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To elucidate the extent of genomic heterogeneity of human hepatitis A virus (HAV) strains and to characterize genotype III HAV strains over the entire genome, the full-length sequence of three subgenotype IIIA isolates (HA-JNG04-90F, HA-JNG08-92F, and HAJ95-8F) and one IIIB isolate (HAJ85-1F) was determined. The HA-JNG04-90F, HA-JNG08-92F, and HAJ95-8F genomes which comprised 7463 or 7464 nt excluding the poly(A) tail, were closest to a reported nearly entire sequence of a IIIA isolate (NOR-21) with identities of 94.4–97.8% over the entire ORF sequence, and the HAJ85-1 genome (7462 nt) to HA-JNG06-90F of IIIB with an identity of 98.6%. The phylogenetic trees constructed based on the complete ORF sequence or the 168-nt VP1/2A junction sequence and comparative analysis with reported HAV isolates suggested the presence of three distinct clusters within IIIA represented by HA-JNG04-90F, HA-JNG08-92F, and HAJ95-8F. The extreme 5′ end sequences of IIIA and IIIB were well-conserved, beginning with the sequence UUCAAGAGGG. A single base deletion of G at nt 20, which is involved in the formation of a small loop in domain I, was characteristic of both IIIA and IIIB. Conserved and divergent amino acid sequences as well as amino acids unique to genotype III, IIIA or IIIB were recognized.

Mongolia is highly endemic for hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections among apparently healthy adults. However, the age-specific prevalence of ongoing HBV, HCV, and HDV infections among children in Mongolia remains unknown. Therefore, samples obtained from a total of 655 apparently healthy children of 0.3-15 years of age (307 boys and 348 girls; age, mean +/- standard deviation [SD], 8.4 +/- 4.2 years) living in Mongolia, between October 2005 and January 2006, were tested for serological and molecular markers of HBV, HCV, and HDV infections. Although 88.7% of the 655 children studied were immunized against hepatitis B, 64 (9.8%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA and 13 (2.0%) for HDV RNA. Twenty-seven children (4.1%) had detectable HCV RNA. Collectively, 82 (12.5%) were viremic for one or more of these viruses, including eight children with dual viremia of HBV/HCV and one child with triple HBV/HCV/HDV viremia. When children without anti-HBc, anti-HCV and anti-HDV IgG (n = 510) served as a control, a history of hospitalization was significantly associated with HBV viremia (P < 0.0001), anti-HBc positivity (P < 0.0001), and HCV viremia (P = 0.0001). HBsAg mutation was found in 18 (31.6%) of the 57 children with viremia, including those at amino acid position 126, 127, 129, 131, 134, 143 or 144. There were no significant differences in the frequency of HBsAg mutation in relation to age, sex, and hepatitis B vaccination status of the children, suggesting that HBsAg mutation plays a limited role in failure of vaccination in Mongolia.

A 59-year-old man who had received chronic hemodialysis developed left occipital pain and hypoglossal nerve palsy. He was diagnosed as having skull base metastasis from renal cell carcinoma related to acquired cystic kidney. Retrospective analysis revealed the patient had had elevated serum C-reactive protein and alkaline phosphatase levels before the symptoms appeared. Radiotherapy to the skull base relieved the pain. Finally he died with generalized metastases. Serum interleukin-6 levels measured during admission had been elevated, and interleukin-6 mRNA was detected in the autopsy specimen of renal cell carcinoma. Interleukin-6 might be involved in the etiology of paraneoplastic signs.

Background: Little is known about the prevalence of hepatitis B virus (HBV) DNA and the genotype distribution among patients with liver diseases in Nepal, where obstruction of the hepatic portion of the inferior vena cava (IVCO) is common. The aim of the present paper was to assess the roles of HBV infection and IVCO in liver cirrhosis (LC) and hepatocellular carcinoma (HCC) in Nepal. Methods: Serum samples from 121 patients (89 male, 32 female; age, 55.0 ± 13.6 years) with or without IVCO consisting of 70 LC patients and 51 HCC patients in Nepal, were tested for HBV-DNA. Results: The HBV-DNA was detected in 68 patients (56%) including 20 hepatitis B surface antigen (HBsAg)-negative patients: 33 LC patients (47%) and 35 HCC patients (69%) had detectable HBV-DNA (P = 0.0303). Among the 89 patients with IVCO, HBV-DNA was detected in HCC patients significantly more frequently than in LC patients (80%vs 43%, P = 0.0005). The frequency of HBV viremia was significantly higher among HCC patients with IVCO than those without (80%vs 44%, P = 0.0236), and that of HBV viremia with IVCO was significantly higher among HCC patients than among LC patients (55%vs 27%, P = 0.0153). The HBV genotypes A and D were predominant, and genotype A was significantly more frequent among HCC patients than among LC patients (22%vs 6%, P = 0.0090). Among HCC patients, those with genotype A HBV were significantly younger than those with genotype D (43 ± 13 vs 57 ± 12 years, P = 0.0252). Conclusion: Hepatitis B virus alone (especially genotype A) or in concert with IVCO may be responsible for development of HCC in Nepal.

Although all eight genotypes of hepatitis B virus (HBV) strains are circulating in Japan, no cases of acute hepatitis with foreign HBV strains of genotype H have thus far been reported in Japan. Here, we report a 35-year-old Japanese patient with severe acute hepatitis who was domestically infected with genotype H HBV. On admission, he had a high HBV load of 1.0 x 10(9) copies/ml, elevated levels of total bilirubin (7.0 mg/dl) and alanine aminotransferase (3606 IU/l), and reduced prothrombin activity of 39.0%. The HB-JAIW05 isolate obtained in the present study was composed of 3215 nucleotides and had the highest similarity of 99.7% with the reported genotype H HBV isolate recovered from a Japanese blood donor. The HB-JAIW05 isolate had neither precore (A1896) nor core promoter (T1762/A1764) mutations. However, upon comparison with the consensus sequence of ten reported HBV isolates of the same genotype, the HB-JAIW05 isolate had 17 nucleotide substitutions including five missense mutations in the P gene, which may be related to vigorous replication of HBV in this case. He had no history of traveling abroad, but had had extramarital sexual contact with two Japanese women living in Iwate, Japan, 2 weeks and 2 months before the disease onset, respectively. Our results suggest that rare HBV genotypes such as H may be spreading in Japan via sexual contact. Further molecular epidemiological studies on HBV to clarify the exact changing profiles of de novo HBV infection in Japan in relation to genotype and genomic variability are warranted.

To compare the epidemiologic profiles of hepatitis A virus (HAV) and hepatitis E virus (HEV) infections in Japan, the prevalence of clinical or subclinical HAV and HEV infections was investigated serologically and molecularly among 128 consecutive patients (age, mean +/- standard deviation, 37.5 +/- 14.7 years) who contracted acute hepatitis between 1989 and 2005 in a city hospital, and among 416 hemodialysis patients (60.1 +/- 12.6 years) and 266 medical staff members (34.6 +/- 11.4 years) at the same hospital, using stored periodic serum samples collected since the start of hemodialysis or employment, respectively. Between 1989 and 1995, among 93 patients with acute hepatitis, 51 (54.8%) were diagnosed with hepatitis A and only one patient with hepatitis E. Between 1996 and 2005, however, among 35 patients, only 3 (8.6%) were diagnosed with hepatitis A and 2 (5.7%) with hepatitis E. Although subclinical HEV infection was recognized in four hemodialysis patients (one each in 1979, 1980, 1988, and 2003) and two medical staff members (1978 and 2003) in previous studies, none of the 191 hemodialysis patients who had been negative for anti-HAV at the start of hemodialysis contracted HAV infection during the observation period of 7.6 +/- 6.4 years. Only one (0.4%) of the 246 medical staff members who had been negative for anti-HAV at the start of employment acquired hepatitis A during the observation period of 7.9 +/- 8.0 years: none had subclinical HAV infection. Clinical or subclinical HEV infection has occurred rarely during the last three decades, while HAV infection has markedly decreased at least since 1996.

One hundred ten consecutive patients (60 males and 50 females; age, mean +/- standard deviation [SD], 22.6 +/- 6.4 years; range 16-48 years) who were clinically diagnosed with sporadic acute hepatitis between December 2004 and January 2005 in Ulaanbaatar, Mongolia, were studied. IgM antibodies to hepatitis A virus were detected in 18 patients (16.4%), IgM antibodies to hepatitis B core (anti-HBc IgM) in 38 patients (34.5%) including two patients with concurrent hepatitis delta virus (HDV) infection, and hepatitis C virus RNA in nine patients (8.2%). There were 30 hepatitis B virus (HBV) carriers who had detectable hepatitis B surface antigen and antibodies to HDV but were negative for anti-HBc IgM, suggesting that they acquired type D acute hepatitis due to superinfection of HDV on a background of chronic HBV infection. None had IgM antibodies to hepatitis E virus (HEV). Consequently, 16.4, 32.7, 6.4, 1.8, and 27.3% of the patients were diagnosed as having acute hepatitis of type A, B, C, type B + D (HBV/HDV coinfection), and type D (superinfection of HDV), respectively. The cause of hepatitis was not known in the remaining 17 patients (15.5%). All 18 HAV isolates were genotyped as IA, all 9 HCV isolates were genotyped as 1b, and all 32 HDV isolates were classified into genotype I. The distribution of HBV genotypes among the 67 HBV isolates was A (1.5%, n = 1) and D (98.5%, n = 66). The present study indicates that de novo infections of HAV, HBV, HCV, and HDV are prevalent among young adults in Mongolia.

Mongolia is known for its high endemicity for hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) infections among apparently healthy individuals. However, there are little or no data on the prevalence and genotype distribution of HBV, HCV, and HDV among patients with chronic liver disease in Mongolia. Therefore, serum samples obtained in 2004 from 207 patients (age, mean+/-standard deviation, 51.0+/-11.9 years) including those with chronic hepatitis (n=90), liver cirrhosis (n=41), and hepatocellular carcinoma (n=76) were tested for serological and molecular markers of HBV, HCV, and HDV infections. Of the 207 patients, 144 (69.6%), 106 (51.2%), and 117 (56.5%) tested positive for hepatitis B surface antigen (HBsAg) and/or HBV DNA, HCV RNA, and HDV RNA, respectively. Collectively, 172 patients (83.1%) were viremic for one or more of these viruses, including dual viremia of HBV/HDV (26.6%) or HBV/HCV (7.7%) and triple HBV/HCV/HDV viremia (30.0%). Of note, triple ongoing infection was significantly more frequent among patients with hepatocellular carcinoma than among those with chronic hepatitis (63.2% vs. 14.4%, P