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ABSTRACT: To determine the evolution of transient elastography (TE) in patients with alcoholic liver disease according to alcohol cessation or continuation.
We retrospectively selected in our local database all patients who had two TE between June 2005 and November 2010 with chronic alcohol excessive consumption and excluded those with associated cause of liver disease. TE was performed at least one week apart by senior operator. TE examinations with less than ten successful measures or with an interquartile range above 30% were excluded. We retrospectively reviewed file of all patients to include only patient followed up by trained addictologist and for which definite information on alcohol consumption was available. Concomitant biological parameters [aspartate amino transferase (AST), alanine amino transferase and gamma-glutamyl transpeptidase (GGT)] within 4 wk of initial and final TE were recorded. Putative fibrosis score according to initial and final TE were determined with available cut-off for alcoholic liver disease and hepatitis C. Initial and final putative fibrosis score were compared according to alcohol consumption during follow-up.
During the study period 572 patients had TE examination for alcoholic liver disease and 79 of them had at least two examinations. Thirty-seven patients met our criteria with a median follow-up of 32.5 wk. At the end of the study, 13 (35%) were abstinent, and 24 (65%) relapsers. Eight patients had liver biopsy during follow-up. TE decreased significantly during follow-up in 85% of abstinent patients [median (range): -4.9 (-6.1,-1.9)], leading to a modification of the putative fibrosis stage in 28%-71% of patient according to different cut-off value. In relapsers TE increased in 45% and decreased in 54% of patient. There was no statistical difference between initial and final TE in relapsers. In the overall population, using 22.6 kPa as cut-off for cirrhosis, 4 patients had cirrhosis at initial TE and 3 patients had cirrhosis at final TE. Using 19.5 kPa as cut-off for cirrhosis, 7 patients had cirrhosis at initial TE and 5 patients had cirrhosis at final TE. Using 12.5 kPa as cut-off for cirrhosis, 16 patients had cirrhosis at initial TE and 15 patients had cirrhosis at final TE. Evolution of biological data was in accordance with the relapse or abstinent status: abstinence ratio (duration of abstinence/duration follow-up) was correlated with AST ratio (r = -0.465, P = 0.007) and GGT ratio (r = -0.662, P < 0.0001). GGT was correlated with initial (r = 0.488, P = 0.002) and final TE (r = 0.49, P < 0.005). Final TE was correlated with AST (r = 0.362, P < 0.05). Correlation between TE ratio and AST ratio (r = 0.44, P = 0.01) revealed that TE varied proportionally to AST for all patients irrespective of their alcohol status. The same relationship was observed between TE ratio and GGT ratio (r = 0.65, P < 0.0001). Evolution of TE was significantly correlated with the ratio of time of abstinence to observation time (r = -0.387, P = 0.016) and the evolution of liver enzymes.
TE significantly decreased with abstinence. Results of TE in alcoholic liver disease cannot be interpreted without taking into account alcohol consumption and liver enzymes.
World Journal of Gastroenterology 01/2013; 19(4):516-22. · 2.47 Impact Factor
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ABSTRACT: Guidelines recommend 6 months of alcohol abstinence before treating hepatitis C (HCV). Abstinence is difficult for alcohol-dependent patients to achieve. This study evaluated HCV treatment in alcoholic patients with ongoing consumption or less than 6 months of abstinence.
A multidisciplinary management model was built by a liver unit and two centers involved in the care of addict patients. Patients were included in a prospective observational study of treatment with pegylated interferon and ribavirin if they presented alcohol dependence with ongoing intoxication or abstinence of less than 6 months. Pre-therapeutic evaluation and follow-up were multidisciplinary, and addiction care was personalized to patient condition and willingness. Alcohol abstinence or reduction was encouraged but not mandatory. The primary end point was sustained virological response (SVR). Results were compared to a control group of patients matched for genotype, viral load, fibrosis stage, sex, and age.
A total of 73 patients treated between 2002 and 2008 were included in the study. Intent to treat analysis showed an SVR in 48% (35/73) of patients versus 49% (36/73) of controls. Low viral load and length of abstinence during treatment were independently associated with SVR. During treatment, 20 (27%) patients were abstinent, 23 (32%) had controlled consumption, and 24 (33%) had excessive consumption. At the end of the follow-up, 22 (30%) patients were durably abstinent.
A multidisciplinary approach allowed HCV treatment in alcohol-dependent patients with a satisfactory SVR rate and positive effects on addiction behavior.
Journal of Hepatology 07/2011; 56(2):334-40. · 9.26 Impact Factor
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ABSTRACT: The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm(3)] x prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis.
Hepatology 09/2006; 44(2):472-7. · 11.66 Impact Factor
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ABSTRACT: Intra-arterial injections of 131I-lipiodol (131I-Lip) provide an effective treatment for hepatocellular carcinoma. In hepatocellular carcinoma cell cultures, concurrent administration of cisplatin increases the cytotoxicity of 131I. The efficacy and tolerance of intra-arterial injections of 131I-Lip combined with systemic cisplatin was tested in a phase II trial.
The inclusion criteria were proven unresectable nonmetastatic hepatocellular carcinoma, compensated liver disease, and adequate laboratory test findings. Treatment comprised the combination of intra-arterial injection of 131I-Lip (2.2 GBq) with intravenous infusion of low-dose cisplatin. The combined treatment could be repeated.
A total of 41 patients were included; 37 had cirrhosis and 38 had measurable tumors. One to four treatments (median, two) were given. The cisplatin dose was 75 mg for the first course and 72 mg for the second. Grade 3-4 (n/n) adverse effects were observed in 14 patients, polymorphonuclear leukocytes (3/0), platelets (5/1), asthenia (1/0), pain (1/0), and vomiting (1/0). Four patients developed pulmonary toxicity; 2 cases were likely related to 131I-Lip administration and 1 was fatal. The response rate was 47% (18 of 38), and the 1- and 2-year survival rate was 73% +/- 7% and 48% +/- 9%, respectively.
This combination had a tolerable toxicity profile and provided an objective response rate, warranting a phase III trial.
International Journal of Radiation OncologyBiologyPhysics 04/2006; 64(3):745-50. · 4.11 Impact Factor
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Fabrice Lainé,
Claude Bendavid,
Romain Moirand,
Sabrina Tessier,
Michèle Perrin, Anne Guillygomarc'h,
Dominique Guyader,
Emmanuelle Calon,
Alain Renault,
Pierre Brissot,
Bruno Turlin,
Yves Deugnier
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ABSTRACT: The aim of this study was to determine noninvasive predictive factors of significant liver fibrosis in patients with increased serum aminotransferases associated with features of metabolic syndrome (abdominal obesity, systemic hypertension, fasting hyperglycemia, and dyslipidemia). One hundred seventy-three patients were prospectively examined, regardless of alcohol consumption. Biometric, metabolic, and hepatic biochemical variables were tested for association with fibrosis assessed on liver biopsy according to the Metavir score system. Significant fibrosis, defined as Metavir scores F2, F3, or F4, was observed in 42 of 173 patients (24%). A logistic regression model and receiver operating characteristic curve were used to construct a simple index predictive of significant fibrosis. None of the patients with serum hyaluronate levels of 35 microg/L or less had significant fibrosis. In patients with serum hyaluronate levels >35 microg/L, no case of fibrosis stage F3 or F4 was found when serum carbohydrate-deficient transferrin/transferrin ratio was less than 0.9. In conclusion, in patients with increased serum aminotransferases associated with features of metabolic syndrome, a simple algorithm, including serum hyaluronate and serum carbohydrate-deficient transferrin/transferrin ratio, allows the exclusion of clinically relevant hepatic fibrosis, regardless of current or past alcohol consumption.
Hepatology 06/2004; 39(6):1639-46. · 11.66 Impact Factor
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ABSTRACT: The phenotypic screening for genetic haemochromatosis (GH) relies upon the determination of transferrin saturation (TS). In large-scale screening programs, the time of blood sampling can be uneasy to control. We studied the circadian variations of TS at 08.00 hours, 12.00 hours, 18.00 hours and 00.00 hours in 46 C282Y homozygous patients (GH) and 47 non-GH patients (NH), to determine whether the time of blood sampling influenced the results of screening. In both groups, there were significant circadian variations in TS, with the highest values at 08.00 hours and the lowest at 00.00 hours. For any given time-point, TS was significantly higher in the GH group when compared with the NH group (P < 0.0001). For both groups, there was a significant decrease in TS between 08.00 hours and 00.00 hours (P < 0.0001) but this decrease was not as significant in GH when compared with NH patients (interaction P < 0.0073). Receiver operating characteristics (ROC) curves generated for TS at 08.00 hours, 12.00 hours, 18.00 hours and 00.00 hours, presented the same efficiency of diagnosis of GH, with TS threshold varying between 64% at 08.00 hours and 36% at 00.00 hours. In conclusion, for screening studies of C282Y homozygosity, determination of transferrin saturation may be performed at any time during the day.
British Journal of Haematology 01/2003; 120(2):359-63. · 4.94 Impact Factor
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ABSTRACT: The aim of our study was to evaluate the proportion of patients with severe alcoholic cirrhosis who would need orthotopic liver transplantation (OLT) and to determine the optimal delay to evaluate an abstinent patient for transplantation.
Survival without OLT, improvement in liver function and need for OLT were studied in all patients admitted in 1997 for a first episode of Child-Pugh C alcoholic cirrhosis.
Twenty-six percent (19/74) of patients died during the initial hospitalization. The cumulative survival rates after 6 months and 1, 2 and 3 years were 56, 36, 35 and 24%, respectively. One liver transplantation (1.3%, 95% confidence interval 0.0-3.9) was performed for persisting liver failure despite abstinence. Improvement of the Child-Pugh score was observed within 3 months in 66% of the abstinent patients. OLT was indicated in four patients without liver improvement despite abstinence, but was contraindicated in three.
Only a few patients with severe alcoholic cirrhosis undergo OLT, since most of them do not stop drinking and/or die soon, and those becoming abstinent often improve their liver function. OLT should be considered when improvement in liver function is lacking after 3 months of abstinence.
Journal of Hepatology 02/2002; 36(1):93-8. · 9.26 Impact Factor
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ABSTRACT: This review examines the clinical consequences for the practicing hematologist of remarkable new insights into the pathophysiology of disorders of iron and heme metabolism. The familiar proteins of iron transport and storage-transferrin, transferrin receptor, and ferritin-have recently been joined by a host of newly identified proteins that play critical roles in the molecular management of iron homeostasis. These include the iron-regulatory proteins (IRP-1 and -2), HFE (the product of the HFE gene that is mutated in most patients with hereditary hemochromatosis), the divalent metal transporter (DMT1), transferrin receptor 2, ceruloplasmin, hephaestin, the "Stimulator of Fe Transport" (SFT), frataxin, ferroportin 1 and others. The growing appreciation of the roles of these newly identified proteins has fundamental implications for the clinical understanding and laboratory evaluation of iron metabolism and its alterations with iron deficiency, iron overload, infection, and inflammation. In Section I, Dr. Brittenham summarizes current concepts of body and cellular iron supply and storage and reviews new means of evaluating the full range of body iron stores including genetic testing for mutations in the HFE gene, measurement of serum ferritin iron, transferrin receptor, reticulocyte hemoglobin content and measurement of tissue iron by computed tomography, magnetic resonance imaging and magnetic susceptometry using superconducting quantum interference device (SQUID) instrumentation. In Section II, Dr. Weiss discusses the improved understanding of the molecular mechanisms underlying alterations in iron metabolism due to chronic inflammatory disorders. The anemia of chronic disorders remains the most common form of anemia found in hospitalized patients. The network of interactions that link iron metabolism with cellular immune effector functions involving pro- and anti-inflammatory cytokines, acute phase proteins and oxidative stress is described, with an emphasis on the implications for clinical practice. In Section III, Dr. Brissot and colleagues discuss how the diagnosis and management of hereditary hemochromatosis has changed following the identification of the gene, HFE, that is mutated in most patients with hereditary hemochromatosis, and the subsequent development of a genotypic test. The current understanding of the molecular effects of HFE mutations, the usefulness of genotypic and phenotypic approaches to screening and diagnosis and recommendations for management are summarized.
Hematology 02/2000; · 1.49 Impact Factor
