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1.
Rev Med Interne ; 32(6): 341-6, 2011 Jun.
Article in French | MEDLINE | ID: mdl-21269740

ABSTRACT

PURPOSE: Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by the accumulation of copper in the body due to defective biliary copper excretion by hepatocytes. We report a series of 19 patients with WD. PATIENTS AND METHODS: This is a retrospective and descriptive case series of patients with WD followed in two hospitals of North East of France. RESULTS: Eight men and 11 women were studied. Median follow-up time was 16 years, median age at diagnosis was 18 years (range: 5-71 years). Median age at first symptom was 16 years. In addition to four cases diagnosed by familial screening, clinical manifestations at diagnosis were fatigue (n=5), jaundice (n=5), bleeding (n=1), abnormal movement disorders (n=2) and fortuitous (n=2). Cirrhosis was identified in 14 patients, neurological involvement occurred in seven patients and four patients presented with psychiatric disorders. d-penicillamine was the first treatment in 18 patients, discontinued for severe adverse events in seven patients. Trientine or zinc salts were then prescribed. Medical treatment was successful in 13 patients, but five patients underwent liver transplantation. Haemochromatosis was associated in one case, and one patient developed cholangiocarcinoma. CONCLUSION: WD is severe. Medical treatment allows disease control if it is correctly observed. Conversely, worsening with irreversible damage can occur if the treatment is discontinued.


Subject(s)
Hepatolenticular Degeneration , Adolescent , Adult , Aged , Child , Child, Preschool , Female , Hepatolenticular Degeneration/diagnosis , Hepatolenticular Degeneration/therapy , Humans , Male , Middle Aged , Retrospective Studies , Young Adult
2.
Eur J Gastroenterol Hepatol ; 13(2): 143-7, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11246613

ABSTRACT

OBJECTIVE: The natural history of mild chronic hepatitis C is not well-known and the benefit of treating this form of the disease is not well-defined. We conducted a pilot study to answer this question. DESIGN: Mild chronic hepatitis C was defined by positivity for anti-HCV antibodies, detectable serum HCV RNA by PCR, and a Knodell score < or = 5 on a liver biopsy performed within the previous 6 months. Eighty patients from six centres were randomized into two groups receiving interferon alpha-2b, 3 MU three times a week for 6 months (group 1, n = 39) or no treatment (group 2, n = 41). Sustained response was defined by the loss of detectable serum HCV RNA at 6 months after therapy. RESULTS: The two groups were not different at entry with respect to age, sex ratio, source of infection, disease duration, genotype, viral load and Knodell score. One patient (group 1) was excluded from the study, while two patients in group 1 (5%) and seven in group 2 (17.1 %) did not complete the trial. A sustained response was observed in seven patients (18%) in group 1 versus none in group 2 (P < 0.01). The difference in mean Knodell score remained non-statistically significant between the two groups at the end of the study. Reduction or interruption of interferon was necessary in eight patients (24.2%). CONCLUSIONS: This first randomized controlled study in mild chronic hepatitis C shows a proportion of sustained responders to interferon alpha-2b similar to that observed in active chronic hepatitis C.


Subject(s)
Antiviral Agents/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Adult , Aged , Double-Blind Method , Female , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C Antibodies/blood , Hepatitis C, Chronic/diagnosis , Humans , Interferon alpha-2 , Male , Middle Aged , Pilot Projects , RNA, Viral/blood , Recombinant Proteins , Viral Load
3.
Dig Liver Dis ; 32(1): 29-33, 2000.
Article in English | MEDLINE | ID: mdl-10975752

ABSTRACT

AIMS: This prospective randomized trial was carried out in order to determine whether the long-term administration of ursodeoxycholic acid after discontinuation of interferon had any beneficial effect on the clinical course of hepatitis C virus infection. METHODS: Enrolled in the study were 203 patients with chronic active hepatitis C. They were all given: interferon alpha-2a (3 MU subcutaneously thrice a week) and ursodeoxycholic acid (10 mg/kg/day) for 9 months. At month 9, biochemical responders only were randomized into ursodeoxycholic acid treatment or placebo for 12 additional months (double blind study). RESULTS: At the end of interferon therapy, 71 patients (37%) were virological responders and 107 (56%) patients were biochemical responders and were randomized: 54 into the ursodeoxycholic acid group and 53 into the placebo group. Sustained response was evaluated 12 months after withdrawal of interferon. Sustained biochemical and virological responses were, respectively, 30% and 22% in the ursodeoxycholic acid group and 46% and 32% in the placebo group, which did not significantly differ. Histological evolution of fibrosis and necrotic inflammatory activity were similar in the two groups. CONCLUSION: Continuation of ursodeoxycholic acid therapy after withdrawal of interferon in patients with end-of-treatment response did not result in any significant improvement either in the maintenance of response to interferon or in liver histology.


Subject(s)
Antiviral Agents/therapeutic use , Cholagogues and Choleretics/therapeutic use , Hepatitis C, Chronic/drug therapy , Interferon-alpha/therapeutic use , Ursodeoxycholic Acid/therapeutic use , Adolescent , Adult , Aged , Biopsy , Double-Blind Method , Drug Therapy, Combination , Enzyme-Linked Immunosorbent Assay , Female , Hepacivirus/genetics , Hepacivirus/immunology , Hepatitis C Antibodies/analysis , Hepatitis C, Chronic/pathology , Hepatitis C, Chronic/virology , Humans , Interferon alpha-2 , Male , Middle Aged , Prospective Studies , RNA, Viral/analysis , Recombinant Proteins , Reverse Transcriptase Polymerase Chain Reaction
4.
Scand J Gastroenterol ; 35(6): 642-9, 2000 Jun.
Article in English | MEDLINE | ID: mdl-10912666

ABSTRACT

BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.


Subject(s)
Antiviral Agents/administration & dosage , Cholagogues and Choleretics/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Ursodeoxycholic Acid/administration & dosage , Adult , Aged , Dose-Response Relationship, Drug , Double-Blind Method , Drug Resistance, Microbial , Drug Therapy, Combination , Female , Follow-Up Studies , Hepatitis C, Chronic/diagnosis , Humans , Interferons/administration & dosage , Male , Middle Aged , Reference Values , Statistics, Nonparametric , Treatment Outcome
5.
Hepatology ; 27(3): 862-7, 1998 Mar.
Article in English | MEDLINE | ID: mdl-9500719

ABSTRACT

The purpose of this study is to compare a combination of interferon (IFN)-alpha2a (Roferon) + Tenoxicam with IFN-alpha2a alone in the treatment of chronic hepatitis C. This prospective, randomized double-blind study included 149 patients, all of whom were diagnosed with active chronic hepatitis C but non-cirrhotic (ALT > or = 1.5 upper limit of normal, anti-hepatitis C virus (HCV) positive by enzyme-linked immunosorbant assay2 and RIBA3). The patients were randomized in two groups, as follows: G1 (n = 76): IFNalpha2a 3 million units times per week during 6 months + placebo; and G2 (n = 73): IFNalpha2a 3 million units three times per week + Tenoxicam (20 mg/day) during 6 months. Alanine aminotransferase (ALT) and HCV RNA were determined before and at months 6 and 12 of treatment. 2'5' oligoadenylate synthetase activity (2'5' AS) was dosed in mononuclear cells before and at 3-month treatment intervals in 28 patients. Liver biopsy was performed before and 6 months after the end of therapy. Parameters were similar before therapy for both groups. Biochemical and virological responses were similar for both groups at month 6 (49.3% vs. 42.9% and 43.3% vs. 38.3%, respectively) and month 12 (28.3% vs. 23.8% and 17.2% vs. 17.5%, respectively). HCV RNA level significantly decreased in both groups at month 6, with no difference whatever the therapy; however, the HCV RNA level returned to initial values at month 12 and was the only significant prognostic factor of a sustained response. No peak of 2'5' AS activity was observed during treatment in patients with dual therapy. A histological improvement was also noted in both groups without difference, regardless of therapy. The percentage of adverse events was identical for both groups. Paracetamol intake, assessed in 80 patients, was 49.1 g per 6 months in the G1 group and 22.5 g per 6 months in the G2 group (not significant). In conclusion, the non-steroid anti-inflammatory drug, Tenoxicam, does not increase IFNalpha efficacy in the treatment of chronic hepatitis C. This combination is well tolerated and partially lowers Paracetamol intake, but not preexisting alpha-IFN adverse events.


Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Hepatitis C, Chronic/drug therapy , Interferon-alpha/administration & dosage , Piroxicam/analogs & derivatives , 2',5'-Oligoadenylate Synthetase/metabolism , Adult , Double-Blind Method , Drug Therapy, Combination , Female , Humans , Interferon alpha-2 , Interferon-alpha/adverse effects , Male , Middle Aged , Piroxicam/administration & dosage , Piroxicam/adverse effects , Recombinant Proteins
8.
Ann Chir ; 49(7): 580-6; discussion 587-8, 1995.
Article in French | MEDLINE | ID: mdl-8554268

ABSTRACT

From March 1992 to March 1994, 26 patients underwent Transjugular Intrahepatic Portosystemic Shunt (TIPS) for emergency treatment of variceal bleeding. Patients were all cirrhotic, with a mean age 55 +/- 13 yrs, Child's score was A = 4, B = 10, C = 12. TIPS was performed in case of failure or impossibility to obtain hemostasis after endoscopic and/or medical treatment. Hemostasis was successful in all cases of TIPS, and the portocaval gradient was lowered from 19 to 9 mmHg. Early complications occurred in 30% of cases. They consisted of: spontaneously regressive hemobilia (15%) and shunt thrombosis (15%) (3/4 were repermeabilized). Early mortality accounted for 15% of patients in the whole group and 25% in Child C'patients. During follow-up (m = 8 +/- 6 m), only one patient rebled, de novo hepatic encephalopathy occurred in 15% of patients always regressive in response to Lactulose therapy. One year mortality rate was 57%. A comparison between TIPS and other emergency hemostasis methods: endoscopic sclerotherapy, surgical portocaval shunt and esophageal transsection was performed on the early mortality rate according to the percentage of Child C'patients in the various series. TIPS is better than other methods in series with a low percentage of Child C'patients. TIPS should be proposed: in case of failure of endoscopic methods; for patients waiting for liver transplantation; when portal vein patency is compromised by thrombosis. This last indication implies that portal patency must be confirmed with angiography or better by with duplex sonography once primary hemostasis of variceal bleeding has been completed.


Subject(s)
Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/surgery , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis/complications , Portasystemic Shunt, Surgical/methods , Adult , Aged , Emergency Medicine , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/etiology , Hepatitis C/complications , Humans , Male , Middle Aged , Postoperative Complications
9.
Ann Chir ; 47(5): 407-13, 1993.
Article in French | MEDLINE | ID: mdl-8215163

ABSTRACT

Transjugular intrahepatic portosystemic stent-shunt (TIPS) is a new technique in interventional radiology. This procedure is based on the creation of an intrahepatic channel between a main branch of the portal vein and an hepatic vein. A metallic stent is implanted to keep this shunt patent. From July 1990 to March 1992, 28 out of 32 patients with a history of gastric or esophageal variceal rebleeding, were treated by TIPS and followed for up to 20 months (mean 9.36 +/- 5.42). According to the Child Pugh's classification, 9 patients had class A cirrhosis, 17 class B and 6 class C. TIPS led to reduction of the portal pressure gradient by 57% and improvement of the portal blood flow by 250%. Early complications were: one technique-related death due to a medial stent implantation on the portal bifurcation (massive extrahepatic bleeding), other cases consisted of hemobilias (3 patients), intra-abdominal bleeding (1 patient) and gastrointestinal bleedings (4 patients). All of the complications except the deat were spontaneously reversed after withdrawal of Heparin. Follow-up showed a considerable improvement of ascites, seen in 55% of the patients with 100% reduction or disappearance after 3 months. Duplex-sonography follow-up found shunt stenosis in 43% of the patients, allowing preventive redilatation to restore patency of the shunt. Variceal rebleeding occurred in 20% of cases. These results remain interesting with regard to the high risk of bleeding in the patients of this preliminary study.(ABSTRACT TRUNCATED AT 250 WORDS)


Subject(s)
Gastrointestinal Hemorrhage/surgery , Hypertension, Portal/complications , Liver Cirrhosis, Alcoholic/complications , Liver Cirrhosis/complications , Portacaval Shunt, Surgical/methods , Adult , Aged , Aged, 80 and over , Esophageal and Gastric Varices/complications , Follow-Up Studies , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/etiology , Gastrointestinal Hemorrhage/mortality , Hemodynamics , Humans , Middle Aged , Portography , Recurrence , Time Factors
11.
Gastroenterol Clin Biol ; 17(6-7): 422-30, 1993.
Article in French | MEDLINE | ID: mdl-8243926

ABSTRACT

Transjugular implantation of a metallic prosthesis between main portal branch and a hepatic vein is a new intrahepatic portosystemic shunt method to treat portal hypertension. Forty-nine cirrhotic patients with portal hypertension were treated using this technique. The success rate of implantation was 94%. Mortality due to the procedure was 2%. Early complications decreased with the operator's learning curve consisting of bleeding (20%): digestive hemorrhage (n = 5; 12%), hemobilia (n = 4; 8%), which ceased after withdrawal of post-operative heparin. Early thrombosis following shunt implantation occurred in 13% of the patients. Shunt implantation resulted in a 53 +/- 16% decrease in the portocaval pressure gradient (21 +/- 5 to 10 +/- 4 mmHg). Shunts were performed in 45 patients to prevent a recurrence of variceal bleeding. Follow-up of 41 patients showed 12.2% with variceal rebleeding and 16 patients (39%) with a stenosis requiring a redilation. Ascites improved in 95% of the patients and hepatic encephalopathy occurred in 17%. One year survival was 85%. Controlled studies are needed to determine the indications of this new treatment for ascites and bleeding.


Subject(s)
Ascites/surgery , Esophageal and Gastric Varices/complications , Gastrointestinal Hemorrhage/prevention & control , Hypertension, Portal/complications , Portacaval Shunt, Surgical/methods , Actuarial Analysis , Adult , Aged , Aged, 80 and over , Ascites/etiology , Budd-Chiari Syndrome/etiology , Esophageal and Gastric Varices/blood , Esophageal and Gastric Varices/diagnostic imaging , Female , Follow-Up Studies , Gastrointestinal Hemorrhage/blood , Gastrointestinal Hemorrhage/diagnostic imaging , Gastrointestinal Hemorrhage/etiology , Humans , Liver Cirrhosis/complications , Liver Cirrhosis, Alcoholic/complications , Male , Middle Aged , Portacaval Shunt, Surgical/adverse effects , Portacaval Shunt, Surgical/mortality , Postoperative Complications , Radiography , Recurrence , Ultrasonics
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