Haruhiko Imai

Transmission of hepatitis C in an isolated area in Japan : community-acquired infection

Abstract Background/Aims: The spread of hepatitis C virus (HCV) infection not due to drug needle sharing or transfusion is largely unknown in communities. A search for risk factors for HCV infection in an endemic area might elucidate inapparent modes of transmission. Methods: We conducted screening for hepatitis virus markers and parenteral exposures to blood among 435 inhabitants in an isolated area known for its endemicity for non-A, non-B hepatitis and in a nonendemic area with 1542 inhabitants. Results: The prevalence of hepatitis B surface antigen was the same in both areas. The prevalence of antibody to HCV verified by the recombinant immunoblot assay was 32.4% in the highly endemic area and 2.3% in the nonendemic area ( P Conclusions: Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives should be considered as possible routes of HCV transmission not associated with blood transfusion or sharing of drug paraphernalia.

Detection of anti-double and anti-single stranded DNA antibodies in chronic liver disease : significance of anti-double stranded DNA antibody in autoimmune hepatitis

Anti-DNA antibodies were determined by an enzyme-linked immunosorbent assay in 116 patients with chronic liver disease consisting of 21 cases of autoimmune hepatitis (AIH), 17 of primary biliary cirrhosis (PBC), and 78 of non-autoimmune-type of chronic liver disease. The assay was also performed on 83 patients with collagen disease, as a control group. Anti-double stranded DNA antibody (anti-dsDNA) was detected in 10/21 (48%) of the AIH patients and in 3/17 (17%) of the PBC patients, but not in those with other liver diseases. In contrast, anti-single stranded DNA antibody (anti-ssDNA) was positive not only in AIH and PBC, but also in those with non-autoimmune-types of chronic liver disease. Follow-up liver histology disclosed that the 2 patients with AIH who were positive for anti-dsDNA developed liver cirrhosis, whereas the 4 patients who were negative for anti-dsDNA, and those who showed a disappearance of anti-dsDNA following corticosteroid therapy, improved from chronic active to chronic persistent hepatitis.

Prevalence and disease association of TT virus infection in Japanese patients with viral hepatitis

Abstract Prevalence and disease association of the TT virus (TTV) were studied in Japanese patients with various types of viral hepatitis. A total of 317 patients with viral hepatitis were analyzed, and the results were compared to those of 100 apparently healthy controls. TTV DNA in serum was measured by semi-nested polymerase chain reaction. Prevalence of TTV DNA was significantly higher in patients with hepatitis A (36%, 5/14), hepatitis B (35%, 35/101), hepatitis C (61%, 90/148), and non-A-E hepatitis (41%, 22/54) than in healthy controls (12%, 12/100), respectively. In each type of hepatitis, the prevalence did not differ between acute and chronic liver diseases, and did not increase with the complication of hepatocellular carcinoma. The clinical backgrounds did not differ between TTV DNA positive and negative patients, in patients with acute hepatitis or in those with chronic liver diseases. Similarly, no liver function test showed a significantly higher level of in TTV DNA positive patients than in negative ones. In conclusion, TTV infection was highly prevalent in patients with viral hepatitis, especially in those with hepatitis C. TTV was suggested to have a weak pathogenicity (or no pathogenicity), at least when co-infecting with an established hepatitis virus.

Clinical application of hepatitis C virus core protein in early diagnosis of acute hepatitis C

Abstract: A fluorescence enzyme immunoassay (FEIA) for the quantitative measurement of hepatitis C virus (HCV) core protein has recently been developed. In this study, we studied the clinical usefulness of this measurement in patients with acute hepatitis C. Eighteen patients with post-transfusion acute hepatitis C were enrolled in the study; 5 patients showed resolution of hepatitis with disappearance of HCV viremia, while the remaining 13 patients did not. A second generation HCV antibody, HCV RNA, and HCV core protein were measured in serial serum samples taken within 1 month of the onset of acute hepatitis and 3, 6, 12, 24, and 36 months after onset. Within the first month after disese onset, the positivity rates of HCV RNA (100%; P = 0.0014) and HCV core protein (89%; P = 0.0300) were both significantly higher than that of HCV antibody (56%). Six months after disease onset, the positivity rate of HCV antibody had increased, to 100%, and the pasitivity rates of HCV RNA and HCV core protein began to decrease. HCV core protein levels did not differ between patients with resolved and unresolved disease in the first month after disease onset. These findings indicate that FEIA, a simple assay, for the measurement of HCV core protein was useful for the early diagnosis of acute hepatitis C.

TT virus infection in an area of high-endemicity for hepatitis C

TT virus (TTV) was recently identified as a candidate for a new hepatitis virus. In the present study, the clinical features and transmission routes of TTV infection were analyzed in an area highly endemic for hepatitis C virus (HCV) infection, and compared to those in an area not endemic. In conclusion, the prevalence of TTV infection was as high as 58% in the high-endemicity area for HCV infection. The main transmission route for TTV appeared to be different from that of HCV and HGV. TTV infection showed a reciprocal association with HCV infection, and had limited pathogenetic effect on hepatitis.

Autoimmune hepatitis type 1 without evidence of hepatitis G virus infection

Abstract Hepatitis G virus (HGV) RNA was measured in sera from 60 patients satisfying the international diagnostic criteria of definite autoimmune hepatitis type 1 using a reverse transcription and polymerase chain reaction with primers of the putative NS5 region of the HGV genome. Five patients had a history of blood transfusion. Of the 60 patients, 55 (92%) were confirmed as having human leukocyte antigen (HLA) DR4 or DR2 which are genetic markers for susceptibility to autoimmune hepatitis in Japanese. None of the 60 patients had any serum markers suggesting hepatitis B virus infection and 5 (8%) had evidence of on-going hepatitis C virus infection. No patients had HGV RNA in serum. The absence of active HGV infection in this cohort suggests that HGV does not play a casual role in the development of autoimmune hepatitis in Japan.

Comparison of anamnestic history, alcohol intake and smoking, nutritional status, and liver dysfunction between thorotrast patients who developed primary liver cancer and those who did not.

In order to clarify the differences in past history, nutritional condition and, consumption of alcohol and tobacco, and liver dysfunction between the thorotrast patients who developed primary liver cancer and those who did not, 103 persons who had no primary liver cancer in January 1980 were studied. All subjects were military men who had undergone angiography with thorotrast between 1943 and 1946. Twenty persons developed hepatocellular carcinoma and 16 developed intrahepatic bile duct carcinoma by April 1987, whereas 67 are still alive without any cancer. There was no difference in age or period after thorotrast infusion between those two groups of patients in January 1980. A difference in history of hepatitis and/or jaundice and presence of hepatic dysfunction was found between the subjects who developed primary liver cancers and those who did not. These findings suggest that an anamnestic history of hepatitis and liver dysfunction are risks for development of thorotrast-induced liver cancer. On the basis of the above findings, early detection of liver dysfunction offers a possibility of early diagnosis of primary liver cancer.

Hepatitis G virus/GB virus C infection in an area of high endemic hepatitis C virus infection

We previously reported an area of high endemic hepatitis C virus (HCV) in which over 30% of the inhabitants were positive for HCV antibody. Folk remedies such as acupuncture and cutting of the skin using nonsterilized knives were considered to be possible routes of HCV transmission in this area. Hepatitis G virus/ GB virus C (HGV/GBV-C), a newly discovered hepatitis virus, was analyzed to determine the role and transmission of its infection in this area. A total of 100 individuals were selected randomly from 420 inhabitants who were medically screened for liver disease in 1993, and were subjected to this study. HGV/GBV-C RNA in serum was measured by reverse transcription and polymerase chain reaction with primers in the putative non-structural 5 region. Of the 100 subjects, five (5%) were positive for HGV/GBV-C RNA and 40 (40%) were positive for HCV antibody (34 were also positive for HCV RNA). The prevalence of HCV antibody in five individuals with HGV/GBV-C RNA (100%) was significantly (P < 0.008) higher than in 95 individuals without HGV/GBV-C RNA (37%). None of five individuals with HGV/GBV-C infection had a history of blood transfusion, but 80% of those had a history of folk remedies. Serum level of alanine aminotransferase was similar between individuals with HCV and HGV/GBV-C infections and those with only HCV infection. In conclusion, 5% of the inhabitants in an area of high endemic HCV were infected with HGV/GBV-C. HGV/GBV-C infection in this area was closely associated with HCV infection and seems to have mainly been spread by folk remedies.

Intrahepatic expression of HBsAg and HBcAg in asymptomatic HBsAg carriers and its follow-up

Intrahepatic expression of hepatitis B surface antigen (HBsAg) and hepatitis B core antigen (HBcAg) was investigated in 46 asymptomatic HBsAg carriers by a direct immuno‐fluorescent method. In 21 HBeAg positive carriers, HBsAg was expressed diffusely on the membrane of hepatocytes, with associated cytoplasmic localization in a few scattered hepato‐cytes. HBcAg was expressed in the nucleus of many hepatocytes and in the cytoplasm of a few scattered hepatocytes, but not on the cell membrane. In 25 anti‐HBe positive carriers, HBsAg was expressed on the surface and in the cytoplasm of hepatocytes diffusely and/or focally, but neither intrahepatic HBcAg nor serum HBV‐DNA was detected. Repeat liver biopsies were performed in 17 patients. In eight of 13 HBeAg‐positive HBsAg carriers, who developed histologically proven chronic hepatitis and liver cirrhosis, the localization of HBsAg in liver had changed from a membranous to a mixed (membrane and cytoplasm) pattern, and localization of HBcAg in liver had changed from a predominantly nuclear to a predominantly membranous and cytoplasmic pattern. However, in two HBeAg and two anti‐HBe positive cases who showed no biochemical and histologic change at follow‐up, the intrahepatic expressions of HBsAg and HBcAg in the second biopsies remained unchanged. Thus, decrease in membranous expression of HBsAg and increase in membranous and cytoplasmic expression of HBcAg were associated with progression to chronic liver disease. This suggests that membranous HBcAg may represent the major target in the process of injury to hepatocytes.

A case of cholangiocarcinoma detected after followup for seven years for thorotrast deposition

SummaryA 73-year-old former soldier in whom a deposition of thorotrast had been detected 7 years previously was admitted to our hospital because of high fever and epigastric pain. He had been well with standard liver function tests within the normal range until 4 months before admission. Laboratory examination on admission showed marked abnormalities in the liver function tests and an elevated level of CEA. Abdominal ultrasonography and computerized tomography, which had shown no spaceoccupying lesion in the liver one year earlier, revealed an abnormal mass in the right hepatic lobe. Angiographic examination revealed low vascularity and encasement of the intrahepatic artery. The disease was diagnosed as thorotrast-induced cholangiocarcinoma. Despite chemotherapy, the patient’s condition worsened rapidly and he died on the 78th day after admission. At autopsy, the primary tumor in the right hepatic lobe and metastatic nodular tumors throughout the liver were found. The histological diagnosis was cholangiocarcinoma.Thorotrast-induced liver cancers are inclined to grow rapidly, so early diagnosis of liver tumor accompanied by thorotrastosis is very difficult, as in this case. Repeated examinations at frequent intervals are required for early diagnosis.