Hepatitis C Virus Infection in a Japanese Leprosy Sanatorium for the Past 67 Years

ArticleinJournal of Medical Virology 82(4):556-61 · April 2010with19 Reads
Impact Factor: 2.35 · DOI: 10.1002/jmv.21612 · Source: PubMed

Oku-Komyo-En is one of the national leprosy sanatoria, located on a small island in Setouchi city, Okayama prefecture of Japan since 1938. Since autopsies were carried out routinely on almost all patients who had died in the sanatorium up to 1980, approximately 1,000 formalin-fixed autopsy tissue samples were available for analysis. When these samples were reviewed, the pathological data indicated a sharp rise in the death rate caused by cirrhosis of the liver and hepatocellular carcinoma (HCC) since 1960 and 1970, respectively. Hepatitis C virus (HCV) infection is a common cause of HCC in Japan. The presence of HCV RNA was demonstrated in paraffin sections prepared from the autopsied liver tissue fixed in formalin for a prolonged period of time, by employing nested RT-PCR using type-specific primers. The data showed that HCV RNA was detectable in samples of the liver archived as early as 1940, representing the liver tissues kept in formalin for up to 67 years. HCV genotypes 1b and 2a were found by RT-PCR at 85.7% and 14.3%, respectively, in patients with leprosy.

    • "Total RNA was extracted from dewaxed sections using RecoverAll Total Nucleic Acid Isolation kit (Applied Biosytems, Austin, TX, USA), according to the manufacturer's protocol, and stored at −80 ∘ C until use. Nested RT-PCR for HCV genotyping was performed, as described previously [24]. "
    [Show abstract] [Hide abstract] ABSTRACT: . In situ hybridization (ISH) with high sensitivity has been requested to demonstrate hepatitis C virus (HCV) RNA in formalin-fixed, paraffin-embedded (FFPE) sections of the liver. Methods . ISH employing a locked-nucleic-acid- (LNA-)modified oligonucleotide probe and biotin-free catalyzed signal amplification system (CSAII) was applied to HCV-RNA detection in the liver tissue. Nested reverse-transcription polymerase chain reaction (RT-PCR) was performed for HCV genotyping using total RNA extracted from FFPE sections. The target tissues included FFPE tissue sections of humanized livers in HCV-infected chimeric mice (HCV genotypes 1a, 1b, and 2a and noninfected) and of needle-biopsied livers from HCV-infected patients. Results . HCV-RNA was demonstrated with the ISH technique in HCV-infected liver tissues from both chimeric mice and 9 (82%) of 11 patients with HCV infection. The HCV signals were sensitive to RNase. Nested RT-PCR confirmed the genotype in 8 (73%) of 11 livers (type 1b: 6 lesions and type 2a: 2 lesions). HCV-RNA was not identified in chronic hepatitis B lesions, fatty liver, autoimmune hepatitis, and hepatocellular carcinoma. Conclusion . ISH using the LNA-modified oligonucleotide probe and CSAII was applicable to detecting HCV-RNA in routinely prepared FFPE liver specimens.
    Full-text · Article · Jun 2013
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    • "More recently , other investigators described a 2.6% prevalence of anti-HCV antibodies in 191 LPs in Central Brazil, but the study was limited by the low number of positive subjects , lack of a control group and the absence of a confirmatory test for HCV (Ramos et al. 2011). A study of autopsies from a Japanese sanatorium detected HCV RNA in liver samples collected since 1940 and found an increase in the prevalence of cirrhosis of the liver and hepatocellular carcinoma in the leprosy inpatients over time (Shiogama et al. 2010). Taken together, these data show that HCV coinfection should be evaluated at least in LPs who may be considered at higher risk like in-patients, LL cases and those living in endemic regions for HCV. "
    [Show abstract] [Hide abstract] ABSTRACT: Leprosy spectrum and outcome is associated with the host immune response against Mycobacterium leprae. The role of coinfections in leprosy patients may be related to a depression of cellular immunity or amplification of inflammatory responses. Leprosy remains endemic in several regions where human T cell lymphotrophic virus type 1 (HTLV-1), hepatitis B virus (HBV) or hepatitis C virus (HCV) are also endemic. We have evaluated the evidence for the possible role of these viruses in the clinical manifestations and outcomes of leprosy. HTLV-1, HBV and HCV are associated with leprosy in some regions and institutionalization is an important risk factor for these viral coinfections. Some studies show a higher prevalence of viral coinfection in lepromatous cases. Although HBV and HCV coinfection were associated with reversal reaction in one study, there is a lack of information about the consequences of viral coinfections in leprosy. It is not known whether clinical outcomes associated with leprosy, such as development of reactions or relapses could be attributed to a specific viral coinfection. Furthermore, whether the leprosy subtype may influence the progression of the viral coinfection is unknown. All of these important and intriguing questions await prospective studies to definitively establish the actual relationship between these entities.
    Full-text · Article · Dec 2012 · Memórias do Instituto Oswaldo Cruz
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    • "It is unknown if injured skin resulting from leprosy may facilitate the spread of bloodborne infectious agents. However, reports such as that by Shiogama et al. (2010) have indicated a progressive increase in the liver-related death rate among inpatients of a Japanese sanatorium and there was a high rate of detection of HCV RNA in liver specimens obtained by necropsy, suggesting that blood-borne hepatitis viruses may circulate at higher rates among these individuals. There are few studies assessing the prevalence of viral hepatitis among leprosy patients in Brazil, but none have been performed in MT (Ottati & Candeias 1979, Rosa et al. 1992, 1996). "
    [Show abstract] [Hide abstract] ABSTRACT: Leprosy and hepatitis B virus (HBV) are highly endemic in some regions of the state of Mato Grosso, in central Brazil. The association of leprosy with HBV and hepatitis C virus (HCV) was assessed using a seroprevalence study and 191 leprosy outpatients were included. Demographic data and the clinical classification of leprosy were recorded. Evidence of previous HBV infection was present in 53 patients (27.7%, 95% confidence interval: 21.9-34.5) and two (1%) were HBsAg positive. Five (2.6%) had antibodies to HCV. The prevalence of previous exposure to HBV was higher than expected for an adult population in central Brazil. In contrast, the prevalence of anti-HCV antibodies was not much higher regarding the age range of participants. HBV markers were associated with a higher number of sex partners and the use of injections without proper sterilisation of the syringes. The number of HBV carriers was small, suggesting that there was no increased likelihood of chronification among these patients.
    Preview · Article · Aug 2011 · Memórias do Instituto Oswaldo Cruz
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