Tatsuya Aikawa

Hepatitis G infection in drug abusers with chronic hepatitis C.

To the Editor: The detection of hepatitis C virus (HCV) infection by enzyme immunoassay and molecular biologic techniques still leaves unidentified other hepatitis viruses that may be responsible f...

Simultaneous Detection of Immunoglobulin A (IgA) and IgM Antibodies against Hepatitis E Virus (HEV) Is Highly Specific for Diagnosis of Acute HEV Infection

ABSTRACT Serum samples collected from 68 patients (age, mean ± the standard deviation [SD], 56.3 ± 12.8 years) at admission who were subsequently molecularly diagnosed as having hepatitis E and from 2,781 individuals who were assumed not to have been recently infected with hepatitis E virus (HEV; negative controls; 52.9 ± 18.9 years), were tested for immunoglobulin M (IgM) and IgA classes of antibodies to HEV (anti-HEV) by in-house solid-phase enzyme immunoassay with recombinant open reading frame 2 protein expressed in the pupae of silkworm as the antigen probe. The 68 patients with hepatitis E had both anti-HEV IgM and anti-HEV IgA. Among the 2,781 controls, 16 (0.6%) had anti-HEV IgM alone and 4 (0.1%) had anti-HEV IgA alone: these IgA/IgM anti-HEV-positive individuals were not only negative for HEV RNA but lack IgG anti-HEV antibody as well (at least in most of the cases). Periodic serum samples obtained from 15 patients with hepatitis E were tested for HEV RNA, anti-HEV IgM, and anti-HEV IgA. Although HEV RNA was detectable in the serum until 7 to 40 (21.4 ± 9.7) days after disease onset, both IgM and IgA anti-HEV antibodies were detectable until 37, 55, or 62 days after disease onset in three patients and up through the end of the observation period (50 to 144 days) in 12 patients. These results indicate that detection of anti-HEV IgA alone or along with anti-HEV IgM is useful for serological diagnosis of hepatitis E with increased specificity and longer duration of positivity than that by RNA detection.

Obstruction of the Inferior Vena Cava in the Hepatic Portion and the Hepatic Veins

From the First Department of Internal Medicine, Tohoku University School of Medicine, Sendai, Japan. In 1845 Budd’ reported three cases of obstruction of the hepatic veins. In 1899, after studying the results of three of his own cases and seven cases from literature, Chiari‘-’ emphasized that obstruction of the hepatic veins due to obstructive phlebitis should be classified as a distinct disease. Following the report of three cases by Yamagiwa3 in 1906, additional cases were studied and reported in Japan. By recent progress of venous catheterization techniques, the authors could diagnose clinically obstruction of the hepatic veins and/or the inferior vena cava in the hepatic portion in eight patients. In Japan, obstruction of the hepatic veins is frequently associated with obstruction of the inferior vena cava in the hepatic portion, peculiar features of which

Fulminant hepatitis E in Japan.

To the Editor: Hepatitis E virus (HEV) is the leading cause of water-borne epidemics of hepatitis in many developing countries in Asia and Africa, where high mortality has been reported among infec...

Prolonged Fecal Shedding of Hepatitis E Virus (HEV) during Sporadic Acute Hepatitis E: Evaluation of Infectivity of HEV in Fecal Specimens in a Cell Culture System

ABSTRACT To investigate the duration of fecal shedding and changing loads of hepatitis E virus (HEV) in feces and serum from patients with acute HEV infection, HEV RNA was quantitated in periodic serum and fecal specimens obtained from 11 patients with sporadic acute hepatitis E. All 11 patients had detectable HEV RNA in serum at admission, with the highest viral load being 1.9 × 103 to 1.7 × 107 copies/ml, and HEV viremia lasted until days 17 to 48 (mean, 28.3) after the onset of hepatitis. Even at the initial examination on days 10 to 29 (mean, 17.6), the HEV load in fecal supernatant was less than 5.7 × 104 copies/ml for 10 of the 11 patients, while for the remaining patient (patient 1) it was markedly high, 2.0 × 107 copies/ml on day 22. In addition, although HEV RNA in fecal supernatant continued to be positive until days 14 to 33 (mean, 22.4) for patients 2 to 11, that for patient 1 was detectable even on day 121. HEVs in fecal specimens obtained on days 22, 24, 26, 28, and 30, but not day 121, from patient 1 grew efficiently in PLC/PRF/5 cells, reaching the highest titer of up to 107 copies/ml in culture medium on day 50 postinoculation. The HEV genome recovered from patient 1 had 29 unique nucleotides that were not seen in any of the 25 reported HEV isolates of the same genotype over the entire genome, with six amino acid substitutions in the ORF1 protein.

HLA DRB1 and DQB1 alleles and haplotypes influencing the progression of hepatitis C

Some HLA class II alleles and haplotypes were examined by restriction fragment length polymorphism of corresponding DNA fragments amplified by the polymerase chain reaction in 117 patients with chronic hepatitis C in Japan. The prevalence rates were compared between patients and 1216 controls and in 67 patients with liver cirrhosis, of whom 20 had hepatocellular carcinoma and 50 patients with chronic hepatitis who did not have cirrhosis or hepatocellular carcinoma. Notably, DRB1*0405 (49% [95% confidence range 38‐60%] vs. 26% [16‐40%]; P < 0.05, relative risk [rr] = 2.8) and DQB1*0401 (43% [33‐54%] vs. 22% [13‐34%]; P < 0.05, rr = 2.1) were detected more frequently in patients with cirrhosis than in those without cirrhosis. By contrast, DRB1*0901 (11% [6‐19%] vs. 28% [18‐40%]; P < 0.05; rr = 0.3) and DQB1*0303 (11% [6‐19%] vs. 36% [25‐49%]; P < 0.01; rr = 0.2) were detected less frequently in patients with cirrhosis than those without cirrhosis. Accordingly, the DRB1*0405‐DQB1*0401 haplotype was more common (43% [33‐54%] vs. 22% [13‐34%]; P < 0.05; rr = 2.7), while the DRB1*0901‐DQB1*0303 haplotype was less common (9% [4‐17%] vs. 28% [18‐40%]; P < 0.05; rr = 0.3) in patients with cirrhosis than in those without cirrhosis. These results suggest that there would be HLA class II alleles and haplotypes which may be associated with an accelerated or slower progression of chronic hepatitis C towards cirrhosis and eventually to hepatocellular carcinoma.

Identification of Indigenous Hepatitis E Virus from a Japanese Patient Who Contracted Sporadic Acute Hepatitis in 1982

Figure 1. Phylogenetic tree constructed by the neighbor-joining method and based on the partial nucleotide sequence (301 nt) of the open reading frame 2 region of 50 human and swine hepatitis E virus (HEV) isolates. The nucleotide sequences of 49 known human and swine HEV isolates were retrieved from GenBank/DDBJ/EMBL databases on 22 July 2002. The partial nucleotide sequence of HE-JO-1982 obtained in the present study is deposited under accession no. AB088418 and is boxed for visual clarity. All human and swine HEV strains of Japanese origin are indicated by boldface type. Bootstrap values 170% are indicated for the major nodes as a percentage of the data obtained from 1000 resamplings [9]. Identification of Indigenous Hepatitis E Virus from a Japanese Patient Who Contracted Sporadic Acute Hepatitis in 1982

The pharmacokinetics of glycyrrhizin and its restorative effect on hepatic function in patients with chronic hepatitis and in chronically carbon-tetrachloride-intoxicated rats

The relationships between the pharmacokinetic behaviour of glycyrrhizin and its restorative effect for hepatic function were investigated in patients with chronic hepatitis and in rats chronically treated with carbon tetrachloride (CCl4‐treated rats). In patients, the restorative effects in plasma aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activities were 62·2±7·4 and 64·4±7·5%, respectively, after daily 80 mg intravenous (i.v.) doses of glycyrrhizin for 2 weeks, and 63·1±19·1 and 68·7±15·2% after 120 mg doses. The present work suggests that the threshold plasma glycyrrhizin concentration for sufficient effect is near 5 μg mL−1. In rats, the total body clearance (Cltot) for glycyrrhizin in the CCl4‐treated rats after i.v. administration of glycyrrhizin (5 mg kg−1 dose) was three‐tenths of that of the control, and the t1/2 for glycyrrhizin was 3·4‐fold longer than that of the control. A good correlation was observed between Cltot and AST (r=−0·838) or ALT (r=−0·873) activity in both rats. When glycyrrhizin was administered intraperitoneally (i.p.) three times a week for 2 weeks, both the AST and ALT activities in the CCl4‐treated rats showed a greater improvement than for a 10 mg kg−1 dose. Furthermore, the finding on the threshold plasma concentration in patients as above was also supported from the results of the experiments in rats.

Interferon-α2a for chronic hepatitis B with e antigen or antibody: comparable antiviral effects on wild-type virus and precore mutant

Summary. Recombinant interferon‐α2a (IFN‐α2a) in a total dose of 702 MU was given to 31 patients: nine with wild‐type hepatitis B virus (HBV) and hepatitis B e antigen (HBeAg) (A); four with HBeAg and a mixed infection with wild‐type HBV and precore mutants (B); 11 with antibody to HBeAg (HBeAb) and a mixed infection (C); and seven with HBeAb and precore mutants alone (D). HBV DNA was not cleared in any patient in groups A and B. By contrast, in patients with HBeAb, HBV DNA was ultimately lost in four patients in group C, as well as in 10 patients in group D. Thus, patients with HBeAb and infected with precore mutants alone (D) lost serum HBV DNA more often than those with HBeAg and wild‐type HBV (A). Patients with low pre‐treatment levels of HBV DNA cleared virus more frequently, and the response of precore mutant to IFN was comparable with that of wild‐type HBV in patients who had a mixed infection. Based on these results, precore mutants do respond to IFN, and therefore, IFN is indicated in patients with HBeAb, especially those with low serum HBV DNA levels.

Response to Interferon-α2a in Patients with e Antigen-negative Chronic Hepatitis B

Sixty-eight consecutive patients with chronic hepatitis B received 702 million units of recombinant interferon-alpha 2a. Of the 24 patients negative for hepatitis B e antigen (HBeAg) in serum, the normalization of serum transaminase occurred in 14 (58%) at the completion of interferon therapy and in 13 (54%) at 12 months thereafter; it was normalized in 17 (39%) and 13 (30%), respectively, of the 44 HBeAg-positive patients. Of the HBeAg-negative patients, hepatitis B virus DNA was cleared from serum in six (25%) at the completion and in one (4%) at 12 months thereafter, in contrast to only one (2%, p < 0.05) and none of the HBeAg-positive patients, respectively. The 1896th nucleotide of G (G1896) for codon 28 for tryptophan or A (A1896) for the stop codon 28 in the precore region was determined by restriction fragment length polymorphism. The ten HBeAg-negative patients with A1896 only in the precore region had lower pretreatment levels of viral markers, which decreased more rapidly and extensively after interferon than in the 14 HBeAg-negative patients with a mixture of G1896 and A1896 or in the 44 HBeAg-positive patients. These results indicate that patients with HBeAg-negative chronic hepatitis B may respond better to interferon than HBeAg-positive patients, and that the precore mutant with the stop codon 28 may be sensitive to interferon.