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Peter Ferenci

Publications and source records attributed to Peter Ferenci.

At least 19 recordsLinked to original sources
PubMed2006

Platelet autoantibodies are common in hepatitis C infection, irrespective of the presence of thrombocytopenia.

OBJECTIVE: To investigate the generation of platelet antibodies in hepatitis C virus (HCV)-infected individuals and their relation to the development to thrombocytopenia with the aim of using their detection as a diagnostic aid of immune thrombocytopenia in these patients. MATERIALS AND METHODS: We tested by the monoclonal antibody-specific immobilization of platelet antigen assay (MAIPA) for the presence of platelet antibodies against specific glycoprotein (GP) targets (GPIIb/IIIa, GPIb/IX, GPIa/IIa, GPIIIb, GPV, and FcRgammaIIa) in 48 HCV-infected individuals of various stages of disease and compared the results with those from 35 patients with alcoholic liver cirrhosis. RESULTS: Thirty-two HCV-infected individuals (66%) had detectable platelet antibodies. The most common target was GPIIb/IIIa, but all other GP were also targets. Results were not different from patients with alcoholic liver cirrhosis. There was no correlation between antibodies and platelet counts, or the stage of disease, or the viral genotype, or a discernible influence of treatment with alpha-interferon. CONCLUSION: While platelet autoantibodies are common in individuals with HCV infection, their detection does not assist in the diagnosis of immune thrombocytopenia.

Adult↗
PubMed2006

Regional distribution of mutations of the ATP7B gene in patients with Wilson disease: impact on genetic testing.

Wilson disease is an autosomal recessive inherited disorder of copper metabolism. The Wilson disease gene codes for a copper transporting P-type ATPase (ATP7B). Molecular genetic analysis reveals at least 300 distinct mutations. While most reported mutations occur in single families, a few are more common. The most common mutation in patients from Central, Eastern, and Northern Europe is the point mutation H1069Q (exon 14). About 50-80% of Wilson disease (WD) patients from these countries carry at least one allele with this mutation with an allele frequency ranging between 30 and 70%. Other common mutations in Central and Eastern Europe are located on exon 8 (2299insC, G710S), exon 15 (3400delC) and exon 13 (R969Q). The allele frequency of these mutations is lower than 10%. In Mediterranean countries there is a wide range of mutations, the frequency of each of them varies considerably from country to country. In Sardinia, a unique deletion in the 5' UTR (-441/-427 del) is very frequent. In mainland Spain the missense mutation M645R in exon 6 is particularly common. Data from non-European countries are scarce. Most data from Asia are from Far Eastern areas (China, South Korea and Japan) where the R778L missense mutation in exon 8 is found with an allele frequency of 14-49%. In summary, given the constant improvement of analytic tools genetic testing will become an integral part for the diagnosis of WD. Knowledge of the differences in the worldwide distribution of particular mutations will help to design shortcuts for genetic diagnosis of WD.

Adenosine Triphosphatases↗
PubMed2006

Copper toxicosis gene MURR1 is not changed in Wilson disease patients with normal blood ceruloplasmin levels.

AIM: To analyze our Wilson disease patient cohort (n=106) for alterations in the gene coding for MURR1. METHODS: Patients with an established diagnosis of Wilson disease but normal ceruloplasmin blood levels were chosen for our study (n = 14). Patients with two known disease-causing mutations in the ATP7B gene were not included. The three exons of the human MURR1 gene were sequenced after amplification of the genomic DNA by polymerase chain reaction. RESULTS: Our study did not reveal any mutations leading to an amino acid change in the MURR1 sequence of Wilson disease patients. A polymorphism at 472 bp of the coding sequence could be confirmed. CONCLUSION: The MURR1 gene plays no role in the pathogenesis of Wilson disease patients with normal serum ceruloplasmin levels.

Adaptor Proteins, Signal Transducing↗
PubMed2006

Prospective study of viral clearance and CD4(+) T-cell response in acute hepatitis C primary infection and reinfection.

BACKGROUND: The outcome of acute hepatitis C is determined by early host-virus interactions, particularly involving the antiviral T-cell response. OBJECTIVES: To identify early prognostic markers of spontaneous resolution of acute hepatitis C by performing a comprehensive analysis of viral and immunological factors during the natural course of acute HCV infection and reinfection. STUDY DESIGN: 20 patients were investigated prospectively during acute HC or confirmed reinfection and 18 of them during follow up after spontaneous or treatment-induced elimination of the virus and resolution of the disease. Multiparameter flow cytometry was used to functionally characterize virus-specific CD4(+) T-cell responses relative to the virologic outcome. RESULTS: Parallel immunologic and virologic monitoring of patients with acute HC identified distinct patterns of host-virus interaction related to HCV persistence or clearance. The highest frequency of antiviral Th1 cytokine-producing CD4(+) T-cells was observed in patients with HCV reinfection, preceding rapid viral clearance within 3 weeks after disease onset. In all patients who subsequently cleared viremia, CD4(+) T-cells produced Th1 cytokines following stimulation with non-structural HCV antigens (NS3 and NS4). In contrast, a chronic course of disease was associated with the absence of antiviral Th1 cytokine producing cells from the first weeks after onset of disease (acute persistent HC), or with fluctuating RNA levels (yo-yo pattern) and gradual waning of antiviral Th1 cells. CONCLUSIONS: The results highlight the variability of immune response pattern in acute hepatitis C. Most importantly, "acute persistent hepatitis C" and a lack of TH1 effector cells within the first months of acute hepatitis C represent efficacious predictors of viral persistence and could thus be used as criteria in selecting candidates for early antiviral treatment.

Adolescent↗
PubMed2006

Early identification of HCV genotype 1 patients responding to 24 weeks peginterferon alpha-2a (40 kd)/ribavirin therapy.

Approximately one third of hepatitis C virus (HCV) genotype 1 patients achieved a sustained virological response (SVR) after 24 weeks of treatment with peginterferon alpha-2a (40 kd) plus ribavirin in a randomized, multinational trial. We aimed to identify factors associated with a rapid virological response (RVR) at week 4 (HCV RNA <50 IU/mL) and a SVR (HCV RNA <50 IU/mL at the end of follow-up) in these patients. Stepwise multiple logistic regression analysis was used to explore the prognostic factors for a RVR and SVR in genotype 1 patients treated for 24 weeks. Fifty-one of 216 (24%) genotype 1 patients in the 24-week treatment groups had a RVR. SVR rates were considerably higher in patients with than without [corrected] a RVR (89% vs. 19%, respectively). Patients with a baseline HCV RNA of less than 200,000 IU/mL (OR 9.7, 95% CI 4.2-22.5; P < .0001) or 200,000-600,000 IU/mL (OR 5.6, 95% CI 1.5-9.1; P = .0057) were more likely to achieve a RVR than those with HCV RNA greater than 600,000 IU/mL. HCV subtype (1b vs. 1a) was also independently associated with RVR (OR 1.8, 95% CI 0.9-3.7; P = .0954). RVR (OR 23.7 vs. no RVR, 95% CI 9.1-61.7) and baseline HCV RNA less than 200,000 IU/mL (OR 2.7 vs. > 600,000 IU/mL, 95% CI 1.1-6.3; P < .026) were significant and independent predictors of SVR in patients treated for 24 weeks. In conclusion, patients infected with HCV genotype 1 and treated with peginterferon alpha-2a/ribavirin sustained a RVR 24% of the time. This portends an 89% probability of a SVR after 24 weeks of treatment.

Adult↗
PubMed2006

Standard interferon-alpha in combination with ribavirin for hepatitis C patients with advanced liver disease and thrombocytopenia.

BACKGROUND AND AIM: Patients with advanced liver disease due to thrombocytopenia and chronic infection with hepatitis C virus (HCV) are difficult to treat in view of concerns about the efficacy and safety of interferon-based therapy. Nevertheless, antiviral therapy might have a substantial benefit in these patients as it potentially minimizes disease progression and prevents recurrence after liver transplantation. We evaluated the safety, efficacy and tolerability of standard interferon-alpha in an accelerating dose regimen in combination with ribavirin in patients with HCV-induced liver cirrhosis and thrombocytopenia. PATIENTS: Nine patients (M=8, age: 48.4 +/- 9.9, mean +/- SD) with HCV-related advanced liver disease and thrombocytopenia were prospectively investigated. The Child-Pugh stage was A in six patients and B in three, the MELD score was 11 [6-17] (median [range]). Four patients were interferon naive. HCV-genotype distribution was 1b (n=3), 3a (n=4) and 4 (n=2). The patients received 1-1.5 MU/d standard interferon-a2b with increasing dose regimen and weight-based ribavirin for 48 weeks (genotype 1), or 24 weeks (genotype 3), or until liver transplantation, respectively. RESULTS: The baseline platelet count was 64.3 +/- 8.7 (G/l, mean +/- SD) and remained remarkably stable during treatment (58.0 +/- 12.4 G/l at week 4, 51.7 +/- 20.5 G/l at week 8, P=0.1). All patients had adverse events such as weight loss, fever and anorexia. Hospitalization because of decompensation or infection was necessary in three patients. Three patients underwent liver transplantation. A virological response on treatment was achieved in eight patients and sustained in three (33.3%) patients. CONCLUSION: Treatment with standard interferon-alpha2b/ribavirin could be of benefit in patients with advanced liver cirrhosis and thrombocytopenia however, a vigilant monitoring of these high risk patients is mandatory.

Adult↗
PubMed2006

Tongue and skin hyperpigmentation during PEG-interferon-alpha/ribavirin therapy in dark-skinned non-Caucasian patients with chronic hepatitis C.

Various skin disorders may occur during antiviral therapy with interferon (IFN) and ribavirin (RBV) for chronic hepatitis C. This article describes to our knowledge the first report of lingual hyperpigmentation during pegylated (PEG)-IFN/RBV combination therapy in five dark-skinned hepatitis C virus (HCV) patients. Lingual pigmentation during antiviral therapy was not associated with age, gender, HCV genotype, doses of RBV, or duration of the treatment or treatment outcome. Since IFN increases the expression of alpha-melanocyte-stimulating hormone (MSH) surface receptors, the use of PEG-IFN having a longer plasma half-life may even increase incidence for such cutaneous side effects particularly in dark-skinned HCV patients.

Adult↗
PubMed2006

Erythropoietin treatment is associated with more severe thrombocytopenia in patients with chronic hepatitis C undergoing antiviral therapy.

BACKGROUND: Erythropoietin (EPO) not only stimulates erythropoiesis but also thrombopoiesis. As pegylated-interferon-alpha(PEG-IFN-alpha)-induced thrombocytopenia may become a limiting factor for continuation of therapy, the present study investigated if EPO can alleviate PEG-IFN-alpha induced thrombocytopenia. Further, we hypothesize that EPO increases platelet reactivity and protease activated receptor 1 (PAR-1) expression during combination antiviral therapy. METHODS: Forty patients with chronic hepatitis C received either 10,000 IU EPO 3 x/week or placebo in a randomized, placebo-controlled, double-blinded fashion for 4 wk and combination antiviral therapy with PEG-IFN-2a and ribavirin. RESULTS: EPO alleviated the decrease in hemoglobin during combination antiviral therapy with ribavirin (10%vs 20%, p < 0.0001). Platelet counts decreased stronger in EPO than in placebo group on day 28 (p= 0.007). EPO induced a 40% increase in PAR-1 (p < 0.0001), which was accompanied by 100% increase in platelet reactivity (p < 0.0001). PFA-100 platelet plug formation time and PEG-IFN-alpha-induced vWF-increase were not different between study groups. CONCLUSIONS: Treatment with EPO alleviated the decrease in hemoglobin but worsened PEG-IFN-alpha induced thrombocytopenia after the first 4 wk of combination therapy. EPO caused PAR-1 receptor upregulation on platelets, which promoted an increase in platelet reactivity without affecting PFA-100 platelet plug formation time. EPO is not a useful option for short-term support of platelet production during antiviral therapy.

Adult↗
PubMed2006

Antiviral therapy decreases GpIIb/IIIa activation of platelets in patients with chronic hepatitis C.

Interferon alpha (IFN-alpha) is used to treat haematological and solid malignancies and is the gold standard therapy for chronic hepatitis C infection in combination with ribavirin. It has a well known platelet lowering effect and was recently shown to impair platelet aggregation in the presence of various agonists and has been accused to increase patients' bleeding risk during IFN-alpha therapy. Thus, we hypothesised that antiviral treatment decreases GpIIb/IIIa activation and affects global platelet function. In a prospective clinical trial, we examined the effects of combination therapy with pegylated IFN-alpha 2a (PegIFN-alpha 2a) and ribavirin on platelet GpIIb/IIIa activation and platelet secretion in 20 patients with chronic hepatitis C at week 2, 4, 8 and 12 after the beginning of therapy. In addition, we determined global platelet function (CEPI-CT) with the PFA-100 and vWF-Ag levels. Antiviral therapy significantly decreased GpIIb/IIIa activation in a time dependent manner, whereas markers of platelet secretion (P-selectin, beta-thromboglobulin) remained unchanged. Despite a marked elevation of vWF-Ag levels, CEPI-CT did not change compared to baseline levels. Antiviral therapy significantly decreases GpIIb/IIIa activation in patients with chronic hepatitis C, while vWG-Antigen levels are markedly increased and alpha-granule secretion is not affected. This does not result in an alteration of global platelet function as assessed by the PFA-100, because elevated vWF-Antigen levels might compensate for the acquired defect.

Adult↗
PubMed2005

Randomized, double-blind, placebo-controlled study of peginterferon alfa-2a (40KD) plus ribavirin with or without amantadine in treatment-naïve patients with chronic hepatitis C genotype 1 infection.

BACKGROUND/AIMS: Amantadine may augment virological response rates to interferon-based therapy in chronic hepatitis C patients. Using a novel design, amantadine was studied in naïve genotype 1 patients treated in combination with peginterferon alfa-2a (40KD)/ribavirin. METHODS: Patients enrolled in this randomized, placebo-controlled multicenter trial were stratified by single-dose interferon sensitivity (stratum I, 24-h HCV-RNA decline >1.4-log10; II, 0.8-1.39-log10; III, <0.8-log10; a reliable means of identifying nonresponders to interferon/ribavirin) and fibrosis grade (F0/1/2 vs. F3/4) at baseline. All patients received peginterferon alfa-2a (40KD) 180 microg/week plus ribavirin 1000-1200 mg/day and were randomized to receive amantadine 100 mg twice daily (N = 114) or placebo (N = 95) for 48 weeks. RESULTS: Week-24 virological response rates in strata II and III, the primary outcome, were similar in patients treated with amantadine (63.7%) or placebo (65.7%), as were sustained virological response rates at week 72 (46.5 and 51.6%, respectively). Adverse event profiles were similar and amantadine did not improve health-related quality of life compared with placebo. Interferon sensitivity was the only significant predictor of treatment outcome. CONCLUSIONS: Adding amantadine to peginterferon alfa-2a (40KD)/ribavirin combination therapy does not augment virological response rates in genotype 1 patients. Virological response was almost exclusively determined by interferon sensitivity at baseline.

Adult↗
PubMed2005

Efficacy of 24 weeks treatment with peginterferon alfa-2b plus ribavirin in patients with chronic hepatitis C infected with genotype 1 and low pretreatment viremia.

BACKGROUND/AIMS: Previous studies using standard interferon and ribavirin combination therapy suggested that patients infected with HCV-1 and a low pretreatment HCV-RNA level can be treated for 24 weeks without compromising sustained virologic response rates. The aim of the present study was to investigate this schedule in the era of pegylated interferon-alpha plus ribavirin. METHODS: Patients chronically infected with HCV-1 (n=235) and a screening viremia < or =600,000 IU/mL (real-time PCR) were treated with peginterferon alfa-2b 1.5 microg/kg subcutaneously once weekly plus ribavirin 800-1400 mg/day based on body weight for 24 weeks. RESULTS: End-of-treatment and sustained virologic response rates were 80 and 50%, respectively. The 48-week historical control (Manns et al., Lancet 2001;358:958-65) had similar end-of-treatment (74%) but higher sustained virologic response rates (71%). This difference was due to a high virologic relapse rate after 24 weeks of therapy (37%) compared with the historical control (4%). A subset of patients who had undetectable serum HCV-RNA at treatment week 4, however, achieved similar sustained virologic response rate (89%) as in the control group (85%). CONCLUSIONS: HCV-1 infected patients with a low baseline HCV-RNA concentration who become HCV-RNA negative at week 4 may be treated for 24 weeks without compromising sustained virologic response rates.

Adolescent↗
PubMed2005

Prediction of progression to cirrhosis by a glutathione S-transferase P1 polymorphism in subjects with hereditary hemochromatosis.

BACKGROUND: Oxidative stress plays an important pathogenic role in hereditary hemochromatosis (HHC) and chronic hepatitis C virus infection (CHC). Several enzymes involved in the degradation of reactive oxidants and xenobiotics, such as glutathione S-transferase P1 (GSTP1) and manganese superoxide dismutase (MnSOD), reveal polymorphisms that affect their antioxidant capacity and may therefore modulate the progression to cirrhosis. Our objective was to establish the role of the functional polymorphisms of GSTP1 (codon 105 Ile-->Val) and MnSOD (codon 16 of precursor protein Ala-->Val) on the evolution of cirrhosis in patients with HHC and CHC. METHODS: One hundred seventy-two patients with HHC who were homozygous for the C282Y mutation and 285 patients with CHC underwent liver biopsy and genotyping for the GSTP1 and MnSOD polymorphisms. RESULTS: In HHC, the GSTP1 Val/Val genotype was more common in patients with than in those without cirrhosis (14.8% vs 2.1%, P = .009), whereas the distribution of MnSOD variants was not different. Logistic regression analysis identified GSTP1 Val/Val genotype, serum ferritin level, male sex, and age as independent predictors for the presence of cirrhosis. The odds ratio for the GSTP1 Val/Val genotype for the development of cirrhosis was 3.85 (95% confidence interval, 1.18-12.62; P = .03). However, in patients with CHC, the GSTP1 and MnSOD genotypes were not associated with cirrhosis. CONCLUSIONS: Cirrhosis is more likely to develop in C282Y homozygotes with the GSTP1 Val/Val genotype than in those with non-Val/Val genotypes, which in part explains the variable phenotypic expression of HHC and highlights the central role of oxidative stress in its pathogenesis.

Adult↗
PubMed2005

TGF-beta1 codon 25 gene polymorphism is associated with cirrhosis in patients with hereditary hemochromatosis.

Hereditary hemochromatosis (HHC) is an autosomal recessive disorder of iron metabolism with variable penetrance. Only a minority of C282Y homozygotes develop clinical overt disease and cirrhosis. The phenotypic heterogeneity of HHC may be due to host genetic factors influencing fibrogenesis such as cytokine gene polymorphisms. In this respect, we investigated the impact of functional genetic polymorphisms of TGF-beta1 (codon 10 Leu/Pro, codon 25 Arg/Pro), TNF-alpha (-308 G/A, -238 G/A) and angiotensinogen (-6 G/A) on the development of cirrhosis in HHC. One hundred and forty-nine (111 male, mean age: 51.0+/-12.9) C282Y homozygotes who underwent liver biopsy were studied. Genotyping was performed by RFLP analysis. TGF-beta1 codon 25 genotypes Arg/Pro and Pro/Pro were more common in patients with cirrhosis than in those without (23.6% vs. 7.4%, p = 0.005). In contrast, the distribution of TGF-beta1 codon 10, TNF-alpha and angiotensinogen genotypes was not different. Logistic regression analysis identified male sex, age, serum ferritin and TGF-beta1 codon 25 Arg/Pro and Pro/Pro as independent predictors for the presence of cirrhosis. The adjusted odds ratio for TGF-beta1 codon 25 Arg/Pro and Pro/Pro was 2.8 (95% CI 1.4-5.7, p = 0.004). In conclusion, C282Y homozygotes carrying TGF-beta1 genotypes Arg/Pro and Pro/Pro are more likely to develop cirrhosis than those with genotype Arg/Arg.

Adult↗
PubMed2005

Association of myeloperoxidase promotor polymorphism with cirrhosis in patients with hereditary hemochromatosis.

BACKGROUND/AIMS: Hereditary hemochromatosis (HHC) is a disorder of iron metabolism with variable penetrance. Oxidative stress plays a central role in the progression to cirrhosis. Several enzymes involved in the production or degradation of reactive oxidants, like myeloperoxidase (MPO) and heme oxygenase (HO)-1 are influenced by promotor polymorphisms. This study assessed the impact of polymorphisms of the MPO (-463G/A) and the HO-1 promotors of Vienna (GT)n on the evolution of cirrhosis in patients with HHC. METHODS: One-hundred and fifty-eight C282Y homozygotes without cofactors for fibrosis progression (119 males; mean age: 51.0+/-13.3) were studied. All patients underwent liver biopsy. Hepatic iron content was measured by atom absorption spectrophotometry. MPO polymorphism was assessed by RFLP analysis; HO-1 microsatellite polymorphism by a laser-based semi-automated DNA sequencer. RESULTS: The MPO genotypes GG, GA, and AA were found in 102 (64.6%), 45 and 11 patients, respectively. The GG-genotype was more common in patients with cirrhosis than in those without (78.7 vs. 55.7%, P=0.003). The distribution of HO-1 genotypes was not different. Logistic regression analysis revealed MPO genotype-GG, serum ferritin, age and male sex as independent predictors for cirrhosis. CONCLUSIONS: MPO genotype GG is associated with cirrhosis in patients with hereditary hemochromatosis.

Adult↗
PubMed2005

Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations.

AIM: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD. METHODS: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP. RESULTS: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%, P<0.0001). SNP8/R702W (10.8% vs 6%, P = 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P = 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (OR(het) = 1.71, 95%CI = 1.12-2.6, P = 0.0001, OR(two-risk alleles) = 25.2, 95%CI = 4.37-8, P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P = 0.0006), ileal disease (81.9% vs 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P = 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69, 95%CI = 1.13-2.55, P = 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P = 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years. CONCLUSION: These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.

Adult↗
PubMed2005

Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials.

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.

Antiviral Agents↗
PubMed2005

Dysfunction of the liver affects the sense of smell.

BACKGROUND: Cirrhosis of the liver (CL) has been reported to be accompanied by olfactory loss. The aim of the present study was to re-investigate previous work with a special focus on differential olfactory function, the relation between CL etiology and olfactory function, and the correlations between laboratory/psychological parameters and olfactory function. MATERIALS AND METHODS: A total of 45 CL patients participated. Olfactory function was tested using the "Sniffin' Sticks" technique, which provides measures for butanol odor thresholds, odor discrimination and odor identification. Serum levels of zinc and bilirubin were obtained. Psychometric measurements included the trailmaking test. RESULTS: The study provided the following major results: (1) Olfactory function was compromised in 76% of CL patients; in addition, the patient's ability to identify odors, but not odor thresholds or odor discrimination, was related to the degree of CL. This pattern may be an expression of a stronger effect of CL on the central- nervous processing of odors than on the periphery of the system. (2) Neither etiology of the CL (e.g., alcoholism) nor serum levels of bilirubin and zinc were correlated with olfactory function. However, (3) there was a relation between the results from psychometric function tests and the ability to identify odors. CONCLUSION: Although the reason for olfactory dysfunction in CL is far from clear, future investigations should focus on the hypothesis that endogenous intoxication may lead to a stronger deficit in the central-nervous processing of olfactory information than to peripheral lesions in the olfactory system. In addition, while more specific research is needed, olfactory dysfunction may serve as a subclinical indicator of hepatic encephalopathy.

Adult↗