Hepatitis B in a nonresponder to hepatitis B vaccine.
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Biomedical subjects
Publications and source records attributed to F Bortolotti.
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During a prospective study of acute symptomatic viral hepatitis, started in 1978, 664 consecutive adult patients, including 223 drug abusers, fulfilled the diagnostic criteria (anti-HBc IgM positivity) for acute type B hepatitis. In order to evaluate the outcome of the disease, 443 patients were followed for up to 12 months after the onset. 2.4% of the infections became chronic; the rate did not significantly differ between drug addicts and non-drug abusers, suggesting that chronic hepatitis is a rare complication of acute symptomatic hepatitis type B. Ongoing liver damage after clearance of HBsAg from serum was observed in drug abusers only (14% of the cases). Clinical, biochemical and virological features of the acute phase in patients with ongoing infection were compared with those of uncomplicated cases. Anicteric hepatitis and lower transaminase values were significantly (p less than 0.05) associated to a chronic evolution of the disease, as well as a higher prevalence of HBV-DNA, DNA polymerase and HBcAg positivity in serum. Testing HBV-DNA and DNA polymerase early in the course of the infection appeared to be of high predictive value for the subsequent outcome of the illness.
The epidemiological pattern of acute type B hepatitis has been investigated in 1,107 consecutive patients during an 11-year prospective study conducted in Padua (Northern Italy) between 1978 and 1988. Remarkable changes were observed: 1) the attack rate of the disease increased significantly (p less than 0.05) between 1978 (18/10(5) inhabitants) and 1982 (29/10(5) inhabitants), particularly in male subjects and in the 15-19-year age group. The proportion of drug addicts also increased from 8.8 to 42% (p less than 0.05). These changes coincide in time with the spread of parenteral drug abuse in our area; 2) the attack rate dropped significantly (p less than 0.05) between 1983 and 1988 reaching the lowest levels ever observed before (4.7/10(5) inhabitants). The proportion of drug addicts decreased significantly (p less than 0.05), although the number of subjects starting narcotic abuse did not decline in recent years. Two major events could explain this pattern: a partial exhaustion of the susceptible population after spread of infection among drug abusers and, later on, the changing risk behaviours observed in our drug abusers after the AIDS prevention campaign. Other factors, including vaccination of some high risk groups, could have contributed to these changes.
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During a survey of acute symptomatic viral hepatitis conducted in Padua over the last 16 years, 404 (20%) cases of non-A, non-B hepatitis were observed, including 55% with overt parenteral exposure (35% drug abusers) and 45% with unknown exposure. Between 1978 and 1982 the attack rate of the disease increased significantly (p < 0.01) in males, (from 3.8 to 17.3/10(5) inhabitants), in adolescents and in youths. The prevalence of drug abusers rose up to 58% in 1982 suggesting the occurrence of an outbreak in this risk group. In subsequent years the attack rate returned to initial levels in males, although drug abuse still remains the single most important route of infection, and declined in females, especially after the disappearance of post-transfusion hepatitis since 1991. Retrospective anti-HCV testing of patients seen up to 1990 and prospective investigation of patients hospitalized later have shown an antibody prevalence of 88% among parenterally transmitted cases, and of 29% in the other patients, without significant differences between the prospective and the retrospective study. These findings suggest that an outbreak of hepatitis C occurred in our area in the early eighties and that drug abuse is still the most important mode of transmission of acute hepatitis C.
A high-performance liquid chromatographic (HPLC) method for the separation of the opioid heptapeptide dermorphin and related fragments has been developed. The chromatographic system was applied in the study of the kinetics of degradation of dermorphin (Der) in various tissues. Der was found to be extremely resistant to human and rat plasma (T 1/2 greater than 180 min). Upon incubation with homogenates of rat brains and kidneys, Der was cleaved with a half-life of 20.8 +/- 2.2 min and 2.4 +/- 0.3 min respectively. The catabolite formed was identified, in both tissues, as the N-terminal tetrapeptide H-Tyr-D-Ala-Phe-Gly-OH. The stability to rat kidney and brain of the N-terminal hexa- and pentapeptides and of the [4 psi 5, NHCO] Der analogue was also investigated. The nature of the enzyme systems involved in the in vitro degradations is discussed.
A new computer-assisted image analysis procedure was developed for the analysis of striatal compartments of the rats visualized in this case by means of c-fos immunocytochemistry after morphine and/or d-amphetamine treatments. In particular it has been shown that d-amphetamine can induce an activation of the c-fos early gene in various subregions of the neostriatum and that morphine treatment can antagonize this activation. A different pattern of morphine antagonistic action could be detected at the rostral versus the caudal striatal level. In fact, at the rostral level the morphine antagonistic action was very marked only in the dorsomedial striatum, while at the caudal level the morphine antagonistic action was marked in all subregions. The developed computer-assisted procedure can detect differences in the pattern of distribution of profiles present in a certain neuroanatomical area. Therefore, this procedure may represent a powerful tool to study integrative functional compartments in the neostriatum. In the present study high level integrative compartments appear to be created by D1/mu-opiate receptor interactions especially within the classical patch system.
Two series of peptidomimetics containing a novel C(2) pseudosymmetrical hydroxyalkyldiamino core structure were prepared from amino acid starting materials and tested for inhibitory activity against the HIV-1 protease (HIV-1 Pr) and the virus in cell culture. In the 2,3-diamino-1-hydroxypropane series, compound 6a, containing P1/P1(I) benzyl and P2/P2(I) Fmoc substituents, displayed modest HIV-1 Pr inhibition (IC(50) = 430 nM). The corresponding 2,4-diamino-1-hydroxybutane derivative (6b) was the best inhibitor of the series (IC(50) = 160 nM). Interestingly, 6a and 6b showed satisfactory inhibition of HIV replication in cell culture (ED(50) = 340 and 110 nM, respectively), a result which suggests good cell membrane penetration by this class of compounds.
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A prospective study of acute symptomatic viral hepatitis in childhood was started at the Department of Infectious Diseases of Padua (Italy) in 1978. During an 8-year period, 93 consecutive patients (aged 3 months to 12 years) fulfilled the diagnostic criteria, including five (5.5%) cases classified as non-A, non-B hepatitis. This figure is lower than that generally reported in adult patients, probably because of a lower exposure of children to blood and contaminated materials. Two of the five children with non-A, non-B hepatitis had received blood transfusions, while three had no history of parenteral exposure. Although the outcome of the illness was favorable in all five patients, a variety of clinical features could be observed: two children had a mild, short-lasting disease, anicteric in one case, while three had a polyphasic pattern of transaminases with delayed biochemical resolution, including one patient with deep jaundice and severe early phase features. These findings suggest that in children, as well as in adults, non-A, non-B hepatitis is probably a heterogeneous entity induced by different agents with different modes of transmission.
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To aid in the objective diagnosis of chronic alcohol abuse in both clinical and medico-legal environments, reliable biochemical markers are needed. In addition to the conventional indicators, which include y-glutamyl transferase, erythrocyte mean corpuscular volume, aspartate aminotransferase, and alanine aminotransferase, carbohydrate-deficient transferrin (CDT) has recently been introduced. According to a reliable body of literature, CDT is the most reliable marker of chronic excessive alcohol intake. CDT is the collective name for minor isoforms of human transferrin, and therefore highly selective and sensitive methods are required for its analysis in serum. Moreover, the need for precise quantification poses additional problems of accuracy and precision. For these purposes, capillary electrophoresis shows excellent potential in terms of quantitative accuracy, precision, speed, automation, economy, and simplicity of operation. The simple, optimized capillary zone electrophoretic analysis of CDT in human serum is discussed in this paper and is compared to the traditional analytical method based on microcolumn ion exchange chromatography followed by immunoassay.
Chronic Hepatitis B virus (HBV) infection in children is commonly associated with Hepatitis B e antigen (HBeAg) seropositivity and histologic features of minimal to moderate hepatitis. Remission of liver disease is the rule following HBeAg to antiHBe seroconversion and clearance of HBV DNA from serum. In intermediate and low endemicity areas chronic HBV infection is usually acquired postnatally, and more than 80% of children are likely to achieve stable remission during the pediatric age. Severe sequelae, namely cirrhosis and HCC, have been observed only in less than 4% of children followed over two decades. In all cases cirrhosis was an early complication. Chronic HCV infection is usually silent in children. The chronicity rate seems to be high (50-80%) in post-transfusion hepatitis C as well as in perinatally acquired infection. HCV-associated liver disease is characterized by fluctuations of ALT which remain below two times the normal in about half of the cases. Liver histology shows minimal to mild hepatitis in the large majority of patients and cirrhosis is rare. Few patients achieve spontaneous remission and progression to a more severe liver disease might occur in adult life.
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