Australia Antigen and Liver Function Tests Following Infectious Hepatitis—A Study of 111 Patients in Quest of Aids in Blood Donor Screening

An epidemic of infectious hepatitis involving 99 patients and employees of a state mental hospital revealed Australia antigen Au(1) to be absent from the blood of all but one of the subjects when tested at six weeks, three months, nine months and 12 to 18 months after onset of jaundice. The single patient with Au(1) at 12 months had no enzyme abnormality to indicate residual liver disease.If Au(1) is the virus of hepatitis these data would support the concept that persistent or long standing viremia is not a feature of epidemic hepatitis. Moreover, results of this study suggest that the Au(1) test should not be used to establish the absence of a past history of hepatitis in blood donors. These data do not establish the value of the Au(1) test in blood donors with active viremia, but do suggest that of 111 patients with recent hepatitis 1 percent had persistent antigenemia and 4 percent probably had circulating antigen antibody complexes and constituted a potential risk to recipients of their blood. The degree of risk to recipients from transfused blood of post-hepatitis patients without demonstrable Au(1) cannot be assessed.     

A filterable virus as a causative agent of epidemic hepatitis

Summary In four patients suffering from epidemic hepatitis we succeeded in isolating from the blood during the fever period and from the urine during the jaundice, a filterable virus, which is pathogenic to the guinea pig and which can be inoculated to this animal in different ways, but by preference intraperitoneally. Fever, which sometimes lasts only one day, is the only morbid symptom observed in guinea pigs.In these animals the virus can be shown in the organs and in the blood during the fever period; after that it is excreted with the urine during apparently a short period. The virus has been grown on the chorioallantois of the chick embryo so far during 20 passages. The virus is resistant to glycerol, drying and low temperatures, not to formaline and heating.In the livers of the guinea pigs focal changes (degeneration, dissociation, necrobiosis, yellow liver-atrophy) may be found. After dulling through the disease immunity occurs, whilst in the serum of recovered patients and guinea pigs neutralizing antibodies can be detected.     

The use of blood at a large Red Cross center; an evaluation of various aspects of utilization

During the past ten years over 1,000,000 pints of blood have been collected at the Los Angeles Regional Red Cross Blood Center. In addition to the progressive increase in the number of whole blood transfusions there has been a greater use of specific blood elements which results in purposeful and economical hemotherapy. With the increased use of blood there has also been a growing awareness of transfusion reactions and dangers. Serious transfusion complications reported have been due to bacterial contamination, to hemolytic reactions, to homologous serum jaundice, and to a mistake in cross-matching. Surgeons and anesthetists must pay strict attention to the use of blood since anesthesia masks severe hemolytic transfusion reactions. At present there is no way of eliminating the danger of the transmission of virus disease (infectious hepatitis and homologous serum jaundice) in blood transfusions.     

THE USE OF BLOOD AT A LARGE RED CROSS CENTER—An Evaluation of Various Aspects of Utilization

During the past ten years over 1,000,000 pints of blood have been collected at the Los Angeles Regional Red Cross Blood Center.In addition to the progressive increase in the number of whole blood transfusions there has been a greater use of specific blood elements which results in purposeful and economical hemotherapy.With the increased use of blood there has also been a growing awareness of transfusion reactions and dangers. Serious transfusion complications reported have been due to bacterial contamination, to hemolytic reactions, to homologous serum jaundice, and to a mistake in cross-matching.Surgeons and anesthetists must pay strict attention to the use of blood since anesthesia masks severe hemolytic transfusion reactions.At present there is no way of eliminating the danger of the transmission of virus disease (infectious hepatitis and homologous serum jaundice) in blood transfusions.     

戊型肝炎病毒研究新进展

戊型肝炎病毒(hepatitis E virus,HEV)是引起全球多地区大规模流行和散发病例的急性病毒性肝炎的病原体,发展中国家尤为突出;我国是戊型肝炎(hepatitis E,HE)流行的高发区.HE是一种人畜共患病,猪是人HEV病毒的主要储库,因而HE已成为一个全球性的的公共卫生问题.对HEV的病毒学和基因组特征、临床表征、流行病学、主要抗原表位以及HEV诊断试剂和疫苗研制的进展进行了综述.     

Detection of hepatitis B virus DNA in mononuclear blood cells.

The Southern transfer hybridisation technique was used to test mononuclear blood cells for hepatitis B virus DNA. Viral DNA sequences were detected in mononuclear cells of 10 out of 16 patients with hepatitis B virus infection and in none of 21 normal controls. Blood contamination was excluded by the absence of hepatitis B virus DNA in the corresponding serum samples in all cases. Free monomeric hepatitis B virus DNA was found in three patients positive for hepatitis Be antigen (HBeAg) and one positive for anti-HBe, and integrated hepatitis B virus DNA was present in four patients positive for anti-HBe. In two other patients the small size of the samples did not allow a distinction between free and integrated viral DNA. The state of the virus in the mononuclear cells seemed to correlate with the HBeAg or anti-HBe state, as has been noted in the liver. These results indicate that hepatitis B virus may infect mononuclear blood cells, thereby expanding the tissue specificity of this agent beyond the liver, as has been reported for pancreatic, kidney, and skin tissue. They also suggest that hepatitis B virus infection of mononuclear cells might be related to immunological abnormalities observed in carriers of the virus.     

De novo acute infection and reactivation of hepatitis B virus in established cirrhosis.

Five patients with cirrhosis proved by biopsy had clinical, biochemical, and serological evidence of an acute hepatitis B infection. In two the illness was fulminant and led to death. Only one patient completely recovered. Serological markers for the hepatitis B virus were absent before the onset of the acute illness in four patients, which suggested that a de novo infection had been acquired as a result of recent transfusions of blood or blood products. The fifth patient, who had Goodpasture''s syndrome, had antibody to the core of hepatitis B virus, indicating previous exposure to the virus; his acute hepatitis may have been related to immunosuppressive drug treatment, which may have reactivated a dormant virus infection. Thus an acute type B viral hepatitis due to either a de novo or a reactivated infection may be superimposed on cirrhosis.     

Coagulation factor therapy for hemophilia: relation to hepatitis B and to liver function.

Therapy with concentrated coagulation factors has greatly improved the management of hemophilia, but the consequence of repeated infusion of these blood products are unknown. Hepatic dysfunction is frequent in patients with hemophilia, and the use of these products may be responsible. The relation between liver function and both the frequency and type of therapy with coagulation factors was studied in a group of patients with hemophilia. Of the 36 patients studied, 75% were found to have antibody to hepatitis B surface antigen in their serum and 44% had high levels of serum glutamic oxaloacetic transaminase (SGOT). The infusion of concentrated coagulation factor more than once per year was significantly associated with the presence of antibody to hepatitis B surface antigen and with a high SGOT level. The patients treated with concentrates prepared from blood obtained from large donor pools were significantly more likely to have antibody to hepatitis B surface antigen in their serum but no more likely to have a high H-SGOT level than the patients treated exclusively with cryoprecipitate, plasma or whole blood. These findings suggest that in patients with hemophilia the frequency of coagulation factor treatment may be a more important determinant of hepatic dysfunction than the type of treatment.     

Hepatitis E virus infection in Europe: regional situation regarding laboratory diagnosis and epidemiology

Hepatitis E virus (HEV) was first identified in the excreta of an experimentally infected human volunteer and further confirmed by similar findings in clinical specimens from patients with acute jaundice disease different from hepatitis A and B. The HEV is a 27- to 34-nm spherical non-enveloped virus obviously represented by a single serotype; however, its final taxonomic definition remains to be established. Studies on molecular biology of this virus revealed some peculiar characteristics showing no homologies in its nucleotide sequence to any entries in the Genbank database. The HEV infection was experimentally transmitted to non-human primates producing a disease in many features similar to that occurring in humans. Recently cell lines persistently infected with the HEV have also been obtained. These studies provided valuable virus-specific reagents which were used in diagnostic tests. Currently immune electron microscopy, fluorescent antibody technique, latex agglutination, cDNA hybridization, and Western blotting are employed to prove the etiological involvement of HEV in suspected hepatitis cases; serological tests with synthetic substances analogous to HEV antigens are expected to be available soon. Reliable diagnostic procedures can be carried out in a number of laboratories with the locally produced reagents. The HEV infection is common in many hot climate countries being responsible for more than 50% of jaundice cases among young adults. The European region is considered to be free of natural foci of this infection, however, several sporadic cases of HEV disease were reported to occur in Europeans who developed jaundice shortly after returning from endemic areas. It is suspected that in the Mediterranean countries (Italy and Spain) the cases of HEV infection could be causatively related to the consumption of shell-fish cultivated in sewage-polluted waters.     

New mutation causing hereditary hepatitis in the laboratory rat

A new mutant causing hereditary hepatitis associated with severe jaundice has been discovered in the LEC strain of rats. Hepatitis appears suddenly in adult rats three to four months after birth. The clinical signs of hepatitis are characterized by severe jaundice, subcutaneous bleeding, oliguria, and loss of body weight. The affected rats showed a high lethality and histological changes of the liver with focal necrosis of enlarged hepatocytes without inflammatory cell response. Genetic tests indicate that at least a single autosomal recessive gene is responsible for the major cause of hepatitis. Furthermore, liver cancer appears in long survived rats after recovery from jaundice as well as a few asymptomatic rats without jaundice. The LEC rats thus provide an animal model useful for the basic and clinical studies of hepatitis and liver cancer, including their pathogenesis, prevention, and treatment.     

乙肝大蛋白检测在乙肝抗病毒治疗中价值的研究

目的探讨乙型肝炎病毒大蛋白(HBV-LP)在抗病毒治疗过程中的临床诊断价值。方法选取乙型肝炎患者1 000例为研究对象和100例健康体检者为对照组进行HBV-DNA、HBV-LP和ALT检验;然后筛选志愿者进行拉米夫定抗病毒治疗,在治疗前、治疗中和治疗后分别采集血清标本进行HBV-LP、HBV-DNA、ALT检验。结果在HBVM模式中,HBV-LP和HBV-DNA的阳性率分别为42.64%和43.91%(P>0.05)。HBV-LP阳性标本中HBV-DNA、HBeAg和ALT阳性符合率分别为96.27%、65.01%和98.55%,HBV-DNA和ALT优于HBeAg(P<0.05)。志愿者进行拉米夫定抗病毒治疗中HBV-LP与HBV-DNA均下降,HBV-DNA下降更快。结论 HBV-LP可以检测病毒复制、抗病毒疗效观察和反映肝损伤。     

A multiplexed protein microarray for the simultaneous serodiagnosis of human immunodeficiency virus/hepatitis C virus infection and typing of whole blood

All donor blood samples must be tested pretransfusion to determine the donor blood type. Standard testing protocols require that assays be performed for important bloodborne pathogens such as hepatitis C, syphilis, hepatitis B, and human immunodeficiency virus. We have demonstrated proof of the concept that a protein microarray can type whole blood and detect antibody to significant pathogens simultaneously from the same donor blood sample. The data collected demonstrate the ability of the array to accurately type blood samples while also detecting the presence of antibodies against both human immunodeficiency virus and hepatitis C virus. In conclusion, we have successfully developed a platform capable of typing human whole blood samples, while at the same time testing for the presence of antibodies specific for human immunodeficiency virus/hepatitis C virus. The major benefits of this system are its amenability to expansion with additional assays, for example, rhesus typing and syphilis and/or hepatitis B virus detection, and also the adaptability of the assay to higher-throughput analysis, currently 16 individual samples per slide, but readily expandable to a 96-well format.     

Clinico-pathological studies of LEC rats with hereditary hepatitis and hepatoma in the acute phase of hepatitis

The LEC rat, which suffers from hereditary hepatitis, was examined for elucidation of its clinicopathological characteristics during development of the acute phase of hepatitis by quantitative analyses of histological observations of the liver in combination with laboratory data on various serum enzymes. The progression of acute hepatitis in the LEC rat was observed to begin insidiously early in life, i.e., a few enlarged hepatocytes and Councilman bodies appeared at around 8 weeks of age without clinical signs. Furthermore, it was revealed that the acute phase of hepatitis started with a remarkable increase of Councilman bodies, large nuclei and hepatocytes in mitosis in the liver 3 to 4 weeks before the onset of fulminant hepatitis, which is characterized by the elevation of serum enzyme activities such as GOT, GPT and gamma-GTP, and the onset of jaundice. From those observations, three stages were proposed for the progression of acute hepatitis in the LEC rat.     

Idiopathic Neonatal Hepatitis: Discordance in Monozygotic Twins

Idiopathic neonatal hepatitis is the uncommon syndrome of prolonged obstructive jaundice associated with giant cell transformation in the liver and patent bile ducts. Either hepatitis virus or an inherited abnormality has been suggested as a likely pathogenic agent for the syndrome.Recent observation of discordance for idiopathic neonatal hepatitis in monozygotic twins is felt to be inconsistent with either an infectious or a simple genetic etiology. Immaturity of the hepatic parenchymal cell bilirubin excretory pathway is postulated as a cause of jaundice in some of these babies.     

Surveys of Respiratory Virus Antibodies in an Arctic Indian Population

A study was undertaken to determine the etiological agents responsible for epidemics in a small and relatively isolated Arctic community.Three serological surveys were carried out over a four-year period employing complement fixation tests. Clinical information from the resident nurse was also available.The results indicated that of the two clinical epidemics of “influenza” which occurred during the period of study one was due to influenza virus type A; the other was unidentified. However, influenza virus type B affected approximately 30% of the population at some time during a two-year period without being clinically recognized. An epidemic affecting mainly children, which was clinically considered to be whooping cough, was probably caused by an adenovirus. A mumps epidemic with a high attack rate for all age groups which had occurred a few months prior to the first survey was confirmed. Sendai virus and psittacosis virus are probably endemic in this community.     

Fatal hepatitis E viral infection in pregnant women in Ghana: a case series

ABSTRACT: BACKGROUND: Viral infections during pregnancy can pose serious threats to mother and fetus from the time of conception to the time of delivery. These lead to congenital defects, spontaneous abortion and even death. The definitive diagnosis and management of pregnancy-related viral infections may be challenging especially in less resourced countries. CASE PRESENTATION: We present clinical and laboratory responses to the diagnosis and management of three cases of fulminant hepatitis secondary to Hepatitis E viral infection in pregnancy.Case 1 was a 31-year-old Ghanaian woman who presented with a week's history of passing dark urine as well as yellowish discoloration of the eyes. She subsequently developed fulminant hepatitis secondary to Hepatitis E viral infection, spontaneously aborted at 24 weeks of gestation and later died.Case 2 was also a 31-year-old Ghanaian woman who was admitted with a four-day history of jaundice. She had low grade fever, but no history of abdominal pain, haematuria, pale stool or pruritus. She next developed fulminant hepatitis secondary to Hepatitis E viral infection. However, she did not miscarry but died at 28 weeks of gestation.Case 3 was a 17-year-old Ghanaian woman who was referred to the tertiary health facility on account of jaundice and anaemia. She had delivered a live male infant at maturity of 32 weeks but noticed she was jaundiced and had a presentation of active disease 3 days prior to delivery. The baby was icteric at birth and on evaluation, had elevated bilirubin (mixed type) with normal liver enzymes. Hepatitis E virus infection was confirmed in both mother and baby. However, the jaundice and the hepatomegaly resolved in mother and baby after 5 and 12 days respectively. CONCLUSION: To the best of our knowledge, these are the first documented cases of fatal fulminant hepatic failures resulting from HEV infection in Ghana.     

Hepatitis B virus DNA and e antigen in serum from blood donors in the United Kingdom positive for hepatitis B surface antigen.

Serum samples from 214 blood donors in the United Kingdom who were carriers of hepatitis B surface antigen (HBsAg) were examined for hepatitis B virus deoxyribonucleic acid (DNA) by DNA:DNA hybridisation and for hepatitis B e antigen (HBeAg) and its antibody. One fifth of the donors carried infectious virus in their circulation. The presence of hepatitis B virus DNA correlated well with that of HBeAg, although hepatitis B virus DNA was found in five serum samples that were negative for HBeAg. It is concluded that analysis of serum samples for hepatitis B virus DNA by hybridisation should be the method of choice for determining whether carriers of HBsAg are infectious.     

Prospective study of post-transfusion hepatitis after cardiac surgery in a British centre.

A series of 248 consecutive patients undergoing cardiac surgery were examined in a prospective study of post-transfusion hepatitis in a single British centre. Patients received a total of 1796 units of blood or blood products (mean blood transfusion 6.28 units per patient). During five to 30 days after operation 38 of the patients showed an increase in serum transaminase activities. There was no serological evidence for fresh infection by hepatitis A or B virus, cytomegalovirus, Epstein-Barr virus, or herpes virus in any of these patients. The increase in transaminase activities was unexplained and reached over 100 IU/l (normal less than 40 IU/l) in six patients. The incidence of acute short incubation post-transfusion non-A, non-B hepatitis was therefore thought to be 2.4%. These six patients had normal liver function six months after transfusion but a further two of the surviving 228 patients had raised serum transaminase activities at six months. In one of these, liver biopsy disclosed chronic persistent hepatitis; in the other, alcoholic liver disease was suspected. The incidence of significant chronic liver disease after blood transfusion possibly attributable to a non-A, non-B hepatitis agent was therefore only 0.4%.