[Interview: questions to professeur Dominique Valla].
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Anticoagulants↗
Biomedical subjects
D Valla
Publications and source records attributed to D Valla.
Multiple mixed adenoma-focal nodular hyperplasia of the liver associated with spontaneous intrahepatic porto-systemic shunt: a new type of vascular malformation associated with the multiple focal nodular hyperplasia syndrome?
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Adenoma, Liver Cell↗
Treatment of chronic hepatitis C virus in allogeneic bone marrow transplant recipients.
We recently reported an increased incidence of cirrhosis in hepatitis C virus (HCV)-infected stem cell transplant (SCT) recipients. Here, we describe our experience in the treatment of these patients, which has been, to date, poorly reported in the literature. Among 99 HCV-infected HCT recipients, 36 had HCV-related liver lesions on biopsy requiring therapy. Owing to HCV treatment contraindications, only 61% of patients (22/36) could be treated. In all, 12 patients received more than one course of anti-HCV treatment if they had HCV RNA still detectable after the first course of treatment and no treatment contraindications. Combined therapy (pegylated interferon (IFN): n=9, or standard IFN: n=9, in combination with ribavirin) led to sustained virological response in 4/18 (20%) patients as compared to 2/20 (10%) in patients who received IFN alone. Hematological toxicity was more frequent with combined therapy. While anemia responded to erythropoietin and/or dose modification, thrombocytopenia usually led to treatment interruption (n=3). This study thus highlights the efficacy of combined therapy and emphasizes the fact that the undue safety concerns are not a problem when treating this particular population.
Adolescent↗
Safety and efficacy of peginterferon plus ribavirin in patients with chronic hepatitis C and bridging fibrosis or cirrhosis.
The combination of pegylated interferon and ribavirin is the most effective therapy in patients with chronic hepatitis C. We evaluated this combination in unselected patients with bridging fibrosis or cirrhosis. Eighty patients were treated with peginterferon alpha-2b plus ribavirin. Hepatitis C virus serum RNA was monitored. Tolerance and safety were evaluated by the rate of treatment's discontinuation for any reason, and occurrence of serious clinical adverse events, respectively. Sustained virologic response (SVR) rate was 36.3% overall, and was observed in every group of patients except those who had previously failed to respond to the combination of interferon and ribavirin. No serious clinical adverse event occurred. Treatment was withdrawn in 18.7% of patients. Variables associated with discontinuation of treatment were low prothrombin index [OR: 1.16 (1.05;1.27)] and low body mass index [OR: 1.47 (1.12;1.92)]. Initial blood count abnormalities were not associated with cessation of treatment. Furthermore, early virologic response at week 8 and week 12 of treatment had similar predictive value for SVR. Combination therapy with peginterferon plus ribavirin seems effective in this group of patients, except in those who had previously failed to respond to the combination of interferon and ribavirin. This therapy is safe with appropriate monitoring, but tolerance seems worse in patients with the most advanced liver disease.
Adult↗
Splanchnic vein thrombosis in candidates for liver transplantation: usefulness of screening and anticoagulation.
BACKGROUND AND AIMS: Splanchnic vein thrombosis is a significant source of complications in candidates for liver transplantation. The aims of this study were: (a) to determine the prevalence of and risk factors for splanchnic vein thrombosis in cirrhotic patients awaiting transplantation and (b) to assess the usefulness of anticoagulation. METHODS: A total of 251 cirrhotic patients listed for transplantation were analysed. All underwent systematic screening for thrombosis with Doppler ultrasonography. During the second period of the study, all patients with thrombosis received anticoagulation up to transplantation while during the first period none had received anticoagulation. RESULTS: The incidence of splanchnic vein thrombosis at evaluation was 8.4%. Seventeen additional patients (7.4%) developed de novo thrombosis after evaluation. Independent risk factors for thrombosis were low platelet count (77.4 (36.3) v 111.6 (69.2) 10(9)/l; p = 0.001), a past history of variceal bleeding (47.4% v 29.1%; p = 0.003), and a prolonged interval from listing to transplantation (8.5 (6.8) v 4.8 (4.4) months; p = 0.002). The proportion of partial or complete recanalisation was significantly higher in those who received (8/19) than in those who did not receive (0/10, p = 0.002) anticoagulation. Survival was significantly lower in those who had complete portal vein thrombosis at the time of surgery (p = 0.04). CONCLUSION: These results support a systematic screening for splanchnic vein thrombosis in patients awaiting transplantation. They suggest that in these patients, anticoagulation is safe and has a significant impact on recanalisation as well as prevention of extension of thrombosis.
Adolescent↗
Association of idiopathic hepatic sinusoidal dilatation with the immunological features of the antiphospholipid syndrome.
BACKGROUND: Isolated sinusoidal dilatation is an uncommon hepatic lesion and the cause is largely unknown. OBJECTIVE: To investigate whether prothrombotic disorders or perisinusoidal cell changes could be involved in pure idiopathic hepatic sinusoidal dilatation (HSD). METHODS: Evaluation for associated conditions, prothrombotic disorders, and studies of hepatic perisinusoidal cell activation in consecutive patients, seen between 1993 and 2002, with isolated sinusoidal dilatation unrelated to outflow block, sinusoidal infiltration, or hepatic granulomas. RESULTS: Among 11 patients, associated conditions were prothrombotic disorders (n = 5) and oral contraceptive use (n = 3). Prothrombotic disorders were polycythemia vera (n = 1) and anticardiolipin antibodies combined with lupus anticoagulant (n = 4). No genetic thrombophilia factor was found. Of four patients with lupus anticoagulant, three had antinuclear factors and high serum levels of anticardiolipin antibodies at repeated testing. There was no evidence of intrahepatic or extrahepatic thrombosis in any of the patients. Sinusoidal dilatation was marked in six of 11 patients (54%), including two patients with antiphospholipid antibodies. Activated perisinusoidal cells were only found around markedly dilated sinusoids. CONCLUSION: Idiopathic pure HSD is frequently associated with the immunological features of the antiphospholipid syndrome. Therefore, finding pure HSD in a liver biopsy specimen should prompt the search for antiphospholipid antibodies.
Adult↗
Nosocomial and community-acquired spontaneous bacterial peritonitis: comparative microbiology and therapeutic implications.
In order to compare the microbiological characteristics of nosocomial and community-acquired episodes of bacterial peritonitis, 95 consecutive, spontaneous episodes were reviewed. Seventy of these episodes were bacteriologically documented. Fifty-three (55.8%) episodes were nosocomial and 42 (44.2%) were community acquired. A total of 78 pathogens were isolated, including 40 gram-positive cocci (34 streptococci, 6 Staphylococcus aureus), 35 gram-negative bacilli (including 23 Escherichia coli), 2 gram-positive bacilli and 1 yeast. Streptococci were found more frequently in community-acquired episodes (53.8%) than in nosocomial episodes (33.3%). Gram-negative bacilli were significantly more frequent in nosocomial episodes than in community-acquired episodes (56.4% vs. 33.3%, P<0.05). Nosocomial isolates were significantly more resistant to amoxicillin-clavulanic acid (48.7% vs. 18.4%, P<0.01) and cefotaxime (33.3% vs. 13.2%, P<0.05) than community-acquired isolates, but no difference was detected regarding resistance to ciprofloxacin. The results indicate that the empirical treatment of spontaneous bacterial peritonitis should differ for nosocomial and community-acquired cases.
Adult↗
Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patients.
The transmission of viral hepatitis from health care workers (HCW) to patients is of worldwide concern. Since the introduction of serologic testing in the 1970s there have been over 45 reports of hepatitis B virus (HBV) transmission from HCW to patients, which have resulted in more than 400 infected patients. In addition there are six published reports of transmissions of hepatitis C virus (HCV) from HCW to patients resulting in the infection of 14 patients. Additional HCV cases are known of in the US and UK, but unpublished. At present the guidelines for preventing HCW to patient transmission of viral hepatitis vary greatly between countries. It was our aim to reach a Europe-wide consensus on this issue. In order to do this, experts in blood-borne infection, from 16 countries, were questioned on their national protocols. The replies given by participating countries formed the basis of a discussion document. This paper was then discussed at a meeting with each of the participating countries in order to reach a Europe-wide consensus on the identification of infected HCWs, protection of susceptible HCWs, management and treatment options for the infected HCW. The results of that process are discussed and recommendations formed. The guidelines produced aim to reduce the risk of transmission from infected HCWs to patients. The document is designed to complement existing guidelines or form the basis for the development of new guidelines. This guidance is applicable to all HCWs who perform EPP, whether newly appointed or already in post.
DNA, Viral↗
Liver fibrosis is not associated with steatosis but with necroinflammation in French patients with chronic hepatitis C.
BACKGROUND: In chronic hepatitis C, it has been suggested that steatosis could accelerate progression of fibrosis. However, results of the few published studies are controversial. AIM: To determine the characteristics (epidemiological, biological, and histological) associated with steatosis and its relationship with liver lesions (grade of necroinflammation and stage of fibrosis) in patients with chronic hepatitis C. METHODS: From November 2000 to July 2001, untreated consecutive adults with chronic hepatitis C admitted for liver biopsy were included in this study. On the day of liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis. RESULTS: Our study included 290 patients (143 men, 147 women). Mean body mass index (BMI) was 24 (3.8) kg/m(2). Proportions of patients with genotypes 1 and 3 were, respectively, 48% and 18%. A total of 135 patients (46.6%) had steatosis. Liver steatosis, in multivariate analysis, was associated with hepatitis C virus genotype 3, higher grade of necroinflammation, and higher BMI. There was no significant association between stage of fibrosis and liver steatosis. In multivariate analysis, high stage of fibrosis was associated with male sex, age over 50 years, high BMI, and high grade of necroinflammation. CONCLUSION: In our population of patients with chronic hepatitis C, steatosis does not seem to be an important determinant of liver fibrosis. High grade of necroinflammation is associated with a high stage of fibrosis.
Adult↗
Second infection with a different hepatitis C virus genotype in a intravenous drug user during interferon therapy.
The prevalence of antibodies against hepatitis C virus (anti-HCV) among intravenous drug users (IVDU) has consistently been very high. Cross challenge studies in chimpanzees provide evidence that reinfection with different HCV strains may occur. In humans, reinfection with different HCV strains has been reported in multitransfused haemophiliacs and recently in IVDU but no case has been reported while on interferon (IFN) therapy. We report on a 22 year old woman who was treated with IFN alpha for HCV genotype 3a chronic infection. At six months, HCV RNA was undetectable by reverse transcription-polymerase chain reaction. In October 1997, while still on IFN, she developed an acute hepatitis after an intravenous drug injection and HCV genotype 1a infection was identified using genotyping and sequencing methods. IFN therapy was continued until August 1998, and in January 1999 HCV-RNA was not detectable. Our case indicates that the previous HCV infection might have prevented development of chronicity. An alternative explanation is that IFN, while not preventing acute hepatitis C, may prevent chronicity. The risk of multiple infection in IVDU underlines the need for preventive strategies.
Acute Disease↗
Hypervariable region 1 quasispecies in hepatitis C virus genotypes 1b and 3 infected patients with normal and abnormal alanine aminotransferase levels.
The role of hepatitis C virus (HCV) heterogeneity in the severity of chronic hepatitis C infection remains unclear. Our aim was to study the hypervariable region 1 (HVR1) heterogeneity in patients with chronic hepatitis C infected with genotype 1b or 3 and with normal or abnormal alanine aminotransferase (ALT). HVR1 quasispecies were assessed by single strand conformational polymorphism (SSCP) in 67 patients with chronic hepatitis C, including 35 with persistently normal ALT and 32 with abnormal ALT. Sixty-two patients underwent a liver biopsy. Among the 67 patients, 40 were infected with genotype 1b and 27 with genotype 3. In univariate analysis, low heterogeneity (<or= 3 bands at SSCP) was significantly associated with normal ALT (P < 0.001), milder histological lesions (activity, P=0.02; fibrosis, P=0.04), and at the limit of significance for genotype 1b (P=0.07). In multivariate analysis, low heterogeneity was significantly and independently associated with normal ALT (P=0.09) and genotype 1b (P=0.03). In patients with chronic hepatitis C, a low viral heterogeneity is significantly and independently associated with normal ALT and genotype 1b. These results are consistent with the view that patients with normal ALT have a different immune response against HCV resulting in a low HCV heterogeneity.
Adult↗
Comparison of the effect of terlipressin and albumin on arterial blood volume in patients with cirrhosis and tense ascites treated by paracentesis: a randomised pilot study.
BACKGROUND: Patients with cirrhosis and tense ascites treated by paracentesis alone have a decrease in effective arterial blood volume after ascites removal. Although intravenous albumin is effective in preventing paracentesis induced decreased arterial blood volume, its clinical use is controversial. As paracentesis induces arteriolar vasodilation which plays a role in the development of decreased effective arterial blood volume, administration of a vasoconstrictor (terlipressin) could prevent circulatory alterations due to paracentesis. AIMS: To perform a pilot study comparing the effects of terlipressin and albumin on effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites. METHODS: Twenty patients with cirrhosis and tense ascites were randomly assigned to be treated by either paracentesis and terlipressin or paracentesis and albumin. Terlipressin (3 mg) or albumin (8 g/l of removed ascites) were administered on the day of paracentesis. Effective arterial blood volume was assessed by measuring plasma renin concentrations at baseline and on the day of hospital discharge (4-6 days after treatment). Decreased effective arterial blood volume was defined as an increase in plasma renin concentrations on the day of hospital discharge of more than 50% of baseline values. RESULTS: Irrespective of the treatment group, mean values for plasma renin concentrations at hospital discharge did not differ from their respective baseline values (p=0.10). Baseline plasma levels of renin concentrations did not differ between the terlipressin and albumin groups (p=0.61). Changes from baseline in plasma renin concentrations did not differ between groups (p=0.39). Three patients in the terlipressin group and three in the albumin group developed decreased arterial blood volume. CONCLUSIONS: This randomised pilot study suggests that terlipressin may be as effective as intravenous albumin in preventing a decrease in effective arterial blood volume in patients with cirrhosis treated by paracentesis for tense ascites.
Albumins↗
Idiopathic non-cirrhotic intrahepatic portal hypertension in the West: a re-evaluation in 28 patients.
BACKGROUND: Non-cirrhotic portal hypertension of unknown cause is a poorly understood condition attributed to obstructive portal venopathy. AIM: To reassess the manifestations, course, and causes, with special attention to thrombosis. METHODS: Analysis of a cohort of 28 patients. RESULTS: Gastrointestinal bleeding occurred in 11 patients. Liver failure developed at the time of concurrent disease in eight patients, including all four patients who died. Portal vein thrombosis developed in 13 patients. A prothrombotic disorder was found in 12 of 23 fully investigated patients. Hepatoportal sclerosis was observed in 11 patients (with associated perisinusoidal fibrosis and/or nodular regenerative hyperplasia in six); periportal fibrosis, perisinusoidal fibrosis, nodular regenerative hyperplasia, or a combination thereof were observed in other patients. A morphometric evaluation showed an increased number of portal vessels in patients with hepatoportal sclerosis. There was no relation between pathological results and haemodynamic findings or prothrombotic disorders. CONCLUSIONS: Outcome was related to associated conditions. Overlap in pathological, haemodynamic, and causal features suggests a single entity, with prothrombotic disorders as major causal factors, and injury to sinusoids as well as to portal venules as the primary mechanism. Activated coagulation could mediate vascular injury in the absence of thrombosis. Anticoagulation should be considered.
Adult↗
[Code of professional ethics in clinical research].
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Authorship↗
Regression of liver fibrosis after biliary drainage in patients with chronic pancreatitis and stenosis of the common bile duct.
BACKGROUND: Chronic obstruction of the common bile duct may cause hepatic fibrosis and secondary biliary cirrhosis. METHODS: We studied liver-biopsy specimens from 11 patients with chronic stenosis of the common bile duct due to chronic pancreatitis; all the patients had undergone liver biopsy before or at the time of surgical biliary decompression and underwent a subsequent liver biopsy for various clinical reasons. The patients were followed as part of a prospective study of 501 patients who had been treated for chronic pancreatitis. Two pathologists, who were unaware of the sequence of specimens, graded fibrosis on a scale of 0 (none) to 3 (cirrhosis). RESULTS: The 11 patients were all men. Chronic pancreatitis was due to alcohol abuse in 10 of the men; 1 had idiopathic disease. The median age at diagnosis was 38 years. The median interval between the first and second liver biopsies was 2.5 years (range, 0.3 to 9.0). The two patients who had restenosis of the biliary anastomosis were excluded from the analysis of fibrosis. In the group of nine patients without restenosis, the second specimen showed significant improvement in fibrosis (P=0.01). The fibrosis improved by two grades in two patients and by one grade in four patients; in three patients, the grade did not change. The pathologists agreed on the grading of specimens from 10 of the 11 patients. CONCLUSIONS: In patients with chronic pancreatitis and stenosis of the common bile duct, liver fibrosis may regress after biliary drainage.
Adult↗
Hepatitis after intravenous buprenorphine misuse in heroin addicts.
BACKGROUND: Sublingual buprenorphine is used as a substitution drug in heroin addicts. Although buprenorphine inhibits mitochondrial function at high concentrations in experimental animals, these effects should not occur after therapeutic sublingual doses, which give very low plasma concentrations. CASE REPORTS: We report four cases of former heroin addicts infected with hepatitis C virus and placed on substitution therapy with buprenorphine. These patients exhibited a marked increase in serum alanine amino transferase (30-, 37-, 13- and 50-times the upper limit of normal, respectively) after injecting buprenorphine intravenously and three of them also became jaundiced. Interruption of buprenorphine injections was associated with prompt recovery, even though two of these patients continued buprenorphine by the sublingual route. A fifth patient carrying the hepatitis C and human immunodeficiency viruses, developed jaundice and asterixis with panlobular liver necrosis and microvesicular steatosis after using sublingual buprenorphine and small doses of paracetamol and aspirin. CONCLUSIONS: Although buprenorphine hepatitis is most uncommon even after intravenous misuse, addicts placed on buprenorphine substitution should be repeatedly warned not to use it intravenously. Higher drug concentrations could trigger hepatitis in a few intravenous users, possibly those whose mitochondrial function is already impaired by viral infections and other factors.
Administration, Sublingual↗
Assessment of the benefits and risks of percutaneous biopsy before surgical resection of hepatocellular carcinoma.
BACKGROUND/AIMS: Because of a potential risk of needle tract seeding, the use of ultrasound (US)-guided biopsy for the diagnosis of hepatocellular carcinoma (HCC) is controversial. This study was aimed at determining the usefulness, accuracy and safety of this technique as well as the incidence of needle tract seeding. METHODS: From 1986 to 1996, 137 patients who underwent resection or transplantation for suspected HCC had US-guided biopsy before surgery. The analysis of the resected liver was compared to the results of biopsy. Patients were assessed with a mean follow up of 38 months. RESULTS: The diagnosis of HCC was established by biopsy in 122 patients (89%). Thirteen of the 15 patients with negative biopsy were shown to have HCC after surgery. The remaining two patients had non-malignant nodules. Sensitivity and accuracy of US-guided biopsy were 90 and 91%, respectively. Accuracy was significantly influenced by the location of the nodule but not by its size. Needle tract seeding occurred in two patients (1.6%). CONCLUSIONS: In this series, the incidence of needle tract seeding was less than 2% and no recurrence was observed after local excision. This risk should be balanced with the risk of deciding an aggressive treatment in a patient without malignancy. Patients with negative biopsy should undergo a second biopsy and/or repeated investigations by imaging techniques.
Adult↗
Quantitation of hepatic hepatitis C virus RNA in patients with chronic hepatitis C. Relationship with severity of disease, viral genotype and response to treatment.
BACKGROUND/AIMS: To determine the correlation between hepatic hepatitis C virus (HCV) RNA and histological lesions, viral genotype or response to alpha interferon therapy. METHODS: Forty-three patients with chronic hepatitis C (14 sustained responders (SR) and 29 non-sustained responders (NSR)) were studied. A liver tissue sample was obtained before and 1 year after treatment. Quantitation of hepatic HCV-RNA was performed by competitive PCR. RESULTS: Before treatment, HCV-RNA was detectable in all liver samples. There was no association between hepatic HCV-RNA and the severity of liver lesions. There was a significant association between old age and hepatic HCV-RNA (P = 0.03). There was an association, at the limit of significance, between genotype 1 and high hepatic HCV-RNA amounts (15 x 106 and 4.1 x 10(6) copies/g, P = 0.05). Pre-treatment hepatic HCV-RNA amounts were lower in SRs than in others (0.65 x 10(6) and 13.2 x 10(6) copies/g, P = 0.0002). After treatment, no liver HCV-RNA was detectable in the SRs while in the NSRs, the HCV-RNA amounts were unchanged. CONCLUSIONS: The amount of hepatic HCV-RNA is correlated to genotype and response to interferon therapy but not to histologic lesions. Hepatic HCV-RNA clearance is observed in SRs, suggesting viral eradication.
Adult↗