non-B Group Research Articles

Fulminant viral hepatitis: Indian experience

Thirty-six patients with fulminant viral hepatitis were studied. Enzyme immunoassay was used to detect the presence of HBsAg, IgM anti-HBc, and IgM anti-HAV. Non-A, non-B virus was the most common aetiological agent (61.1%) followed by hepatitis B virus (HBV; 30.6%) and hepatitis A virus (8.3%). Presence of IgM anti-HBc confirmed the diagnosis of HBV infection in three cases who were negative for HBsAg. Similarly, in one case who was positive for HBsAg, absence of IgM anti-HBc suggested superinfection with some other agent. Survival was significantly higher (P less than 0.01) in the hepatitis A virus (HAV) group (66.6%) compared with non-A, non-B (31.2%) and HBV groups (27.3%). Fever at the onset of illness was seen in all patients with HAV, 54.5% of patients with HBV and 38.88% of patients with non-A, non-B infection (P less than 0.01). The median time interval between the first symptom and the onset of encephalopathy was 16, 13 and 8 days in HAV, HBV and non-A, non-B groups, respectively, but this difference was statistically not significant (P greater than 0.05).

Non-A, non-B hepatitis; factors involved in progression to chronicity.

A cross-sectional, longitudinal study was undertaken on a group of acute non-A, non-B hepatitis patients, as well as on a control group of hepatitis B patients, in order to assess both the prevalence of the most important factors favoring infection, and the relevance of these factors in promoting evolution towards chronic liver disease. Exposures to unknown risk factors were present in 47.4% of acute non-A, non-B infections, followed by blood transfusions (17.9%), sporadic exposures (17.9%) and drug addiction (16.6%). Unknown as well as sporadic exposures showed a greater prevalence in control population if compared to non-A, non-B cases, while drug addiction was equally represented in the two groups, and blood transfusion nearly absent from control group. The risk of evolution to chronic liver disease was about 13 times greater in non-A, non-B group than in controls, with the greatest risk for drug addicts and the lowest for patients with unknown exposures. Among patients with known exposures, the lowest risk of chronic hepatitis was observed in post-transfusion and in sporadic cases, while the greatest was observed in drug addicts.

Epidemiological aspects of acute viral hepatitis in São Paulo, Brazil.

As few reports on the prevalence of each type of viral hepatitis have been published in our country, we studied 154 patients with acute viral hepatitis consecutively seen at the Liver Unit from November 1980 to November 1984. The frequency of hepatitis A, B and non-A, non-B was 52.6%, 27.3% and 20.1% respectively. Greater frequency in young people, previous contact with infected patients and ingestion of suspected foods were the predominant epidemiological features in the hepatitis A group. Hepatitis B was characterized by the parenteral, non-transfusional exposure, previous contact and a high occurence in health-care workers. A history of blood transfusion was a significant finding in the hepatitis non-A, non-B group. Finally, the routes of transmission were unknown in 30-40% of the three groups of patients.

Isoenzyme studies in human leukemia-lymphoma cell lines — I. Carboxylic esterase

The isoenzyme patterns of carboxylic esterase (E.C. 3.1.1.1) were studied in 74 proven human leukemia-lymphoma and 12 normal B-lymphoblastoid cell lines. These cell lines have been extensively phenotyped using poly- and monoclonal antibodies. Esterase isoenzymes were separated by isoelectric focusing and visualized by histo-cytochemical techniques. No leukemia-specific or (except for monocytes) blood cell type-specific isoenzyme or isoenzyme pattern could be detected. The monocytic element in some cell lines was characterized by a strong isoenzyme band which could be selectively and completely inhibited by sodium fluoride. The enzyme phenotypes were stably expressed in all subcultures of a given cell line and did not appear to have any cell cycle dependency. The leukemia-lymphoma cell lines have been subclassified into four major groups according to immunological parameters: T-cell, B-cell, myelomonocytic and non-T, non-B-cell. On the basis of immunological data the T-cell lines were assigned to five stages of differentiation. The number and staining intensity of the isoenzymes increased with differentiation of the T-cells parallelling the expression of immunological markers. The B-cell leukemia-lymphoma cell lines were divided into pre B-, B-, Burkitt lymphoma, multiple myeloma and hairy cell leukemia cell lines. Substantial variability among the isoenzyme patterns was detected ranging from immature profiles of pre B-cell lines to complete isoenzyme repertoires of multiple myeloma cell lines. No significant difference was seen between the isoenzymes of mature B-cell lines and normal B-lymphoblastoid cell lines. The most prominent feature seen in myelomonocytic cell lines was the monocytic band indicating a monocytic origin and separating the ‘monocytoid’ from the ‘pure myeloid’ cell lines. Considerable heterogeneity in the isoenzyme patterns was observed in the non-T, non-B cell groups which comprised erythroleukemia cell lines and cell lines arrested at a very early stage of lymphoid differentiation. These latter cell lines together with some T- and B-cell lines shared the common characteristics of positivity for cALLA, Tdt and Ia antigens and an immature, incomplete isoenzyme profile. The results support the notions of maturation arrest and normal gene expression in leukemic cell populations. Furthermore, the importance of biochemical studies as part of the multiple marker analysis could be demonstrated.

A study on anti-ATLA antibody in Nagano Prefecture.

A study was made on and-ATLA antibody among general inhabitants, those with hematologic disease and those with hepatic disease in Nagano Prefecture.Among 2, 299 inhabitants (990 males and 1, 309 females), anti-ATLA antibody was found to be positive in two males (0.1 %)The number of patients with hematologic disease was 155. Of them, malignant lymphoma accounted for 50 (T: 24.3 %, B: 37.8 %), acute leukemia 32 and other hematologic malignancy 28. No ATL was found among them. It was revealed that 56 of them underwent transfusion ranging from 2 to 346 units of blood, averaging at 49.7 units. The number of person whose anti-ATLA antibody was positive was one only, who was diagnosed as AML and was transfused 170 units.Of 42 patients with hepatic disease, HB virus-related liver disease (hepatitis, cirrhosis, hepatocellular carcinoma) accounted for 10, non-B group HBAg (-) for 18, alcoholic liver dysfunction 5 and other hepatic disorders 9. Three out of these 42 patients were found to be positive for anti-ATLA antibody, each three patients belonged to the “non-B” group (3/18, 16.6 %).The total number of positivist was thus six. Of them, five had a history of transfusion, and all five positivists excluding the one with AML were suffering from hepatic disease with HBAg (-).From the above, it was considered that in Nagano Prefecture, those whose anti-ATLA antibody was positive were conspicuously small in number, but main cause of the positivity was attributable to the transfusion. Most of the positivists were suffered from non-B hepatic disease with a history of transfusion, and the number of positivist was significantly greater even when compared with patients with hematologic disease with frequent transfusion. Accordingly, it is suggested that some of the hepatic diseases with HBAg (-) might be associated with HTLV.

Are the Causes and Presentation of Chronic Hepatitis Changing? An Analysis of 104 Cases Over 15 Years

We describe the features at presentation of 104 patients with biopsy-proven chronic hepatitis who presented in Brisbane in the period 1968-32. The mean period of follow-up was 59 months. Sex ratio (female : male) was 70 : 34 and the mean age was 37 years (range 3-83). Eighty-five (82 per cent) were born in Australia. Serological evidence of hepatitis B (HBV) infection was present in 24 (23 per cent). Analysis of the HBV marker positive and negative (non-B) groups revealed that the clinical and laboratory features of HBsAg positive chronic hepatitis were much less florid than those of non-B patients. However, the disturbances seen in hepatic histopathology were similar in severity, and the mortality in the HBsAg positive group exceeded that in the non-B group. The relative risk calculated on an actuarial basis was higher in HBsAg positive patients. In contrast to the experience of others, severe chronic active hepatitis remains an important problem in Brisbane but some features of the disease are altering. Several changes may be attributable to the increasing incidence of HBV-associated disease, and in addition, patients aged under 20 with non-B chronic hepatitis are now rarely seen. This is of interest in view of recent reports of decreased incidence of another disease of disordered immune response, rheumatoid arthritis.

Clinical and prognostic differences in fulminant hepatitis type A, B and non-A non-B.

In 73 patients with fulminant viral hepatitis, non-A non-B hepatitis (NANB) was most common (43.8%), with hepatitis type A (HAV) diagnosed in 31.5% and hepatitis type B (HBV) in 24.7%. The non-A non-B group had a significantly longer duration from the onset of symptoms to the appearance of encephalopathy (median 21 days) compared with the HAV and HBV groups (medians 10 and seven days, p less than 0.01 and p less than 0.005 respectively). In the HAV group the severity of liver damage, judged by the maximum prolongation of the prothrombin time, was significantly less than in the HBV group (58 and 150 seconds prolonged respectively, p less than 0.005), and cerebral oedema was significantly less frequent (39% and 72% respectively, p less than 0.05). Consistent with this, the survival rate was higher in the HAV group (43.4%) compared with the HBV group (16.6%) and NANB group (9.3%) (p less than 0.005). These variations in presentation and clinical course may be a consequence of differences in the pathogenesis of the hepatic necrosis.

Acute hepatitis non-A non-B in Cairo residents (a preliminary report)

Of 110 patients admitted with jaundice to the Abbassia Fever Hospital (AFH) in Cairo, 49 had acute hepatitis A infection (positive for anti-hepatitis A specific IgM), 28 had hepatitis B infection (positive for HBsAg) and seven had both markers. Of great interest, however, was the finding that 26 patients had no markers for either A or B virus infection. Clinically and biochemically, the non-A non-B hepatitis group resembled the other two infections. None of the 26 patients lacking both markers gave a history of previous blood transfusion or parenteral injections. Thus, the possibility of a faecal-oral or water-borne infection must be considered in these cases.

Hepatitis A and Non–A, Non–B Viral Hepatitis in São Paulo, Brazil: Epidemiological, Clinical, and Laboratory Comparisons in Hospitalized Patients

During a 33-month period, 295 patients with acute viral hepatitis were admitted to a state hospital for civil servants and their dependents in São Paulo, Brazil. Seventy-nine per cent (232) were HBsAg negative. To define the contribution of non-A, non-B viral hepatitis to hepatitis morbidity in this population, further serological studies were performed in 147 confirmed HBsAg-negative patients. One hundred and twelve (76%) were serologically classified as hepatitis A based on identification of IgM antibody to hepatitis A virus. Thirty patients (20%) without IgM antibody to hepatitis A virus, HBsAg, or anti-HBc were categorized as the non-A, non-B hepatitis group. The remaining five patients had probable hepatitis B (IgM antibody to hepatitis A virus negative, HBsAg negative, anti-HBs negative but anti-HBc positive). These data suggest that all three etiological forms of viral hepatitis are endemic in São Paulo. Epidemiological, clinical, and laboratory features were compared to the hepatitis A and non-A, non-B hepatitis groups. Patients with non-A, non-B hepatitis were significantly older than patients with hepatitis A (mean age +/- S.D.: 30 +/- 22 years vs. 9 +/- 9 years, p less than 0.001). Contact with hepatitis or jaundice was recognized in 26 (23%) of 112 hepatitis A patients and 3 (10%) of 30 non-A, non-B patients, a difference which was not statistically significant. Parenteral exposures were identified in 13 (43%) of 30 patients with non-A, non-B hepatitis and 23 (21%) of the 112 hepatitis A patients. Blood transfusion in the 2 months preceding onset of illness was reported in 5 (17%) of the 30 non-A, non-B patients and in none of the hepatitis A group (p less than 0.001). Although prodromal symptoms and fever were more common in patients with hepatitis A, neither these nor other clinical features appeared to be distinguishing characteristics. Similarly, mean peak SGPT levels, peak SGPT levels of greater than or equal to 1,000 IU/per liter, and the mean duration of SGPT elevations for each group were not significantly different. Mean peak serum bilirubin levels were slightly higher in the non-A, non-B group than in the hepatitis A group (7.6 +/- 8.0 mg per dl vs. 5.1 +/- 2.7, p less than 0.01) and peak bilirubin levels greater than or equal to 10 mg per dl were found in 27% of the non-A, non-B group and 5% of the hepatitis A group (p less than 0.001). Whether the higher bilirubin levels reflect an agent-related phenomenon or an older population of affected patients is uncertain.

Chromosome studies in acute lymphoblastic leukaemia (ALL).

Chromosome banding studies of the bone marrow were performed in 35 adult (greater than 14 years) patients with acute lymphoblastic leukaemia (ALL). Surface marker analysis was done in 24 of these and revealed 4 B-ALL, 5 T-ALL and 15 non-T non-B ALL. Most patients were studied at diagnosis before any treatment. A clonal karyotypic abnormality was found in 16 patients (46 %) initially. A Philadelphia chromosome was found in 3 patients, all belonging to the non-T non-B group. 5 patients, who all had blast cells with morphologic characteristics of Burkitt type L, were found to have bone marrow cells with a 14q + marker chromosome. In at least 4 cases this was due to a t(8;14). The cytogenetic findings showed some correlation to the ALL subgroup, but not to the response to treatment or the prognosis.

Prognostic significance of cell surface phenotype in adult acute lymphoblastic leukaemia

Forty-two adults with acute lymphoblastic leukaemia were subgrouped according to the membrane marker characteristics of their blast cells. All patients received the same treatment at St. Bartholomew's Hospital. The results indicate that the group expressing the common ALL antigen have a superior remission duration to the ALL antigen-negative, non-T, non-B ALL group and the T-ALL group. No correlation was evident between the first two subgroups and the clinical features of disease.

Cytochemical profiles in acute lymphoblastic leukemia

Lymphoblasts from 61 untreated patients with acute lymphoblastic leukemia (ALL), classified according to the French-American-British (FAB) morphologic classification, were studied for cytochemical characteristics and membrane surface markers. Seventy-three % (eight of 11) of patients with E-rosette positive lymphoblasts (T ALL) had strong focal paranuclear acid phosphatase (AcP) activity in more than 75% of their lymphoblasts; lymphoblasts from only 6% (three of 48) (p = 0.005) of patients with E-rosette negative, surface immunoglobulin negative lymphoblasts (non-T, non-B ALL) exhibited this characteristic AcP activity. The non-T, non-B ALL cases that manifested focal paranuclear AcP activity had clinical features more characteristic of the T ALL cases. The distribution of beta-glucuronidase activity in the lymphoblast cytoplasm was similar to that of AcP for T ALL and non-T, non-B ALL but the stain was generally more difficult to interpret THan the AcP and was a less reliable indicator of immunologic type of ALL. The periodic acid-Schiff (PAS) and nonspecific esterase stains were not useful in distinguishing between T ALL and non-T, non-B ALL but PAS negativity was associated with certain clinical features within the non-T, non-B ALL group. Cytochemical evaluation of the lymphoblasts at diagnosis in patients with ALL may be useful in identifying subsets of ALL that have distinct immunologic and clinical characteristics and important therapeutic and prognostic implications.

Etiology of sporadic hepatitis B surface antigen-negative hepatitis.

We studied serologically 45 adults who had sporadic acute viral hepatitis that was hepatitis B surface antigen (HBsAg) negative. Two cases were due to hepatitis B virus, as demonstrated by the appearance of antibody to hepatitis B core antigen. In three other patients, the serologic pattern was inconclusive. Of 40 non-B cases, 20 were type A hepatitis and 20 were non-A, non-B hepatitis. Clinically, type A and non-A, non-B hepatitis were indistinguishable; one case of fulminant disease occurred in each group. The type A cases were more frequent in young adults; non-A, non-B disease predominated in women 35 years or older. Epidemiologic backgrounds were generally similar, including illicit self-injection; but four transfusion-associated cases were limited to the non-A, non-B group. We conclude that relatively few HBsG-negative cases are due to hepatitis B virus, and that hepatitis A virus and non-A, non-B viruses are both important in acute non-B disease.