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P Marcellin

Publications and source records attributed to P Marcellin.

At least 37 records · Page 2Linked to original sources
PubMed2003

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↗
PubMed2003

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↗
PubMed2002

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↗
PubMed2002

Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis.

Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0-1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0-1) to mild fibrosis (0-3) and mild HAI (5.5). Serum TNF-alpha and TGF-beta levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-alpha levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-beta and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-beta levels when comparing initial and follow-up levels. In conclusion, serum TNF-alpha reflects the progression of inflammation as seen in liver biopsies and TGF-beta reflects the degree of fibrosis in HCV patients.

Adult↗
PubMed2001

Integrin up-regulation in chronic liver disease: relationship with inflammation and fibrosis in chronic hepatitis C.

In 94 patients with chronic hepatitis C, the pattern of integrin expression was correlated with firstly, the histological activity index, necro-inflammatory grade, and stage of fibrosis; secondly, the expression of inflammatory markers including ICAM-1; and thirdly, the extent and intensity of laminin deposition in the perisinusoidal matrix. Immunohistochemical results were evaluated according to a semi-quantitative scoring system or by image analysis. Increased beta1 expression was observed in 88.2% of cases. The expression of alpha1 and alpha5 was increased in 55% and 58.5% of cases, respectively. alpha6 chain was detected in 78.7% of cases. There were no statistically significant differences in integrin expression level according to Knodell's score, inflammatory grade, or stage of fibrosis. ICAM-1 expression was higher in patients with high scores for beta1 expression, but the differences were not statistically significant. There were significantly more patients with high scores for beta1 expression among those with continuous perisinusoidal deposition of laminin. Moreover, a close statistical correlation was observed between alpha6 induction and perisinusoidal laminin deposition (p<0.001). The results suggest that integrin up-regulation in chronic hepatitis C is more closely related to the fibrotic process than to the inflammatory lesions. This reinforces the idea that integrin induction in chronic liver disease is part of a coordinated process involved in the progression of liver fibrosis.

Adult↗
PubMed2001

Cytokines as predictors for sustained response and as markers for immunomodulation in patients with chronic hepatitis C.

OBJECTIVES: (i) To characterize serum cytokine levels of tumor necrosis factor alpha (TNF alpha), interleukin 6 (IL 6), IL 8 and IL 12 in non-cirrhotic patients with chronic hepatitis C, (ii) to correlate the levels of these cytokines with the degree of the disease at the basal level, (iii) to correlate these levels with the response to therapy, (iv) to compare profiles of cytokines in monotherapy (MT) versus combination therapy (CT), and (v) to compare the immunomodulatory effects of MT versus CT. DESIGN AND METHODS: 47 patients were enrolled in the study. The controls were 120 volunteers (recruited from students and staff) that did not present HCV RNA positive and were not known to suffer any other metabolic disease. Thirty patients formed the other group of controls, with alcoholic liver disease (ALD). Serum cytokine levels were assessed using enzyme-linked immunosorbent assay (ELISA). RESULTS: The sustained responders (SRs) have basal values much lower than relapsed responders (RRs) and non-responders (NRs) regardless of the therapy. CONCLUSIONS: Cytokines can be used as non-invasive markers for sustained response and as monitors for the outcome of therapy.

Adult↗
PubMed2001

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↗
PubMed2001

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↗
PubMed2001

Influence of cirrhosis on lamotrigine pharmacokinetics.

AIMS: Lamotrigine, an antiepileptic drug, is cleared from the systemic circulation mainly by glucuronidation. The possibility of changes in the pharmacokinetics of lamotrigine in plasma owing to hepatic dysfunction has been evaluated. METHODS: Thirty-six subjects, including 24 patients with various degrees of liver cirrhosis and 12 healthy volunteers received a single 100 mg dose of lamotrgine. Blood samples were taken for 7 days in all subjects, except nine with severe cirrhosis, who had a 29 day blood sampling period. RESULTS: The pharmacokinetics of lamotrigine were comparable between the patients with moderate cirrhosis (corresponding to Child-Pugh grade A) and the healthy subjects. Plasma oral clearance mean ratios (90% confidence interval) in patients with severe cirrhosis without or with ascites (corresponding, respectively, to Child-Pugh grade B and C) to healthy subjects were, respectively, 60% (44%, 83%) and 36% (25%, 52%). Plasma half-life mean ratios (90% confidence interval) in these two patient groups to healthy subjects were, respectively, 204% (149%, 278%) and 287% (202%, 408%). CONCLUSIONS: Lamotrigine administered as a single oral dose of 100 mg was well tolerated in all groups. Initial, escalation and maintenance doses should generally be reduced by approximately 50 or 75% in patients with Child-Pugh Grade B or C cirrhosis. Escalation and maintenance doses should be adjusted according to clinical response.

Adult↗
PubMed2001

Prospective study on anti-hepatitis C virus-positive patients with persistently normal serum alanine transaminase with or without detectable serum hepatitis C virus RNA.

A significant proportion of patients with detectable antibodies to hepatitis C virus have normal serum alanine transaminase levels. Our aim was to study the outcome of this group. Between 1992 and 1999, 135 consecutive anti-HCV-positive patients with persistently normal ALT were followed for 3.6 +/- 2.3 years (0.5 to 8.5 years), 108 had a liver biopsy at inclusion, and 24 had a second liver biopsy 3.5 +/- 1.0 years later. Serum HCV RNA was detectable with PCR in 94 patients (69%) and not detectable in 41 patients (31%). Patients with and without detectable serum HCV RNA had similar epidemiological characteristics. Serum ALT levels and anti-HCV ratio were lower (P =.001), and histological lesions had lower grade and stage in patients without detectable serum HCV RNA (P =.001). Liver HCV RNA was not detectable with PCR in the 12-serum HCV RNA-negative patients tested. During follow-up, all patients without detectable serum HCV RNA remained HCV RNA-negative and kept normal serum ALT; all patients with detectable serum HCV RNA remained HCV RNA-positive, 20 (21%) had a slight fluctuation of serum ALT above the upper limit of normal. No significant changes were observed in the liver lesions of the 24 patients who underwent a second liver biopsy. In anti-HCV-positive patients with persistently normal serum ALT, histological lesions are significantly lower in HCV RNA-negative than in HCV RNA-positive patients. During follow-up, the HCV RNA status of patients remained unchanged; 21% of the patients with detectable serum HCV RNA had slight increase in serum ALT levels, but histological lesions remained stable.

Adult↗
PubMed2001

The influence of human immunodeficiency virus coinfection on chronic hepatitis C in injection drug users: a long-term retrospective cohort study.

In this study we analyzed the influence of human immunodeficiency virus (HIV) infection on the course of chronic hepatitis C through multivariate analysis including age, alcohol consumption, immune status, and hepatitis C virus (HCV)-related virologic factors. Eighty HIV-positive and 80 HIV-negative injection drug users included between 1980 and 1995 were matched according to age, gender, and duration of HCV infection and followed-up during 52 months. The progression to cirrhosis was the primary outcome measure. The impact of HIV on HCV-RNA load, histologic activity index, response to interferon therapy, and liver-related death was also considered. In HIV-positive patients, chronic hepatitis C was characterized by higher serum HCV-RNA levels (P =.012), higher total Knodell score (P =.011), and poorer sustained response to interferon therapy (P =.009). High serum HCV-RNA level was associated with low CD4-lymphocyte count (P =.001). Necroinflamatory score was higher in HIV-positive patients (P =.023) independently of the CD4-lymphocyte count, whereas increased fibrosis was related to decreased CD4-lymphocyte count (P =.011). The progression to cirrhosis was accelerated in HIV-positive patients with low CD4 cell count (RR = 4.06, P =.024) and in interferon-untreated patients (RR = 4.76, P =.001), independently of age at HCV infection (P =.001). Cirrhosis caused death in 5 HIV-positive patients. The risk of death related to cirrhosis was increased in heavy drinkers (RR = 10.8, P =.001) and in HIV-positive patients with CD4 cell count less than 200/mm(3) (RR = 11.9, P =.007). In this retrospective cohort study, HIV coinfection worsened the outcome of chronic hepatitis C, increasing both serum HCV-RNA level and liver damage and decreasing sustained response to interferon therapy. Age and alcohol were cofactors associated with cirrhosis and mortality. Interferon therapy had a protective effect against HCV-related cirrhosis no matter what the patient's HIV status was.

Adult↗
PubMed2001

Ectopic hepatocellular carcinoma arising in the left chest wall: a long-term follow-up.

We report the case of a 66-year-old man with chronic hepatitis C and a slowly growing left chest wall mass. Two years after the patient first noticed the mass, it was resected. A diagnosis of hepatocellular carcinoma (HCC) was established. The liver was studied by ultrasound, computed tomography (CT), magnetic resonance imaging (MRI) and angiography, but no mass was found. Blind liver biopsy showed mild chronic hepatitis without cirrhosis or HCC. Three years after the discovery of the chest wall HCC, no liver mass had appeared at CT and MRI. We conclude that solitary extrahepatic HCC (i) may arise in ectopic liver tissue; (ii) should not be considered as a metastasis of an occult HCC; and (iii) can be amenable to cure through resection.

Carcinoma, Hepatocellular↗
PubMed2001

Haemobilia causing acute pancreatitis after percutaneous liver biopsy: diagnosis by magnetic resonance cholangiopancreatography.

Magnetic resonance cholangiopancreatography (MRCP) has received much attention as a non-invasive alternative to endoscopic retrograde cholangiopancreatography, primarily for investigation of choledocholithiasis, but also for evaluation of less common biliary anomalies. We present a case of haemobilia causing acute pancreatitis after percutaneous liver biopsy in which the diagnosis could be made clearly by MRCP, thus avoiding endoscopic retrograde cholangiopancreatography and sphincterotomy.

Acute Disease↗
PubMed2001

Tolerability of treatments for viral hepatitis.

Interferon-alpha is the most widely used antiviral drug in chronic hepatitis B and C. Tolerability is usually good and serious adverse effects are rare. Most of the adverse effects are mild or transient and do not necessitate drug withdrawal. More than 90% of patients who are given interferon-alpha achieve 6 months to 1 year of treatment without serious adverse effects. The serious adverse effects usually occur in predisposed patients with pre-existing organ dysfunction. Nevertheless, careful selection of patients for therapy and observation during therapy are recommended. Nucleoside analogues are promising drugs in the treatment of chronic hepatitis B through inhibition of viral DNA polymerase. Lamivudine has been licensed for use in this indication. Its tolerability is excellent even when used for periods of 1 year or more. The main concern is the relatively high incidence of viral resistance resulting in breakthrough during or relapse after therapy. In the treatment of chronic hepatitis C, ribavirin, in combination with interferon-alpha is currently the reference therapy. The main adverse effect is haemolytic anaemia, which necessitates careful monitoring and adjustment of dosage in many cases. Recently, large trials showed the better efficacy of pegylated interferons as compared with standard interferon. The combination of pegylated interferon with ribavirin is under evaluation.

Antiviral Agents↗