Hepatitis: Vallet-Pichard A

Vallet-Pichard A, Fontaine H, Pol S. · Unité d'Hépatologie et U-370, Hôpital Necker, Paris. · Gastroenterol Clin Biol. · Pubmed #12483129 No free full text.

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Pol S, Vallet-Pichard A. · Unité d'hépatologie, Hôpital Cochin, 27, rue du faubourg Saint Jacques, 75014 Paris, France. · Gastroenterol Clin Biol. · Pubmed #18662608 No free full text.

Abstract: Parenteral and community-acquired routes of contamination sanguins of hepatitis B virus (HBV) explain its frequency (9 to 20%) in dialysis patients and kidney recipients. In dialysis, HBV infection has few impact on morbidity and mortality; by contrast, in kidney recipients HBV: 1. reduces the allograft survival; 2. the patients survival in association with a frequent and rapid evolution to cirrhosis and hepatocellular carcinoma or rare cholestatic fibrosis. Finally, cirrhosis contra-indicates renal transplantation alone given its poor short-term prognosis and a combined liver-kidney transplantation has to be discussed. Thus, it is necessary to evaluate the liver severity of the liver disease. The treatement of HBV in allograft recipients and dialysis is based on nucleos(t)idic analogues like in the general population with the same advantages and questions. The variations of the immune status either in an HBV-infected patients at the induction or at the reduction of chemotherapies (solid tumors or hemopathies) or allograft transplantation may result in two, potentially severe, events in miror: a reactivation or a spontaneous discontinuation of viral replication (seronconversion). These risks evidence that any HBs Ag carrier exposed to immune suppression has to be diagnosed, evaluated for viral replication and underlying liver disease and has to be treated by a so-called pre-emptive treatment based on analogues.

Roulot D, Vallet-Pichard A. · Unité d'hépatologie, Hôpital Avicenne, 125 route de Stalingrad, Bobigny. · Gastroenterol Clin Biol. · Pubmed #18166873 No free full text.

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Vallet-Pichard A, Pol S. · Inserm U-370 et Unité d'Hépatologie, Hôpital Necker; Faculté Paris V, 149 Rue de Sèvres, 75015 Paris, France. · J Hepatol. · Pubmed #16343684 No free full text.

Abstract: Co-infection by the hepatitis C virus (HCV) is observed in up to 30% of HIV-infected individuals. In studies conducted in the 'pre-HAART era', the late consequences of HCV-related chronic liver disease were overshadowed by extra-hepatic causes of deaths, related to severe immune deficiency, and the impact of HCV infection on mortality of HIV-infected patients was low. While the development of HAART has resulted in a significant decrease in morbidity and mortality amongst HIV-infected patients, this clear benefit allowed the expression of liver-related complications associated with HCV chronic infection. The impact of HCV on HIV remains debated but HIV infection significantly modifies the natural history of HCV infection. HIV infection increases levels of HCV viraemia by 2- to 8-fold, resulting in a significant decrease in spontaneous recovery of acute hepatitis. HIV co-infection also worsens the histological course of HCV infection by increasing and accelerating the risk of cirrhosis or leading to rare but lethal fibrosing cholestatic hepatitis. Liver disease is now one of the leading causes of morbidity and mortality in co-infected patients, even if HAART and especially protease inhibitors, may decrease the severity of the liver disease and the liver-related mortality. Several non-exclusive pathogenic processes explain the increasing rate of liver complications associated with HCV-related liver disease.

Vallet-Pichard A, Pol S. · Unité d'Hépatologie et Inserm U-370, Hôpital Necker, 149 Rue de S èvres, 75015 Paris, France. · J Hepatol. · Pubmed #15246224 No free full text.

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Lebray P, Vallet-Pichard A, Michel ML, Fontaine H, Sobesky R, Bréchot C, Pol S. · Service d'Hépatologie, Hôpital Necker Enfants Malades, 75730 Paris Cédex 15, France. · J Hepatol. · Pubmed #14708695 No free full text.

This publication has no abstract.

Pol S, Vallet-Pichard A, Fontaine H, Lebray P. · Unité d'Hépatologie et Inserm V-370, Hôpital Necker, Paris, France. · Semin Nephrol. · Pubmed #12118398 No free full text.

Abstract: Hepatitis C virus (HCV) infections are frequent in hemodialyzed patients and are mainly related to transfusions and nosocomial contamination. HCV-related infection may result in cirrhosis in 10% of dialysis patients and is worsened by transplantation because of the immunosuppressive therapy for prevention of graft rejection. Because there is a risk for significant liver disease and because cirrhosis contraindicates a renal transplantation, a liver biopsy should be performed early in HCV-RNA positive hemodialysis patients to evaluate histologic impact of the liver disease. A combined liver-kidney transplantation should be discussed in dialysis patients with cirrhosis. Standard alpha-interferon is the only treatment for HCV in dialysis patients because ribavirin is contraindicated by a high risk for hemolytic anemia. It leads to an overall 30% rate of sustained viral eradication. It is indicated in dialysis patients with acute hepatitis C, significant liver disease (fibrosis score > or =2), or symptomatic cryoglobulinemia, and to candidates for renal transplantation, whatever the severity of the liver disease. Indeed, alpha-interferon is contraindicated in kidney recipients given the risk for rejection. Preventive treatment for HCV is only respect for universal hygiene rules in the dialysis setting because there is no available vaccine.

Pol S, Vallet-Pichard A, Fontaine H. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, Paris, France. · J Viral Hepat. · Pubmed #11851897 No free full text.

Abstract: Interactions between human immunodeficiency virus (HIV) and hepatitis C virus (HCV) have been widely studied before the introduction of highly active antiretroviral therapies (HAART). We reviewed the potential impact of HAART on hepatitis C as well as the interactions between HIV and HCV therapies. Physicians should be aware of the potential risk of: (i) symptomatic liver disease in HCV-HIV-coinfected patients at the era of triple antiretroviral therapy; (ii) potential liver deterioration paralleling immune restoration; (iii) lack of impact of triple antiretroviral therapy on HCV load; and (iv) potential drug-related hepatitis which may modify the natural history of HCV-related liver disease. Liver biopsies should be performed regularly in these patients in order to identify patients with severe liver disease who require early initiation of anti-HCV therapy under close monitoring of their immune status. Treatment is, to date, based on the combination of ribavirin and interferon with an expected sustained response rate around 25%. An important unresolved issue is to better delineate the temporal place of anti-HCV and anti-HIV antiviral therapies. At least in coinfected patients with significant liver disease, namely necro-inflammatory activity and/or fibrosis >or= 2, we believe that anti-HCV therapy is the priority since it lessens the risk of drug-induced hepatitis and of hepatitis due to immune restoration.

Pol S, Fontaine H, Vallet-Pichard A. · Unité d'Hépatologie et INSERM U-370, Hôpital Necker, 149, rue de Sèvres, 75743 Paris Cedex 15. · Gastroenterol Clin Biol. · Pubmed #11395676 No free full text.

This publication has no abstract.

Fontaine H, Vallet-Pichard A, Chaix ML, Currie G, Serpaggi J, Verkarre V, Varaut A, Morales E, Nalpas B, Brosgart C, Pol S. · Liver Unit, Necker Hospital, Paris, France. · Transplantation. · Pubmed #16278590 No free full text.

Abstract: BACKGROUND: This study analyzes the biochemical, serological, and virological efficacy and the safety of adefovir dipivoxil in patients with renal disturbances. METHODS: Twelve patients with lamivudine-resistant hepatitis B virus (HBV) chronic infection were treated for a median time of 15 (3-19) months. The daily dosage was 10 mg initially and then adjusted according to renal function. RESULTS: Median (range) ALT values remained stable: 55 (13-117) and 37 (17-266) UI/L. After the 12th month, the median decline in serum HBV DNA was from 8.76 (6.3-9.7) to 2.97 (1.15-5.65) log10 Eq/ml (median decline of -5.5 log10). No virologic breakthrough was observed. One of the six HBeAg-positive patients lost HBe Ag but without HBe seroconversion; none had HBs Ag loss. There were no significant clinical and biochemical adverse effects. In the 11 nonhemodialysed patients, the creatinine clearance significantly improved from 70 (30-100) to 88 (38-125) ml/mn (P=0.01) and the mean serum creatinine levels increased only slightly from 114 (91-839) to 130 (81-561) micromol/ml (NS). Serum phosphorus remained stable. The urinary level of protein decreased from 0.16 (0.08-8.63) to 0.12 (0.01-0.74) g/day (NS). CONCLUSIONS: Adefovir dipivoxil is safe for the treatment of chronic hepatitis B in patients with varying degrees of renal dysfunction and lamivudine-resistant HBV and results in biochemical and virological efficacy similar to that reported in the general population.

Quioc JJ, Trabut JB, Drouhin F, Malbrunot C, Vallet-Pichard A, Pol S, Denis J. · Hepatology Unit, Cochin Hospital, Paris, France. · Eur J Gastroenterol Hepatol. · Pubmed #19212211 No free full text.

Abstract: Liver involvement is an unusual manifestation of Mycoplasma pneumoniae infection. Cases of cholestatic hepatitis without pulmonary involvement have been described in children with M. pneumoniae infection but only two cases of cytolytic hepatitis have been reported in adults. We report here the case of an 18-year-old woman who presented with febrile epigastric pain of short duration associated with an elevation of gamma-glutamyl transpeptidase and alkaline phosphatase levels and with a mononuclear syndrome. Serological tests for M. pneumoniae were positive for IgG and IgM. Clinical symptoms and blood test perturbations completely resolved after treatment with macrolide.

Mallet V, Dhalluin-Venier V, Roussin C, Bourliere M, Pettinelli ME, Giry C, Vallet-Pichard A, Fontaine H, Pol S. · Université Paris Descartes, Paris, France. · Aliment Pharmacol Ther. · Pubmed #19035983 No free full text.

Abstract: BACKGROUND: The Fib-4 index is a simple and inexpensive biomarker to delineate liver fibrosis in chronic hepatitis C. AIM: To assess the accuracy of the FIB-4 index in chronic hepatitis B. METHODS: We compared the FIB-4 index with 138 synchronous liver biopsies and with 372 synchronous FibroTest performed either in France or in an endemic area (Mayotte, an overseas collectivity of France). RESULTS: The FIB-4 index allowed the correct identification of patients with nil-to-moderate fibrosis with an area under the receiving operating characteristic curve of 0.81 (P < 0.001), increasing as a function of the length of the liver biopsy (up to 0.94 for liver biopsies >or=20 mm). A cut-off value <or=1.45 differentiated moderate fibrosis from severe fibrosis with a negative predictive value of 86%, a sensitivity of 71.1% and a specificity of 73.1%. Beyond 1.45, the FIB-4 index was not informative. The FIB-4 index was more precise than the AST-to-platelet ratio index and correlated with the FibroTest in 89% of the cases (kappa = 0.27, P < 0.001) to exclude severe fibrosis. CONCLUSION: The FIB-4 index is a simple, accurate and inexpensive method to exclude significant liver fibrosis in chronic hepatitis B, a major advantage in HBV-endemic developing countries.

Mallet V, Gilgenkrantz H, Serpaggi J, Verkarre V, Vallet-Pichard A, Fontaine H, Pol S. · Université Paris Descartes; Assistance Publique-Hôpitaux de Paris, Hôpital Cochin, INSERM U 567, Paris, France. · Ann Intern Med. · Pubmed #18794559 links to  free full text

Abstract: BACKGROUND: The effect of regression of cirrhosis in chronic hepatitis C is unknown. OBJECTIVE: To evaluate the relation between regression of cirrhosis and clinical outcome in patients with chronic hepatitis C after antiviral therapy. DESIGN: A cohort of patients with cirrhosis treated between 1988 and 2001. SETTING: Hepatology unit of a tertiary care center in France. PATIENTS: 96 patients with chronic hepatitis C and biopsy-proven cirrhosis (METAVIR score F4) who were treated with an interferon-based regimen and had at least 1 posttreatment liver biopsy. Patients were followed until November 2006. MEASUREMENTS: Occurrence of a combined end point of liver-related events (ascites, hepatic encephalopathy, variceal bleeding, spontaneous bacterial peritonitis, hepatocellular carcinoma, or liver transplantation) and death in patients with regression of cirrhosis (defined as a decrease from 4 to <or=2 METAVIR units on posttherapy liver biopsy). RESULTS: The median follow-up was 118 months (interquartile range, 86 to 138 months). Eighteen patients had regression of cirrhosis. The incidence of the combined end point per 100 patient-years was 0 in patients with regression of cirrhosis and 4 in patients without regression of cirrhosis (P = 0.002, log-rank test). The transplantation-free survival rate at 10 years was 100% in patients with regression of cirrhosis and 74.2% in patients without regression of cirrhosis (P = 0.025). LIMITATIONS: Selection of patients was retrospective; selection and survival biases may have influenced the estimates of the overall rate of regression of cirrhosis. The low number of patients who experienced regression of cirrhosis precludes analysis of factors that could predict regression of cirrhosis. CONCLUSION: Regression of cirrhosis occurs after antiviral therapy in some patients with chronic hepatitis C. Regression is associated with decreased disease-related morbidity and improved survival.

Trabut JB, Plat A, Thepot V, Fontaine H, Vallet-Pichard A, Nalpas B, Pol S. · Unité d'Hépatologie-Hôpital Cochin, 27, rue du Faubourg St Jacques, 75014 Paris, France. · Alcohol Alcohol. · Pubmed #18621800 No free full text.

Abstract: BACKGROUND: Liver biopsy indication for the evaluation of alcoholic liver disease is controversial. Our aim was to investigate the influence of the biopsy on the patients' motivation for abstinence. METHODS: We retrospectively analysed, in a population of 324 patients hospitalized for alcohol withdrawal, the impact of liver biopsy on the following clinical outcomes: rapid loss to follow-up (immediately after hospital discharge), early relapse (< 3 months) and long-lasting abstinence (> 12 months). The biopsy was performed in 136 patients who had liver enzymes perturbations. Hepatic lesions were graded as mild (isolated steatosis and/or non-bridging fibrosis), moderate (bridging fibrosis and/or moderate alcoholic hepatitis) or severe (cirrhosis and/or marked alcoholic hepatitis) in 66 (48%), 41 (30%) and 29 (21%) cases, respectively. RESULTS: In univariate analysis, patients who had a liver biopsy were less likely to be rapidly lost to follow-up (12% versus 27%, P = 0.003) but had a lower rate of long-term abstinence (20% versus 34%, P = 0.025). In multivariate analysis, age was the only factor significantly associated with clinical outcome: older patients had higher rate of long-term abstinence (OR = 1.041; P = 0.010). Among patients who had a biopsy, those with severe hepatic lesions had a lower rate of rapid relapse than those with moderate or mild lesions (32% versus 68% and 56%, P = 0.018) but the rate of long-term abstinence was similar in the three groups. CONCLUSION: This observational study does not support the notion that liver biopsy has a significant influence on the maintenance of alcohol abstinence in patients with alcoholic liver disease.

Sobesky R, Lebray P, Nalpas B, Vallet-Pichard A, Fontaine H, Lagneau JL, Pol S. · INSERM U785, Centre Hepato-Biliaire, Hopital Paul Brousse, Villejuif, France. · World J Gastroenterol. · Pubmed #18609710 links to  free full text

Abstract: AIM: To determine factors associated with fibrosis progression in hepatitis C virus (HCV)-infected patients without significant initial pathological lesions. METHODS: Seventy six untreated HCV-infected patients with initially normal liver as defined by a Knodell score < or = 3, with 2 liver biopsies and detectable HCV-RNA were included. Markers of fibrosis progression were assessed. RESULTS: Median duration of infection and time between paired biopsies was 13 (95% CI: 1-28) and 4 (95% CI: 2-16) years respectively. Alanine-transaminase (ALT) activity was normal in 43.4% of cases. 50% demonstrated progression of the necro-inflammation and 34% of fibrosis after a median time evolution of 4 years (95% CI: 2-16). The median difference in the necro-inflammation and fibrosis score between biopsies was low, 1.5 and 0.0 respectively. Univariate analysis showed there was no difference between fibrosis activity or evolution according to genotype or viral load. A higher fibrosis progression (P = 0.03) was observed in patients with body mass index (BMI) > 25. Fibrosis progression correlated with the time interval between biopsies (P = 0.01). A significant progression of activity (1.7 vs 0.4, P < 0.05) or fibrosis (0.9 vs 0.0, P < 0.01) was observed in patients with elevated ALT. There was a significant correlation between activity progression and fibrosis progression (P = 0.003). Multivariate analysis demonstrated that fibrosis progression was associated with elevated ALT, BMI > 25 and the time interval between 2 biopsies. CONCLUSION: There is no fibrosis progression in 66% of patients without significant initial histopathological lesion. Fibrosis progression is associated with elevated ALT and BMI > 25.

Vallet-Pichard A, Mallet V, Nalpas B, Verkarre V, Nalpas A, Dhalluin-Venier V, Fontaine H, Pol S. · Université Paris-Descartes, Paris, France. · Hepatology. · Pubmed #17567829 No free full text.

Abstract: To optimize the management of patients with chronic hepatitis C virus (HCV) infection, noninvasive tests to determine the degree of hepatic fibrosis have been developed. The aims of this study were (1) to validate a simple, inexpensive, noninvasive test called FIB-4, which combines standard biochemical values (platelets, ALT, AST) and age, in a series of 847 liver biopsies performed in HCV-monoinfected patients; and (2) to compare the results of 780 FIB-4 and FibroTests performed the same day in a series of 592 HCV-infected patients. The FIB-4 index enabled the correct identification of patients with severe fibrosis (F3-F4) and cirrhosis with an area under the receiver operating characteristic curve of 0.85 (95% CI 0.82-0.89) and 0.91 (95% CI 0.86-0.93), respectively. An FIB-4 index <1.45 had a negative predictive value of 94.7% to exclude severe fibrosis with a sensitivity of 74.3%. An FIB-4 index higher than 3.25 had a positive predictive value to confirm the existence of a significant fibrosis (F3-F4) of 82.1% with a specificity of 98.2%. Using these ranges, 72.8% of the 847 liver biopsies were correctly classified. The FIB-4 index was strongly correlated to the FibroTest results for a score <1.45 or >3.25 (kappa = 0.561, P < 0.01). A FIB-4 value <1.45 or >3.25 (64.6% of the cases) was concordant with FibroTest results in 92.1% and 76%, respectively. CONCLUSION: For values outside 1.45-3.25, the FIB-4 index is a simple, accurate, and inexpensive method for assessing liver fibrosis and proved to be concordant with FibroTest results.

Serpaggi J, Carnot F, Nalpas B, Canioni D, Guéchot J, Lebray P, Vallet-Pichard A, Fontaine H, Bedossa P, Pol S. · Service d'Hépatologie et INSERM U-567, Hôpital Necker Enfants-Malades, Paris, France. · Hum Pathol. · Pubmed #16997354 No free full text.

Abstract: The aim of this study was to assess the reversibility of cirrhosis after therapy in a large series of patients with cirrhosis from various etiologies. We performed a retrospective study of 113 patients with biopsy-proven cirrhosis who underwent specific therapy and follow-up biopsies. Two pathologists performed blinded analyses of indirect biochemical and morphological signs of cirrhosis. Fourteen (12.4%) of the 113 cirrhotic patients had biopsy-proven disappearance of cirrhosis, defined as a decrease of 2 or greater in their METAVIR fibrosis score: 8 were related to hepatitis C virus, 3 to hepatitis B virus, and 3 to autoimmune cirrhosis. Necro-inflammatory activity decreased from 2.4 +/- 0.65 to 0.85 +/- 0.9 (P = .004), and fibrosis from 4 to 1.7 +/- 0.61 (P = .001). Prothrombin time (n = 1), platelet count (n = 2), serum albumin level (n = 2), and ultrasound abnormalities (n = 6) normalized in patients who had initial abnormalities. Hyaluronic acid and procollagen type III serum level decreased in all. In the 11 patients with regression of viral cirrhosis, 2 were nonresponders and 9 were responders, including 2 relapsers. The 3 patients with regressive autoimmune cirrhosis were complete responders to immunosupressive therapy. Using repeated liver biopsies, clinicobiochemical, radiologic, and endoscopic tests, we provide evidence for potential reversibility of cirrhosis after long-lasting suppression of the necro-inflammatory activity of liver disease.

Vallet-Pichard A, Mallet V, Pol S. · No affiliation provided · Hepatology. · Pubmed #16941681 No free full text.

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Serpaggi J, Chaix ML, Batisse D, Dupont C, Vallet-Pichard A, Fontaine H, Viard JP, Piketty C, Rouveix E, Rouzioux C, Weiss L, Pol S. · Hepatology Unit, Necker Hospital, Paris, France. · AIDS. · Pubmed #16511416 No free full text.

Abstract: BACKGROUND: Recent studies have suggested an increased risk of acute hepatitis C (HCV) infection in homosexual HIV-infected men and that early treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin, significantly reduces the risk of chronic evolution in HIV-infected patients. METHODS: A retrospective analysis of 12 HIV-infected patients who were consecutively diagnosed as developing acute HCV infection, defined by both seroconversion of anti-HCV antibodies and detection of serum HCV RNA in those with previous negative results. Ten of these patients received early antiviral treatment with standard or pegylated interferon-alfa, alone or associated with ribavirin. RESULTS: The only risk factor in these patients was unprotected sexual intercourse with men. Acute HCV infection was asymptomatic in 10 patients, and the HCV genotype was 4d in 10 patients. The 10 genotype 4d viruses formed a monophylogenetic group and clustered separately from other local sequences of HCV genotype 4d, suggesting a common source of infection. None of the 10 patients who were treated early with antiviral therapy had a sustained virological response, as defined by undetectable HCV RNA 6 months after therapy. CONCLUSIONS: There is a risk of sexual transmission of HCV in HIV-infected men who have sex with men; the cluster of HCV genotype 4d suggested a common source of infection and a failure in prevention counselling. Early treatment with standard interferon-alfa failed to prevent chronic evolution of HCV infection in this particular group of HIV-infected patients who had acquired this peculiar cluster of genotype 4 strains.

Varaut A, Fontaine H, Serpaggi J, Verkarre V, Vallet-Pichard A, Nalpas B, Imbertbismuth F, Lebray P, Pol S. · Liver Diseases Unit, INSERM U-370, Pathological Anatomy Department, Hôpital Necker, 149 rue de Sèvres, 75015 Paris, France. · Transplantation. · Pubmed #16371924 No free full text.

Abstract: BACKGROUND: An accurate diagnosis of hepatitis C virus (HCV)-related liver lesions is mandatory in dialysis patients and kidney recipients to better define the treatment of and contraindications to kidney transplantation. The aim of this study was to assess the diagnostic accuracy of the fibrotest (a noninvasive method to assess liver fibrosis in HCV on a scale from 0 to 1) in hemodialysis and renal transplant patients infected by chronic HCV. METHODS: In all, 110 patients with biopsy-proven HCV (60 renal transplant recipients and 50 hemodialysis patients), determined using the METAVIR scoring system, were studied. RESULTS: Forty-six percent of patients had fibrosis > or =F2. A positive predictive value of a score >0.6 for the presence of significant fibrosis by comparison with liver biopsy was 71%, and an negative predictive value of < 0.2 for excluding significant fibrosis was 77%, respectively. The areas under the ROC curves for the diagnosis of significant fibrosis were 0.66, 0.47, and 0.71 in the global population, hemodialysis patients, and renal transplant patients, respectively. In all, 75% of patients were correctly classified using the fibrotest. If biopsy was restricted to scores in the intermediate range (< 0.6 and >0.2), the index could reduce the indication for biopsy by 47%. The results did not differ significantly in hemodialysis and renal transplant patients. CONCLUSION: The fibrotest has a diagnostic value in hemodialysis and renal transplant patients which is similar to that reported in the general population (75%) and its use could avoid 32% of liver biopsies if it were interpreted in detail in nephrology patients.

Lebray P, Nalpas B, Vallet-Pichard A, Broissand C, Sobesky R, Serpaggi J, Fontaine H, Pol S. · Unité d'Hépatologie, Hôpital Necker, Paris, France. · Antivir Ther. · Pubmed #16218177 No free full text.

Abstract: AIM: To evaluate the benefits of haematopoietic growth factors (HGFs) during the treatment of chronic hepatitis C virus (HCV) infection with severe haematotoxicity. METHODS: This was a 1-year retrospective study of HCV-positive patients receiving pegylated interferon and ribavirin. Patients received different HGFs, depending on certain criteria: they received erythropoietin (EPO) when their haemoglobin (Hb) levels were less than 10 g/dl and granulocyte colony-stimulating factor (G-CSF) when their neutrophil count was less than 750 cells/mm3. Haematological data, adherence and virological response were analysed and compared according to HGF use. RESULTS: In total, 132 patients were studied and 31 (23.5%) required HGF. Under multivariate analysis, baseline Hb levels of less than 13g/dl or a drop in Hb levels of over 2% per week predicted severe anaemia, and a baseline neutrophil count under 2900/mm3 predicted severe neutropaenia. HGF administration restored Hb values and the neutrophil count to above 10 g/dl and 1500 cells/mm3, respectively, in all 31 patients. Adherence to antiviral treatment was achieved in 25% of patients versus 58% of controls without severe haematotoxicity. The primary and sustained virological response did not differ statistically between HGF support and the control group (61% versus 57% and 32% versus 39%, respectively). CONCLUSION: HGF administration counteracts the severe haematological adverse effects which occur during antiviral therapy and maintains the rate of sustained response.

Fontaine H, Vallet-Pichard A, Equi-Andrade C, Nalpas B, Verkarre V, Chaix ML, Lebray P, Sobesky R, Serpaggi J, Kreis H, Pol S. · Unité d'Hépatologie, Hôpital Necker, Paris, France. · Transplantation. · Pubmed #15385804 No free full text.

Abstract: BACKGROUND: The deterioration of chronic hepatitis C is frequent in kidney recipients and results in a decrease in survival of patients and allografts. Interferon is contraindicated because of the risk of rejection and its low efficacy. The aim of this study was to analyze the biologic, virologic, and histopathologic efficacy of ribavirin alone in kidney allograft recipients with hepatitis C. METHODS: Thirteen kidney recipients (eight men and five women, 46+/-11 years of age) with severe Metavir score of fibrosis (eight F3 and five F4) were treated with ribavirin alone during 22.4+/-13.9 months. Liver biopsy was performed before and during therapy, with a mean interval time of 5.7+/-9.3 years. RESULTS: The transaminase level decreased significantly (128+/-77 vs. 53+/-28, P=0.001) without significant change of serum quantitative hepatitis C virus load. The comparison of pretreatment and on-treatment biopsy specimens showed a significant decrease in the activity Metavir score (1.23+/-1.01 vs. 2.46+/-0.78, P=0.05) and a nonsignificant trend for a decrease in the fibrosis score. Ribavirin tolerance was fair, and only one patient required erythropoietin therapy. CONCLUSIONS: Ribavirin alone in kidney allograft recipients results in biologic and histologic improvement without a virologic response and is reasonably well tolerated.

Pol S, Lebray P, Vallet-Pichard A. · Unité d'Hépatologie and INSERM U-370, Hôpital Necker, Paris, France. · Clin Infect Dis. · Pubmed #14986277 No free full text.

Abstract: Liver enzyme elevations are common in human immunodeficiency virus (HIV)-infected patients, and their diagnosis or management may be difficult because of the intricacies of the pathogenic mechanisms involved. These include hepatotoxicity related to the highly active antiretroviral therapy (HAART) regimen, idiosyncratic or immunoallergic mechanisms, and direct cytotoxicity enhanced by an underlying liver disease. Liver enzyme abnormalities may also reflect hepatitis B (HBV) or hepatitis C (HCV) infection, which each have their own risks for chronic immune-mediated liver disease (including hepatitis flare after immune reconstitution) and of direct cytotoxicity. Finally, other factors may affect liver deterioration, including alcohol-related liver disease, nonalcoholic steatohepatitis associated with metabolic syndromes (e.g., hyperlipidemia, diabetes, or being overweight) that are potentially HAART related, and use of medication or illicit drugs (e.g., methamphetamine). A better understanding of these complex interactions, including adjustments of dosages of antiretroviral drugs, will probably help in the management of HIV-infected patients with liver enzyme abnormalities.

Vallet-Pichard A, Pol S. · Service d'hépato-gastro-entérologie, hôpital Necker, 75743 Paris. · Rev Prat. · Pubmed #12412311 No free full text.

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