Hiroki Nakasone

Hepatitis delta virus genotype IIb predominates in an endemic area, Okinawa, Japan.

Hepatitis delta virus (HDV) infection is relatively common in the Miyako Islands, Okinawa, Japan, where the infection has been reported to be associated with low pathogenicity. HDV RNA extracted from each of 6 patients with HDV‐related chronic liver disease living in the islands was amplified by reverse transcription‐polymerase chain reaction and examined genetically to determine the HDV genotype. All isolates from the 6 patients were classified as genotype II by the neighbor‐joining method. However, these isolates had relatively low homology (75–81%) to the HDV genotype II isolate reported from Japan, and showed relatively high identity (83–95%) to the novel genotype II isolate (HDV genotype IIb) recently reported from Taiwan. Phylogenetic analysis showed that the 6 isolates form a novel group within HDV genotype II. Furthermore, there was notable variation in sequence among the 6 isolates compared with the relatively close clustering of HDV isolates within limited areas (e.g., United States, Archangelos, Turkey, Albania, Peru). HDV genotype II in the Miyako Islands is therefore unique, and HDV infection may have been introduced at a relatively early time in this area. J. Med. Virol. 58:366–372, 1999.

Quantitation of the Level of Hepatitis Delta Virus RNA in Serum, by Real-Time Polymerase Chain Reaction—and Its Possible Correlation with the Clinical Stage of Liver Disease

Some hepatitis B virus (HBV) carriers with chronic hepatitis delta virus (HDV) superinfection show progressive chronic hepatitis, whereas others show no apparent signs of liver disease. In the present study, we established a sensitive method for the quantitation of the level of HDV RNA in serum on the basis of real-time reverse-transcription polymerase chain reaction (RT-PCR), to clarify the role that the level of HDV RNA in serum plays in the diverse natural course of clinical manifestation. In 48 subjects who were positive for hepatitis B surface antigen and for anti-hepatitis delta antibody, the levels of HDV RNA in serum were quantitated by RT-PCR. The levels of HBV DNA in serum were determined by a transcription-mediated amplification assay. The levels of HDV RNA in serum of subjects with chronic hepatitis and of subjects with liver cirrhosis were significantly higher than those in asymptomatic carrier subjects. The levels of HBV DNA in serum did not differ significantly among these 3 groups. In conclusion, HDV RNA quantification by real-time RT-PCR is possibly a useful tool for understanding the pathophysiology of HDV infection.

Correlation between serum transaminase activity and virus load among patients with chronic liver disease type B

Newly developed hepatitis B virus (HBV)-DNA quantitative assays, transcription-mediated amplification and hybridization protection assay (TMA-HPA) and branched-DNA assay were clinically evaluated. The subjects consisted of 160 chronic HBV carriers; 48 were hepatitis Be antigen (HBeAg)-positive, whereas 109 were anti-HBe-positive (three were both negative). All subjects with HBeAg, except one, showed high HBV-DNA replication levels (>/=10(5.8) copies/ml). In HBeAg negative subjects, there was a strong correlation between the serum HBV-DNA and alanine aminotransferase (ALT) levels; ALT level was usually normal if the samples tested showed an HBV-DNA level less than 10(5)/ml, whereas, the majority of the sera with an HBV-DNA concentration greater than 10(7)copies/ml showed elevation in serum ALT level. An intermediate range of HBV-DNA level (10(5)-10(7) copies/ml) was associated with variable ALT activity. In conclusion, a serum HBV-DNA level associated with ALT elevation was lower in patients with type B chronic liver disease negative for HBeAg compared with their HBeAg-positive counterparts. There was usually no or mild liver disease activity when patients with chronic HBV infection have serum HBV-DNA levels less than 10(5)copies/ml.

Alcoholic liver cirrhosis complicated with torsade de pointes during plasma exchange and hemodiafiltration

A 36-year-old man with severe alcoholic hepatitis was treated with plasma exchange combined with hemodiafiltration to remove endotoxins and inflammatory cytokines. During the treatment, he had critical arrhythmia (torsade de pointes [TdP]). His laboratory data showed hypomagnesemia, which was suspected to be responsible for the development of TdP. Patients with alcoholic liver disease tend to have hypomagnesemia and Q-T interval prolongation. Furthermore, hemodiafiltration may cause hypomagnesemia. Careful observation for electrolytic imbalance is necessary when clinicians treat patients with alcoholic liver failure with a liver support system.

Seroepidemiological study on hepatitis delta virus infection in the Irabu Islands, Okinawa, Japan

A seroepidemiological study was performed to clarify the prevalence of hepatitis delta virus (HDV) infection among the general population in the Irabu islands, Okinawa, Japan. Of 2028 healthy people examined who had received their annual health check‐up in 1994–95, 195 (9.6%) were positive for hepatitis B surface antigen (HBsAg). Of these 195 HBsAg‐positive individuals, 46 (23.6%) showed a positive reaction for antibody to HDV (anti‐HDV). The positivity rate of anti‐HDV among HBsAg‐positive subjects tended to increase with age up to 50–59 years of age. The prevalence of anti‐HDV also varied among the seven districts in the islands (0–63.3%). None of the anti‐HDV‐positive subjects was included in the high risk group for parenterally transmitted diseases. The unusually high prevalence of anti‐HDV among HBsAg‐positive individuals, particularly in the older age groups, seemed to reflect the natural prevalence or previous HDV infection, rather than a current or imported infection of HDV. Although the great majority of HBsAg‐positive subjects with anti‐HDV were asymptomatic, abnormally high values of serum transaminases were more frequently seen in these subjects compared with HBsAg‐positive subjects without anti‐HDV.

A patient with primary biliary cirrhosis associated with autoimmune hemolytic anemia.

Abstract: Primary biliary cirrhosis is often associated with autoimmune conditions, such as thyroid disease, sicca complex, and rheumatoid arthritis. However, an association with autoimmune hemolytic anemia has rarely been reported. We present a case of primary biliary cirrhosis associated with warm type autoimmune hemolytic anemia, and we review prior reports.

Prevalence and clinical features of hepatitis delta virus infection in the Miyako Islands, Okinawa, Japan.

Abstract: The aims of this study were twofold: (1) to determine the prevalence and clinical features of hepatitis delta virus (HDV) infection among subjects positive for hepatitis B surface antigen (HBsAg) living in the Miyako Islands, Okinawa Prefecture, Japan, and (2) to clarify the relationship between HDV-RNA level and severity of HDV-related liver disease. One hundred and ninety-nine HBsAg-positive subjects (123 asymptomatic carriers [ASCs], 3 patients with acute hepatitis [AH], 50 patients with chronic hepatitis [CH], 15 patients with liver cirrhosis [LC], and 8 patients with hepatocellular carcinoma [HCC], were tested for antrbody to HDV (anti-HDV) by radioimmunoassay. Anti-HDV-positive individuals were examined to determine semi-quantified HDV-RNA level by polymerase chain reaction (PCR). The overall prevalence of anti-HDV among the 199 subjects was 21.1%. The positivity rate tended to increase with age or the severity of the underlying liver disease: anti-HDV-positive rates were 10.6% (13/123) in ASCs, 32.0% (16/50) in patients with CH, 40.0% (6/15) in patients with LC, and 87.5% (7/8) in patients with HCC. None of the patients with AH were positive for anti-HDV. There was no correlation between semi-quantified serum HDV-RNA levels and the severity of chronic liver disease in patients positive for anti-HDV. The present study showed the local spread of HDV infection in the Miyako Islands, Okinawa, Japan. Although the anti-HDV positivity rate tended to increase with the severity of the underlying liver disease, the severity of HDV-related liver disease did not correlate with the semi-quantified serum HDV-RNA level.

A rare association of primary biliary cirrhosis and pernicious anemia

12 and the presence of anti-parietal cell antibody and anti-intrinsic factor antibody. Pernicious anemia should be regarded as a possible complication of primary biliary cirrhosis.

Clinical features of patients with chronic liver disease associated with hepatitis C virus genotype 1a/I in Okinawa, Japan.

The clinical characteristics of chronic hepatitis C virus (HCV) carriers with HCV genotype 1a/I infection were investigated and compared with those of chronic HCV carriers infected with 1b/II, 2a/III, 2b/IV and the mixed type of infection. We found that 16 of 408 (3.9%) carriers had HCV genotype 1a infection, comprising four of 67 (6.0%) blood donors, 11 of 263 (4.2%) patients with chronic hepatitis and one of 39 (2.6%) patients with liver cirrhosis. Three of 408 subjects had a mixed infection of genotypes 1a/I and 1b/II. All carriers with genotype 1a (including those with the mixed infection) were of Japanese origin and all, except one who was born in Brazil, were born in Okinawa Prefecture. Nine of 14 patients infected with genotype 1a for whom medical records were obtained had a history suggestive of infection through blood exposure; six had had blood transfusions, one had tattoos, one is a nurse and one had a history of drug addiction. There were no haemophiliacs or other multitransfused patients in the genotype 1a group. Of 10 patients infected with genotype 1a who received interferon (IFN) therapy, four (40%) showed a complete response. Although the small number of patients infected with genotype 1a in the present study precluded statistical analysis of the response to IFN, the response in patients with genotype 1a was better than the response in those infected with genotype 1b and poorer than the response in those patients infected with genotype 2a/III or 2b/IV.

Epidemiology of primary biliary cirrhosis among women with elevated γ-glutamyl transpeptidase levels in Okinawa, Japan

We investigated the conditions among women who had an asymptomatic increase in serum gamma-glutamyl transpeptidase (gamma-GTP) levels, and the prevalence of primary biliary cirrhosis (PBC), in the general population. Among 4048 women who received their annual health check-up, 241 showed an elevated gamma-GTP level and were invited to participate in this study. Of the 241 women, 122 participated and were examined thoroughly, including for antimitochondrial antibody (AMA) and by using liver biopsy to make a clinical diagnosis. Six (4.9%) of the 122 women were AMA positive: five were diagnosed and one was suspected of having PBC. Another two women had the criteria of PBC despite being AMA negative. PBC was detected in 5.7% (95% confidence interval (CI), 1.6-9.9%) of asymptomatic women with raised gamma-GTP levels who were 6.0% of all 4048 women examined. The estimated prevalence of PBC in our area was 3400 per million women mainly over 40 years and 840 per million in the whole population. In 44% of women, the cause of chronic gamma-GTP elevation was unknown; they usually showed mild and non-specific histological change differing from their liver biochemical test results.