non-B Hepatitis Virus Research Articles

Alcoholic Liver Disease in Japan

From these discussions, it is apparent that: Alcoholic liver disease is increasing at a rapid rate in conjunction with an increase of annual gross and per capita consumption of alcohol. Alcoholic hepatitis and alcoholic hyaline are much less common in Japan compared to western countries. Alcoholic hepatic fibrosis and chronic hepatitis are the common types of alcoholic liver disease in Japan. Alcoholic hepatic fibrosis may be a pathological process or entity independent of fatty liver, alcoholic hepatitis, and alcoholic cirrhosis. It is not clear at the present time whether heavy alcohol consumption per se or non-A, non-B hepatitis virus is the cause of chronic hepatitis seen in HBsAg negative alcoholics.

Hepatitis virus non-A, non-B: The cause of a major public health problem in India

Serological studies of hepatitis viruses A and B were carried out on 362 patients with acute viral hepatitis, 130 with fulminant hepatitis, and 56 with subacute hepatitis, and on samples of serum from 230 subjects during epidemics of viral hepatitis. A diagnosis of non-A, non-B viral hepatitis was made when serological tests showed that anti-HAV IgM and anti-HBc IgM were absent. Hepatitis virus non-A, non-B was the causative agent responsible for 58% of cases with acute viral hepatitis, 58% with fulminant hepatitis, 87% with subacute hepatitis, and 66% with epidemic hepatitis. A considerable proportion of patients (6-32%) were infected with both hepatitis virus non-A, non-B and hepatitis virus B. Viral hepatitis non-A, non-B is probably transmitted by infection of drinking-water and is the principal cause of hepatitis in India.

Immune response to purified non-A, non-B hepatitis-related antigen demonstrated by leukocyte migration inhibition in patients recovering from the infection

Eight patients, convalescent from acute hepatitis, all negative for HBsAg, anti-HBc, anti-HA-IgM, anti-CMV and anti-EB, and all positive for non-A, non-B related antigen and/or antibody in at least one sample during the course of disease, were investigated. Their specific cell-mediated immunity was tested using the leukocyte migration inhibition test in presence of a previously described non-A, non-B related antigen. A control group consisted of ten individuals (two normal subjects, six patients recovering from acute hepatitis B and two with autoimmune chronic active hepatitis). Leukocyte migration was inhibited by the antigen in seven of the eight patients. The test was negative in all control subjects. It is thus demonstrated that after recovery, patients with non-A, non-B viral hepatitis develop a cellular immune response specific for purified non-A, non-B related antigen. The association between the described antigen and viral hepatitis non-A, non-B can now be established not only by immunoprecipitation, but also by a cellular test.

Hepatitis B virus, hepatitis non-A, non-B virus and hepatitis delta virus in lyophilized antihemophilic factor: relative sensitivity to heat.

Lyophilized plasma derivatives are more stable to heat than when they are in the liquid state. Commercial Factor VIII (antihemophilic factor) was seeded with a measured quantity of hepatitis B virus. The contaminated material was then lyophilized and subjected to heat of 60 degrees C for 30 hr. Chimpanzees were inoculated with the heat-treated antihemophilic factor or sham-treated antihemophilic factor that had been held at 4 degrees C. Surprisingly, hepatitis B virus survived the heating procedure with no apparent loss in titer: the incubation period to appearance of HBsAg was that expected for the challenge dose of virus. Even more surprising, one chimpanzee (the recipient of the unheated antihemophilic factor) also developed non-A, non-B hepatitis and two chimpanzees (recipients of the heated antihemophilic factor) also developed delta hepatitis. Neither of these agents was a contaminant of the hepatitis B virus challenge pool, since the purity of this hepatitis B virus pool was established previously in chimpanzees. Thus, both a non-A, non-B agent and the delta agent apparently contaminated the commercial antihemophilic factor. This is the first direct evidence for contamination of antihemophilic factor with the delta agent and confirms previous seroepidemiologic evidence for its presence in pooled plasma derivatives. Subsequent inactivation studies were performed with antihemophilic factor experimentally contaminated with the Hutchinson strain of non-A, non-B hepatitis virus. In these studies, heating at 60 degrees C for 30 hr in the dry state rendered antihemophilic factor free of detectable non-A, non-B hepatitis virus.

Industrial Toxins and Fulminant Hepatitis: Dr. Rakela replies

Exposure to industrial toxins was the only noteworthy feature in the history of 2 of our 34 patients with fulminant hepatitis. One patient had used 2,4-dichlorophenoxyacetic acid to spray dandelions in her garden approximately 1 week before the onset of symptoms. The other patient had been exposed to a window cleaner that contained toluene and trichloroethylene about 10 days before the onset of symptoms. At the time of the initial examination, this second patient had evidence of renal failure and pancytopenia attributed to bone marrow impairment. Other etiologic possibilities such as a non-A, non-B hepatitis virus infection could not be excluded. Industrial Toxins and Fulminant HepatitisMayo Clinic ProceedingsVol. 60Issue 9PreviewIn a review of the recent Mayo Clinic experience with fulminant hepatitis in the May 1985 issue of the Proceedings (pages 289 through 292), Rakela and associates noted that 2 of their 34 cases were caused by exposure to industrial toxins. This finding may be of importance. None of the implicated substances—toluene, trichloroethylene, and 2,4-dichlorophenoxyacetic acid (“2,4-D”)—has thus far been shown to cause fulminant hepatitis under the normal conditions of modern industrial operations. Full-Text PDF

Absence of detectable hepatitis B virus DNA in sera and liver of chimpanzees with non-A, non-B hepatitis.

The risk of hepatitis B infections has been reduced by screening of blood donors for hepatitis B surface antigen (HBsAg). However, recipients remain at significant risk of developing post-transfusion hepatitis. Studies have shown that non-A, non-B hepatitis virus(es) are responsible for the majority of post-transfusion hepatitis infections. In spite of many efforts, these non-A, non-B hepatitis viruses have not yet been identified. Epidemiological studies, however, suggest that non-A, non-B hepatitis shares many features with hepatitis B. Recently, Wands et al [1982] showed, in chimpanzees infected with non-A, non-B hepatitis agents, the presence of antigenemia or viremia by radioimmunoassay with monoclonal antibodies directed toward distinct determinants of HBsAg and by molecular hybridization analysis. They suggested that non-A, non-B hepatitis agents may be related, but distinct variant(s) of hepatitis B virus (HBV). In this study, five chimpanzees were inoculated with three different agents that have been shown to transmit non-A, non-B hepatitis. The following inocula were used (I) a factor VIII preparation kindly provided by D.W. Bradley, (II) acute phase serum from a chimpanzee infected with the F strain kindly provided by A.J. Zuckerman, and (III) a DS-antigen serum previously shown by us to transmit non-A, non-B hepatitis [Duermeyer et al, 1983]. All chimpanzees developed a rise in transaminase levels between 8 and 10 weeks after inoculation. None of the chimpanzees was positive for any markers of HBV infection. No evidence was obtained of infection with hepatitis A, cytomegalovirus, or Epstein-Barr virus. One chimpanzee developed chronic liver disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Retrospective investigation of transfusion-related non-A, non-B viral hepatitis associated with M2 antigen

A retrospective study of transfusion-related non-A, non-B viral hepatitis was conducted in seven patients. Findings showed that six recipients had been exposed to at least one unit of blood possessing a putative serological marker for non-A, non-B hepatitis, the M2 antigen or anti-M2IgM. The M2 markers were associated with non-A, non-B hepatitis that developed 3-7 weeks after transfusion. It sees increasingly probable that M2 markers may be useful for diagnosis and/or prevention of post-transfusion hepatitis.

Southwestern Internal Medicine Conference: The Current Status of Non-A, Non-B Viral Hepatitis

It is probable that two or more different viruses account for non-A, non-B hepatitis throughout the world, with a third agent causing epidemic hepatitis in India and neighboring countries. NANB virus(es) is the major cause of transfusion-associated hepatitis, and is responsible for roughly 20% of sporadic hepatitis cases. NANB postransfusion hepatitis progresses to chronic hepatitis in half or more of cases. This form of chronic hepatitis, while usually minimally symptomatic, causes progressive liver destruction and eventual cirrhosis in a significant proportion of cases. To date, the NANB virus(es) has not been specifically identified, either serologically or by electron microscopy. When developed, serologic assays will find their most immediate application in the identification of NANB virus carriers among blood donors, thereby being applied to the prevention of post-transfusion hepatitis. No specific therapy is available for NANB virus infection. Gamma globulin is of uncertain prophylactic efficacy.

Removal of non-A, non-B hepatitis virus from a concentrate of the coagulation factors II, VII, IX and X by hydrophobic interaction chromatography.

The efficacy of a chromatographic procedure based on hydrophobic interaction chromatography to remove non-A, non-B (NANB) infection from a concentrate of coagulation factors II, VII, IX and X (Preconativ, KabiVitrum AB) was evaluated in chimpanzees. For this purpose, NANB infective human plasma (H-strain) was deliberately added to a solution of Preconativ (45 IU factor IX:C/ml) to reach a titre of NANB virus of greater than or equal to 10(2) chimpanzee infectious doses (CID)/ml. The NANB-contaminated preparation was chromatographed on octanohydrazide-Sepharose 4B at a high salt concentration. Groups of 2 chimpanzees were each inoculated intravenously with 45 IU factor IX:C of Preconative before and after this virus adsorption chromatographic step. The experimental animals remained free of any serological and biochemical evidence of hepatitis during a 12-month follow-up period. One of the two control animals developed clear evidence of NANB hepatitis.

Fulminant Hepatitis: Mayo Clinic Experience With 34 Cases

From 1974 through 1982, fulminant hepatitis was diagnosed in 34 patients at our institution. Of these patients, only two survived (survival rate, 6%). This syndrome was caused by viruses (B and non-B hepatitis and herpes simplex) in 23 patients, hepatotoxic drug in 6, Wilson's disease (hepatolenticular degeneration) in 3, and industrial poisons in 2. Most of the patients died within 10 days after the onset of encephalopathy. The poor prognosis in our group of patients was probably related to the preponderance of older patients and cases caused by non-B hepatitis virus. In our patients, the clinical course was complicated by renal failure, ascites, bleeding, sepsis, pancreatitis, and seizures. The major cause of death was hepatic failure.

The agents of non-A, non-B viral hepatitis

Recent studies have provided physicochemical and electron microscopic evidence for the existence of two distinct agents of posttransfusion non-A, non-B (NANB) hepatitis. One of these agents is chloroform-resistant and is not associated with the formation of unique ultrastructural structures in infected liver. The other agent is CHCl 3-sensitive, induces the formation of characteristic hepatocyte cytoplasmic tubules, and interferes with concurrent HAV or HBV infection in experimentally inoculated chimpanzees. The tubule-forming agent (TFA) has also been shown to pass through an 80 nm capillary pore membrane filter, suggesting that it is a small enveloped (or lipid-containing) virus. The TFA can also be recovered from low titer (⩽ 10 5 infectious doses/ml) chronic-phase chimpanzee plasma by use of a multi-step purification procedure that assumes the agent is a small enveloped RNA virus with an approximate buoyant density of 1.24 g/cm 3 and a sedimentation coefficient of 200–280 S. The apparent lack of nucleic acid homology between the NANB-TFA and HBV further suggests that the NANB-TFA is either Togavirus-like or belongs to another or as yet undefined class of RNA or DNA virus.

Removal of Non-A, Non-B Hepatitis Virus from a Concentrate of the Coagulation Factors II, VII, IX and X by Hydrophobic Interaction Chromatography

Removal of Non-A, Non-B Hepatitis Virus from a Concentrate of the Coagulation Factors II, VII, IX and X by Hydrophobic Interaction Chromatography

Asian-african non-A, non-B fulminant viral hepatitis in france

Asian-african non-A, non-B fulminant viral hepatitis in france

Primary Hepatocellular Carcinoma After Chronic Non-A, Non-B Post-Transfusion Hepatitis

Excerpt Epidemiologic evidence of an association between hepatitis B virus and hepatocellular carcinoma is strong, but evidence of a similar association between non-A, non-B hepatitis virus infecti...

ISOLATION OF A VIRUS FROM CHIMPANZEE LIVER CELL CULTURES INOCULATED WITH SERA CONTAINING THE AGENT OF NON-A, NON-B HEPATITIS

A membrane-coated virus having a diameter of 85-90 nm and containing a 40-45 nm core was found to replicate in cell cultures derived from chimpanzee liver after inoculation of serum containing infective non-A, non-B (NANB) hepatitis viruses from two independent sources. Replication of this agent was not observed when the same cells were inoculated with a chloroform-extracted inoculum or were left uninoculated. Replication involves assembly of virus cores on tubular structures similar to those seen in liver cells of chimpanzees infected with most isolates of NANB virus.

A sero-epidemiologic study of a water-borne epidemic of viral hepatitis in Kolhapur City, India.

Between February and March 1981 an epidemic of hepatitis occurred in Kolhapur City, Maharashtra State, India. Approximately 1200 cases of jaundice were reported; more than 300 patients were hospitalized and three died. The epidemiological investigations showed a distinct concentration of cases in municipal ward E of the city. Investigations of the ward E water supply system disclosed gross contamination of raw water with sewage at source. The serological studies revealed that the aetiological agent responsible for this epidemic was neither hepatitis A virus nor hepatitis B virus but was likely to have been due to a non-A, non-B hepatitis virus.

Detection of non-A, non-B hepatitis antigen by immunocytochemical staining.

Liver tissue obtained from a chimpanzee during the acute phase of an experimental non-A, non-B (NANB) hepatitis virus infection was studied by a sensitive immunocytochemical staining procedure for the presence of NANB viral antigens. Initial investigations were conducted with a model system of hepatitis B virus (HBV) antigens for purposes of comparing two immunocytochemical staining methods. Of these two procedures, an immunoperoxidase procedure, utilizing an avidin-biotinylated enzyme complex, was at least 40-fold more sensitive than a conventional immunoperoxidase technique for the detection of HBV-specific tissue antigens. Utilization of the avidin-biotin-amplified immunoperoxidase staining procedure, in conjunction with four primary convalescent antisera obtained from NANB hepatitis-implicated donors, resulted in the observation of NANB virus-associated antigen in the cytoplasm of hepatocytes from an infected chimpanzee liver. These same human antisera were not reactive with a number of uninfected control cells nor with cells infected with HBV, hepatitis A virus, or cytomegalovirus. Preincubation of one of these convalescent NANB sera, or IgG derived thereof, with an acute-phase serum obtained from a NANB hepatitis virus-infected chimpanzee abolished the antibody reactivity. We conclude from these observations that selected convalescent sera from NANB hepatitis virus-infected patients contain low levels of antibody that specifically react with a cytoplasmic antigen associated with NANB virus-infected hepatocytes.

Inactivation of non-A, non-B virus infectivity by a beta propiolactone/ultraviolet irradiation treatment and Aerosil adsorption procedure used for preparation of a stabilized human serum.

Inoculation of chimpanzees revealed that starting material for the preparation of a pooled stabilized human serum preparation was contaminated with non-A, non-B hepatitis virus(es). This material was subjected to beta-propiolactone/ultraviolet irradiation treatment and adsorption with an insolubilized silicic acid under conditions employed for sterilization of the final product (Biseko, Biotest). The treated material did not transmit hepatitis to 2 inoculated chimpanzees. These animals were subsequently found to be susceptible to non-A, non-B infection by challenge with the untreated material. These findings demonstrate a non-A, non-B type hepatitis virus to be susceptible to inactivation by the methods employed for sterilization of this stabilized human serum preparation.

Strategies for detection of transfusion-transmitted viruses eluding identification by conventional serologic tests II. Detection of host DNA in human plasmas with elevated alanine aminotransferase

As a prelude to the development of nucleic acid probes specific for non-A, non-B hepatitis virus(es) (NANBV), plasmas with alanine aminotransferase levels ⩾ 110 IU were assayed for DNA by a radioimmunoassay. Approximately 50% of such plasmas are expected to contain NANBV. One-hundred and seventy-eight of 420 plasma samples tested (42.4%) contained sequestered DNA resistant to DNAse I. The DNA has a molecular weight of ≈ 0.8 to 1.4 × 10 6 daltons and hybridizes with a 32P-labeled human DNA probe. The DNA in plasma is mostly bound to IgM. The presence of host DNA will have to be taken into account in planning experiments aiming at the preparation of nucleic acid probes specific for NANBV using infected plasmas as source material. Such experiments will have to utilize recombinant DNA technology and will require the separation of bacterial colonies containing recombinant DNA with viral DNA sequences from colonies with human DNA inserts. The feasibility of this approach is demonstrated using plasma-containing hepatitis B virus.

Inactivation of Non-A, Non-B Virus Infectivity by a Beta Propiolactone/Ultraviolet Irradiation Treatment and Aerosil Adsorption Procedure Used for Preparation of a Stabilized Human Serum

Inoculation of chimpanzees revealed that starting material for the preparation of a pooled stabilized human serum preparation was contaminated with non-A, non-B hepatitis virus(es). This material was subjected to β-propiolactone/ultraviolet irradiation treatment and adsorption with an insolubilized silicic acid under conditions employed for sterilization of the final product (Biseko®, Biotest). The treated material did not transmit hepatitis to 2 inoculated chimpanzees. These animals were subsequently found to be susceptible to non-A, non-B infection by challenge with the untreated material. These findings demonstrate a non-A, non-B type hepatitis virus to be susceptible to inactivation by the methods employed for sterilization of this stabilized human serum preparation.