Influence of antiviral therapy on the natural history of hepatitis B virus recurrence after liver transplantation: retrospective study of 14 cases.
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Biomedical subjects
Publications and source records attributed to V Cuervas-Mons.
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Visceral leishmaniasis is an infectious disease that occurs only rarely in recipients of solid organ grafts but is associated with an elevated mortality rate despite proper treatment. We report five cases diagnosed in our hospital. All the patients were men aged 30 to 60 years who had undergone kidney transplantation (3 patients), heart transplantation (1), or liver transplantation (1). Three of the patients died, one had multiple recurrences, and one developed post-kala-azar cutaneous leishmaniasis. We review the clinical features, treatments, and outcomes of 26 previously reported cases, pointing out the lower cure rate associated with human immunodeficiency virus infection.
BACKGROUND: Recurrence of autoimmune hepatitis after liver transplantation is not rare, but there is little information about its time of onset, risk factors, response to treatment and prognosis. The aim of this study was to evaluate the rate of recurrence and outcome of autoimmune hepatitis after transplantation. METHODS: The records of patients transplanted in eight centers in our country between 1984 and 1996 were retrospectively analyzed. RESULTS: Forty-three of the 2331 (1.8%) recipients fulfilled diagnostic criteria of autoimmune hepatitis at the time of transplantation. Sixteen patients were excluded from evaluation. Nine (33%) of the 27 patients evaluated fulfilled criteria for recurrence of autoimmune hepatitis, with a mean time of recurrence after orthotopic liver transplantation of 2.6+/-1.5 years. Patients with recurrence had a longer follow-up time after transplantation (5.1 vs. 2.5 years, P=0.0012) and were receiving less immunosuppressive treatment. The estimated risk of recurrence of autoimmune hepatitis in the graft increased over time: 8% over the first year and 68% 5 years after transplantation. None of the seven patients with liver-kidney microsomal-positive antibodies recurred (P=0.059). Fifty percent of the patients failed to respond or responded only partially to therapy, although none of the patients have deteriorated clinically after 2.4+/-1.06 years of follow-up after recurrence. CONCLUSIONS: Recurrence of autoimmune hepatitis in the graft is a common event with an incidence that increases over time as immunosuppression is reduced. Although response to treatment is poor, patient and graft survival do not appear to be decreased.
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Arterial hypertension is commonly observed in orthotopic liver transplantation (OLT) recipients receiving cyclosporin A (CsA), but the precise pathogenetic mechanisms remain partially unknown. The aim of this study was to investigate endothelium-dependent and -independent dilation and adrenergic constriction of resistance vessels of OLT recipients treated with CsA. Vascular reactivity was examined in 22 OLT patients, 10 with and 12 without arterial hypertension, and in 10 control subjects by assessing the forearm blood flow response to the brachial artery infusion of increasing concentrations of methacholine chloride, sodium nitroprusside, and phenylephrine. In 10 OLT patients, the response to methacholine was also examined after acetylsalicylate. The ratio of serum nitrite and nitrate to serum creatinine was lower (P < .05) in OLT patients with hypertension than in nonhypertensive patients and controls. Basal forearm flow was similar in the three groups. Methacholine vasodilation was impaired in the hypertensive patients as shown by a lower maximum forearm vasodilator response and a shift in the dose response curve to methacholine to the right compared with the nonhypertensive OLT patients and the controls. The response to methacholine was not modified after salicylate. Forearm flow response to nitroprusside was similar in the three groups. No differences between the patients and the controls were found in the maximum forearm flow contraction in response to phenylephrine. An impairment in endothelium-dependent vasodilation could mediate arterial hypertension in OLT patients immunosuppressed with CsA.
Eighty-four adult patients were recruited from four centres in Spain to evaluate the efficacy and safety of low-dose (0.1 mg/kg per day) oral tacrolimus plus corticosteroid immunosuppression in liver transplantation. The median daily dose of tacrolimus was increased during the first 3 weeks of therapy from an initial dose of 0.1 mg/kg per day to a maximum of 0.145 mg/kg per day and was subsequently decreased gradually to a minimum of 0.076 mg/kg per day at 1 year. At 7 days posttransplantation, 87.7% of patients had trough whole blood levels of tacrolimus within the therapeutic range (5-20 ng/ml), and the median levels remained fairly constant during the rest of the year (10.1-11.8 ng/ml). None of the patients required intravenous administration of tacrolimus. At 1 year, Kaplan-Meier estimates showed that 73.8% of the patients were receiving tacrolimus monotherapy without the need for corticosteroids. One-year patient and graft survival were 75.9% and 72.3%, respectively. The incidence of acute rejection was 51.2%; 9.5% of cases resolved spontaneously without antirejection therapy and 10.7% were corticosteroid resistant. Only 1 patient (1.2%) developed chronic rejection. The most important adverse events were hypertension (45.2%), tremor (44.0%), diabetes mellitus (33.3%), diarrhoea (31%) and nephrotoxicity (29.8%). Severe neurotoxicity-like convulsions (4.8%), dysarthria (9.5%), delirium (1.2%), coma (1.2%) and the need for haemodialysis (3 patients) were uncommon. In conclusion, low-dose oral tacrolimus immunosuppression is associated with low toxicity without compromising efficacy.
A prospective, randomized, multicenter study addressed the safety and efficacy of fluconazole therapy in 143 liver transplant patients. Seventy-six patients received daily oral fluconazole (100 mg), and 67 received nystatin (4 X 10(6) U) during the first 28 days after transplantation. Candida colonization occurred in 25% and 53% of patients in the fluconazole and nystatin groups, respectively (P = .04), and 13% and 34% of patients in the respective groups had Candida infections (P = .022). Of these patients, 10.5% in the fluconazole group and 25.3% in the nystatin group had superficial candidal infections (P = .024). Invasive candidiasis developed in 2 patients in the fluconazole group (2.6%) and 6 in the nystatin group (9.0%) (P = .12). There was no increased hepatotoxicity, cyclosporine interaction, or emergence of clinically relevant resistant Candida strains attributable to fluconazole. Thus, oral fluconazole (100 mg) is safe and reduces Candida colonization and infection after liver transplantation.
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Hypergammaglobulinemia is a well-known feature of liver cirrhosis, but studies on serum IgE in this setting are limited. The present study evaluates serum IgE concentration in a group of cirrhotic patients and examines their relationship with aetiological, clinical and analytical parameters (including liver function tests and hepatic phagocytic activity). The presence of specific IgE against common dietary antigens was also investigated. Total serum IgE was determined by enzyme immunoassay (EIA) in 52 cirrhotics (27 alcoholic and 25 non-alcoholic, including eight virus B and seven virus C-related cirrhosis, three primary biliary cirrhosis, three cryptogenic, three haemochromatosis and one Wilson's disease) and 34 healthy subjects (used as controls). Serum IgE (IU/ml) in controls was not significantly different from that of cirrhotic patients (median 42, range 2-726 vs median 86, range 2- > 1000, respectively) (P = NS). However, serum IgE among alcoholics (median 199, range 19- > 1000) was higher than that of controls (P < 0.001), virus B-related cirrhotics (median 25, range 3- > 1000) (P < 0.05), virus C-related cirrhotics (median 47, range 2-170) (P < 0.05), or non-alcoholic cirrhotics as a whole (median 23, range 2- > 1000) (P < 0.01). High IgE levels (> or = 170 IU/ml) were detected in 55.5% of alcoholics compared with only 12% of non-alcoholic cirrhotics (P < 0.01). Moreover, IgE levels were very high (> 1000 IU/ml) in six patients of the alcoholic group (22.2%) compared with only one non-alcoholic patient (4%).(ABSTRACT TRUNCATED AT 250 WORDS)
The aim of the present study was to evaluate the influence of Kupffer cell phagocytosis blockade (KCPB) on the production of reaginic (IgE) and non-reaginic (IgG1) ovalbumin antibodies in an experimental animal model. Forty-two female heterozygous Gunn rats were injected with two 100 micrograms doses of ovalbumin separated by 13 days, into jugular vein (Group I, n = 10), portal vein (Group II, n = 10), jugular vein with prior KCPB (Group III, n = 10) and portal vein with prior KCPB (Group IV, n = 12). KCPB was induced with gadolinium chloride (5 mg/kg body weight, 24 hr before each ovalbumin administration). Antibodies were determined by passive cutaneous anaphylaxis in sera obtained 12 days after the first dose of ovalbumin and 8 days after the second one. No antibodies were detected at any time in Group II. The maximum response was observed in Group IV in which, after two doses of ovalbumin, 100% of the animals presented IgG1 and 58% presented detectable IgE antibodies. Differences between group IV and the other groups were statistically significant. This phenomenon does not seem to be due to a systemic effect of gadolinium chloride since humoral response was not increased in Group III with respect to Group I. It is concluded that the liver represents a barrier to IgE and IgG1 sensitization. KCPB not only eliminates this barrier, but also clearly increases antibody production to a protein antigen (ovalbumin) arriving at the liver through the portal vein.
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