Hepatitis C virus (HCV) infection causes chronic liver diseases and is a global public health problem. Detailed analyses of HCV have been hampered by the lack of viral culture systems. Subgenomic replicons of the JFH1 genotype 2a strain cloned from an individual with fulminant hepatitis replicate efficiently in cell culture. Here we show that the JFH1 genome replicates efficiently and supports secretion of viral particles after transfection into a human hepatoma cell line (Huh7). Particles have a density of about 1.15–1.17 g/ml and a spherical morphology with an average diameter of about 55 nm. Secreted virus is infectious for Huh7 cells and infectivity can be neutralized by CD81-specific antibodies and by immunoglobulins from chronically infected individuals. The cell culture–generated HCV is infectious for chimpanzee. This system provides a powerful tool for studying the viral life cycle and developing antiviral strategies.

Production of infectious hepatitis C virus in tissue culture from a cloned viral genome

Mortality, morbidity, and risk factors in China and its provinces, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017

https://aasldpubs.onlinelibrary.wiley.com/doi/pdf/10.1002/hep.26744

Expanded classification of hepatitis C virus into 7 genotypes and 67 subtypes: Updated criteria and genotype assignment web resource

Hepatitis E virus (HEV) is considered an agent responsible for acute hepatitis that does not progress to chronic hepatitis. We identified 14 cases of acute HEV infection in three patients receiving liver transplants, nine receiving kidney transplants, and two receiving kidney and pancreas transplants. All patients were positive for serum HEV RNA. Chronic hepatitis developed in eight patients, as confirmed by persistently elevated aminotransferase levels, serum HEV RNA, and histologic features of chronic hepatitis. The time from transplantation to diagnosis was significantly shorter and the total counts of lymphocytes and of CD2, CD3, and CD4 T cells were significantly lower in patients in whom chronic disease developed.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa0706992

Hepatitis E virus and chronic hepatitis in organ-transplant recipients.

https://www.thelancet.com/pdfs/journals/lancet/PIIS0140-6736(03)14025-1.pdf

Zoonotic transmission of hepatitis E virus from deer to human beings

To the Editor-As was reported in the Journal, by Takahashi et al. [ 1 ] as well as by the authors of a letter to the editor about Takahashi et al.'s article [2], hepatitis E virus (HEV) infection caused by genotypes III and IV seems to be cryptically endemic in Japan, with the transmission mode yet to be resolved. Zoonotic risks have been suggested for sporadic HEV infections, particularly in industrialized countries [3]. We hereby report our recent experience in Japan, which may support the zoonosis hypothesis. A 53-year-old man (patient A) was admitted to one of our hospitals for acute hepatitis on 12 March 2003. His hepatitis was a severe type, as indicated by the levels of total bilirubin (10.2 mg/dL) and prothrombin (only 17%). Despite the initial severity of the disease, he showed a rapid recovery, without developing fulminant hepatic failure. Convalescence serum obtained on 15 April was positive for both IgM and IgG classes of anti-HEV but was negative for HEV RNA. Acute-phase serum from this patient was not available. Later, to our surprise, it was revealed that, on the same day that patient A had been admitted, one of his friends (a 70year-old man; patient B) had been admitted to another hospital, for similarly severe hepatitis (total bilirubin, 17.1 mg/ dL; prothrombin, 40%). Patient B developed hepatic coma and died of fulminant hepatic failure on 13 April. Acute-phase serum obtained on 13 March was found, retrospectively, to be positive for HEV RNA. Determination of a 326-nt partial open-reading frame-1 sequence of his HEV RNA (accession no. AB114178) indicated that this isolate segregates to genotype IV During the 3 months preceding the onset of disease, neither patient A nor patient B had traveled to areas where HEV is endemic, but patient A mentioned that he and patient B had enjoyed eating uncooked boar liver together a total of 5 times from late January to early February. Among the patients' family members and friends, no one had eaten the boar liver and no one had contracted hepatitis. Chandler et al. [4] reported serological evidence suggesting boars and pigs as candidate animal reservoirs for HEV Although we could not prove that the uncooked boar liver was the source of the HEV infection (since it all had been eaten), it appears likely that this was the case.

/pdf/severe-hepatitis-e-virus-infection-after-ingestion-of-3k3pkygjbd.pdf

Kazuaki Takahashi

Papers

Zoonotic transmission of hepatitis E virus from deer to human beings

Severe Hepatitis E Virus Infection after Ingestion of Uncooked Liver from a Wild Boar

Complete or near-complete nucleotide sequences of hepatitis E virus genome recovered from a wild boar, a deer, and four patients who ate the deer.

Very high prevalence of TT virus (TTV) infection in general population of Japan revealed by a new set of PCR primers

Non-A, non-B hepatitis specific antibodies directed at host-derived epitope: implication for an autoimmune process