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ABSTRACT: Hepatitis E virus (HEV) infection has previously been reported in wild mongooses on Okinawa Island; to date however, only one HEV RNA sequence has been identified in a mongoose. Hence, this study was performed to detect HEV RNA in 209 wild mongooses on Okinawa Island. Six (2.9%) samples tested positive for HEV RNA. Phylogenetic analysis revealed that 6 HEV RNAs belonged to genotype 3 and were classified into groups A and B. In group B, mongoose-derived HEV sequences were very similar to mongoose HEV previously detected on Okinawa Island, as well as to those of a pig. This investigation emphasized the possibility that the mongoose is a reservoir animal for HEV on Okinawa Island.
Journal of Veterinary Medical Science 07/2012; · 0.85 Impact Factor
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ABSTRACT: Genetic recombination plays a significant role in the survival and evolution of hepatitis C virus (HCV), but methodological limitations have hindered the exploration of genetic recombination. HCV serotypes were evaluated in 104 patients with chronic hepatitis C when they initially presented in hospitals. Subsequently, HCV genotypes were analyzed using primers for core gene and NS5B gene. Near-complete nucleotide sequences of eight HCV isolates from two suspected patients with 2b/1b recombinant HCV were analyzed by amplification of nine overlapping regions of HCV-specific oligonucleotide primers at different time points: (i) at the first admission; (ii) before and (iii) after interferon therapy; and (iv) after development of hepatocellular carcinoma. The nucleotide sequence of eight HCV isolates obtained was 9,321-9,471 nucleotides in length, comprising a single ORF (polyprotein of 3,014 amino acids.) and segregated into discordant genotypes of 2b and 1b HCV with a recombination junction in NS2. This study highlights the need for more precise characterization of HCV in clinical samples where there is a discrepancy between immunoassays and sequencing. It also demonstrates the circulation of novel inter-genotypic recombinant HCV in Japan, because the cross over point of 2b/1b recombinant HCV in eight clinical isolates of these two patients differed from previously reported HCV recombinant from the Philippines and Japan.
Journal of Medical Virology 07/2012; 84(7):1018-24. · 2.82 Impact Factor
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Kencho Miyashita,
Jong-Hon Kang,
Akiyoshi Saga,
Kazuaki Takahashi,
Tsuyoshi Shimamura,
Atsushi Yasumoto,
Hiraku Fukushima,
Susumu Sogabe,
Kouhei Konishi,
Takumi Uchida,
Akira Fujinaga,
Takeshi Matsui,
Yasuo Sakurai,
Kunihiko Tsuji,
Hiroyuki Maguchi,
Masahiko Taniguchi,
Natsumi Abe,
Sheikh Mohammad Fazle Akbar,
Masahiro Arai, Shunji Mishiro
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ABSTRACT: Aim: In developed countries including Japan, the transmission route of indigenous hepatitis E virus (HEV) infection is obscure. Accordingly, public health implications of indigenous HEV infection have not been well addressed. The aim of this study was to clarify the route of transmission of a small outbreak of acute hepatitis E and assess the public health implications of indigenous zoonotic HEV transmission. Methods: Three patients with non-A, B and C acute hepatitis, two of whom presented in a critical condition, were assessed for HEV infection using polymerase chain reaction and their route of infection; the genome sequences of the infecting HEV were also analyzed. A phylogenetic tree based on the full, or near full, HEV RNA sequences were constructed by neighbor-joining method. Results: All three patients ingested grilled pork meat and entrails at the same barbecue restaurant in Abashiri, Hokkaido, Japan. When comparing partial to entire, or nearly entire, nucleotide sequences of HEV detected in these patients, they were 99.9-100% identical to each other. These genotype 4 isolates had great resemblance to the genome sequences of the isolates from the mini-outbreak in 2004 in Kitami, a city adjacent to Abashiri. These Kitami/Abashiri strains were segregated into a single cluster on the phylogenetic tree of HEV genotype 4 indigenous to Japan. Conclusion: Indigenous HEV transmission via a zoonotic food-borne route has been demonstrated in Kitami and Abashiri via pork meat and entrails contaminated with virulent HEV strains. Because a similar outbreak can recur in the future, infection sources and distribution routes should be clarified rapidly for public health.
Hepatology Research 03/2012; 42(9):870-8. · 2.20 Impact Factor
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Tatsunori Nakano,
Kazuaki Takahashi,
Oliver G Pybus,
Naoaki Hashimoto,
Hideaki Kato,
Hiroshi Okano,
Makoto Kobayashi,
Naoki Fujita,
Katsuya Shiraki,
Yoshiyuki Takei,
Minoru Ayada,
Masahiro Arai,
Hiroaki Okamoto, Shunji Mishiro
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ABSTRACT: Since previous studies have investigated the population dynamics of Japan-indigenous genotype 3 hepatitis E virus (HEV) using virus sequences, more nucleotide sequences have been determined, and new techniques have been developed for such analysis.
To prevent future hepatitis E epidemic in Japan, this study aimed to elucidate the cause of past HEV expansion.
The epidemic history of Japan-indigenous genotype 3 HEV was determined using the coalescent analysis framework. Bayesian skyline plot (BSP) and Bayesian estimate of phylogeny with relaxed molecular clock models were calculated using Markov chain Monte Carlo sampling.
Japan-indigenous strains consist of New World strains (subtype 3a), Japanese strains (3b) and European strains (3e). The oldest lineage, 3b, appeared around 1929. Lineages 3a and 3e appeared around 1960. BSPs indicated similar radical population growth of the 3a and 3b lineages from 1960 to 1980.
Population dynamics of the three lineages shared some common characteristics, but had distinguishing features. The appearance of 3a and 3e lineages coincides with the increase of large-race pig importation from Europe and the USA after 1960. The epidemic phase of 3a and 3b strains from 1960 to 1980 could be related to increased opportunity for HEV infection arising from large-scale pig breeding since 1960. Our observations revealed new findings concerning the close relationship between the epidemic history of Japan-indigenous genotype 3 HEV and the improvement of the Japanese pig industry. Infection control in pig farms should be an effective method of preventing HEV infection in humans.
Liver international: official journal of the International Association for the Study of the Liver 12/2011; 32(4):675-88. · 3.82 Impact Factor
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Anis Khan,
Yasuhito Tanaka,
Fuat Kurbanov,
Abeer Elkady,
Zaigham Abbas,
Zahid Azam,
Amna Subhan,
Sajjad Raza,
Sajjad Razza,
Saeed Hamid,
Wasim Jafri,
James Shih,
Ningshao Xia,
Kazuaki Takahashi, Shunji Mishiro,
Masashi Mizokami
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ABSTRACT: Hepatitis E is a classic water-borne disease in developing countries. Detection of anti-HEV IgM and IgG antibodies, in addition to HEV RNA are useful epidemiological markers in diagnosis of hepatitis E. This study was conducted to investigate an outbreak of acute viral hepatitis in South-Pakistan. Anti-HEV IgM and IgG were assessed comparatively with serological kits manufactured by Abbott, Cosmic, TGH, and Wantai, selecting HEV RNA as reference assay. Molecular evolutionary analysis was performed by phylogeny and HEV spread time analysis by Bayesian Coalescent Theory approach. Of the 89 patients, 24 (26.9%) did not have acute hepatitis viral marker. Of the remaining 65 cases, 4 (6.1%) were positive for anti-HAV IgM, one (1.5%) for anti-HBc IgM, 2 (3%) for HCV, 53 (81.5%) for anti-HEV IgM, and 5 (7.7%) were hepatitis-negative. The Wantai test was 100% sensitive and specific followed by Cosmic (98.1% and 100%), TGH (98.1% and 97.2%) and Abbott (79.2% and 83.3%). Two HEV variant strains were detected by phylogeny responsible for this acute hepatitis outbreak. Estimates on demographic history of HEV showed that HEV in Pakistan has remained at a steady nonexpanding phase from around 1970 to the year 2005, in which it expanded explosively with the emergence of new HEV variants. In conclusion, the limited sensitivity of available assay (Abbott anti-HEV EIA) may be a concern in HEV diagnosis in Pakistan. This study cautions that the dissemination of the variant strains to other areas of Pakistan may lead to explosive HEV outbreaks.
Journal of Medical Virology 04/2011; 83(4):622-9. · 2.82 Impact Factor
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ABSTRACT: The treatment of individuals infected with hepatitis B virus (HBV) is a complex issue in practical settings, despite the explosion of new and effective antiviral agents.
To assess the scope and limitations of ongoing treatment guidelines against HBV from a global perspective.
Present therapeutic guidelines against HBV have been discussed with emphasis on their value in developing countries that harbor about 90% of the total number of global patients who are infected with HBV.
Treatment of HBV-infected patients should be appropriately followed up and healthcare delivery systems should be able to combat treatment-induced adverse side effects. Current therapeutic guidelines should be optimized based on the socio-economic conditions of developing countries.
Expert Opinion on Pharmacotherapy 08/2009; 10(10):1605-14. · 3.20 Impact Factor
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Kazuaki Takahashi,
Hiroaki Okamoto,
Natsumi Abe,
Manri Kawakami,
Hiroyuki Matsuda,
Satoshi Mochida,
Hiroshi Sakugawa,
Yoshiki Suginoshita,
Seishiro Watanabe,
Kazuhide Yamamoto,
Yuzo Miyakawa, Shunji Mishiro
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ABSTRACT: Hepatitis E virus (HEV) genotype 3, which usually causes asymptomatic infection in Japan, induced severe hepatitis in 8 patients. To better understand genetic features of HEV associated with increased virulence, we determined the complete or near-complete nucleotide sequences of HEV from these 8 patients and from 5 swine infected with genotype 3 strain swJ19. Phylogenetic analysis showed that the isolates from the 8 patients and the 5 swine grouped separately from the other genotype 3 isolates to create a unique cluster, designated JIO. The human JIO-related viruses encoded 18 amino acids different from those of the other HEV genotype 3 strains. One substitution common to almost all human HEV strains in the JIO cluster was located in the helicase domain (V239A) and may be associated with increased virulence. A zoonotic origin of JIO-related viruses is suspected because the isolates from the 5 swine also possessed the signature V239A substitution in helicase.
Emerging Infectious Diseases 06/2009; 15(5):704-9. · 6.79 Impact Factor
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Miyuki Taniguchi,
Soo Ryang Kim, Shunji Mishiro,
Kazuaki Takahashi,
Myung Hee Shin,
Haesun Yun,
Man Suk Park,
Zhong Min Li,
Mi Kyung Kim,
Jinnv Fang,
Yoshitake Hayashi
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ABSTRACT: The seroprevalence of hepatitis E virus (HEV) infection in Northeastern Asia is unknown. This study was conducted to gain insight into the epidemiology of HEV that has been obscure in Northeastern China, South Korea and Japan.
A total of 1500 samples of serum were collected (300 each) from 5 groups of inhabitants over 40 years of age (Korean Chinese, indigenous Chinese, South Koreans, Koreans living in Japan, and indigenous Japanese) and screened for antibodies to HEV by the antigen-antibody-antigen sandwich Enzyme Linked Immunosorbent Assay system.
The positivity for HEV antibodies was 50.7% (95%CI: 45.0-56.3) in Korean Chinese, 47.7% (95%CI: 42.1-53.3) in indigenous Chinese, 34% (95%CI: 28.9-39.5) in South Koreans, 14.3% (95%CI: 10.8-18.8) in Koreans living in Japan, and 6.0% (95%CI: 3.8-9.3) in indigenous Japanese.
This result emphasizes that HEV is endemic in Northeastern Asia and tends to accumulate in developing countries. Further studies are needed to elucidate the genotype of HEV circulating in these areas and its transmission route-water-borne outbreaks, smaller outbreaks or sporadic forms attributed to zoonosis-with reference to past epidemics, food culture, and sanitary conditions.
The Journal of infection 03/2009; 58(3):232-7. · 4.13 Impact Factor
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Keiji Matsubayashi,
Jong-Hon Kang,
Hidekatsu Sakata,
Kazuaki Takahashi,
Motohiro Shindo,
Masaru Kato,
Shinichiro Sato,
Toshiaki Kato,
Hiroyuki Nishimori,
Kunihiko Tsuji,
Hiroyuki Maguchi,
Jun-Ichi Yoshida,
Hiroshi Maekubo, Shunji Mishiro,
Hisami Ikeda
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ABSTRACT: Five cases of transfusion transmission of hepatitis E virus (HEV) have been reported so far. The infection routes of the causative donors remain unclear, however. Also, the progress of virus markers in the entire course of HEV infection has not been well documented.
Nucleic acid testing was performed by real-time reverse transcription-polymerase chain reaction targeting the open reading frame 2 region of HEV. Full-length nucleotide sequences of HEV RNA were detected by direct sequencing.
Lookback study of a HEV-positive donor revealed that the platelets (PLTs) donated from him 2 weeks previously contained HEV RNA and were transfused to a patient. Thirteen relatives including the donor were ascertained to enjoy grilled pork meats together in a barbecue restaurant 23 days before the donation. Thereafter, his father died of fulminant hepatitis E and the other 6 members showed serum markers of HEV infection. In the recipient, HEV was detected in serum on Day 22 and reached the peak of 7.2 log copies per mL on Day 44 followed by the steep increase of alanine aminotransferase. Immunoglobulin G anti-HEV emerged on Day 67; subsequently, hepatitis was resolved. HEV RNA sequences from the donor and recipient were an identical, Japan-indigenous strain of genotype 4. HEV RNA was detectable up to Day 97 in serum, Day 85 in feces, and Day 71 in saliva.
A transfusion-transmitted hepatitis E case by blood from a donor infected via the zoonotic food-borne route and the progress of HEV markers in the entire course are demonstrated. Further studies are needed to clarify the epidemiology and the transfusion-related risks for HEV even in industrialized countries.
Transfusion 07/2008; 48(7):1368-75. · 3.22 Impact Factor
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ABSTRACT: We investigated the prevalence of antibody against hepatitis E virus (HEV) in Japanese patients with hemophilia.
IgG antibody against HEV was measured in serum of 80 Japanese patients with hemophilia by enzyme-linked immunosorbent assay. The prevalence of HEV antibody was compared with the reported prevalence of HEV antibody in Japanese patients undergoing hemodialysis and in Japanese healthy blood donors. Characteristics of patients and coinfection with other transfusion-transmissible viruses were compared in patients with and without HEV antibody.
Anti-HEV IgG antibody was detected in 13 of 80 patients (16.3%). The prevalence was far higher than that reported in Japanese blood donors (3.7%) and was higher than that in Japanese patients undergoing hemodialysis (9.4%). The patients with HEV antibody were significantly older than those without. HEV antibody was not detected in patients <20 years of age and in patients who had received only virus-inactivated coagulation factors. No association was observed between positivity for anti-HEV antibody and severity of hemophilia or coinfection with other parenterally transmissible viruses.
Our results suggest that the parenteral transmission of HEV may have occurred in Japanese patients with hemophilia via non-virus-inactivated coagulation factors.
Intervirology 01/2008; 51(1):21-5. · 2.34 Impact Factor
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ABSTRACT: Aims: Transmission of hepatitis E virus (HEV) from wild boar to humans has been reported, particularly from Japan. We attempted to clarify this issue. Methods: We assessed the IgG class antibodies against HEV (anti-HEV) in serum samples taken from 406 boar living in the Ehime area of western Japan from 2001 to 2004, of which 392 were captured in the wild (wild-caught boar) and 14 had been kept in a breeding farm (bred boar). Results: Anti-HEV positive rate in the bred boar (10/14, 71.4%) was significantly higher than in the wild-caught boar (100/392, 25.5%) (P < 0.001). Of the 392 wild-caught boar, 12 (3.1%) were positive for HEV-RNA, 10 of which were then subjected to phylogenetic analyses by sequencing an 821-nt fragment within ORF1. All the 10 isolates segregated to genotype 3, and eight of them were mutually related to form a cluster. All the eight HEV isolates in this cluster were from the wild-caught boar living in one and the same habitat within the studied area, while the other two independent isolates were from different regions. Conclusion: HEV infection is endemic in wild boar in the Ehime area, and we should regard the wild boar as an important reservoir of HEV.
Hepatology Research 03/2007; 37(3):214-20. · 2.20 Impact Factor
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ABSTRACT: Aim: With advent of reverse-transcription (RT)/polymerase chain reaction (PCR) for detection of the hepatitis E viral genome, we carried out retrospective examinations. Methods: Serum samples collected from 68 patients diagnosed as viral hepatitis with unknown etiology were tested for viral markers of hepatitis virus. Results: Two of them were found positive for hepatitis E viral RNA. While the clinical course of one patient (patient 1) was typical as acute hepatitis E, another patient (patient 2) was persistently infected with HEV. Patient 2 was infected with the virus via blood transfusion during chemotherapy against T-cell lymphoma. The entire viral genome from the donor was identical with that from the serum of patient 2 obtained on day 170 after the transfusion of the implicated red blood cell (RBC) product, confirming the transmission of HEV by transfusion. The patient remained negative for anti-HEV antibodies for the follow-up period of six months, probably due to immune suppression by lymphoma and chemotherapy. Conclusion: We report here an unusual case of long-term HEV infection in a patient with T-cell lymphoma. Persistent infection with HEV was probably due to the absence of anti-HEV antibodies, which was caused by lymphoma and chemotherapy.
Hepatology Research 03/2007; 37(2):113-20. · 2.20 Impact Factor
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ABSTRACT: Stimulation of inducible nitric oxide synthase gene expression by Helicobacter pylori, with subsequent overproduction of nitric oxide, has been implicated in gastric carcinogenesis. We investigated whether inducible nitric oxide synthase promoter gene polymorphisms are associated with (a) inducible nitric oxide synthase mRNA expression in the gastric mucosa, and (b) the risk of gastric carcinoma.
The relationship between gastric inducible nitric oxide synthase mRNA expression and inducible nitric oxide synthase promoter polymorphisms (CCTTT repeat polymorphism and -2445 C-->G SNP) was examined in 74 H. pylori-infected patients with gastric cancer, peptic ulcer, or functional dyspepsia. In a case-control study the prevalence of the polymorphisms was examined in H. pylori-infected gastric carcinomas (n=77) and noncancerous controls (n=154).
Inducible nitric oxide synthase mRNA levels were significantly higher in long CCTTT repeat (either allele>11) carriers than in short ones (P=0.015). Multivariate regression analysis showed that inducible nitric oxide synthase mRNA expression was significantly linked to long CCTTT repeat and gastric cancer (P=0.026), but not to -2445 C-->G SNP and other parameters. The case-control study showed that long CCTTT repeat carriers had an increased risk of gastric cancer with an odds ratio of 2.0 (P=0.021). -2445 C-->G SNP was not associated with the risk.
Helicobacter pylori induces higher inducible nitric oxide synthase mRNA expression in carriers of long CCTTT repeats of inducible nitric oxide synthase promoter, and this polymorphism is associated with an increased risk of gastric carcinoma.
European Journal of Gastroenterology & Hepatology 02/2007; 19(2):139-45. · 1.76 Impact Factor
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ABSTRACT: Although the majority of hepatitis E virus (HEV) infections in Japan are 'domestic' due to the presence of indigenous strains, there are still 'imported' cases as well. Among 83 patients with non-A, non-B and non-C acute liver diseases admitted to Saitama Medical University Hospital, 7 (8.4%) were positive for serum HEV-RNA, of whom 2 had a recent history of traveling to China, one to Xian and another to Shanghai. We determined the full-genome sequences of HEV from these 2 patients (isolate names are JKO-ChiSai98c and JYI-ChiSai01c, genotype 4 in both) for phylogenetic analyses. Initially, when compared only to the 13 full-genome sequences of genotype 4 so far reported, our 2 isolates were thought to be novel strains because they showed a significant genetic difference from the sequences known to date. However, when we included a set of short sequences (150 nt) recently reported from China in the comparison, we found that our 2 isolates represent a subgroup of genotype 4, which seems to be restricted to eastern China. In conclusion, the 2 HEV isolates reported here could serve as full-genome prototypes for an eastern China-indigenous subgroup of the genotype 4 HEV.
Intervirology 02/2007; 50(3):181-9. · 2.34 Impact Factor
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ABSTRACT: The epidemiology of hepatitis B, C,E viruses (HBV, HCV, HEV) and human immunodeficiency virus(HIV) has been obscure in Indonesia, particularly remote areas.
We undertook serological surveys for HBV/HCV/HEV/HIV infections in the general population of Tahuna, the capital city of Sangihe-Talaud Archipelago,outlier in the northeastern part of Indonesia.
Of 581 sera collected in April 2005, 1.4% was reactive for HBsAg,0.2% for anti-HCV, and 5.9% for anti-HEV, but none for HIV. All the HBsAg-positive sera were also positive for DNA, the nucleotide sequence of which is segregated within subgenotype C5. Most of the preschool children were positive for anti-HBs as a result of an HB immunization initiated in 1997. The titer of anti-HCV in the only individual detected was very low, with a negative result of HCV RNA detection,suggesting a nonspecific reaction. Anti-HEV was significantly more frequent in those over 30 years of age than in the younger age group (24 vs. 1.9%, p ! 0.0001).
Thus, it seems that HCV and HIV have fortunately not made it as far as the Sangihe-Talaud Archipelago. Although HBV infection remains a major problem in adults (with the HBsAg-positive rate at 4.9%), HB immunization has begun to protect the younger generation.
Intervirology 02/2007; 50(6):408-11. · 2.34 Impact Factor
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ABSTRACT: In Japan, indigenous acute hepatitis E is not a rare disease, and is mainly caused by hepatitis E virus (HEV) genotypes 3 and 4. Whether there is a difference in clinical features between the two genotypes remains unclear. This study compares the clinical features of patients infected with the two. From January, 1994, to December, 2003, 9 infected with HEV genotype 3 and 27 patients with genotype 4 were enrolled. Patients with genotype 4 had significantly higher peak alanine aminotransferase levels (median 3430IU/L, interquartile range 1747-4763 versus 1052IU/L, 845-2707; p=0.01). The lowest prothrombin time was lower in the genotype 4 group (61%, 42-77 versus 84%, 70-96; p=0.05). In our series, patients with genotype 4 had longer median duration of hospital stay (26.5 days, 18-31 versus 18 days, 12-23.5; p=0.06). The patients with genotype 4 infection tended to have more severe clinical manifestations than those with genotype 3 infection.
Hepatology Research 01/2007; 36(4):301-7. · 2.20 Impact Factor
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Yasuhito Tanaka,
Kazuaki Takahashi,
Etsuro Orito,
Yoshiyasu Karino,
Jong-Hon Kang,
Kazuyuki Suzuki,
Atsushi Matsui,
Akiko Hori,
Hiroyuki Matsuda,
Hiroshi Sakugawa,
Yasuhiro Asahina,
Tsuneo Kitamura,
Masashi Mizokami, Shunji Mishiro
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ABSTRACT: The ancestor(s) of apparently Japan-indigenous strains of Hepatitis E virus (HEV) was probably of foreign origin, but it remains unclear when and from where it made inroads. In this study, 24 genotype 3 and 24 genotype 4 HEV strains recovered in Japan each showed a significant cluster, clearly distinct from those of foreign strains, in the phylogenetic tree constructed from an 821 nt RNA polymerase gene fragment. The evolutionary rate, approximately 0.8 x 10(-3) nucleotide substitutions per site per year, enabled tracing of the demographic history of HEV and suggested that the ancestors of Japan-indigenous HEV had made inroads around 1900, when several kinds of Yorkshire pig were imported from the UK to Japan. Interestingly, the evolutionary growth of genotype 3 in Japan has been slow since the 1920s, whereas genotype 4 has spread rapidly since the 1980s. In conclusion, these data suggest that the indigenization and spread of HEV in Japan were associated with the popularization of eating pork.
Journal of General Virology 05/2006; 87(Pt 4):949-54. · 3.36 Impact Factor
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ABSTRACT: Hepatitis E virus (HEV), a single-strand RNA virus, has been recovered not only from human beings but also from various species of animals. Here we report our results suggesting that mongoose should be added to the list of reservoir animals of HEV. Of 100 mongooses we examined in Okinawa, Japan, 21 were thought to be positive for anti-HEV antibodies, among which one was definitely positive for HEV RNA. Full-genome sequencing of the HEV isolate revealed that it segregates to a unique subgroup within genotype III. Interestingly, this mongoose strain was closely related to a swine isolate previously reported from Okinawa, implicating the possibility of interspecies transmission between these animals.
Hepatology Research 04/2006; 34(3):137-40. · 2.20 Impact Factor
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Masashi Naito,
Atsushi Matsui,
Mie Inao,
Sumiko Nagoshi,
Makoto Nagano,
Nobuko Ito,
Tohru Egashira,
Michie Hashimoto, Shunji Mishiro,
Satoshi Mochida,
Kenji Fujiwara
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ABSTRACT: The T-helper (Th)1 immune reaction is essential for the eradication of hepatitis C virus (HCV) during interferon (IFN) therapy in patients with chronic hepatitis C. Osteopontin is a cytokine crucial for the initiation of the Th1 response. Recently, we identified four single-nucleotide polymorphisms (SNPs) in the promoter region of the osteopontin gene (OPN), at nucleotide (nt) -155, -443, -616, and -1748, and suggested that the SNP at nt -443 was a marker reflecting hepatitis activity in patients with HCV. Therefore, we examined the possibility that SNPs in OPN were also markers predicting the therapeutic efficacy of IFN in patients with chronic hepatitis C.
Blood was collected from 77 patients with chronic hepatitis C who had received either IFN monotherapy or IFN-ribavirin combination therapy (IFN-based therapies). SNPs in OPN, MxA, MBL, and LMP7 were analyzed by Invader assay.
Promoter SNPs of OPN at nt -155, -616, and -1748 showed linkage disequilibrium at 100% to each other. Sustained virological response (SVR) was observed in 58% of all patients. The SVR rate was higher in patients with the G/G or G/A alleles in the OPN promoter SNP at nt -1748 than in those with A/A (85% vs 45%; P < 0.05). The SVR rate was also higher in patients with T/T at nt -443 than in those with C/C or C/T (86% vs 47%; P < 0.05). Such differences were particularly evident in patients with HCV genotype 1b who had a pretreatment viral load greater than 100 KIU/ml. All the patients who had G/G or G/A at nt -1748 and T/T at nt -443 obtained an SVR. On the other hand, there was no relationship between the efficacy of IFN-based therapies and SNPs in MxA, MBL, and LMP7, which had been shown to have association with the response to IFN monotherapies.
SNPs in the promoter region of OPN may be useful as a marker to predict the efficacy of IFN-based therapies in patients with chronic hepatitis C, and further investigation regarding their real significance is warranted in a large series of patients.
Journal of Gastroenterology 04/2005; 40(4):381-8. · 4.16 Impact Factor
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ABSTRACT: Except for hepatitis B virus (HBV), there have been few data on serological markers of hepatitis viruses such as hepatitis C virus (HCV) and E virus (HEV), and human immunodeficiency virus type-1 (HIV) in Bali, Indonesia. During 5 months from April to August 2003, sera were collected from 2,450 pregnant women at eight jurisdictions in Bali, and they were tested for markers of these viruses. Only one (0.04%) was positive for antibody to HCV, but none for antibody to HIV. Hepatitis B surface antigen (HBsAg) was detected in 46 (1.9%) at a prevalence significantly lower than that in 271 of the 10,526 (2.6%) pregnant women in Bali surveyed 10 years previously (P < 0.045). The prevalence of hepatitis B e antigen in pregnant women with HBsAg decreased, also, from 50% to 28% during the 10 years (P < 0.011). Antibody to HEV (anti-HEV) was examined in 819 pregnant women who had been randomly selected from the 2,450. The overall prevalence of anti-HEV was 18%, and there were substantial regional differences spanning from 5% at Tabanan district to 32% at Gianyar district. Furthermore, the prevalence of anti-HEV differed substantially by their religions. In the Sanglah area of Denpasar City, for instance, anti-HEV was detected in 20 of the 102 (20%) Hindus, significantly more frequently than in only 2 of the 101 (2.0%) Muslims (P < 0.001). Swine that are prohibited to Muslims, therefore, is likely to serve as a reservoir of HEV in Bali. In conclusion, HBV is decreasing, HCV and HIV have not prevailed, as yet, while HEV is endemic probably through zoonotic infection in Bali.
Journal of Medical Virology 04/2005; 75(4):499-503. · 2.82 Impact Factor
