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Biomedical subjects

J Guardia

Publications and source records attributed to J Guardia.

At least 91 records · Page 5Linked to original sources

Long interval between HCV infection and development of hepatocellular carcinoma.

A high prevalence of HCV infection has been reported in patients with hepatocellular carcinoma. The progression from acute transfusion-associated hepatitis to hepatic cirrhosis and hepatocellular carcinoma has been suggested in several studies to be very long. We have investigated the prevalence of anti-HCV and the interval between HCV infection and hepatocellular carcinoma among 191 consecutive patients with cirrhosis and liver-cell carcinoma. Serum samples from 191 patients with cirrhosis and hepatocellular carcinoma, consecutively diagnosed in our hospital between 1988 and 1993, were tested for serological markers of HBV and HCV infection. One hundred and forty-eight patients (77.5%; 95% confidence interval (c.i): 76% to 80%) were anti-HCV positive by 2nd generation enzyme immunoassay (confirmed by 2nd generation recombinant immunoblot assay) and 152 patients (79.5%; 95% c.i: 76% to 80%) were anti-HCV positive by 3rd generation enzyme immunoassay, while only 14 (7.4%; 95% c.i: 5% to 10%) were HBsAg positive. Of the 29 anti-HCV positive patients with previous transfusion, the interval between the date of blood transfusion and the diagnosis of hepatic cirrhosis was 24 +/- 12.5 years and that of hepatocellular carcinoma was 26.8 +/- 12.4 years. These results confirm the high prevalence of HCV infection in patients with hepatocellular carcinoma and the slow sequential progression from HCV infection through cirrhosis and hepatocellular carcinoma.

Carcinoma, Hepatocellular↗

Determination of hepatitis delta virus RNA by polymerase chain reaction in acute and chronic delta infection.

The objective of this study was to evaluate the usefulness of hepatitis delta virus (HDV) RNA detection by polymerase chain reaction (PCR) in acute and chronic D hepatitis and to correlate with HDV-RNA detection by dot blot and hepatic delta antigen. Serum samples from 33 patients with acute hepatitis B surface antigen (HBsAg)-positive hepatitis (15 with hepatitis B and D coinfection, 8 with HDV superinfection, and 10 with acute hepatitis B), 85 patients with chronic HBsAg-positive hepatitis (73 with chronic D hepatitis and 12 with chronic B hepatitis), and consecutive serum samples from nine patients with chronic D hepatitis treated with interferon alfa-2b were studied. HDV-RNA was detected by PCR in 93% of the patients with hepatitis B and D coinfection, in 100% of the patients with hepatitis D superinfection, and in 1 of the 10 patients with acute hepatitis B who subsequently seroconverted to total antibody to hepatitis delta antigen (HDAg), whereas HDV-RNA was found by dot blot technique in 60% of the hepatitis B and D coinfection cases, in 62.5% of the patients with hepatitis D superinfection, and in none of the acute hepatitis B cases. In chronic D hepatitis, HDV-RNA tested positive by PCR assay in 97% of patients with intrahepatic HDAg, in one patient with undetectable hepatic HDAg, and in none of the patients with chronic hepatitis B. In the treated patients, HDV-RNA was observed to become negative by PCR only in the three patients who had a persistent response to interferon.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Comparative analysis of serological markers of chronic delta infection: HDV-RNA, serum HDAg and anti-HD IgM.

To study the concordance, sensitivity and specificity of HDV-RNA determination by molecular hybridization, serum HDAg by immunoblot and anti-HD IgM by commercial enzyme immunoassay as compared to intrahepatic HDAg detection by an immunoperoxidase method, a statistical analysis was applied to the results of serum sample and liver biopsy determinations in 50 patients with chronic delta hepatitis (38 positive to tissue HDAg and 12 negative). Of the 38 patients with hepatic HDAg, HDV-RNA was found in 31 (82%), serum HDAg by immunoblot in 27 (71%) and anti-HD IgM in 33 (87%). Among the 12 patients without hepatic HDAg, one was found with serum HDAg using the immunoblot technique, two (17%) had HDV-RNA, and 7 (58%) had anti-HD IgM. Serum HDAg determination by immunoblot was the most specific test, followed by HDV-RNA analysis. The least specific was the anti-HD IgM technique. The anti-HD IgM test was the most sensitive, followed by HDV-RNA and serum HDAg. The concordance with intrahepatic HDAg detection was highest for HDV-RNA determination, followed by HDAg in serum. The least degree of concordance was found with anti-HD IgM determination. These results suggest that the determination of HDV-RNA by the hybridization method can be of great value for the diagnosis and monitoring of chronic delta hepatitis.

Adolescent↗

Etiology of acute sporadic hepatitis in Spain: the role of hepatitis C and E viruses.

The aim of this study was to determine the prevalence of hepatitis viruses and analyze the epidemiological features in acute hepatitis in Spain. Consecutive serum samples from 341 patients with acute hepatitis were tested for IgM anti-hepatitis A virus, IgM anti-hepatitis B core antigen and HBsAg. The antibody to hepatitis C virus was determined using a second-generation enzyme immunoassay. In selected cases, serum was tested for antibodies for hepatitis E virus by enzyme immunoassay and hepatitis C virus-RNA by polymerase chain reaction. One hundred and fourteen (33.2%) cases of acute hepatitis were due to hepatitis A virus, 68 (20%) to hepatitis B virus, 21 (6%) to hepatitis D virus and 74 (21.8%) to hepatitis C virus infection. Of the 74 hepatitis C virus infections, 48 (65%) were anti-HCV positive at the time of diagnosis, while 26 (35%) seroconverted to anti-HCV later during follow-up. No case of hepatitis E virus infection was detected. The remaining 64 cases were negative to all acute serological markers and were classified as non-A, non-B, non-C, non-E hepatitis. Hepatitis C virus was implicated in 65/119 (54.6%) of the cases among intravenous drug users but in only in 9/199 (4.5%) of the sporadic cases (p < 0.01). Progression to chronic hepatitis was observed more frequently in anti-hepatitis C virus-positive than in antibody-negative-cases (42/70; 60% vs. 3/52 or 5.5%) (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗

Detection of hepatitis B precore mutants by the fluorescent linear polymerase chain reaction sequencing method.

To evaluate the presence of precore mutants, serum samples from 25 patients with chronic hepatitis B, HBV-DNA positive (5 HBeAg and 20 anti-HBe positive) were studied. The complete precore-core region of HBV-DNA was directly sequenced after polymerase chain reaction amplification by a fluorescent linear polymerase chain reaction sequencing method. Precore variants were detected in one HBeAg positive and in all 20 anti-HBe positive patients: in 19 cases, G to A at position 1896, with or without the substitution G to A at position 1899, in two cases C to T substitution at position 1817 which also produces a stop codon (CAA to TAA), one accompanied by the mutation G to A at position 1896. The only mutation observed in the patient who was initially HBeAg positive patient was a G to A substitution at position 1899. Consecutive serum samples from a patient with chronic hepatitis B, initially had the simultaneous presence of wild type and variant strains. Elimination of the wild-type strain was associated with reactivation of liver disease. Analysis of the sequences obtained demonstrated the heterogeneity of the hepatitis B virus genome in the precore-core region. These results indicate that the main cause of non-expression of HBeAg in chronic hepatitis B in our country is the substitution of G to A at nucleotide 1896, alone or accompanied by other variants. Fluorescent linear polymerase chain reaction is a fast and sensitive method to study heterogeneity in the precore-core region.

Amino Acid Sequence↗

Incidence and outcome of hepatitis C virus infection after liver transplantation.

The objective of this study was to determine the incidence and outcome of hepatitis C virus (HCV) infection after liver transplantation (OLT). Fifty-two transplanted patients were studied. Serum samples were examined for antibodies to HCV (anti-HCV) and HCV-RNA by PCR, before and after OLT. Patients were distributed into two groups: group 1 consisted of 24 patients (pretransplant anti-HCV positive) and group 2 consisted of 28 patients (pretransplant anti-HCV negative). One year after OLT, HCV-infected patients were evaluated by liver biopsy. HCV-RNA was detected in 28 of the 52 (53.9%) patients after OLT. Twenty-two patients in group 1 (96%) were reinfected. In group 2, acquired HCV infection was detected in six (21.4%) patients. At 6 and 12 months, one and five of six patients had seroconverted, respectively. Liver biopsy in 23 HCV-infected patients showed chronic hepatitis in 18 (78%) cases (2, chronic persistent hepatitis; 3, chronic lobular hepatitis and 13, chronic active hepatitis). Fourteen of the 23 (60.8%) patients were asymptomatic. Most symptomatic patients had chronic hepatitis with cholestasis. Overall, 18 of 20 cases of chronic hepatitis diagnosed in OLT recipients were HCV related. Mortality beyond 6 months after OLT was slightly higher in the HCV-infected group (P = 0.055). In conclusion, HCV reinfection is almost universal. Acquired HCV infection post-OLT is frequent. HCV-infected patients frequently develop chronic hepatitis. Most chronic hepatitis after transplantation are HCV related.

Adult↗

Dynamic behavior of hepatitis C virus quasispecies in patients undergoing orthotopic liver transplantation.

We have studied the distribution of viral sequences from the 5' noncoding region and from a fragment of the E2/NS2 region of the hepatitis C virus (HCV) genome in samples obtained before and after liver transplantation in two patients with HCV cirrhosis. The population of viral sequences in both regions were established by sequencing cloned PCR products. In both cases, the complexity of the viral quasispecies decreased after transplantation, although the consensus nucleotide and amino acid sequences remained unchanged. It is suggested that both positive and negative selection and random sampling events contribute substantially in shaping the genetic composition of HCV quasispecies and that recurrence of HCV infection may occur under equilibrium conditions.

Amino Acid Sequence↗

[Hepatocellular carcinoma: clinical aspects, diagnosis, and survival in 140 cases].

BACKGROUND: Hepatocellular carcinoma (HCC) constitutes a frequent clinical problem in the follow up of patients with liver cirrhosis. The clinical features and diagnoses and survival in a group of 140 cases of HCC are reviewed. METHODS: All the clinical histories of the patients diagnosed of HCC between 1987 and 1991 in the Unit of Hepatology of the General Hospital of the Vall d'Hebron were retrospectively reviewed. The clinical, analytical, diagnostic, therapeutic and evolutive data were collected. RESULTS: One hundred forty patients (121 males and 19 females) were included. In 92% of the cases the HCC was established on liver cirrhosis in which alcohol was the most frequent etiologic factor. According to the Pugh-Child classification 31% of the patients were in group A, 32.5% in group B and 36.4% in group C. Clinically, diagnosis was carried out in the course of periodic out patient follow up in 21% of the cases. HBsAg was positive in 8.5% of the cases and anti HCV was 55% and in 78% by ELISA 1 and ELISA 2, respectively. Alphafetoprotein (AFP) was greater than 500 ng/dl in 37% of the cases. The treatment received was: surgical resection in 18 cases, liver transplantation in 3, intraarterial chemotherapy in 11 and intratumoral alcoholization in 8. Symptomatic treatment was administered in 71% of the cases. Global mean survival was 4.4 +/- 0.5 months. Mean survival was greater in patients with better liver function and smaller tumor size in the patients surgically treated and in those diagnosed in the periodic controls. CONCLUSIONS: Hepatocellular cancer is normally established in patients with liver cirrhosis. The high prevalence of infection by the hepatitis C virus and the low prevalence by hepatitis B virus is of note. The patients with greater survival were those surgically treated and those diagnosed in periodic controls.

Aged↗

Detection of hepatitis delta virus RNA in human liver tissue by non-radioactive in situ hybridization.

Several studies have demonstrated the presence of serum HDV-RNA by molecular hybridization in patients with chronic D infection, but there is scarce information about the presence of HDV-RNA in hepatic tissue. The presence of HDV-RNA by in situ hybridization (ISH) with a non-radioactive probe in paraffin-embedded hepatic tissue was studied in 29 patients with chronic delta hepatitis (20 with and 9 without intrahepatic delta antigen) and correlate their presence with the expression of hepatic delta antigen and serum HDV-RNA by dot-blot hybridization. HDV-RNA was detected by in situ hybridization in 18 cases: 16 of the 20 (80%) biopsies with intrahepatic delta antigen and 2 of the 9 (22%) without. HDV-RNA was not detected in any of the control cases. Serum HDV-RNA was found in 19 cases: 18 (90%) of 20 chronic delta hepatitis cases with tissular delta antigen and one of the 9 without intrahepatic delta antigen. All patients except one, who was positive for intrahepatic HDV-RNA, showed serum HDV-RNA. However, in two cases ISH detected hepatic HDV-RNA without tissular HDAg; one of these also had serum HDV-RNA and in the other positivity for hepatic HDV-RNA by ISH was the only marker of viral delta replication. In conclusion, detection of HDV-RNA in hepatic tissue by in situ hybridization with a digoxygenin-labelled probe is a rapid and sensitive method that could be a useful tool for diagnosis of HDV infection in clinical laboratories.

DNA Probes↗

Disappearance of serum hepatitis B virus DNA by polymerase chain reaction after adenine arabinoside 5'-monophosphate therapy in chronic hepatitis B.

The aim of antiviral therapy in chronic hepatitis B is the cessation of viral replication, which may be demonstrated by the loss of hepatitis B "e" antigen (HBeAg) and serum hepatitis B virus DNA (HBV-DNA) detected by dot-blot hybridization. With the development of the sensitive polymerase chain reaction (PCR) technique for detecting HBV-DNA, it has become apparent that many HBeAg negative patients may still have small amounts of circulating viral DNA. We assessed 19 of 25 patients with chronic hepatitis B who seroconverted from HBeAg to anti-HBe after adenine arabinoside 5'-monophosphate therapy (5 mg.kg-1.day-1 for 7 weeks) to determine whether serum HBV-DNA became undetectable. Sixteen of the 19 HBeAg negative patients remained hepatitis B surface antigen (HBsAg) positive, and the other three lost HBsAg during follow-up. All of them were HBV-DNA negative by dot-blot hybridization. Using the PCR technique, HBV-DNA became negative in 13 (81.2%) of the 16 patients who seroconverted to anti-HBe without losing HBsAg, and in all the patients who lost HBsAg. These data suggest that the majority of patients who respond to adenine arabinoside 5'-monophosphate show a complete inhibition of hepatitis B virus replication, as demonstrated by the absence of viral DNA by PCR. This inhibition was present in all patients who, at the same time, lost HBsAg.

Adult↗

Hepatitis C virus markers in patients with acute post-transfusion hepatitis treated with interferon alfa-2b.

This trial was undertaken to establish the long term biochemical and serological outcome of patients with acute post-transfusion hepatitis C virus infection after treatment with interferon alfa-2b. After 12 months, 12 patients (eight treated, four controls) had self limited disease and 16 patients (seven treated, nine controls) had chronic disease. After a total mean 31 months of follow up in 23 patients, nine (six treated, three controls) had self limited disease while 14 (five treated, nine controls) developed chronic liver disease; all patients with spontaneous or self limited hepatitis C (HCV) infection maintained normal serum alanine amino-transferase activity and absence of HCV-RNA, and tended to lose anti-HCV antibodies.

Acute Disease↗

Findings on Doppler echocardiography in asymptomatic intravenous heroin users.

To detect potential cardiac abnormalities induced by intravenous heroin use, 68 persons without a previous episode of infective endocarditis were studied by Doppler echocardiography. A control group of 41 normal subjects was studied for comparison. The following measurements were considered: (1) diameter of heart chambers, (2) systolic left ventricular function, (3) morphologic valvular abnormalities, (4) presence of valve regurgitations, (5) Doppler indexes of diastolic function, and (6) estimation of pulmonary arterial resistances. Results showed no significant differences regarding the size of the heart chambers or systolic left ventricular function. A significantly higher incidence of valvular abnormalities (focal thickening or valve prolapse) was found in drug addicts (p = 0.0009) at the mitral and tricuspid valves, as was valvular regurgitation detected by Doppler (p = 0.04). Also, a significantly prolonged deceleration time of mitral and tricuspid early diastolic Doppler flow was found in the study group (p = 0.0001 and 0.027, respectively) although a different hemodynamic condition in the study group (pharmacologically reduced preload) precluded these findings to be attributable to an actual diastolic dysfunction. No differences were observed in pulmonary arterial resistances. It is concluded that mitral and tricuspid valve abnormalities can be detected by echocardiography in asymptomatic intravenous heroin users, whereas no apparent effects are observed in morphologic or functional parameters of cardiac structures other than the valves.

Adolescent↗