Effectiveness and tolerability of pegylated Interferon alpha-2a and ribavirin combination therapy in Romanian patients with chronic hepatitis C: from clinical trials to clinical practice.

BACKGROUND AND AIM: Pegylated interferon alpha in combination with ribavirin represents nowadays the gold standard therapy in patients with chronic hepatitis C. The aim of this study was to assess early (EVR) and sustained virological response (SVR), tolerability and baseline predictive factors for SVR in patients with chronic hepatitis C treated with peginterferon alpha-2a and ribavirin combination therapy in day-to-day clinical practice. METHODS: The analysis included 174 consecutive patients with chronic hepatitis C (naive, relapsers and non-responders after standard therapy) managed in two expertise gastroenterology centers in Romania, mainly on an outpatient basis. The combination therapy was initiated between 1st of June 2002 - 30th of June 2003. RESULTS: The mean age of the study population was 47 years; 41% were men, mean BMI was 26.5 kg/sq.m. Only 7.5% of them had bridging fibrosis/cirrhosis on liver biopsy. EVR and SVR were noted in 78.7% and 51.1%, respectively. Multivariate analysis showed two independent variables associated with SVR: absence of bridging fibrosis/cirrhosis and absence of hepatic steatosis. The rate and profile of side effects associated with pegylated interferon alpha-2a and ribavirin in our clinical setting were all predictable, based on previous experience in the literature. Side effects resulted in interferon and ribavirin dose reductions in 9.2% and, respectively, 25.3%, but permanent discontinuation of the combination therapy was required in only 5.74% of patients. CONCLUSION: Combination antiviral therapy can be safely and successfully used outside clinical trials. To achieve high response rates and tolerability, similar or better than those reported in clinical trials, hepatitis C patients have to be managed in expertise centers, by experienced physicians, aiming at minimizing side effects, optimizing dosing, and enhancing compliance.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

OBJECTIVES: To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. METHODS: Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). RESULTS: From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. CONCLUSION: Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.

Overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis complicated by hepatocellular carcinoma.

The risk of hepatocellular carcinoma superimposed in the evolution of autoimmune hepatitis or primary biliary cirrhosis is low, even in patients with long-standing cirrhosis. We report a case of hepatocellular carcinoma occurring in a 46 year old woman with liver cirrhosis following overlap syndrome between autoimmune hepatitis and primary biliary cirrhosis, routinely followed while on the waiting list for liver transplantation. The patient had combined biochemical (elevated aminotransferases, alkaline phosphatase and gamma-glutamyl-transpeptidase in the range of 2-3 times above the upper limit of the normal) and serological (anti-smooth muscle antibody > 1/80 and anti-mitochondrial antibody anti-M2 > 1/40) criteria of autoimmune hepatitis and primary biliary cirrhosis. Hepatocellular carcinoma was diagnosed in the setting of chronic liver disease by the combination of two concordant imaging technics (Doppler ultrasound and magnetic resonance imaging) showing a hepatic nodule with arterial hypervascularization and elevated serum levels of alpha-fetoprotein up to 950 ng/ml. Liver transplantation is the best treatment both for the solitary nodule less than 5 cm and underlying autoimmune cirrhosis. Using the new Model for End-Stage Liver Disease allocation system our patient was placed in a prior position for liver transplantation (MELD 29). Unfortunately, a sudden fulminant liver failure complicated with intravascular disseminated coagulopathy was fatal for our patient while awaiting liver transplantation.

Infliximab for Crohn's disease in clinical practice: the experience of a single center in romania.

AIM: The aim of the study was to report the efficacy and tolerability of infliximab therapy in the first 24 patients with refractory and fistulizing Crohn's disease (CD) treated at our center between August 2000-May 2002. PATIENTS AND METHODS: The medical records of 24 patients (13 males, 11 females) treated with infliximab for refractory or fistulizing CD were reviewed. CD was diagnosed using conventional clinical, endoscopical and histological criteria. Infliximab was administered at a dose of 5 mg/kg body mass as a 2-hours i.v. infusion in a single infusion for inflammatory CD, and a triple infusion regimen for fistulizing CD (at 0, 2, and 6 weeks). Efficacy was analysed by means of 1) clinical outcome, 2) mucosal healing, 3) steroid tapering/sparing effect and 4) need for surgery. RESULTS: Sixteen patients were treated for inflammatory CD, 7 patients for fistulizing CD and 1 patient for both inflammatory and fistulizing CD. A total number of 49 infusions were administered during the study interval (median number 2); the median time of follow-up was 26 weeks (12-79 weeks). An overall positive clinical response was seen in 12/16 patients (75 % with inflammatory CD and 5/7 patients (71.4 %) with fistulizing CD. The median time to clinical response was 5.6 days (range 1-11 days) and the median duration of clinical response was 6.53 mo. (4 weeks-21 months). Mucosal healing was noted in 10/17 (58 %). Steroid tapering or cessation was succesfully attempted in 17 patients (80.9 %), complete steroid withdrawal being possible in 15 patients (71.4 %). Three non-responder patients required surgical therapy. Infusion-related adverse reactions were seen in 4 patients (16.6 %). Two patients (8.3 %) developed severe adverse events; one of them, a young female patient with intrapartum onset of a severe CD developed sepsis and deceased from intavascular disseminated coagulopathy. During the follow-up, none of our patients developed serious infections, tuberculosis or malignancy. CONCLUSION: Our study provides additional evidence that infliximab is beneficial and safe in clinical practice for refractory and fistulizing CD patients. Additionally, our study proved the high mucosal healing rate and the steroid-sparing and surgery-saving properties of infliximab