Biomedical subjects
H Allende
Publications and source records attributed to H Allende.
Serological diagnosis of chronic delta infection: correlation between serological markers and hepatitis delta virus RNA in hepatic tissue.
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Interferon-alpha in acute posttransfusion hepatitis C: a randomized, controlled trial.
To assess the efficacy of interferon-alpha in acute hepatitis C, 28 patients with acute posttransfusion hepatitis were randomized to receive 3 million units of recombinant interferon-alpha three times weekly for 12 wk or no treatment. Biochemical, histological and serological parameters were monitored during 1 yr of follow-up. Serum ALT levels were normal at the end of therapy in 73% of treated patients and only in 38% of control patients (p = 0.06); these differences disappeared at 6 and 12 mo of follow-up. Anti-hepatitis C virus seroconversion occurred later and at a lower rate in the group of patients who received interferon-alpha. Treated patients had a trend toward less severe hepatic lesions with lower histological activity as compared with the control group, but no statistical differences were observed. No severe side effects of interferon-alpha were detected during the study. In summary, a 3-mo course of interferon-alpha in acute hepatitis C is safe and might have some effect in diminishing disease activity only during the treatment period; however, and probably because of a small sample size, no benefit of interferon-alpha in the long-term outcome of this disease was demonstrated.
Treatment of chronic type D hepatitis and concomitant human immunodeficiency infection with alpha-interferon.
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Cirrhotic changes in livers from children undergoing transplantation. Image analysis.
The pattern and extent of disorganization of the liver architecture were studied in 25 children undergoing orthotopic liver transplantation for cirrhosis. Image analysis techniques based on mathematical morphology were used to define seven parameters for each case, including fibrosis index (percentage of Sirius-red-stained areas), three categories of regenerative nodules (< 0.8, 0.8-1.6 and > 1.6 mm in diameter) and three categories of fibrous septa (< 0.4, 0.4-1.2 and > 1.2 mm in width). Fibrosis index ranged from 10.2% to 51.9%. Percentage of small nodules of infralobular size (< 0.8 mm in diameter) varied from 31.4% to 98.2%. Percentage of large nodules, > 1.6 mm in diameter, in only four cases was > 15%. Multivariate clustering analysis classified the cases into three main groups. One of them included only cases of cirrhosis secondary to parenchymal disease or to inborn errors of metabolism. In their pattern, tiny nodules predominated, and the percentage of slender septa, < 0.4 mm in diameter, was very high, although the overall fibrosis index was relatively low. Patients with biliary cirrhosis were classified into two groups. In one the fibrosis index was low and the size of the nodules variable, with 12% large nodules. In the other the fibrosis index was high, and small nodules, < 0.8 mm in diameter, predominated. No relationship was found with age at transplantation or previous portoenterostomy. A presumptive explanation for this divergent evolution might be the occurrence of cholangitic episodes. Overall fibrosis that the liver can sustain without failure is apparently limited.(ABSTRACT TRUNCATED AT 250 WORDS)
Mathematical morphologic analysis of liver cirrhosis. Correlation with etiology, clinical score and hepatocellular carcinoma.
Remodeling of the cirrhotic liver was studied retrospectively by mathematical morphologic methods in 75 autopsy cases (40 alcoholic, 17 hepatitis B virus (HBV)-related and 18 cryptogenetic cirrhosis), including 28 hepatocellular carcinomas. The aim was to obtain objective measurements of cirrhotic patterns that could be correlated with liver function evaluated by the Pugh-Child score, establish the relationship among different morphogenetic features and evaluate the implications of an objective classification of cases by numerical taxonomy in terms of their etiology, liver function and malignant transformation. The results indicate that the Pugh-Child score was closely related to the global amount of fibrosis or to the percentage of regenerative nodules < 0.8 mm in diameter. In contrast, the higher the percentage of lobular-sized regenerative nodules (0.8-1.6 mm), the better the functional score, suggesting that they are probably residual lobules, albeit completely surrounded by fibrous tissue, rather than true regenerative pseudolobules. The four groups of cases obtained by numerical taxonomy (cluster analysis) showed different distributions for alcoholic and HBV-related cirrhosis. The pattern of the latter was practically analogous to that in classically labeled cryptogenetic cirrhosis, suggesting its viral etiology. Taxonomic classification had functional implications. The Pugh-Child score showed a definite relationship with the different clusters obtained. The incidence of malignant transformation gradually decreased from group G1 to G4, with a steeper descent between G2 and G3. These results might contribute to a more dynamic concept of morphologic changes in liver biopsies from patients with cirrhosis.
High rate of infectivity and liver disease in blood donors with antibodies to hepatitis C virus.
OBJECTIVE: To determine the epidemiologic, clinical, serologic, and histologic importance of antibodies to hepatitis C virus (anti-HCV) in blood donors. DESIGN: Cross-sectional identification and prospective evaluation of seropositive donors; retrospective assessment of infectivity; and nested case-control study for risk factors. SETTING: Liver unit of a referral-based university hospital. SUBJECTS: Of 30,231 consecutive donors, 368 (1.2%) were found to be anti-HCV-reactive by enzyme-linked immunosorbent assay (ELISA). Two hundred and fifty-four of these 368 donors were evaluated for risk factors by comparison with 284 age- and sex-matched controls. Eighty-six spouses of seropositive donors were also evaluated. MEASUREMENTS AND MAIN RESULTS: Twenty-four percent of the seropositive donors had a history of percutaneous exposure to blood. This rate increased to 45% when only those donors confirmed to be anti-HCV positive by a second-generation recombinant immunoblot assay (RIBA-2) were considered. A family history of liver disease (odds ratio, 2.8; 95% Cl, 1.6 to 4.8), previous blood transfusion (odds ratio, 6.1; 95% Cl, 3 to 12.5), and a history of tattooing or intravenous drug abuse (odds ratio, 8.4; 95% Cl, 2.3 to 31) were associated with anti-HCV seropositivity. An elevated alanine aminotransferase (ALT) level was found in 58% of the seropositive donors. Of the 150 donors tested, 104 (69%; Cl, 62% to 77%) were confirmed by RIBA-2 to be anti-HCV positive. Of the 105 donors who had a biopsy, 16% had normal histologic findings, 11% had minimal changes, 21% had chronic persistent hepatitis, 45% had chronic active hepatitis, and 7% had active cirrhosis. All 77 donors with RIBA-2-confirmed seropositivity had histologic abnormalities. Of 43 donors evaluated in an infectivity study, 82% were implicated in previous HCV transmission. Only 2.3% of the spouses were anti-HCV positive. The ELISA, RIBA-2, and ALT results correlated with infectivity and abnormal histologic findings. CONCLUSIONS: In our geographic area, almost 70% of donors who are anti-HCV positive by ELISA are confirmed to be positive by RIBA-2; most of these donors appear to be chronic carriers of HCV and have substantial liver disease.
[A study of 158 cases of acute delta hepatitis].
We have prospectively studied 158 cases of acute hepatitis delta observed during the last 7 years in a general hospital. Among them 136 were male and 22 female. The mean age was 22.7 years with a range between 16 and 61 years. The epidemiologic factors were drug addiction by parenteral route in 145 cases (92%), sexual transmission in 5 (3%), post transfusional in 2 (1%) and unknown in 6 (4%). With respect to the delta type infection, 105 cases (66%) were coinfections with type B and delta, and 53 patients had a type delta superinfection (34%). The clinical course was a fulminant hepatitis in three cases (two cases of coinfection B and delta an one case of delta superinfection), and an acute benign hepatitis in 155 patients. The follow-up of 118 patients revealed that 96% of coinfections by type B and delta evolved to the chronicity showing findings of active chronic hepatitis or hepatic cirrhosis. It should be noted that in 4 cases of superinfection delta type (11%) the HBsAg was negative after several months of positivity. In these patients the level of transaminases normalized and the hepatic histology evidenced alterations of chronic active hepatitis (2 cases) and hepatic cirrhosis (2 cases) without identification of tissular delta antigen.
[Diagnosis of acute hepatitis caused by herpes simplex virus using in situ hybridization].
A 50-year-old male without relevant past history was admitted because of fever lasting for 23 days. Physical examination showed hepatomegaly and splenomegaly without other findings. Laboratory studies only revealed mildly abnormal hepatic enzymes. The remaining investigations (markers, serologies, antinuclear antibodies, blood and urine cultures) were negative. Chest and abdomen X-ray films were normal. In abdominal echogram a homogeneous liver without space occupying lesions was seen, and computed tomography disclosed enlarged liver, spleen and lymph nodes. Needle hepatic biopsy was reported as showing reactive hepatitis. Although clinically meningeal antibody seroconversions were not found, DNA chains of cytomegalovirus, Epstein-Barr virus, hepatitis B virus and herpes virus simplex were investigated with the in situ hybridisation technique. Its result was a strongly positive hybridisation for herpes virus and negative for the other investigated viruses.
Serological profile of tissue autoantibodies during acute and chronic delta hepatitis.
In order to assess the serological profile in relation to other serological and histological markers of hepatitis delta virus (HDV) infection we have investigated the presence of autoantibodies during acute and chronic delta infection in 353 serum samples from different patients with acute and chronic hepatitis and autoimmune diseases. Basal cell layer antibodies (BCLA) were found in 58% acute hepatitis B, in 73% chronic hepatitis D and in 4% primary biliary cirrhosis. Stellate thymic epithelial cell antibodies (SECA) were detected in 40% acute D hepatitis and in 49% chronic D hepatitis. No tissue autoantibodies were detected in 50 acute B hepatitis, 35 autoimmune chronic liver diseases, 24 connective tissue diseases or 25 controls. In addition, two previously unreported specificities of anti-thymic antibodies reacting with reticular (TRA) and perithymocytic cells (PTA) were identified in 33% and 9% acute D hepatitis, respectively, and in 13% and 6% chronic D hepatitis cases. Among patients with acute HBV-HDV coinfection these antibodies were detected transiently (less than 4 weeks) and at low titer, whereas in those with chronic infection autoantibodies levels tend to be high and persistent throughout the follow-up. Among patients with chronic HDV infection no correlation was found between the presence of tissue autoantibodies and hepatic delta antigen expression and serum HDV-RNA which suggest that autoimmune phenomena observed during chronic delta infection are not related to the level of viral replication.
[New perspectives in liver-based metabolic errors: liver transplantation].
Liver transplantation offers an actual alternative to patients end-stage liver disease. The aim of this study is to show our results of liver transplantation in paediatric patients with hepatic-based metabolic disorders. Survival rates in these indications can be high and these good results may enlarge the indications. Liver might transplantation therefore be offered earlier to patients with this kind of metabolic disease.
Epidemiology of delta infection in Spain.
The prevalence of hepatitis D virus infection was studied in 954 sera samples collected in Spain between 1974 and 1986 from 838 patients in a variety of epidemiological categories with HBsAg-positive liver disease, and from 116 haemophiliacs and drug addicts with hepatitis B antibodies. Hepatitis D markers were detected in 64% of drug addicts and 33% of HBsAg-positive haemophiliacs but were absent in asymptomatic chronic carriers, homosexual males, mentally retarded patients and haemodialysis patients. Hepatitis D markers were found in 6% of patients with acute hepatitis, in 5.6% of those with chronic hepatitis B from general population, and in 65% of those with acute hepatitis B and 67% of those with chronic hepatitis B among drug addicts. During the 12-year study, no changes were observed in the frequency of Delta infection. The prevalence was less than 10% in chronic HBsAg-positive hepatitis. These findings indicate that in Spain Delta infection is restricted mainly to HBsAg-positive drug addicts and multitransfused haemophiliacs, while in the general population only 6.7% of those with chronic hepatitis B show D superinfection. Anti-HD sera detection is correlated with more severe forms of chronic hepatitis such as chronic active hepatitis and cirrhosis.
Chronic hepatitis D in intravenous drug addicts and non-addicts. A comparative clinico-pathological study.
In recent years chronic infection by the hepatitis delta virus (HDV) has become an important cause of chronic liver disease among drug addicts. To evaluate the influence of addiction to i.v. drugs on the course of this disease we have analyzed the clinical, histopathological, virological and evolutive features in 18 addicts and 11 non-addicts with chronic delta infection. Recent acute hepatitis D, documented as HDV superinfection, was observed in 14 addicts (77%) and in 2 non-addicts (18%) (P less than 0.02). At the time of evaluation for chronic liver disease, the frequency of symptoms, the degree of biochemical disturbances and the histopathological severity were similar in the two groups but the duration of HDV infection was probably shorter in drug addicts. HBV replication, as indicated by the presence of HBeAg and HBV-DNA in serum and HBcAg in liver, was more frequent in addicts. The amount of HDAg in liver tissue was also greater in addicts (P less than 0.005). Antibodies against the human immunodeficiency virus were detected in all of the addicts (P less than 0.001). Although most patients remained asymptomatic, significant histological worsening occurred in one half of the cases after a relatively short period of follow-up (25.1 +/- 16.3 months). The tendency to deteriorate in addicts (61% of cases) was greater than in non-addicts (36%). These observations suggest that the prognosis of chronic HDV infection is particularly poor in drug addicts in whom rapid deterioration may be related to simultaneous and inadequately controlled replication of hepatotropic viruses.
Anti-HD IgM as a marker of chronic delta infection.
The value of anti-HD IgM as a marker of chronic delta infection was evaluated by correlating its presence in serum with that of HD-Ag in liver cells and with the degree of inflammatory activity. Thirty-six patients with HBsAg-positive chronic hepatitis and anti-HD at high titers were studied. Overall, the liver cells of 26 patients contained HD-Ag and 27 were positive for IgM anti-HD. The correlation between both markers was excellent: 25 cases were positive for both serum anti-HD IgM and intrahepatic HD-Ag and 8 were negative for both markers. There was only 1 HD-Ag-positive patient, who was anti-HD IgM-negative. Two patients were anti-HD IgM-positive and HD-Ag-negative. Histological damage was more severe in anti-HD IgM-positive cases than in those negative for this marker (Knodell's index 13.5 vs 11.9, P less than 0.01). We conclude that anti-HD IgM is a good marker of chronic active delta infection.
Clinical and serological outcome of acute delta infection.
To assess the clinical and serological outcome of hepatitis delta virus (HDV) infection, 59 patients with acute delta hepatitis were followed for 6-28 months. Forty-two patients had simultaneous HDV and HBV coinfection (anti-HBc IgM-positive, group I) and 17 were HBsAg carriers with HDV superinfection (anti-HBc IgM-negative, group II). Overall, serum HD-Ag and anti-HD IgM were the most sensitive markers for diagnosis of delta infection during the first 2 weeks after onset of symptoms. The clinical presentation was similar in both groups; 4 patients (1 in group I and 3 in group II) (7%) developed fulminant hepatitis, but none of them died. The majority of patients with HBV-HDV coinfection (group I) eventually recovered, whereas all HBsAg carriers with HDV superinfection (group II) developed chronic liver disease. Liver histology in these patients showed chronic active hepatitis and/or cirrhosis in 90%. The hepatic lesion was probably due to persistent HDV infection, as indicated by the presence of intrahepatic HD-Ag and/or persistence of serum anti-HD IgM in 90% of the patients.
Liver transplantation in metabolic diseases. Report of five pediatric cases.
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Segmental liver transplantation in pigs: use of a fibrin sealant and collagen as hemostatic agents.
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[Serologic and hepatic correlation of the markers of hepatitis B and D virus].
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