Search PubMed⌕ Search

Biomedical subjects

P Ferenci

Publications and source records attributed to P Ferenci.

At least 19 recordsLinked to original sources
PubMed2006

Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study.

BACKGROUND: Wilson's disease is a rare inborn disease related to copper storage, leading to liver cirrhosis and neuropsychological deterioration. Clinical data on larger cohorts are limited owing to low disease frequency. OBJECTIVE AND METHODS: We performed a retrospective analysis of 163 patients with Wilson's disease, examined at the University of Heidelberg, Heidelberg, Germany, to determine clinical presentation, diagnostic course and long-term outcome. RESULTS: Diagnostic criteria for non-caeruloplasmin-bound serum copper, serum caeruloplasmin, 24-h urinary copper excretion, liver copper content, presence of Kayser-Fleischer rings and histological signs of chronic liver damage were reached in 86.6%, 88.2%, 87.1%, 92.7%, 66.3% and 73% of patients, respectively. By analysis of the coding region of ATP7B (except exons 2, 3 and 21), disease-causing mutations were detected in 57% and 29% of patients with Wilson's disease on both chromosomes and on one chromosome, respectively. No mutations were detected in 15% of patients with Wilson's disease. No significant differences were found in clinical parameters or initial presentation between patients grouped according to their mutations. The patients with neurological symptoms were significantly older at the onset of symptoms than patients with hepatitic symptoms (20.2 v 15.5 years of age, p<0.05), and the neurological symptoms were associated with a significantly longer time from onset to diagnosis than hepatic symptoms (44.4 v 14.4 months, p<0.05). After initiating treatment, 76.1% of the patients had a stable or improved course of the disease. Disease progression under treatment was more likely for neuropsychiatric than for hepatic symptoms. Side effects of treatment occurred in 74.4% of patients. CONCLUSIONS: Patients with Wilson's disease having predominantly neuropsychiatric symptoms manifest symptoms later, have a longer time delay from onset of symptoms until definitive diagnosis and have a poorer outcome than patients with hepatic symptoms.

Adenosine Triphosphatases↗
PubMed2006

ESPEN Guidelines on Enteral Nutrition: Liver disease.

Enteral nutrition (EN) by means of oral nutritional supplements (ONS) and tube feeding (TF) offers the possibility to increase or to insure nutrient intake in case of insufficient oral food intake. The present guideline is intended to give evidence-based recommendations for the use of ONS and TF in patients with liver disease (LD). It was developed by an interdisciplinary expert group in accordance with officially accepted standards and is based on all relevant publications since 1985. The guideline was discussed and accepted in a consensus conference. EN by means of ONS is recommended for patients with chronic LD in whom undernutrition is very common. ONS improve nutritional status and survival in severely malnourished patients with alcoholic hepatitis. In patients with cirrhosis, TF improves nutritional status and liver function, reduces the rate of complications and prolongs survival. TF commenced early after liver transplantation can reduce complication rate and cost and is preferable to parenteral nutrition. In acute liver failure TF is feasible and used in the majority of patients.

Cost-Benefit Analysis↗
PubMed2006

Long-term follow-up of chronic hepatitis C patients with sustained virological response to various forms of interferon-based anti-viral therapy.

BACKGROUND: Combination anti-viral therapy achieves a sustained virological response (defined as HCV-RNA negativity 6 months after the end of therapy) of 56% of patients with chronic hepatitis C. Little is known about long-term durability of HCV-RNA negativity in patient treated with pegylated interferon. AIM: To evaluate the durability of virologic response in patients with sustained virological response to anti-viral therapy treated at our centre. METHODS: A total of 187 sustained virological responses (50% genotype 1, 42% genotype 2 or 3 and 8% genotype 4; 20% with cirrhosis) with a follow-up of >12 months post-therapy were studied. Twelve patients received monotherapy with interferon-alpha2a or -2b. One hundred and seventy-five received combination therapy with ribavirin and standard interferon-alpha (n = 73) or pegylated interferon-alpha2a or 2b (n = 102). Qualitative serum HCV-RNA was tested by COBAS AMPLICOR HCV test, v2.0. RESULTS: Median follow-up time was 29 months (range 12-172). Recurrence of HCV infection was not observed in any of the 187 sustained virological responders. Alanine aminotransferase values were normal in 90% and two patients showed minimal elevation of alpha-fetoprotein levels. CONCLUSIONS: No recurrence of HCV infection was seen in any patient. Thus, long-term prognosis in chronic hepatitis C patients with a sustained virological response to therapy with pegylated interferon +/- ribavirin is promising, but long-term studies need to continue.

Adult↗
PubMed2006

Centrilobular necrosis in autoimmune hepatitis: a histological feature associated with acute clinical presentation.

AIMS: The characteristic histological feature of autoimmune hepatitis (AIH) is interface hepatitis with predominant portal lymphoplasmacytic necroinflammatory infiltration. Centrilobular necrosis (CN), reminiscent of toxic or circulatory liver injury, has been reported in AIH. The aim of this study was to assess the frequency of CN in patients with AIH and its correlation with laboratory and clinical data. METHODS: Liver biopsies were obtained from 114 patients (90 women, 24 men, mean (SD) age 45.4 (19.4) years) with AIH and were evaluated under code by a single pathologist according to the modified Knodell score. RESULTS: CN was found in 20 (17.5%) patients with virtually unaffected portal areas in four cases. Patients with AIH with CN had a higher total hepatic activity index (median (range) 11 (6 to 15) v 5 (2 to 10)) and presented less frequently with cirrhosis (10% v 38%). Patients with CN had a higher frequency of acute onset (87% v 32%), higher bilirubin (median (range) 12.0 (0.43 to 40.0) v 1.9 (0.36 to 46)) and higher ALT levels (median (range) 25.6 (2.7 to 63.9) v 7.2 (0.7 to 62.6)), than did patients with AIH without centrizonal injury. CONCLUSION: CN with sparing of the portal areas represents a rare histological pattern in AIH. CN is associated with an acute clinical presentation and might reflect an early lesion preceding portal involvement. Recognition of this particular histological appearance enables early diagnosis of AIH and a timely initiation of immunosuppressive therapy.

Acute Disease↗
PubMed2006

Pegylated interferon plus ribavirin for chronic hepatitis C: the role of combination therapy today, tomorrow and in the future.

Approximately 123 million people worldwide are infected with hepatitis C virus (HCV). The majority of those infected with the virus develop chronic progressive liver disease that over time can result in cirrhosis, end-stage liver disease, hepatocellular carcinoma and death. The goal of treatment is viral eradication. The recognised standard of care for chronic hepatitis C is the combination of pegylated interferon plus ribavirin, which has been shown to be effective in treatment-naïve patients, including those with persistently normal ALT levels, and in patients with HIV-HCV coinfection. Two pegylated interferons are commercially available, both of which have distinct pharmacokinetic properties that necessitate different dosing strategies. With the standard of care, overall virological response rates have exceeded 50% in randomised, multinational phase III studies. Viral response rates are heterogenous and are influenced by a range of viral and host-specific factors. By far, the most important factors influencing treatment outcomes are HCV genotype and baseline HCV RNA level. Customisation of therapy based on baseline factors is recommended in treatment guidelines in order to maximise cure rates. Pegylated interferon plus ribavirin has been shown to be effective and safe in patients with HIV-HCV coinfection and is now recommended in this important and growing subpopulation. Ongoing efforts to improve treatment outcomes are focused on dynamic customisation of therapy based on the on-treatment response to therapy. Treatment of nonresponders to previous interferon-based therapies is an important area under investigation. Although several promising oral agents have been identified and are currently in clinical development, it seems likely that pegylated interferon will remain the backbone of therapy for years to come.

Antiviral Agents↗
PubMed2005

Short- and long-term effects of therapy with interferon-alpha and pegylated interferon-alpha/ribavirin on platelet plug formation and von Willebrand factor release in patients with chronic hepatitis C.

BACKGROUND: A pegylated interferon-alpha-induced decrease in platelet counts may become a limiting factor for continuation of therapy. AIM: To evaluate the effect of pegylated interferon-alpha administration on platelet plug formation and von Willebrand factor antigen release in patients with chronic hepatitis C. METHODS: Thirty patients with chronic hepatitis C (genotype 1; fibrosis 1-3: n = 16, cirrhosis: n = 14) received a single dose of 9 MU interferon-alpha2a, followed by weekly administration of 180 mug of pegylated interferon-alpha2a/ribavirin for 48 weeks. Platelet counts, platelet function (collagen-epinephrine-induced closure time) and von Willebrand factor antigen were measured. RESULTS: Platelet counts and collagen-epinephrine-induced closure time decreased by 13% and 16%, respectively, 24 h after the first dose of interferon-alpha2a, and von Willebrand factor antigen levels increased by 31% (P < 0.01) compared with baseline. During a 48-week observation period, platelet counts decreased by a maximum of 33% (P < 0.001), von Willebrand factor antigen levels increased by 69% (P < 0.001) whereas collagen-epinephrine-induced closure time did not change. In noncirrhotic patients, the increase of von Willebrand factor antigen levels was maintained throughout therapy without a change in collagen-epinephrine-induced closure time. In contrast, in cirrhotics, von Willebrand factor antigen levels did not increase, while collagen-epinephrine-induced closure time was prolonged. CONCLUSION: Single-dose interferon-alpha decreases platelet counts but improves platelet function, possibly by the release of von Willebrand factor antigen. Accordingly, long-term antiviral treatment had no effect on collagen-epinephrine-induced closure time, despite the decrease in platelet count in noncirrhotic patients. Such a compensation of decreased platelet counts by increased von Willebrand factor antigen level did not occur in cirrhotics.

Adult↗
PubMed2005

Bi-allelic presence of the interleukin-10 receptor 1 G330R allele is associated with cirrhosis in chronic HCV-1 infection.

Immune response to viral infection is an important determinant of liver injury in chronic hepatitis C (CHC). Experimental and clinical data suggest a protective role of interleukin-10 (IL-10) in hepatic fibrogenesis. The significance of two SNPs of the interleukin-10 receptor 1 (IL-10R1), S138G (SNP3) and G330R (SNP4) was investigated on (i) susceptibility to CHC, (ii) progression of hepatic fibrosis and (iii) response to interferon/ribavirin therapy. DNA and liver biopsies were obtained from 212 patients with HCV (hepatitis C virus)-genotype-1 infection. The allele frequencies were 0.17 for SNP3 and 0.33 for SNP4, both of which were indifferent from healthy controls (0.17 and 0.32, respectively). Stage 1 liver fibrosis was found in 22 cases (10.4%), stage 2 in 108 (50.9%), stage 3 in 27 (12.8%), and stage 4 (cirrhosis) in 55 (25.9%). An association was found between the SNP4 allele and the presence of cirrhosis (P=0.01). Homozygous SNP4 individual variants segregated within the cirrhosis group (P=0.03). We found neither an association with SNP3 nor with the necroinflammatory disease activity (as measured by ALT levels) nor with the response to antiviral therapy. Our work implies that IL-10R1 SNP4 is a recessively inherited risk factor for hepatic cirrhosis in HCV genotype-1 infection.

Adult↗
PubMed2005

Suppression of haematopoiesis during therapy of chronic hepatitis C with different interferon alpha mono and combination therapy regimens.

BACKGROUND: Treatment of chronic hepatitis C with interferon (IFN)-alpha and ribavirin has haematotoxic effects. We evaluated the effects of four different IFN/IFN-ribavirin treatment regimens on haematopoiesis. METHODS: Haematopoiesis was studied in 133 patients with chronic hepatitis C receiving IFN-alpha2b alone (group A) or in combination with ribavirin (group B), pegylated IFN-alpha2a (group C), or pegylated IFN-alpha2b (group D) in combination with ribavirin. RESULTS: At week 4, haemoglobin levels were diminished in all groups receiving combination therapy. In the monotherapy group, haemoglobin decreased slightly after eight weeks. In all groups, haemoglobin remained diminished throughout therapy. In all patients, leucocytes (while blood cells) decreased after four weeks and remained low during treatment. Platelets (peripheral platelet count (PPC)) were decreased in all groups after four weeks and remained below baseline levels during therapy in group A, C, and D whereas in group B PPC recovered early and reached baseline levels at week 16 of therapy. Concomitantly with the decreases in haemoglobin and PPC, erythropoietin increased in all groups receiving combination therapy and thrombopoietin in all groups. Patients treated with pegylated IFN-alpha2a and those who received pegylated IFN-alpha2b combination therapy differed only in leucopoiesis, whereas erythropoiesis and thrombopoiesis were comparable. CONCLUSION: IFN-alpha based therapies are associated with a decrease in all three haematopoietic lineages, irrespective of the type of therapy used. The stronger suppressive effect of pegylated IFN-alpha2a on leucopoiesis could be due to a dose effect. Overall, concentrations of endogenous haematopoietic growth factors are increased but can only partially alleviate haematotoxicity. Potential uses of exogenous haematopoietic growth factors and their impact on the virological response need to be explored.

Adult↗
PubMed2004

Review article: diagnosis and current therapy of Wilson's disease.

Wilson's disease is an autosomal recessive inherited disorder of hepatic copper metabolism resulting in liver disease and/or neuropsychiatric disease. The diagnosis of neurological disease is straightforward if the following symptoms are present: Kayser-Fleischer rings, typical neurological symptoms and low serum ceruloplasmin levels. The diagnosis is more complex in patients presenting with liver diseases. None of the commonly used parameters alone allows a diagnosis with certainty. A combination of various laboratory parameters is necessary to firmly establish the diagnosis. In the future, limited mutation analysis may play an important diagnostic role. Recently, a group of international experts has proposed a score based on a variety of tests and clinical symptoms. The validity of this score needs to be assessed prospectively. Treatment requires life-long administration of copper chelators (d-penicillamine, trientine). A frequently used alternative is zinc. None of these treatments has been tested by prospective randomized controlled studies. Liver transplantation is reserved for severe or treatment-resistant cases with advanced liver disease, whilst experience with refractory neuropsychiatric disease is limited.

Antioxidants↗
PubMed2003

Weight-based dosing of pegylated interferon-alpha in chronic hepatitis C: just a marketing 'gag'?

Today medical-scientific data are diluted by the marketing strategies of the biomedical industry making it difficult for practising physicians to decide what is correct or wrong. One typical example is the use of pegylated interferons for treatment of chronic hepatititis C. In this report the arguments pro and contra weight-based dosing are critically discussed. The factors contributing to success or failure to eradicate the virus are manifold, and include the sensitivity of the virus to interferon, viral genotype, age, gender stage of fibrosis, presence or absense of steatosis. Weight by itself plays just a minor role. The impact of weight-based dosing in general is overestimated and certainly not needed when 40 kD branched PEG-IFNalpha2a with a restricted volume of distribution is used. Whether weight-based dosing of 12 kD linear PEG-IFNalpha2b provides any benefit over a flat dose of the drug remains to be studied.

Antiviral Agents↗
PubMed2003

Early viral kinetics on treatment with pegylated interferon-alpha-2a in chronic hepatitis C virus genotype 1 infection.

Even with pegylated (PEG) interferons (IFN), therapy of chronic hepatitis C (genotype 1) remains unsatisfactory. The initial viral response to IFN identifies patients infected with IFN resistant viruses not responding to standard IFN/ribavirin therapy. The impact of primary IFN unresponsiveness for PEG-IFN-alpha-2a/ribavirin therapy is unknown. Viral load was measured in 22 chronic hepatitis C (genotype 1) patients before and 24 h after 9 MU IFN-alpha-2a (days 0 and 1), and before and during weekly 180 microg PEG-IFN-alpha-2a (days 7, 8, 11, 14 and 21) administration. Thereafter, ribavirin (800 mg/d) was added for 6 months. Virological responders continued treatment for a further 6 months. Twenty-eight patients treated with standard IFN/ribavirin therapy in a previous study using an analogous protocol served as historic controls. After 6 months 15 (68.2%) patients were (HCV-RNA) negative, eight of whom (36.4%) had a sustained response. The decrease in viral load 24 h after 9 MU IFN-alpha-2a was greater in virological responders (1.05 log [0.25-1.67]) than in nonresponders (NR) (0.34 [0.14-0.65]; P=0.003). In contrast, viral decline was not different between responders and NRs during the first 2 weeks on PEG-IFN-alpha-2a. All patients with an initial decline > 1.4 log became sustained responders. Five of 12 patients with a log change < 0.8 became end of treatment responders, two had a sustained response. Antiviral response to PEG-IFN-alpha-2a is different to that on standard IFN. In spite of a lower initial response PEG-IFN-alpha-2a/ribavirin combination therapy may overcome predicted IFN unresponsiveness.

Adult↗
PubMed2003

Twice-weekly administration of peginterferon-alpha-2b improves viral kinetics in patients with chronic hepatitis C genotype 1.

The decline in hepatitis C viral load on treatment with peginterferon-alpha-2b is not continuous. The aim of this study was to investigate whether twice weekly dosing of peginterferon-alpha-2b may improve viral kinetics. Ten interferon-naïve patients with chronic hepatitis C (genotype 1a or b) were randomized to receive either 1.0 microg/kg peginterferon-alpha-2b once (group A) or twice weekly (group B) for 4 weeks. Viral load and serum concentrations of peginterferon-alpha-2b were measured. Peginterferon-alpha-2b reached maximal blood concentrations 24 h after the first dose, followed by a linear decline during the subsequent days. On the day before administration of the next dose, peginterferon-alpha-2b was undetectable in nine patients in group A (once weekly dosing). The same pattern was observed during the next 3 weeks of therapy. In group B (twice weekly dosing) peginterferon-alpha-2b was detectable at any given time point and higher than in group A (P between 0.01 and <0.0001). Viral load decreased in all patients within 2 days after the first dose of peginterferon-alpha-2b, but increased again on day 3. In group A, it further increased until day 7. A similar pattern was observed in the second week. In contrast, in group B, viral load decreased again on day 4 and remained lower until the end of the study (P < 0.001). To achieve continuous drug exposure and to improve initial viral clearance, peginterferon-alpha-2b has to be given at least two times weekly.

Adult↗
PubMed2003

Child-Pugh versus MELD score in predicting survival in patients undergoing transjugular intrahepatic portosystemic shunt.

BACKGROUND: In patients undergoing transjugular intrahepatic portosystemic shunt (TIPS), prognostic scores may identify those with a poor prognosis or even those with a clear survival benefit. The Child-Pugh score (CPS) is well established but several drawbacks have led to development of the model of end stage liver disease (MELD). AIM: The aim of the study was to compare the predictive power of CPS and MELD, to validate the original MELD formula, and to assess the predictive value of the determinants used in the two prognostic scores outside of a study setting. PATIENTS: A total of 501 patients underwent elective TIPS placement and 475 patients fulfilled the inclusion criteria. METHODS: Data of all patients undergoing elective TIPS in one university hospital and four community hospitals in Vienna, Austria, between 1991 and 2001, were analysed retrospectively. The main statistical tests were Cox proportional hazards regression model, the log rank test, Kaplan-Meier analysis, and concordance c statistics. RESULTS: Median follow up was 5.2 years and median survival was 4.6 years. During follow up, 230 patients died, 75 within three months after TIPS placement. In stepwise proportional hazards analyses, independent predictors of death were creatinine level, bilirubin level, age, and refractory ascites. MELD was better in predicting survival in a stepwise Cox model but both scores were equally predictive in c statistics for one month, three month, and one year survival. Renal function was the strongest independent predictor of survival. CONCLUSIONS: Although MELD was the primary predictor of overall survival in multivariate analysis, c statistics showed that both scores can be used for patients undergoing TIPS with equal accuracy. For assessing prognosis in patients undergoing TIPS implantation, there seems little reason to replace the well established Child-Pugh score.

Adult↗
PubMed2003

How to identify the genetic basis of gastrointestinal and liver diseases?

New insights into the genetic basis of disease are being generated at an ever increasing rate. This explosion of information was ignited by technological advances, such as the polymerase chain reaction and automated DNA sequencing. Although its promise is great, the integration of genetics into the everyday practice of medicine remains challenging. This review discusses the application of molecular genetics in general with a specific focus on hereditary diseases of the digestive organs. The application of molecular genetics in everyday clinical routine is hampered by the difficult interpretation of test results. These difficulties include the prediction of disease penetrance, the presence of multiple mutations of a particular gene with varying functional consequences, and the importance of exogenous factors modulating disease expression. To date, the most significant impact of genetics has been to increase our understanding of disease aetiology and pathogenesis and to reliably identify siblings of affected patients with the risk to develop symptomatic disease.

Gastrointestinal Diseases↗
PubMed2003

Peginterferon alfa-2a (40KD) (Pegasys) for the treatment of patients with chronic hepatitis C.

Compared with conventional interferon alfa, peginterferon alfa-2a (40KD) has improved pharmacokinetics, provides sustained therapeutic plasma levels, and can be administered once weekly. In randomised, multinational trials, peginterferon alfa-2a (40KD) 180 microg once weekly was significantly more effective than three times weekly interferon alfa-2a in patients with chronic hepatitis C, including patients with cirrhosis. Peginterferon alfa-2a (40KD) and ribavirin 1000/1200 mg/day for 48 weeks produced significantly higher sustained responses than three times weekly interferon alfa-2b and ribavirin 1000/1200 mg/day in patients with chronic hepatitis C including those with HCV genotype 1, genotypes 2/3 and those with high or low viral loads at baseline. The drug is well tolerated when given alone or in combination with ribavirin. Health-related quality of life was significantly less impaired during treatment with peginterferon alfa-2a (40KD) than interferon alfa-2a in randomised trials. Peginterferon alfa-2a (40KD) is widely approved for use in patients with chronic hepatitis C.

Antiviral Agents↗
PubMed2001

Primary interferon resistance and treatment response in chronic hepatitis C infection: a pilot study.

Only 30% of patients with chronic hepatitis C virus genotype 1 (HCV-1) infection achieve a sustained virological response to interferon and ribavirin combination therapy. We prospectively assessed decline in viral load 24 h after one dose of interferon alfa as a predictor of non-response to 6 months of treatment with interferon and ribavirin. Interferon sensitivity was measured before initiation of combination therapy. We measured viral load in 29 consecutive patients, who had not previously been treated with interferon and who were chronically infected with HCV-1 within 24 h after one dose of 5 MU or 10 MU interferon alfa-2b, and 14 days of daily 5 MU interferon alfa-2b. A 24 h viral load decline by less than 70% of baseline after 5 MU interferon was the best pretreatment measure to identify non-responders (specificity 100%, n=10, 95% CI 74-100], sensitivity 83% [15/18], 59-96]).

Adult↗