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Raúl J Andrade

Publications and source records attributed to Raúl J Andrade.

At least 19 recordsLinked to original sources
PubMed2006

Prolonged cholestasis after raloxifene and fenofibrate interaction: A case report.

Assigning causality in drug-induced liver injury is challenging particularly when more than one drug could be responsible. We report a woman on long-term therapy with raloxifen who developed acute cholestasis shortly after starting fenofibrate. The picture evolved into chronic cholestasis. We hypothesized that an interaction at the metabolic level could have triggered the presentation of hepatotoxicity after a very short time of exposure to fenofibrate in this patient. The findings of an overexpression of vascular endothelial growth factor in the liver biopsy suggest that angiogenesis might play a role in the persistence of toxic cholestasis.

Biopsy↗
PubMed2006

Adverse hepatic reactions associated with calcium carbimide and disulfiram therapy: is there still a role for these drugs?

Disulfiram and calcium carbimide are two alcohol deterrants widely used in alcoholism treatment, however, there exist great concerns over their safety. Reports on hepatotoxicity, mainly related to disulfiram therapy, have been published. The hepatotoxic potential of calcium carbimide is less well characterized. Here, we describe four cases of liver damage related to this therapeutic group that were submitted to a Registry of hepatotoxicity and point out the limitations that we face when prescribing these compounds. A reassessment of the role of these compounds in the management of alcohol dependence is clearly needed.

Adult↗
PubMed2006

Determinants of the clinical expression of amoxicillin-clavulanate hepatotoxicity: a prospective series from Spain.

Amoxicillin-clavulanate (AC) hepatotoxicity has been reported to exhibit a higher predominance of cholestatic types of damage, especially in males. However, the determinants of its clinical expression are unknown. This study prospectively evaluated the profile of AC hepatotoxicity. Data on all cases of hepatotoxicity reported to the Spanish Registry attributed to AC and assessed as definite or probable on the Council for International Organizations of Medical Sciences (CIOMS) scale were collated and compared to published case series. Hepatotoxicity related to amoxicillin-clavulanate was identified in 69 patients (36 males; mean age 56 years) representing 14% of all cases of hepatotoxicity submitted to the Registry. There was an overall sex distribution and the predominant pattern of lesion was hepatocellular (36%) which occurred at a shorter duration of treatment (P < .03). Mean time lapse between therapy initiation and jaundice onset was 16 days. Late onset of symptoms following end of treatment occurred in half the cases. Multiple logistic regression analysis identified advancing age as the factor associated with the development of cholestatic/mixed type of injury (odds ratio for an age interval for 1 year: 1.045 [95% CI = 1.013-1.078; P = .005). An unfavorable outcome was seen in 7% of patients. In conclusion, age is the most important determinant in the biochemical expression of AC hepatotoxicity; younger age is associated with cytolytic damage and shorter treatment duration, whereas cholestatic/mixed type of damage is related to older age and prolonged AC therapy.

Adolescent↗
PubMed2006

Vascular ophthalmological side effects associated with antiviral therapy for chronic hepatitis C are related to vascular endothelial growth factor levels.

We have screened for the incidence of vascular ophthalmological side effects (VOSE) in chronic hepatitis C (CHC) patients undergoing pegylated interferon (peg-IFN) plus ribavirin (RBV) therapy and sought evidence for angiogenesis activation. Thirty-four CHC patients were prospectively evaluated (18 patients with 180 microg/week of peg-IFN-alpha2a plus 800mg/day of RBV and 16 with 1.5 microg/kg/week of peg-IFN-alpha2b plus 800-1,200mg/day of RBV). Complete ophthalmological evaluation and serum vascular endothelial growth factor (VEGF) levels were assessed before and at the end of therapy. Thirteen patients (38.2%) developed VOSE, eight (23.5%) featured subconjunctival haemorrhage, and five (14.7%) had evidence of retinopathy - all were unrelated to age, sex, genotype, the type of antiviral schedule used and response to therapy. At the end of treatment, the VOSE group had significantly higher serum VEGF levels than the group of patients without detectable side effects (median 281 [range 106-386] vs 117 [83-225] pg/ml, P=0.05). These differences increased when VEGF values were corrected by platelet count. In the VOSE group, baseline VEGF and VEGF/platelet values were also significantly higher (164 [55-260] vs 64 [21-172] pg/ml, P=0.046; and 0.920 [0.217-1.543] vs 0.320 [0.100-0.661] pg/10(6) platelets, P=0.024, respectively]. In a multivariate model VEGF/platelet values at end of treatment and hepatic fibrosis stage were the only predictors of VOSE development. In 3 out of 13 patients visual acuity was affected and 2 had residual lesions in the follow-up. In this exploratory study, antiviral therapy of CHC frequently induces VOSE, apparently through an activation of angiogenesis.

Adult↗
PubMed2005

HIV coinfection shortens the survival of patients with hepatitis C virus-related decompensated cirrhosis.

The impact of human immunodeficiency virus (HIV) coinfection on the survival of patients with hepatitis C virus (HCV)-related end-stage liver disease (ESLD) is unknown. Because HIV infection is no longer considered an absolute contraindication for liver transplantation in some countries, it has become a priority to address this topic. The objective of this study was to compare the survival of HIV-infected and HIV-uninfected patients with decompensated cirrhosis due to HCV. In a retrospective cohort study, the survival of 1,037 HCV monoinfected and 180 HCV/HIV-coinfected patients with cirrhosis after the first hepatic decompensation was analyzed. Of the group, 386 (37%) HCV-monoinfected and 100 (56%) HCV/HIV-coinfected subjects died during the follow-up. The median survival time of HIV-infected and HIV-uninfected patients was 16 and 48 months, respectively (P < .001). The relative risk (95% CI) of death for HIV-infected patients was 2.26 (1.51-3.38). Other independent predictors of survival were age older than 63 years (2.25 [1.53-3.31]); Child-Turcotte-Pugh class B versus class A (1.95 [1.41-2.68]) and class C versus class A (2.78 [1.66-4.70]); hepatitis D virus infection (1.56 [1.12-4.77]); model for end-stage liver disease score, (1.05 [1.01-1-11]); more than one simultaneous decompensation (1.23 [1.12-3.33]); and the type of the first hepatic decompensation, with a poorer prognosis associated with encephalopathy compared with portal hypertensive gastrointestinal bleeding (2.03 [1.26-3.10]). In conclusion, HIV coinfection reduces considerably the survival of patients with HCV-related ESLD independently of other markers of poor prognosis. This fact must be taken into account to establish the adequate timing of liver transplantation in HIV-coinfected subjects.

Adult↗
PubMed2005

Drug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period.

BACKGROUND & AIMS: Progress in the understanding of susceptibility factors to drug-induced liver injury (DILI) and outcome predictability are hampered by the lack of systematic programs to detect bona fide cases. METHODS: A cooperative network was created in 1994 in Spain to identify all suspicions of DILI following a prospective structured report form. The liver damage was characterized according to hepatocellular, cholestatic, and mixed laboratory criteria and to histologic criteria when available. Further evaluation of causality assessment was centrally performed. RESULTS: Since April 1994 to August 2004, 461 out of 570 submitted cases, involving 505 drugs, were deemed to be related to DILI. The antiinfective group of drugs was the more frequently incriminated, amoxicillin-clavulanate accounting for the 12.8% of the whole series. The hepatocellular pattern of damage was the most common (58%), was inversely correlated with age (P < .0001), and had the worst outcome (Cox regression, P < .034). Indeed, the incidence of liver transplantation and death in this group was 11.7% if patients had jaundice at presentation, whereas the corresponding figure was 3.8% in nonjaundiced patients (P < .04). Factors associated with the development of fulminant hepatic failure were female sex (OR = 25; 95% CI: 4.1-151; P < .0001), hepatocellular damage (OR = 7.9; 95% CI: 1.6-37; P < .009), and higher baseline plasma bilirubin value (OR = 1.15; 95% CI: 1.09-1.22; P < .0001). CONCLUSIONS: Patients with drug-induced hepatocellular jaundice have 11.7% chance of progressing to death or transplantation. Amoxicillin-clavulanate stands out as the most common drug related to DILI.

Adolescent↗
PubMed2005

Insulin resistance impairs sustained response rate to peginterferon plus ribavirin in chronic hepatitis C patients.

BACKGROUND & AIMS: We evaluated the effect of insulin resistance and viral factors on sustained virological response in patients with chronic hepatitis C treated with peginterferon plus ribavirin. METHODS: Patients (n=159; 94 men; age, 41.7 +/- 11.1 years) with chronic hepatitis C (genotype 1, n=113; non-1 genotype, n=46) received treatment with interferon plus ribavirin. Serum levels of leptin and insulin were measured, and the insulin resistance index (HOMA-IR: homeostasis model of assessment) and body mass index were calculated. RESULTS: A sustained virological response was associated with lower age, insulin resistance index, body mass index, and gamma-glutamyltranspeptidase and serum leptin levels. There was no association with viral load, sex, type of interferon, or cholesterol levels. A sustained virological response was achieved in 43.4% (46/113) of genotype 1 and 89% (32/36) of genotype 2 and 3 (P=.0001) patients. Necroinflammatory activity and steatosis were not associated with the sustained virological response rate. Multivariate regression analysis indicated that the independent variables related to sustained virological response were genotype (odds ratio, 3.57; 95% confidence interval, 1.49-8.3; P=.001), insulin resistance index (odds ratio, 1.82; 95% confidence interval, 1.08-3.06; P=.012), and fibrosis (odds ratio, 1.36; 95% confidence interval, 1.01-1.84; P=.029). A sustained virological response in patients with genotype 1 and insulin resistance (HOMA-IR > 2) occurred in 23 of 70 (32.8%; 95% confidence interval, 21.9%-43.9%) patients, vs. 26 of 43 (60.5%; 95% confidence interval, 45.9%-75.1%) genotype 1 patients without insulin resistance (P=.007; odds ratio, 3.12, 95% confidence interval, 1.42-6.89). CONCLUSIONS: Insulin resistance, fibrosis, and genotype are independent predictors of the response to antiviral therapy in chronic hepatitis C patients treated with peginterferon plus ribavirin.

Adult↗
PubMed2005

The administration of N-acetylcysteine causes a decrease in prothrombin time in patients with paracetamol overdose but without evidence of liver impairment.

OBJECTIVE: To explore the effect of intravenous N-acetylcysteine (NAC) on the prothrombin time (PT) in patients with paracetamol overdose and persistent normal liver profile. MATERIALS AND METHODS: This retrospective case series study examined all admissions with a diagnosis of paracetamol poisoning in a tertiary hospital between 1989 and 2002. Patients were included if they had ever received NAC infusion, had no biochemical evidence of liver damage, and had more than two measurements of PT. Patients who had also ingested other drugs were excluded. RESULTS: Of 65 admissions wtih paracetamol poisoning, 18 patients (10 men) met the inclusion criteria. The median age was 29 years, and the median quantity of paracetamol ingested was 186 mg/kg. The mean number of PT measurements per patient was 4.8. The baseline PT (as a percentage) 8.6 h after paracetamol ingestion was 89.6%. During NAC infusion the PT fell in all patients (range, 4.8-53.4% relative to baseline; P < 0.0001) at 14 h. The PT was less than 60% in 28% of the patients. Eight hours after the initiation of NAC there was a 16% fall in PT (range, 4.3-34%; P < 0.0001). At the end of NAC infusion all PTs returned to values close to baseline. Nine patients were hospitalized. CONCLUSIONS: In patients with paracetamol overdose without evidence of liver damage a marked decrease in PT often occurs, which seems to be due to the overload of NAC infused at the beginning of treatment. This particular feature should be noted in clinical practice guidelines as a potentially misleading indicator of the development of severe liver dysfunction.

Acetaminophen↗
PubMed2004

HLA class II genotype influences the type of liver injury in drug-induced idiosyncratic liver disease.

Drug-induced idiosyncratic liver disease (DIILD) depends largely on host susceptibility factors. Small studies support the genetic influence of human leukocyte antigen (HLA) class II molecules on the predisposition to DIILD. We sought associations between HLA-DRB and -DQB alleles and DIILD considered collectively or according to the biochemical expression of liver damage. We studied a total of 140 patients with a definitive or probable diagnosis of DIILD, as assessed with the Council for International Organizations of Medical Sciences scale, with 635 volunteer bone marrow and blood donors serving as controls. HLA-DRB1* and -DQB1* genotyping was performed by hybridization with sequence-specific oligonucleotides after genomic amplification. The group with DIILD did not differ from control subjects with regard to the distribution of HLA-DRB and -DQB antigens. The frequencies of alleles DRB1*15 (35.4% vs. 18.6% of controls; P =.002; odds ratio [OR] 2.31) and DQB1*06 (61.5% vs. 40.8%; P =.001; OR 2.32) were significantly increased in patients with the cholestatic/mixed type of liver damage in comparison to healthy subjects. By contrast, frequencies of alleles DRB1*07 (16.9% vs. 35.4%; P =.003; OR 0.37) and DQB1*02 (32.3% vs. 55.8%; P =.0003; OR 0.39) were significantly decreased. In conclusion, there is no association between any specific HLA allele and the propensity to develop DIILD. However, the genetic influence associated with HLA class II alleles appears to play a role in the biochemical expression of liver injury in cholestatic/mixed hepatotoxicity and may explain why a given drug may cause different patterns of liver damage.

Adolescent↗
PubMed2004

Serum immunological profile in patients with chronic autoimmune cholestasis.

AIM: To compare patients who had biochemical and histological features of chronic autoimmune cholestasis (CAIC) using serological autoantibody profiling. METHODS: Patients (n = 174 CAIC; 79 AMA(-) and 95 AMA(+)) were profiled for the following antibodies: antinuclear antibodies (ANAs), antimitochondrial antibodies (AMAs), antismooth muscle actin (SMA, mainly F-actin), antiperinuclear cytoplasmic neutrophil antibodies (pANCAs), anti-SP100, anti-GP210, anti-M2 (2-oxo-acid dehydrogenase complexes), and antisoluble liver antigen (SLA). Liver specimens were reviewed according to staging, biliary interface activity, lobular hepatitis, granulomas, cholestasis, and florid ductal lesion. RESULTS: In patients who were AMA(-) by indirect immunofluorescence (IIF), 34.6% were positive for anti-M2 by immunoblotting. In 49 definitively AMA(-) patients, 24 (48.9%) showed ANA-primary biliary cirrhosis (PBC)-related antibodies (rim-like, multiple nuclear dots, anti-SP100, or anti-GP210). There were no differences in immunological, biochemical, or histopathological features between IIF-AMA(+) patients and AMA(-) patients with anti-M2 or ANA-PBC-related antibodies. AIH-related autoantibodies were found in 13 patients (7.5%). Patients with AMAs or ANA-PBC-related antibodies had higher IgM levels, whereas patients with antibodies highly specific for AIH had higher AST, bilirubin, and IgG levels, and AIH scores, and higher grades of lobular hepatitis. Overall, three distinct categories of patients were observed: AMA(+) or AMA(-) patients with ANA-PBC-related antibodies; AMA(-) patients with non-PBC-related ANAs; and patients with AIH-related antibodies together with serum PBC markers. CONCLUSION: Since these three groups had immunological, biochemical, and histopathological differences, they ought to be considered as separate clinical subentities rather than as merely AMA(-) or AMA(+) patients with autoimmune cholestasis.

Autoantibodies↗
PubMed2004

Causality assessment in drug-induced hepatotoxicity.

Drugs are currently an important cause of liver disease, ranked as the most frequent reason for acute liver failure. Despite recent advances in knowledge of the mechanisms implicated in drug-induced hepatocellular damage and cholestasis, as well as the identification of several risk factors, the diagnosis of hepatotoxicity remains a difficult task because specific tests are not available. In a step-by-step approach, the incrimination of a drug in liver symptoms requires a high degree of suspicion on the part of the physician, temporal eligibility, awareness of the drug's hepatotoxic potential, the exclusion of alternative causes of liver damage, and the ability to detect the presence of subtle data that favour a toxic aetiology. Ultimately, the use of diagnostic algorithms may add consistency to the diagnostic process either by translating the suspicion into a quantitative score or by providing a framework that emphasises the features that merit attention in cases of suspected hepatic adverse reactions.

Adult↗
PubMed2003

Drug use for non-hepatic associated conditions in patients with liver cirrhosis.

AIMS: To study the prescribing patterns of practising physicians for the most frequent non-hepatic associated conditions in patients with liver cirrhosis. METHODS: A multi-centre prospective observational study carried out in 25 Spanish hospitals. Inpatients admitted to gastrointestinal and liver units with a diagnosis of liver cirrhosis were included in five centrally assigned index days, between February and June 1999. Information was collected about pharmacological treatments used on admission and recommended at discharge. RESULTS: Five hundred and sixty-eight in-patients with a diagnosis of liver cirrhosis (44% alcoholic cirrhosis) and an average number of 2.5 co-morbid conditions were studied: diabetes mellitus (30%), infectious disorders (24%), cardiovascular disease (20%) and active alcoholism (15%)--the most common associated conditions. Chlormethiazole, amoxicillin-clavulanic acid, paracetamol, gliblenclamide, lorazepam, captopril and tiapride were the drugs used most prevalently. The average prescribed daily dose was <1 defined daily dose per day for most medication classes hepatically handled except for calcium channel blockers. CONCLUSIONS: The present study expands current knowledge of prescribing patterns for associated conditions in patients with underlying liver cirrhosis. Drug dosing was affected in general by the influence of age and hepatic disease on the disposition of drugs, but knowledge on drug selection needs further attention.

Adult↗