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ABSTRACT: The xenobiotic nuclear pregnane X receptor is implicated in many physiological pathways and diseases, including bile acid detoxification and cholestasis. Aim To estimate the contribution of common gene variants of the xenobiotic receptor (pregnane X receptor, PXR) to genetic susceptibility to intrahepatic cholestasis of pregnancy.
A total of 101 intrahepatic cholestasis of pregnancy patients and 171 healthy pregnant women in the third trimester of their pregnancies were included. Four tag single nucleotide polymorphisms (SNPs) (rs12488820 C/T, rs2472671 C/T, rs2461823 A/G, and rs1054191 A/G) encompassing 36 kb in chromosome 3, with a minor allele frequency > or =0.10 and representing 33 polymorphic sites were genotyped. Besides these, three additional SNPs (rs3814057, rs6785049, and rs7643645) were included because they showed previous evidence of functionality.
Genotypic test for single SNPs showed that rs2461823 genotypes were significantly associated with intrahepatic cholestasis of pregnancy (P < 0.0069), OR per G allele: 1.44, 95% CI: 1.01-2.05, P < 0.042. The Cochran-Armitage test for trend and the allelic test showed a significant association with disease status (P < 0.04 and 0.03 respectively), G being the risk allele. A positive association between rs2461823 and ALT, AST, and bilirubin concentrations was observed. Neonate birth weight adjusted by the Capurro index was significantly associated with rs2461823 (P < 0.05); the proportion of the total variation attributed to rs2461823 genotypes was 7.8%.
Common PXR polymorphisms may contribute to the genetic susceptibility to intrahepatic cholestasis of pregnancy.
Alimentary Pharmacology & Therapeutics 12/2009; 31(5):583-92. · 3.77 Impact Factor
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ABSTRACT: Our aim was to investigate if interferon plus ribavirin has any effect on serum HCV quasispecies distribution and the relationship between diversity of HCV quasispecies and treatment response. In all, 21 patients were treated with interferon plus ribavirin for 48 weeks. The presence of HCV quasispecies was determined in serum samples at baseline and at the fourth week of treatment by SSCP analysis of the hypervariable region. SSCP pattern was defined as single or multiple band. A single band was found in six patients and multiple bands in nine. No significant difference was found between SSCP pattern in pretreatment samples and response to the therapy. In none of the patients were observed changes in number of SSCP bands between samples taken at baseline and in the fourth week of the therapy. In conclusion, the complexity of HCV quasispecies before the therapy was not related to treatment response; combined therapy did not affect serum HCV quasispecies.
Digestive Diseases and Sciences 06/2001; 46(5):1067-71. · 2.12 Impact Factor
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The American Journal of Gastroenterology 07/2000; 95(6):1602-4. · 7.28 Impact Factor
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ABSTRACT: The aim of this work was to assess if the diversity of hepatitis C virus (HCV) quasispecies is related to histological severity and duration of infection in a cohort of untreated patients with an estimated onset of the disease. A total of 27 patients with diagnosis of chronic liver disease and history of blood transfusion (n = 16) or intravenous drug use (IDU) (n = 11) were included. All were anti-HCV positive and had detectable serum HCV-RNA. The onset and the duration of the disease were estimated from the time of the transfusion or the first drug injection. Patients who consumed drugs for more than 2 years, or were coinfected with HBV or HIV were excluded. History of alcohol intake (> 80 g/day), ALT level and age at infection were recorded. Histological assessment of grading and staging was performed according to Knodell score. The quasispecies diversity was investigated by single strand conformation polymorphism (SSCP) targeted to HVR-E2 region and SSCP pattern was evaluated as a single or multiple bands. The number of quasispecies did not correlate with the estimated duration of the disease. Patients who acquired hepatitis C by blood transfusion did not differ in number of bands from patients who were IDU. There was no correlation between the heterogeneity of HCV quasispecies and age, serum ALT, Knodell score, HAI and fibrosis. In conclusion the quasispecies diversity of E2 had no correlation with grade and stage of chronic HCV infection and the presence of quasispecies was independent of the duration of the disease.
Medicina 01/2000; 60(5 Pt 1):587-90. · 0.47 Impact Factor
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Archives of Dermatology 09/1999; 135(8):1000-1. · 3.89 Impact Factor
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ABSTRACT: There are increasing molecular and clinical evidences that the effects of human immunodeficiency virus (HIV) infection can be modified by coinfection with other viruses. The objective was to investigate the viral interaction between HIV and hepatitis C virus (HCV) after HCV superinfection. A 16 year-old pregnant woman was evaluated because of icteric acute hepatitis. Admission laboratory tests showed the following results: ALT 877 IU/L; AST 1822 IU/L; bilirubin 6.79 mg/dl. Diagnosis of acute HCV was based on detection of serum HCV RNA by PCR and anti-HCV seroconversion. ELISA for anti HIV testing was positive and confirmed by western blot. Serum markers for other viruses were negative. The patient was followed during 19 months; serum samples were taken monthly during this period for detection of plasma HIV and HCV RNA. Levels of plasma HIV-RNA were positive in all samples tested before and after the onset of acute hepatitis C. Six months later and a for two month period, and 13 months later for a period of one month HIV viremia was undetectable; then HIV-RNA in plasma was detectable again. In conclusion, HCV superinfection may have temporarily interfered with HIV replication in our patient. The following observations support our hypothesis: it has been demonstrated that HIV-1 replication is suppressed by HCV core protein which has transcriptional regulation properties of several viral and cellular promoters. Clinical implications of this event are not generally known and the interaction between these two viruses in dual infections is worth considering.
Medicina 02/1999; 59(4):364-6. · 0.47 Impact Factor
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ABSTRACT: We investigated the possible role of hepatitis G virus (HGV or GBV-C) in the aetiology of acute non-A-E hepatitis in Argentina by detecting viral RNA in sera by reverse transcriptase-polymerase chain reaction (RT-PCR) using primers specific for the putative NS3 helicase region of HGV. Sixty two patients with acute hepatitis were included in this study. The absence of hepatitis A-E was confirmed by serological testing, and all patients were negative for HCV RNA and autoimmune markers. All patients denied alcohol intake and the use of hepatotoxic drugs. Their mean age was 35.3 years and 37 were males. HGV RNA was present in 19/62 (30.6%) of the patients with non-A-E acute hepatitis. Among HGV-positive patients, three had parenteral risk factors within 3 months of onset, one was a health care worker, one was sexually promiscuous, one had travelled to the Middle East and 13 (68.4%) had no history of parenteral exposure. Epidemiological, clinical and biochemical features between HGV-positive and negative patients did not achieve statistical significance. Hence, HGV appears to play a role in the pathogenesis of acute viral hepatitis; however, the etiology of a significant number of hepatitis cases remains unclear, suggesting the existence of an additional agent(s). The absence of parenteral exposure in most of the HGV RNA-positive patients in this study shows that routes of community-acquired HGV infection are not yet completely understood.
Journal of Viral Hepatitis 06/1998; 5(3):161-4. · 4.09 Impact Factor
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ABSTRACT: To analyze the changes in portal pressure, blood flow and resistance after propranolol administration, and to assess the predictive value of the variations of Doppler Duplex Ultrasonography (DDU) measurements according to the response of the hepatic venous pressure gradient (HVPG).
30 cirrhotic patients were studied. Assessment of systemic hemodynamics and HVPG were performed in baseline and after intravenous propranolol administration (0.15 mg/kg). Patients who showed a decrease > or = 20% &/or < 12 mm/Hg in HVPG were considered responders. The DDU study was performed in blind conditions, in baseline and after propranolol. Measurement of blood flow of the portal vein, splenic vein and femoral artery were performed. Portal resistance was calculated as HVPG/portal blood flow.
All patients were beta blocked and 14 (47%) were responders. There were no significant differences in systemic or splachnic hemodynamic baseline data between responders and non responders. Femoral blood flow decreased in both groups. Splenic and portal blood flow decreased significantly only in responders. No significant difference was found in the variation of portal resistance between responders and non responders; when these changes were considered individually, a great variability was found in both groups. A decrease > or = 15% in splenic blood flow showed a positive predictive value of 88%, a lack of a similar decrease in portal blood flow showed a negative predictive value of 86%.
The decrease in portal blood flow was the main factor in determining the response to propranolol.
Acta gastroenterologica Latinoamericana 02/1998; 28(4):291-7.
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J F Quarleri,
B H Robertson,
V Mathet,
S D Sinha,
I Badía,
B Frider,
A Ferro,
C Galoppo,
S Sookoian, G Castaño,
J R Oubiã
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ABSTRACT: HCV genomic characterization was performed by nucleotide sequence analysis (n=50) combined with restriction fragment length polymorphism (RFLP) of the 5' UTR region in 82 isolates corresponding to different Argentine groups. Genotype 1 was detected in 70.7% of the samples (58 out of 82), genotype 2 in 21.9% (18 of 82) and genotype 3 in the remaining 6 sera (7.3%). HCV 1b subtype contributed with 35.3% to the whole population studied (29 to 82) and was detected in 6 out of 21 sporadic cases. Besides their epidemiological significance, these results should be taken into account when future vaccines are considered on the basis of geographical HCV genotypic prevalence.
Medicina 02/1998; 58(2):153-9. · 0.47 Impact Factor
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ABSTRACT: Our aim was to identify prospectively, with a case-control survey, risk factors for hepatitis C virus (HCV) infection in volunteer blood donors and to assess the histological features and their correlation with transaminase (ALT) level and viremia. In a Liver Unit of a referral-based University Hospital, 248 blood donors were evaluated for risk factors, according to definitive ELISA test and 132 were considered true positive. Of these, 132 anti-HCV(+) blood donors were age and sex-matched with the anti-HCV-negative group (n = 116). There was a high frequency in the anti-HCV(+) group of intravenous drug abuse (IVDA) (22%), history of major surgery (20.4%), tattooing (12.1%), non IVDA (17.4%), and multiple sexual partners or history of sexual transmitted diseases (25.7%). At least one risk factor was identified in 76.52% of the antiHCV(+) donors vs 34.4% in the anti-HCV (-) group (p = 0.000). A total of 71 patients accepted a liver biopsy; chronic liver disease was present in 85.9% (n = 61) (mean Knodell score 6.75). ALT was elevated in 69% (n = 49) and HCV RNA was detectable in 76% of patients. It can be concluded that in our study 76.5% of anti HCV positive blood donors showed at least one risk factor for HCV infection detected by a second highly efficient interview. Twenty two percent admitted to prior intravenous drug use although this disqualifies them for blood donation, but was not identified by the screening process. Most blood donors with anti HCV(+) had chronic hepatitis C regardless of their serum ALT levels. Normal ALT did not exclude liver disease.
Medicina 02/1997; 57(6):699-707. · 0.47 Impact Factor
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ABSTRACT: In cases of psoriasis (PS), the etiology of the underlying liver disease is occasionally unknown. To investigate antibodies to hepatitis C virus (anti-HCV), their prevalence and clinical significance, 118 unselected outpatients with PS were studied prospectively.
Anti-HCV was assayed in serum by second-generation enzyme-linked immunosorbent assay (ELISA), considering a serum anti-HCV (+), when the optical density ratio was equal to or greater than three times the cut-off value, in duplicate determinations, whereas anti-HBc, anti-HBs, HBsAg, anti-HBe, and HBeAg were also evaluated by ELISA, as were the transaminases. As controls we took the 1.2% anti-HCV prevalence found in 60,000 blood donors from Buenos Aires city.
Nine of 118 serum samples (7.6%) proved to be anti-HCV (+) (P < 0.001). There were no differences between positive and negative cases as regards gender, age, history of hepatitis, transfusions, or parenteral exposure, disease duration, or psoriasis type, and prior treatment with methotrexate and etretinate. Fifteen percent (17/113) were anti-HBc (+), 64.7% anti-HBs (+) (11/17) and 2.5% HBsAg (+) (3/17), whereas 3/17 (2.5%) showed isolated anti-HBc positivity. Liver biopsies in six anti-HCV patients disclosed four with chronic active hepatitis, one with cirrhosis, and one with steatosis.
In the presence of liver disease in PS patients, an HCV infection should be considered as an alternative diagnosis. The high anti-HCV prevalence in this series is attributable to infection by inapparent parenteral routes, through minute skin abrasions, as reported for hepatitis B virus in PS.
International Journal of Dermatology 12/1996; 35(11):797-9. · 1.14 Impact Factor
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Hepatology 07/1995; 21(6):1764-5. · 11.66 Impact Factor
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Medicina 02/1994; 54(3):285-6. · 0.47 Impact Factor
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ABSTRACT: The aim of this study was to evaluate the prevalence of antibodies to hepatitis C virus (anti-HCV) in health-care workers (HCW). Sera from 439 unselected HCW were assessed for anti-HCV by 2nd generation enzyme-linked immunoassay (ELISA) and anti-HBc by ELISA. Anti-HCV (+) sera were evaluated by line immunoassay (LIA) (LiaTeK, Organon). Anti-HCV proved positive by ELISA in 12 (2.73%) subjects, 6 of whom were reactive by LIA, one was indeterminate and 5 non reactive. The prevalence of anti-HCV confirmed by LIA was 1.59% (7 subjects). Positive anti-HCV results with an ELISA ratio greater than 3 were LIA reactive in 6/6 as compared with 5 LIA non reactive with an ELISA ratio less than 2, while in the indeterminate serum the ratio was 2.5. No differences in age, profession, seniority, history of hepatitis or transfusions were found between anti-HCV (+) and (-) subjects, but females predominate significantly. The areas of higher risk were hemodialysis, obstetrics, surgery and intensive care. Anti-HBc was (+) in 85.7% (6/7) of the anti-HCV (+) subjects. Follow-up of anti-HCV (+) subjects showed raised alaninoaminotransferase levels in 4 cases, while liver biopsies in 3 disclosed cirrhosis, chronic active hepatitis and chronic persistent hepatitis. The anti-HCV prevalence in HCW is low compared with other risk groups perhaps due to the peculiar epidemiological features of HCV. In low risk groups for HCV infection a positive ELISA result with a ratio lower than 3 should be confirmed by more specific tests.
Acta gastroenterologica Latinoamericana 02/1994; 24(2):71-5.
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ABSTRACT: The risk of HBV and HCV liver infection in kidney graft recipients was evaluated in 35 patients. All were tested for anti-HBc, HBsAg, HBeAg, anti-HBs, Anti-HBe, anti-HCV (c-100-3 and c-100-3, c-22, 33-c), anti-HDV and anti-HIV by ELISA, and for HBV-DNA by hybridization. Liver biopsy, immunostaining for HBcAg and Knodell's hepatic inflammatory index were performed in 18. Mean time elapsing form transplant to inclusion was 20.7 months (range 1-108). HBsAg was the only marker searched for prior to transplant. Twenty six (74.2%) patients presented HBV and/or HCV markers, while 9 (25.8%) had none; 16 (45%) proved anti-HBc+, 6(17.1%) HBsAg+, (3 HBeAg+ and 3 anti-HBe+), 7 (20%) anti-HBs+ and 3 (8.5%) isolated anti-HBc. Anti-HCV (C-100-3) was positive in 9/32 (28.1%), while 2nd. generation anti-HCV was positive in 20/35 (57.1%) cases. No false positives for 1st. generation test were found. Both anti-HDV and anti-HIV were negative in all the sample. Raised aminotransferases were present in 13/30 (43.3%), 7 in anti-HCV+, one in HBsAg+ and 3 in HBsAg+/HCV+ cases, but normal in 17/30 (56.6%). History of Transfusion and Hemodialysis time showed no significant differences between anti-HCV+ and anti-HCV negative cases. Biopsy disclosed 10 chronic persistent hepatitis (CPH), one chronic active hepatitis (CAH) with cirrhosis, one inactive cirrhosis (Ci) 4 minimal lesions (MHL) and 2 normal. Seven CPH, 3 MHL. one normal and both cirrhosis cases proved anti-HCV+. HBsAg was positive in the single CAH, in 2 CPH and in one MHL.(ABSTRACT TRUNCATED AT 250 WORDS)
Acta gastroenterologica Latinoamericana 02/1993; 23(2):75-81.
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ABSTRACT: The risk of contracting hepatitis B: (HBV) by health workers is widely accepted. In 1989 our Hepatology Service started a voluntary anti-HBV vaccination program, employing recombinant vaccine (SKF) by intramuscular route with a 0-1-6 month schedule after screening with antibody against the anti-core HBV antigen (AntiHBc Elisa Abbott). Initially, it was planned to monitor antibody titers against superficial antigen (Anti-HBs) 30 days after the last dose. An epidemiological form listing personal data, working area, profession, seniority, written consent for blood extraction and tentative acceptance of vaccination, was completed by 357 hospital staff members. After serological screening, only 184 (51%) workers agreed to receive vaccination. Given the paucity of volunteers, an attempt was made to explain this degree of reluctance by a randomized blind voluntary survey, to which 349 hospital staff members and 40 medical students replied. Questions were related to knowledge concerning vaccination in general, hepatitis and particularly hepatitis B, and specific anti-HBV vaccination. An appraisal of data gathered disclosed a considerable lack of information not only on the risk of HBV infection and its complications, but also on the existence of a suitable vaccine. Non-existent adverse effects of vaccination were mentioned, including AIDS (Acquired Immuno-Deficiency Syndrome), hepatitis and cirrhosis, among others. To overcome this obstacle, we held a two-day workshop on hepatitis B prevention and prophylaxis intended for medical and ancillary staff. After the meeting, which were attended by 221 members, 48 individuals, comprising 25 physicians and 23 nurses, spontaneously requested to be vaccinated.(ABSTRACT TRUNCATED AT 250 WORDS)
Acta gastroenterologica Latinoamericana 02/1992; 22(1):29-35.
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ABSTRACT: Forty-nine patients with a diagnosis of idiopathic haemolytic uraemic syndrome (HUS) were investigated to determine evidence of infection by verotoxin-producing Escherichia coli (VTEC). Free faecal cytotoxin active on Vero cells (VT) was detected in 15 out of 49 patients (31%). Seroconversion or high titres of VT-neutralizing antibodies were detected in 11 out of 18 patients (61%). The results of the present study suggest an association between HUS and infection by VTEC.
Pediatric Nephrology 08/1988; 2(3):288-90. · 2.52 Impact Factor
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ABSTRACT: To study the acute variations in portal and systemic hemodynamics after propranolol and 5-isosorbide mononitrate (IMN) administration in cirrhotic patients.
Seventeen cirrhotic patients with portal hypertension were studied with catheterization and Doppler duplex Ultrasound Systemic hemodynamics. Hepatic venous pressure gradient (HVPG), portal blood flow and resistance were evaluated in baseline, after intravenous propranolol (0.15 mg/kg), and after 20 mg p.o. of IMN. Patients who showed a decrease > or = 20% and/or < 12 mm/hg in HVPG were considered responders.
There were no significant differences in clinical or portal hemodynamic baseline data between responders and non-responders to the drugs. After propranolol administration cardiac index decreased (p < 0.05) and pulmonary capillary pressure increased (p < 0.0001). Six patients (35%) were responders; lack of response was associated with an insufficient decrease in portal blood flow or with an increase in portal resistance. After IMN administration cardiac index decreased (p < 0.05) with normalization of pulmonary capillary pressure (p < 0.05). Seven patients were responders to the addition of IMN (5 non-responders to propranolol) and showed a decrease in HVPG associated with a reduction in portal blood flow and resistance; in the remaining 10 patients HVPG did not decrease despite a reduction in portal blood flow, with an increase in portal resistance.
Addition of IMN increased the number of responders and reduced portal blood flow with a variable effect in portal resistance.
Gastroenterología y Hepatología 23(6):275-81. · 0.73 Impact Factor
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ABSTRACT: Rubella virus antibodies were measured in 85 sera from pregnant women by using a new latex test, and the results were compared with those obtained by using hemagglutination inhibition. The sensitivity of the latex test was 98.4%, specificity was 66.6% and the predictive value of a positive result was 90%. The latex test is a simple test and has much shorter reaction time than that of the hemagglutination inhibition.
Revista Argentina de microbiología 19(4):173-5. · 0.50 Impact Factor
