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Biomedical subjects

R Brenard

Publications and source records attributed to R Brenard.

At least 19 recordsLinked to original sources
PubMed1999

Transjugular intrahepatic portosystemic shunt after adult liver transplantation: experience in eight patients.

BACKGROUND: Transjugular intrahepatic portosystemic shunting (TIPS) has become an effective treatment for the complications of portal hypertension. We assessed the feasibility and outcome of TIPS in liver transplant recipients. METHODS: During the period from December 1992 to January 1998, eight adults presenting recurrent hepatitis C virus (five patients) and hepatitis B virus (one patient) infection, veno-occlusive disease (one patient), and secondary biliary cirrhosis (one patient) had TIPS because of refractory ascites (five patients), bleeding esophageal varices (one patient), refractory hepatic hydrothorax (one patient), retransplantation (two patients), and redo-biliary surgery (one patient). RESULTS: In two patients, the procedure was difficult due to cavo-caval implantation. Ascites, hydrothorax, and variceal bleeding were controlled in all patients. Moderate to severe encephalopathy developed in four patients; two patients had worsening of their existing encephalopathy. Three of five patients treated with cyclosporine needed a drastic dose reduction due to the development of severe side effects. No long-term survivor developed shunt stenosis or occlusion. Two patients did moderately well at 6 and 14 months, respectively; the former died due to chronic rejection while waiting for a retransplantation. Three did well at 14, 36, and 28 months, respectively; the latter patient died of liver failure 32 months after TIPS. One jaundiced patient died after 1.5 months due to necrotic pancreatitis. Two patients died after 4 and 8.5 months, respectively, due to liver failure; the latter was doing well until 7 months after TIPS. CONCLUSIONS: TIPS is feasible in transplant recipients in cases of decompensated allograft cirrhosis, of allograft veno-occlusive disease or when retransplantation or redo-biliary surgery are scheduled in the presence of portal hypertension. At transplantation, the surgeon should keep in mind the eventuality of a later TIPS procedure. Close immunosuppression monitoring is warranted because modified metabolization of cyclosporine (and probably tacrolimus) may cause serious side effects.

Adult↗
PubMed1999

HLA association of amoxicillin-clavulanate--induced hepatitis.

BACKGROUND & AIMS: Drug-induced immunoallergic hepatitis typically affects a minority of patients exposed to a particular drug. Its rarity is believed to be due to metabolic or immunologic idiosyncrasy. The presence of an immunologic idiosyncrasy might imply an HLA association. Previous studies reporting an HLA association of drug-induced hepatitis included only small numbers of patients and used serological HLA typing. METHODS: We studied 35 patients with biopsy-documented amoxicillin-clavulanate-induced hepatitis. HLA-A and -B were typed using alloantisera and compared with those of 300 controls (volunteer bone marrow donors). HLA-DRB and -DWB were typed by polymerase chain reaction-line probe assay, with 60 volunteer bone marrow donors serving as controls. RESULTS: The study group was characterized by a higher frequency of DRB1*1501-DRB5*0101-DQB1*0602 haplotype (57.1% vs. 11.7% in controls, P < 0.000005; after correction for the large number of comparisons, P < 0.0002). Patients with DRB1*1501-DRB5*0101-DQB1*0602 haplotype were more likely than patients without it to have a cholestatic (70% vs. 60%) or mixed (30% vs. 13%) than a hepatocellular pattern of hepatitis (0% vs. 27%) (P < 0.05). CONCLUSIONS: Amoxicillin-clavulanate-induced hepatitis is associated with the DRB1*1501-DRB5*0101-DQB1*0602 haplotype. The data support the view that an immunologic idiosyncrasy, mediated through HLA class II antigens, plays a role in the pathogenesis of drug-induced immunoallergic hepatitis. HLA association has a limited impact on the expression of hepatitis.

Adult↗
PubMed1998

Efficacy of interferon dose and prediction of response in chronic hepatitis C: Benelux study in 336 patients.

BACKGROUND/AIMS: In an attempt to improve the limited efficacy of treatment of chronic hepatitis C with interferon-alpha 3 MU tiw, we studied the effects of double-dose therapy followed by downward titration, and analyzed the pre- and pertreatment factors associated with response or non-response. METHODS: Three hundred and fifty-four consecutive patients in 19 centers were randomized to interferon-alpha 3 MU tiw for 6 months or 6 MU tiw for 8 weeks followed by down-titration (3,1 MU tiw) till alanine aminotransferase remained normal and plasma HCV RNA was repeatedly undetectable. The primary outcome measure was sustained alanine aminotransferase and HCV RNA response 6 months after treatment. RESULTS: Three hundred and thirty-six patients received treatment. The sustained response rate for patients receiving 3 MU tiw for 6 months was 14% (9-21%,) and for patients receiving double dose tiw for 8 weeks and thereafter titrated therapy 15% (10-21%) (p=0.8). Pretreatment factors associated with a sustained alanine aminotransferase plus HCV RNA response were the absence of cirrhosis, presence of genotype 2 or 3, a low viral load and, in addition, a low alanine aminotransferase/aspartate aminotransferase ratio; a model was developed to allow estimation of the chance of response for the individual patient. The most powerful predictor of sustained response, however, was plasma HCV RNA at week 4; a positive test virtually precluded a sustained response (1.7%, 0.4-5.0%). If week 4 HCV RNA was not detectable, the chance of a sustained response was 21% (12-34%) for genotype 1 versus 40% (28-54%) for the others (p=0.02). Six MU tiw led to a significantly higher week 4 HCV RNA response (47% not detectable) than 3 MU (37%) (p=0.02). During down-titration this difference in viral on-treatment response was lost. CONCLUSIONS: In the treatment of hepatitis C, an early HCV RNA response is a prerequisite for long-term efficacy. Doubling the initial interferon dose increases this early response, but subsequent downward titration negates this effect, especially in genotype 1.

Adult↗
PubMed1996

Increased hepatocytic mitotic activity as a diagnostic marker of acute arsenic intoxication. A report of two cases.

We report two patients in whom acute arsenic poisoning was associated with a very peculiar increase in hepatocytic mitotic activity. The recognition of such an unusual picture which is likely to be related to the mitogenic properties of arsenic may be of help in the identification of acute arsenic intoxication, a life-threatening condition which is difficult to diagnose.

Acute Disease↗
PubMed1996

[Fulminant or sub-fulminant hepatocellular failure caused by metastatic invasiveness of the liver: an other cause of hypoxic hepatitis?].

OBJECTIVES: The purpose of this retrospective study was to report a series of 9 new cases of fulminant hepatic failure due to metastatic liver disease and to identify signs to support a theory of hypoxia. METHODS: In these 9 cases and in 38 previously published cases of fulminant or subfulminant liver failure, we looked for clinical (shock, sepsis, and cutaneous signs of circulatory failure), laboratory (marked increase in serum aminotransferases levels) and histological (cell necrosis) parameters compatible with liver hypoxia. RESULTS: Cutaneous signs of circulatory failure or shock were observed in 3 of the 9 cases in this study, and were not due to cardiogenic or septic shock. A marked increase in serum aminotransferases levels, 10 times above the upper limit of normal, was observed in 8 of the 9 cases in the present study and in 23 of 37 cases of the literature. Liver cell necrosis was observed in 6 of the 7 autopsied patients in this series and in 20 of 34 cases in the literature. Generally, liver cell necrosis was more severe than tumor cell necrosis and was related to the degree of sinusoidal involvement by tumoral cells. In one case, hepatic blood flow was decreased despite a high level of cardiac blood flow suggesting impairment of circulation in the liver. CONCLUSIONS: These 9 cases and a review of the literature support the hypothesis of hypoxic liver cell necrosis leading to acute liver failure in cases of metastatic liver disease. However, liver hypoxia cannot explain all the reported cases and was never due to circulatory failure from cardiac or septic causes, but to the sinusoidal involvement by tumor cells.

Adult↗
PubMed1995

Liver injury related to amoxycillin-clavulanic acid: interlobular bile-duct lesions and extrahepatic manifestations.

We report eight cases of liver injury related to amoxycillin-clavulanate. Liver biopsy performed in seven patients revealed varying degrees of injury to interlobular bile ducts in all cases. Lesions included irregularity of the nuclei, vacuolization of the cytoplasm, lymphocytic infiltration, destruction and endothelialization of the bile duct epithelium. Ductopenia was not observed. In two patients liver injury was accompanied by prominent extrahepatic manifestations (acute interstitial nephritis in one and acute lacrimal gland inflammation and sialadenitis with prolonged xerostomia in the other). We conclude that interlobular bile-duct lesions of varying severity are a common feature in liver injury related to amoxycillin-clavulanate. Side effects of the drug include acute interstitial nephritis and sialadenitis.

Aged↗
PubMed1995

Long-term favourable outcome of portal hypertension complicating primary systemic amyloidosis.

An unusual case of systemic amyloidosis complicated by portal hypertension is reported. In this condition, portal hypertension is a rare event associated with poor prognosis. In our patient, severe presymptomatic sinusoidal portal hypertension was demonstrated by hepatic vein catheterization and coincided with abundant perisinusoidal amyloid infiltration. Despite these features and the absence of objective response to 20 courses of melphalan and prednisone, the patient was still in good clinical condition 4 years after initial diagnosis. This observation suggests that in primary amyloidosis, the incidence of sinusoidal portal hypertension might be underestimated and also that it may be associated with a relatively good prognosis.

Amyloidosis↗
PubMed1994

Autoimmune chronic active hepatitis responsive to immunosuppressive therapy evolving into a typical primary biliary cirrhosis syndrome: a case report.

The evolution from a characteristic picture of autoimmune chronic hepatitis type I to primary biliary cirrhosis is reported in a middle-aged woman. The initial diagnosis of autoimmune chronic liver disease was based on clinical, bio-serological and histological grounds. It was further confirmed by complete remission following immunosuppressive treatment and prompt relapses at the time of therapy withdrawal. After 7 years, the characteristics of liver disease were altered with increased biochemical cholestasis and serum IgM concentrations, positivation of previously negative anti-M2 antimitochondrial antibodies and the appearance of a typical histological picture of stage I primary biliary cirrhosis. We believe that this is the first reported case in which autoimmune chronic hepatitis highly responsive to immunosuppressive therapy has been followed by the development of a characteristic picture of primary biliary cirrhosis.

Autoimmune Diseases↗
PubMed1994

Short report: interferon-alpha decreases 14C-aminopyrine breath test values in patients with chronic hepatitis C.

OBJECTIVE: To investigate the effect of interferon-alpha on cytochrome P-450 dependent microsomal function. METHODS: The 14C-aminopyrine breath test was performed before, during and after a standard dose of interferon-alpha (3,000,000 units three times per week) was administered for at least six months (nine patients with chronic hepatitis C). RESULTS: Mean aminopyrine breath test values obtained during therapy were significantly lower than either pre- or post-treatment, the degree of reduction varying widely between individuals. Pre- and post-treatment aminopyrine breath test values did not differ significantly. CONCLUSION: Interferon therapy is associated with a significant and transient inhibition of cytochrome P-450 activity, which should be taken into account when prescribing concurrent therapy with drugs metabolized by this pathway.

Adult↗
PubMed1993

Anti-neutrophil antibodies in chronic hepatitis and the effect of alpha-interferon therapy.

In 34 patients with non-A non-B, 28 with type B and 11 with autoimmune chronic hepatitis, anti-neutrophil antibodies were investigated using indirect immunofluorescence and anti-myeloperoxidase antibodies by enzyme-linked immunosorbent assay. Granulocyte-specific antinuclear antibodies, were detected in 14 patients with advanced stages of non-A, non-B hepatitis (41%). Their presence correlated with histological features of disease activity but not with response to interferon therapy. Within 24 h after the first dose of interferon, 9 of these became negative and 3 more became negative after 1, 3 and 5 months. Myeloperoxidase-positive perinuclear neutrophil cytoplasmic antibodies were detected in a single patient and increased reaching a peak level after 8 weeks of interferon, decreasing thereafter. In type B, all were negative before and during the 6 months of therapy. In 6 patients with autoimmune hepatitis (55%), myeloperoxidase-negative perinuclear neutrophil cytoplasmic antibodies were detected in high titers. The association of granulocyte-specific anti-nuclear antibodies with non-A, non-B hepatitis support the hypothesis that hepatitis C virus infection might trigger humoral autoimmune response. In chronic autoimmune hepatitis, perinuclear neutrophil cytoplasmic antibodies appear as another marker of autoimmunity.

Adult↗
PubMed1992

Hemodynamic and sympathetic responses to human atrial natriuretic peptide infusion in patients with cirrhosis.

To determine the potential usefulness of atrial natriuretic peptide (ANP) in patients with cirrhosis, we examined the effects of the infusion of a low dose of alpha-human ANP (alpha hANP, 25 ng.kg-1.min-1 for 30 min) on renal, splanchnic, systemic hemodynamics and sympathetic outflow in eight patients. Pulmonary arterial plasma ANP concentrations increased from 59 +/- 9 to 328 +/- 41 pg/ml (mean +/- S.E., p less than 0.05). Mean values of glomerular filtration rate and renal plasma flow were not significantly changed. Individual renal plasma flow responses differed from one patient to another. Renal plasma flow increased in two patients, decreased in three and did not change in the other patients. Renal plasma flow changes were correlated with basal renal plasma flow values (r = -0.938, p less than 0.05) but not with arterial pressure changes or renal vein plasma norepinephrine concentration changes. Azygos blood flow increased from 0.43 +/- 0.10 to 0.63 +/- 0.13 l/min (p less than 0.05) and the hepatic-venous pressure gradient decreased from 19.9 +/- 1.5 to 17.5 +/- 2.9 mmHg in post-infusion (p less than 0.05). Mean arterial pressure decreased significantly by 18% and cardiac output by 12%. Systemic vascular resistance and pulmonary arterial plasma norepinephrine concentrations were not significantly modified. Thus, in patients with cirrhosis, alpha hANP appears to have a direct vasodilating action on renal arterioles when basal renal vascular tone is high. In addition, although alpha hANP might exert a portal hypotensive action, alpha hANP induced arterial hypotension as a result of both low cardiac output and a lack of increased sympathetic vascular tone. The arterial hypotensive action may, thus, limit the therapeutic use of low doses of alpha hANP in cirrhotic patients.

Aldosterone↗
PubMed1992

Regenerative nodules in hepatic cirrhosis. Value of gradient-echo MR imaging with a surface coil.

To evaluate the accuracy of surface coil gradient-echo (GRE) imaging in the detection of regenerative nodules of hepatic cirrhosis, 53 patients with diffuse liver disease, among whom 31 had cirrhosis, were prospectively investigated. Three GRE sequences acquired with a surface coil were used in the study: a T2*-weighted, a T1-weighted, and a gadopentetate-enhanced sequence. ROC analysis showed that two surface coil GRE sequences were superior to conventional T2-weighted spin-echo imaging acquired with a body coil for the detection of regenerative nodules. The detection of regenerative nodules was also more accurate for the diagnosis of cirrhosis than the measurement of the caudate-to-right lobe ratio. These results suggest that there could be a potential for surface coil GRE imaging in the assessment of the characteristic macroscopic alterations of cirrhosis.

Adult↗
PubMed1991

Clearance of atrial natriuretic peptide in patients with cirrhosis. Role of liver failure.

In non-cirrhotic patients, splanchnic, renal and pulmonary vascular beds are involved in the plasma clearance for atrial natriuretic peptide (ANP). In patients with cirrhosis, endogenous plasma ANP clearance by these vascular beds has not been systematically studied. In addition, the influence of the severity of liver failure on plasma ANP clearance is not known. Thus, in this study we determined plasma ANP clearance by splanchnic, renal and pulmonary circulations using both arteriovenous differences in plasma ANP concentrations and organ plasma flow in 11 patients with cirrhosis. The role of forearm circulation in plasma ANP extraction was also studied. Splanchnic plasma ANP extraction was 29 +/- 7% (mean +/- S.E.) and splanchnic plasma ANP clearance was 404 +/- 130 ml/min (n = 7). Renal plasma ANP extraction and clearance were 32 +/- 8% and 191 +/- 57 ml/min, respectively. Forearm plasma ANP extraction was 11 +/- 4%. Pulmonary plasma ANP extraction and clearance were 8 +/- 5% and 312 +/- 272 ml/min, respectively. A significant negative correlation was found between logarithm of serum bilirubin concentration, on one hand, and splanchnic and forearm plasma ANP extraction, on the other. A significant negative correlation was found between Pugh's score, on one hand, and renal plasma ANP extraction and clearance, on the other. No significant correlation was found between the severity of liver failure and pulmonary plasma ANP extraction and clearance. As a result, we conclude that in cirrhotic patients splanchnic, renal, forearm and pulmonary vascular beds are involved in plasma ANP extraction and clearance. Plasma ANP extraction and/or clearance may be attenuated in the splanchnic, renal and forearm circulations due to liver failure.

Atrial Natriuretic Factor↗
PubMed1991

Antimitochondrial and antinuclear antibodies in primary biliary cirrhosis: an update in relation to their biochemical characterization and clinical significance.

Antimitochondrial antibodies are found in 85 to 95% of patients with primary biliary cirrhosis. Nine different patterns have been identified but only four are associated with primary biliary cirrhosis. Anti-M2 antibodies are specific for the disease. The M2 antigen was found to be composed of five antigen determinants and related to the E2 component of three multienzyme complexes located within mitochondria. Anti-M4 and M8 antibodies appear invariably associated with anti-M2 and are markers for the "overlap syndrome" between primary biliary cirrhosis and chronic active hepatitis as well as for poor prognosis. Anti-M9 antibodies are preferentially associated with early and/or asymptomatic disease. Antinuclear antibodies are found in 24 to 58% of patients with primary biliary cirrhosis. Six various patterns have been reported. Antibodies directed to the 200 kD polypeptide of the nuclear pore and giving a perinuclear fluorescence are specific for primary biliary cirrhosis. Patients with such antibodies exhibit a less symptomatic disease and lower titers of anti-M2 than those without.

Antibodies, Antinuclear↗
PubMed1991

Sinusoidal portal hypertension in hepatic amyloidosis.

Hepatic venous catheterisation and transvenous liver biopsy were performed in five patients with hepatic amyloidosis. In three patients, hepatic venous pressures were normal and histological examination of the liver biopsy specimen showed discrete and sparse perisinusoidal amyloid deposits. In the other two, however, the gradient between wedged and free hepatic venous pressures was increased (12 and 16 mmHg; normal 1-4 mmHg) and amyloid deposits were abundant and diffuse in the Disse's space. This study shows that portal hypertension in patients with hepatic amyloidosis is of the sinusoidal type and is related to the reduction of vascular space of hepatic sinusoids by massive perisinusoidal amyloid deposits. Furthermore, portal hypertension is associated with a poor prognosis in patients with hepatic amyloidosis.

Aged↗
PubMed1990

Antinuclear antibodies directed to a 200-kilodalton polypeptide of the nuclear envelope in primary biliary cirrhosis. A clinical and immunological study of a series of 150 patients with primary biliary cirrhosis.

Antinuclear antibodies giving a perinuclear fluorescence and directed to a 200-kilodalton polypeptide of the nuclear envelope have been described in primary biliary cirrhosis. The purpose of this study, based on a series of 150 patients with primary biliary cirrhosis, was to ascertain the prevalence of these antibodies and to compare patients with and without these antibodies. Antinuclear antibodies giving a perinuclear fluorescence were demonstrated in 43 of the 150 patients (29%); antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope were found in 40 of these 43 patients. Asthenia, arthralgia, associated extrahepatic diseases, Raynaud's phenomenon, and other antinuclear specificities were significantly less common, and titers of antimitochondrial antibodies were significantly lower in patients with antibodies directed to the 200-kilodalton polypeptide of the nuclear envelope than in patients without these antibodies. Clinical outcome, liver tests, and histological lesions did not significantly differ in patients with and without these antibodies.

Antibodies, Antinuclear↗