Posttransfusion hemoglobinuria and myoglobinuria in neonates.

Posttransfusion positive dipsticks for occult blood do not differentiate hemoglobinuria from myoglobinuria, relatively common events in infants admitted to the neonatal intensive care unit. We studied posttransfusion plasma and urine hemoglobin and myoglobin in relation to occult blood positivity in the urine dipsticks, in 48 consecutive transfusions with packed RBC (28 neonates, birth weight 850-3,700 g, postnatal age 3-167 days). Urine dipsticks show a low sensitivity for detecting hemoglobin and also undervalue myoglobin, both possible in different amounts in the plasma and urine of ill neonates. However, posttransfusion occult blood positive urine dipsticks due to myoglobinuria are present in 10% of transfused neonates.

Alanine and aspartate aminotransferase serum levels in burned patients: a long-term study.

Increased alanine and aspartate aminotransferase (ALT and AST) serum levels are usually considered expressions of cellular necrosis, especially in hepatocytes. They represent cellular damage due to burn which, according to many authors, becomes normal before discharge of patients. We studied 43 consecutive burned patients, both during and after recovery, from a minimum of 120 to a maximum of 640 days, and an average of 18.62 blood samples were taken from each patient. Hepatitis A and B markers were tested. Results showed a 67.44% increase in aminotransferases in patients during recovery and a 25.58% increase after discharge. No neopositivity was observed for hepatitis A and B markers. We therefore conclude that the increase of enzymes during recovery expresses a toxic-infective phase and this increase, contrary to what was believed, does not always drop to normal values at time of discharge. Instead, after discharge, higher values can be a manifestation of a Non-A Non-B hepatitis.

IgM antibody to hepatitis B core antigen in children with chronic type B hepatitis.

IgM antibody to hepatitis B core antigen (anti-HBc IgM) was investigated by an antibody-capture radioimmunoassay (serum dilution 1:4000) in serum samples from 31 untreated children with chronic hepatitis B who were followed prospectively for 1-7 years. At the start, all patients were positive for hepatitis B e antigen (HBeAg), and anti-HBc IgM was detected in 23 cases, including 15 out of 16 with chronic active hepatitis and 7 out of 14 with chronic persistent hepatitis. A significant positive correlation was found between anti-HBc IgM levels and severity of liver damage (P less than 0.05), while an inverse relationship was found between anti-HBc IgM levels and distribution of hepatitis B core (HBcAg) antigen in the liver as detected by immunofluorescence. In fact 75% of anti-HBc IgM positive patients showed a focal HBcAg pattern (less than 40% positive nuclei), whereas 87% of antibody negative cases exhibited a diffuse HBcAg expression (more than 60% stained nuclei). During follow-up, seroconversion from HBeAg to anti-HBe with subsequent remission of liver disease occurred in 82% of patients presenting with detectable levels of anti-HBc, including three out of seven cases with chronic persistent hepatitis, but in none of the cases that were initially negative (P less than 0.01). These results indicate that during the natural course of chronic hepatitis B in children, anti-HBc IgM levels in serum reflect the degree of host immune response to infected hepatocytes. The close correlation between anti-HBc IgM seropositivity and seroconversion from HBeAg to anti-HBe suggests that anti HBc IgM may have a prognostic value during the follow-up of children with chronic HBeAg positive hepatitis B.

Influence of hepatitis delta virus infection on progression to cirrhosis in chronic hepatitis type B.

Serological markers of hepatitis delta virus (HDV) infection were found in 18 (12%) of 146 consecutive patients with chronic hepatitis B, and the characteristics of patients who had antibody to HDV (anti-HDV-positive) were analyzed. During one to 15 years of follow-up, histological deterioration was documented in 77% of anti-HDV-positive patients; however, in hepatitis B surface antigen (HBsAg) carriers without HDV infection, histology deteriorated in 30% but improved or remained unchanged in the majority of patients (P less than .01). In seven (70%) of the 10 anti-HDV-positive patients who showed transition from chronic active hepatitis to cirrhosis, this event was observed within the first two years of follow-up. The probability of evolution to cirrhosis was significantly higher in anti-HDV-positive patients than in patients without antibody to HDV (P less than .001). These findings indicate that HDV infection in patients with chronic hepatitis B is associated with a more-rapid progression to cirrhosis compared with HBsAg carriers with chronic hepatitis and no evidence of HDV infection.

Levamisole therapy in chronic type B hepatitis. Results of a double-blind randomized trial.

A double-blind, randomized, controlled trial has been undertaken to evaluate treatment of chronic hepatitis type B with levamisole. Ten patients received levamisole (150 mg/day, 3 days/wk) and 10 received placebo until seroconversion to antibody to hepatitis B e antigen eventually occurred, or for a maximum of 18 mo. Final evaluation at 24 mo after starting treatment revealed that 60% of the patients in the levamisole group had become hepatitis B e antigen negative, 90% were hepatitis B virus-deoxyribonucleic acid negative in serum, and 8 of 9 (89%) patients had cleared hepatitis B core antigen from the liver. On the other hand, in the placebo group only 4 of the 10 subjects (40%) were hepatitis B e antigen and hepatitis B virus-deoxyribonucleic acid negative in serum and 3 of 8 (37.5%) of them became hepatitis B core antigen free in the liver. Moreover, in 8 patients of the treated group and in 4 of the control cases aminotransferase activities fell into the normal range. A liver biopsy specimen was obtained after treatment in 17 patients and 7 of 9 levamisole recipients showed marked improvement in hepatic histology, compared with 3 of 8 placebo recipients. These data show that patients treated with long-term levamisole therapy have a tendency toward normalization of aminotransferase activities and suppression of hepatitis B virus replication, suggesting that the drug may be of benefit in chronic hepatitis B e antigen-positive hepatitis.

The polymorphism of plasminogen (PLG) by ultrathin-layer isoelectric focusing. Distribution in the Veneto population (Italy).

The distribution of plasminogen phenotypes in the population of Veneto was investigated by ultrathin-layer isoelectric focusing. In our sample (n = 1325), the three common phenotypes PLG1, PLG2, PLG2-1 and two further phenotypes PLG1-V and PLG2-V were, observed and the following frequencies calculated: PLG1 = 0.84038; PLG2 = 0.15811; PLGV = 0.00151. These gene frequencies are compared to those found in other populations. Analysis of 41 mother-child pairs was in agreement with an autosomal codominant inheritance.

Antibody to the hepatitis B virus receptor for polymerized albumin in acute infection and in hepatitis B vaccine recipients.

A receptor for polymerized human serum albumin is encoded by the pre-S region of the hepatitis B virus genome and may mediate attachment of the virion to hepatocytes. To investigate antibody response to the virus receptor we studied sera and their IgG fractions for inhibitory activity on hemagglutination of polyalbumin-coated red cells by virus particles containing the pre-S polypeptide. By this method antibody to the receptor was detected in serum in a goat immunized with pre-S containing particles, with no relation to levels of antibody to hepatitis B surface antigen, and in the sera of 33% and 83%, respectively, of acute hepatitis B patients studied during the early phase of illness and during convalescence. In contrast, antibody to the receptor was not detected in serum in any of the 47 subjects immunized with a commercial, plasma-derived, hepatitis B vaccine. These results demonstrate that natural acute infection with hepatitis B virus leads to production of antibody to the virus receptor for polyalbumin, while such antibody response is absent after immunization with currently licensed hepatitis B vaccines.

One year follow-up study of T-cell subsets and incidence of seropositivity for HTLV-I and HTLV-III antibodies in patients treated "on demand" or sporadically with clotting concentrates.

A 1-year follow-up study of the T-cell subset abnormalities was carried out in 16 severe haemophilia A patients, treated "on demand" with an average amount of 500 U/kg/yr of factor VIII concentrate (group A) and in 15 mild haemophiliacs or von Willebrand patients treated only sporadically with less than 3000 U of factor VIII and no longer exposed to any other blood component in the 2 years preceding the beginning of the study (group B). In group A, 50% and 70% of patients showed a reduced or inverted T 4/T 8 ratio, respectively, at the beginning and at the end of follow-up. These values were of 30% and 20% in patients of group B, suggesting a long-lasting effect of concentrate therapy on T-cell subsets. The low T 4/T 8 ratio was mainly due to an increase of suppressor cells. None of the patients was found positive for anti HTLV-I, whereas 3 patients, all belonging to the group A, showed antibodies against HTLV-III. Thus, in these patients, HTLV-III seems not to be the only cause of low T 4/T 8 ratio.

Risk of hepatitis B virus infection following upper gastrointestinal endoscopy: a prospective study in an endemic area.

A prospective survey, comprising 623 consecutive upper gastrointestinal endoscopies (in 588 patients) was carried out simultaneously at two endoscopy centres of a Mediterranean country, without altering the routine procedures. Each patient was tested for HBsAg, and sera found to be HBsAg-positive were tested for HBeAg/antiHBe: 40/588 (7.1%) subjects were found to be HBsAg-positive and 6 of them were HBeAg-positive. Sera of the first 5 HBsAg-negative patients in whom the same endoscope and/or biopsy forceps were used after a HBsAg-positive subject, were tested for antiHBc to ascertain antecedent HBV immunity: 77/136 (56.6%) were found to be antiHBc-positive. Forty-eight out of the 59 individuals "at risk" lacking evidence of previous HBV infection were contacted 6 months after endoscopy: none reported symptoms of hepatitis; 40 of them had blood tests for HBsAg and antiHBc: none showed serum markers of HBV infection. It is therefore concluded that, in spite of the high number of HBsAg carriers among endoscopy candidates, the risk of HBV spread during upper G.I. endoscopy is very low, even in high prevalence areas.

HBIG efficacy in preventing HBV infection in infants.

Previous studies have confirmed the superiority of HBIG versus ISG and multiple dose versus single dose of HBIG (Beasley) and the time of first HBIG administration in preventing HBV infection. In all studies many treated infants became HBsAg or anti-HBs positive after the HBIG stopped. The present study was undertaken to evaluate the efficacy of multiple dose HBIG therapy in preventing HBV infection, and to establish the optimal dose, the frequency of the dose, the time of administration during the first year of life and to control the occurrence of HBsAg or active anti-HBs during the first two years of life. Seven infants of mothers positive for HBsAg and HBeAg, or positive for HBsAg but negative for HBeAg and anti-HBe, or with hepatitis B in the last trimester of pregnancy, received HBIG at high titer at dose of 0.5 ml/kg from first day until near 5 months of life and then 0.5-0.3 ml/kg until 12 months of life. The interval between the administration was established on the basis of the anti-HBs titer lower than 32. It was not a fixed interval but variable in different cases. Passive anti-HBs antibodies were almost always above 32 during the treatment period with HBIG. All patients remained negative for HBV markers and for liver enzyme tests during the period of the study. HBIG, administered in the first year of life at high dose and at intervals depending upon serum anti-HBs titer (32) systematically controlled, is efficient in preventing the hepatitis B infection in infants at high risk.(ABSTRACT TRUNCATED AT 250 WORDS)

Vertical transmission of HBV from mothers HBsAg positive, anti-HBe positive.

Vertical transmission of HBV from HBsAg carrier mothers to their infants occurs frequently and very early in life. The HBsAg titer, the presence of HBeAg and acute HBV infection in the mother are usually considered facilitating factors; on the contrary anti-HBs and anti-HBe titer would be effectively protecting. However anti-HBc does not prevent HBsAg infection at all. In order to obtain information on the rate of HBV transmission in conditions considered at lower risk, we identified a group of pregnant women who were asymptomatic chronic HBsAg carriers and followed their children for several months after birth with clinical and laboratory examinations. All the 13 mothers were positive for HBsAg, anti-HBe, anti-HBc and negative for anti-HBs and HBeAg. All infants were controlled monthly in the first year of life and then at 16, 20, 24 months. The relatives controlled in the same period proved negative for HBV markers. All infants were negative for antigens at the birth and positive for anti-HBe and anti-HBc. These antibodies disappeared after 3-7 months after birth, indicating maternal transmission. All infants remained negative for HBsAg, HBeAg, anti-HBe and liver enzyme tests during the period of observation (24 months). These observations indicate that in our population the transmission of HBsAg from chronic carrier mothers to their children is not a frequent occurrence; probably the presence of anti-HBe has been protective.(ABSTRACT TRUNCATED AT 250 WORDS)

Epidemiological aspects of acute viral hepatitis in drug abusers.

The epidemiological features of acute symptomatic viral hepatitis were examined in 151 consecutive, hospitalized drug abusers. Hepatitis B was diagnosed in 101 patients (66.8%), hepatitis A in 13 (8.6%) and non-A, non-B hepatitis in 35 (23.1%). Non-A, non-B hepatitis was significantly more prevalent among drug abusers than in an age-matched control population of non-drug abusers. Moreover, the mean duration of parenteral drug abuse was significantly lower among non-A, non-B cases than in patients with hepatitis A or B. These results suggest a wide circulation of both hepatitis B virus and non-A, non-B agent(s) among drug abusers in our area. These patients most likely represent a main reservoir of non-A, non-B infection due to the high rate of chronicity reported for non-A, non-B hepatitis.

Core antigen-specific immunoglobulin G bound to the liver cell membrane in chronic hepatitis B.

The antibody specificity of immunoglobulin G bound to the liver cell membrane during hepatitis B virus infection and chronic liver disease has been studied in 8 patients after antibody elution with high molar urea. Eluted immunoglobulin G showed antibody specificity for hepatitis B core antigen by radioimmunoassay and by indirect immunofluorescence on positive liver tissue. On the contrary, no reaction could be detected against other viral antigens (i.e., hepatitis B surface antigen and hepatitis B e antigen) or against liver-specific proteins. Furthermore, in 5 selected cases, after urea removal of cytophilic antibody, hepatitis B core antigen could be demonstrated by direct immunofluorescence in a granular pattern on the liver cell surface, thus suggesting a masking effect of immunoglobulin G on membranous hepatitis B core antigen in patients with persistent virus replication in the liver.

Virological changes in chronic hepatitis type B treated with levamisole.

8 children, known to have been hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg) positive for more than 6 months and with chronic active hepatitis on biopsy, received 2.5 mg levamisole/kg/day, 2 days a week for 6-18 months. In 6 of the 8 children transaminases normalized within 4-18 months of therapy, with seroconversion to antibody to HBeAg (anti-HBe) and disappearance of HBV-DNA polymerase from serum and of hepatitis B core antigen (HBcAg) from liver. In these cases liver biopsies taken after treatment showed histological regression to chronic persistent hepatitis. Two distinct patterns of response to levamisole were noted: patients having higher pretreatment transaminase levels and lower expression of HBcAg in the liver showed an early transaminase normalization and anti-HBe seroconversion with therapy, while in patients with less active disease and more diffuse HBcAg positivity in pretreatment liver biopsies, longer treatment periods were necessary to achieve these effects. Our results suggest that long-term levamisole therapy may be beneficial in HBeAg-positive chronic hepatitis type B.

Epidemiological aspects on acute viral hepatitis in northern Italy.

Incidence and epidemiological features of acute hepatitis types A, B and non-A non-B have been evaluated in 332 consecutive patients hospitalized in Padova, Italy. Hepatitis B was diagnosed in 59% of cases and was frequently related to drug addition, health care work and household contact with HBsAg-positive subjects. Hepatitis A represented 22% of cases and its peak incidence occurred in the second decade. Non-A non-B hepatitis affected 15% of patients including not only transfusion or drug related forms, but also sporadic cases that prevailed among elderly women.

Expression of HBsAg on the membrane of hepatocytes in chronic carriers of hepatitis B virus infection.

Liver cell membrane localization of hepatitis B surface antigen (HBsAg) was investigated in 31 asymptomatic chronic carriers by a direct immunofluorescence technique. A close relationship was found between absence of inflammatory liver disease, presence of large amounts of HBsAg in the liver and expression of the antigen at the hepatocyte surface. Capping of HBsAg after the addition of anti-HBs serum could be inhibited by factors (temperature, metabolic inhibition) that are known to influence viral antigenic mobility at the cell surface. In two patients with chronic active hepatitis as well as in some cases showing histological features of focal parenchymal necrosis, HBsAg could be detected in the cytoplasm of a few scattered hepatocytes but never at the surface of the cells. Both the cases with CAH and one with focal parenchymal necrosis had IgG bound to the liver cell membrane. These findings are in agreement with the hypothesis that the absence of liver damage in HBsAg healthy chronic carriers is related to immune tolerance to the antigen. In chronic active liver disease the presence of IgG on the membrane of hepatocytes suggests a possible role of blocking antibodies directed against viral antigens expressed at the hepatocyte surface.