic acute hepatitis C (two men, six women). Of the eight patients, three were treated for another illness 1–2 months before the onset of hepatitis, one was a parenteral drug abuser, one had an accidental needlestick injury and two had sexual contact with a partner with chronic hepatitis C virus (HCV) infection. Clinical courses included four women whose HCV RNA and alanine aminotransferase (ALT) became persistently negative without treatment, and four men and two women with the same results following interferon (IFN) treatment. It is thought that IFN therapy may prevent the progression to chronic liver disease. Results from this study might be useful in the future management of patients with sporadic acute hepatitis C.

Lack of anti-GOR antibody among subjects with GB virus C/hepatitis G virus RNA.

Homologies were sought between the putative amino acid sequences of GB virus C/hepatitis G virus (GBV‐C/HGV) and the GOR epitope or the liver/kidney microsome‐1 (LKM‐1) epitope, which share partial sequence identity with the hepatitis C virus (HCV) polyprotein. Anti‐GOR antibody (anti‐GOR) was assayed among 100 subjects with GBV‐C/HGV RNA. Twenty‐one and 25 subjects were coinfected with hepatitis B virus (HBV) or HCV, respectively. Homologies were found between the NS5 or E2 polyproteins of GBV‐C/HGV and the GOR epitope or the LKM‐1 epitope, respectively. These segments of GBV‐C/HGV polyproteins sharing identity with the GOR or the LKM‐1 epitope were well conserved among three genotypes of GBV‐C/HGV. However, only 1 of 55 subjects (1.8%) with GBV‐C/HGV RNA, but not with HBV or HCV, was positive for anti‐GOR. The positivity for anti‐GOR among the group with GBV‐C/HGV RNA alone was significantly lower than that among the groups with HCV RNA (P < 0.01 and P < 0.05, respectively). Only 2 of 55 subjects (3.6%) with GBV‐C/HGV RNA alone exhibited elevation of alanine aminotransferase. The incidence of liver dysfunction among the group with GBV‐C/HGV RNA alone was significantly lower than the incidence among the groups with GBV‐C/HGV RNA and hepatitis B surface antigen (HBsAg) or HCV RNA (P < 0.01 and P < 0.01, respectively). These data indicate that 1) there is no association between GBV‐C/HGV infection and the presence of anti‐GOR, and 2) GBV‐C/HGV infection is not related to chronic liver dysfunction. J. Med. Virol. 55:129–133, 1998.

Sequence Variation of the Hypervariable Region in HCV Carriers with Normal ALT Levels: A Comparison with Symptomatic Carriers

The clinical significance of the hypervariable region (HVR) in the N‐terminus of the E2/NS1 region, which encodes the putative envelope glycoprotein (gp 70) of HCV, has not yet been elucidated. We studied the relation between HVR changes and elevation of the alanine aminotransaminase (ALT) level due to liver cell injury as well as the persistence of HCV infection. Three patients (carrier group) who were HCV RNA positive and had normal ALT levels for as long as five years and three patients with high ALT levels were studied. None of the six patients had a history of treatment. HCV RNA was extracted from serum obtained from each patient in 1990 and 1995. The E2/NS1 region, including HVR‐1 and HVR‐2, was amplified using the RT‐PCR method. PCR products were cloned and nucleotide sequences were determined using the dideoxynucleotide chain termination method. No clear correlation was found between the ALT levels and the number of nucleotide substitutions in HVR‐1. The number of nucleotide substitutions in HVR‐1 during the five years was greater than in other regions. Furthermore, more nucleotide substitutions occurred in the 1st and 2nd codon positions of HVR‐1 than in the control region, even in the carrier group. In conclusion, HVR‐1 changes are probably a more important factor in persistent viral infection than liver cell injury.

GB virus C (GBV-C)/hepatitis G virus (HGV) infection in a hepatitis C virus hyper-endemic area in Japan

Abstract An epidemiologic study was performed to investigate GBV-C/HGV infection in 460 inhabitants of H town where hepatitis C virus (HCV) is hyper endemic. GBV-C/HGV RNA was detected by reverse transcription hemi-nested polymerase chain reaction (RT-heminested PCR) for the 5′ untranslated region (5′-UTR). The nucleotide sequences of GBV-C/HGV 5′-UTR were determined and phylogenetic analysis was performed. GBV-C/HGV RNA, antibody to HCV (anti-HCV), and HCV RNA were detected in 12 (2.6%), 108 (23.5%), and 87 of subjects (18.9%), respectively. The phylogenetic tree analysis indicated that the 12 GBV-C/HGV-positive isolates could be classified as a new GBV-C/HGV group (type 3). No intraspousal transmission of GBV-C/HGV was observed. Four subjects positive for GBV-C/HGV RNA without HCV RNA had normal mean aminotransferase concentration. This study indicated: 1, the prevalence of GBV-C/HGV was lower than that of HCV: 2, Type 3 GBV-C/HGV was the most prevalent; 3. No intraspousal transmission of GBV-C/HGV was observed; and 4, GBV-C/HGV alone may not cause severe liver injury.