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Biomedical subjects

R Poupon

Publications and source records attributed to R Poupon.

At least 37 records · Page 2Linked to original sources
PubMed2001

Polyspecificity of antimicrosomal thyroid antibodies in hepatitis C virus-related infection.

OBJECTIVES: The outcome of dysthyroidism and the presence of antithyroid antibodies in patients with chronic hepatitis C virus (HCV) infection receiving interferon-alpha therapy is clearly established. However, the prevalence and the specificity of antithyroid antibodies in HCV patients before interferon-alpha therapy remain controversial. The aim of the present study is to clarify within a large population of HCV patients the prevalence of antithyroid antibodies before interferon-alpha therapy and to determine whether their immunodominant antigen is the same as described in autoimmune thyroiditis. METHODS: Sera from 99 patients with chronic hepatitis C before (n = 99) and after (n = 37) interferon-alpha treatment were investigated for the presence of antimicrosomal and antithyroperoxidase antibodies assessed by indirect immunofluorescence and ELISA, respectively. Dot blotting on human thyroid lysate was designed to further characterize these autoantibodies. Data were compared to those obtained with sera of patients with autoimmune thyroiditis (n = 75) and healthy subjects (n = 96). RESULTS: In HCV patients, antimicrosomal antibodies were found with a higher proportion before interferon-alpha therapy (12.1%) than after therapy (8%). Thyroperoxidase constitutes the main antigen in only 4% before treatment, a prevalence similar to that observed in healthy controls. CONCLUSIONS: The prevalence of antithyroid antibodies is low in patients with chronic hepatitis C before interferon-alpha therapy. Thyroperoxidase may not be their main target. Further studies are required to determine whether HCV infection leads to a breakdown of tolerance to a thyroid self-protein other than thyroperoxidase.

Adult↗
PubMed2000

Cold preservation injury in rat liver: effect of liposomally-entrapped adenosine triphosphate.

BACKGROUND/AIMS: Energy charge and capacity for adenosine triphosphate (ATP) synthesis have been demonstrated to play a major role in the maintenance of organ function after liver preservation for transplantation. The aim of this study was to evaluate whether a supply of liposomally-entrapped ATP during preservation could improve the energy state and metabolism of cold-stored rat liver. METHODS: In the first set of experiments, the uptake of ATP-containing liposomes and their effects on hepatic viability were determined in isolated perfused unstored rat liver. In the second set of experiments, rat livers were preserved for 18 h at 4 degrees C in UW solution in the presence of these liposomes, and effects on energy state, cell volume and metabolism were evaluated. In each part, data were compared with adequate control, unloaded liposome-treated, and free ATP-treated groups (n=6 in each group). RESULTS: In non-stored livers, ATP-containing liposomes were taken up by the liver; they did not alter hepatic viability and induced a decrease in energy substrate consumption (glucose and amino acids), and an improvement in intrahepatic ATP content (+23% vs. Control). Addition of liposomally-entrapped ATP during cold storage produced a significant attenuation of the decrease in hepatic ATP content (Lip ATP 2: 524+/-45 vs. Control 2: 364+/-106 nmol/g; p<0.05), and induced, during reperfusion, a decrease in proteolysis associated with an increase in cell volume compared with the other groups (Lip ATP 2: 633+/-63 vs. Control 2: 532+/-38, Unloaded Lip 2: 483+/-55 and Free ATP 2: 500+/-29 microl/g; p<0.01). CONCLUSIONS: These data indicate that liposomally-entrapped ATP represents an effective means to improve liver graft energy state and function. The decrease in protein degradation may be related to the modification of cell volume.

Adenosine Triphosphate↗
PubMed2000

Fetal microchimerism in primary biliary cirrhosis.

BACKGROUND/AIMS: Recent studies have suggested a role of fetal microchimerism in the pathogenesis of scleroderma. The present study investigated the potential role of fetal microchimerism in primary biliary cirrhosis (PBC), a closely related disease. METHODS: A quantitative nested polymerase chain reaction was used to detect Y-chromosome sequences in the peripheral blood or the liver of PBC women and controls having male children and no transfusion or miscarriage history. RESULTS: Male microchimerism was found in the peripheral blood from 45% (9 of 20) of PBC women and 25% (5 of 20) of healthy controls matched for the number of male children and age of the youngest son (p=0.28), and in the liver-biopsy specimens from 33% (5 of 15) of PBC women and 32% (8 of 25) of controls. The level of chimerism did not differ between patients and controls either in blood or in liver. Microchimerism was not related to the severity of the disease but was more frequent in PBC patients with anticentromere antibodies (p=0.049). CONCLUSIONS: Fetal microchimerism does not seem to play a major role in most cases of PBC. However, the association with anticentromere antibodies suggests a possible role in the subgroup of patients with CREST syndrome or scleroderma.

Adult↗
PubMed2000

Prognostic value of serum hyaluronan in patients with compensated HCV cirrhosis.

BACKGROUND/AIM: Serum hyaluronan (HA) levels increase according to the degree of liver fibrosis in patients with chronic viral hepatitis C. Patients with liver disease and markedly high serum HA levels have cirrhosis with typical signs of hepatic sinusoidal capillarization, a factor of aggravation of cirrhosis The aim of this study was to evaluate the prognostic value of serum HA for severe complications in asymptomatic patients with HCV cirrhosis. METHODS: Six hundred and sixty-eight patients with anti-HCV antibodies and increased serum alanine aminotransferase were referred to our hospital for evaluation, including liver biopsy. At entry, serum HA levels were measured in 91 patients (64 men, 27 women, 56 +/-11 years old) out of 103 who had asymptomatic, biopsy-proven cirrhosis According to the criteria of Child-Pugh, 82 were classified A and 9 B. The follow-up period was 6 to 82 months (median: 38 months), and 51 of these patients received alpha-interferon therapy during the first year. Severe complications were defined as death or liver transplantation, ascites, bleeding from esophageal varices, encephalopathy, or hepatocellular carcinoma. RESULTS: Serum HA levels at entry were higher in the cirrhotic patients in whom severe complications occurred during the follow-up period (520+/-426 microg/l vs 197+/-146 microg/l, p<0.0001). The patients with serum hyaluronan levels >350 microg/l displayed higher probabilities of occurrence of severe complications (p<0.0001). Other factors associated with the occurrence of complications or death were: serum bilirubin >18mol/l (p = 0.03), platelet count <112x10(9)/l (p= 0.02), prothrombin time <63% (p<0.0001), serum albumin <36 g/l (p=0.002), alkaline phosphatase >81 IU/l (p=0.01), and no interferon treatment (p= 0.0003). Multivariate analysis identified five independent factors predictive of severe clinical complications, namely: hyaluronan (p=0.006), prothrombin time (p=0.04), bilirubin (p=0.04), albumin (p=0.04), and no therapy (p=0.03). CONCLUSION: Serum HA level is predictive for occurrence of severe complications in HCV cirrhosis, and can be used as a prognostic marker, in addition to the parameters of the Child-Pugh score, particularly in patients with compensated cirrhosis.

Aged↗
PubMed2000

Chronic cholestatic diseases.

Chronic cholestatic diseases, whether occurring in infancy, childhood or adulthood, are characterized by defective bile acid transport from the liver to the intestine, which is caused by primary damage to the biliary epithelium in most cases. In this article, approaches to diagnosis and management of the main specific disorders are provided and some of the recent developments in this field are discussed. Major advances in the understanding of the cellular and molecular physiology of bile secretion have led to identification of genetic defects responsible for the different types of progressive familial intrahepatic cholestasis (PFIC). The potential role of the genes involved in PFIC in some adult cholestatic disorders remains to be determined. The majority of adult patients with chronic cholestasis have primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). Recently, variant forms of PBC have been described. The term autoimmune cholangitis is used to describe patients having chronic non-suppurative cholangitis with negative antimitochondrial antibodies (AMA) but positive antinuclear and/or antismooth muscle antibodies. Autoimmune cholangitis and AMA-positive PBC are quite similar in terms of clinical presentation, survival and response to ursodeoxycholic acid (UDCA) therapy. In contrast, autoimmune cholangitis must be distinguished from PBC-autoimmune hepatitis (AIH) overlap syndrome in which biochemical and histological characteristics of both PBC and AIH coexist. Combination of UDCA and corticosteroids is required in most patients with overlap syndrome to obtain a complete clinical and biochemical response. Long-term UDCA treatment improves survival without liver transplantation in PBC patients. Among the putative mechanisms of the beneficial effects of UDCA, description of anti-apoptotic properties and effect on endotoxin disposal in biliary cells have provided new insights. In patients with incomplete response to UDCA, combination of UDCA with antiinflammatory or immunosuppressive drugs is under evaluation. Variant forms of PSC have also been described, including PSC-AIH overlap syndrome, especially in children or young adults, and small-duct PSC, which is characterized by normal cholangiogram in patients having chronic cholestasis, histologic features compatible with PSC and inflammatory bowel disease. Development of cholangiocarcinoma (CC) is a major feature of PSC, occurring in 10-15% of patients. Early diagnosis of CC is a difficult challenge, although positron emission tomography seems a promising tool. Unlike PBC, effective medical therapy is not yet available in PSC, reflecting the lack of knowledge about the exact pathogenesis of the disease. Currently, liver transplantation is the only effective therapy for patients with advanced disease, although recurrence of PSC in the graft may occur.

Adult↗
PubMed2000

PDGF-mediated chemoattraction of hepatic stellate cells by bile duct segments in cholestatic liver injury.

The accumulation of myofibroblasts and fibrosis around proliferating bile ducts in cholestatic liver disease has been attributed to the proliferation and phenotypic modulation of portal fibroblasts, whereas the contribution of hepatic stellate cells remains uncertain. There is increasing evidence to indicate that bile ducts may stimulate chemoattraction of hepatic stellate cells (HSC). In the present study, we undertook dynamic tests to examine such a possibility and to investigate the role of two potential mediators: platelet-derived growth factor-BB (PDGF-BB) and endothelin-1. Cholestasis was induced by bile duct ligation in rats. HSC were isolated from normal rats and culture activated into myofibroblasts expressing PDGF-beta receptors. Migration of myofibroblastic HSC was investigated in a Transwell chemotaxis filter assay. As compared with basal conditions, PDGF-BB (100 microg/l) and endothelin-1 (10(-8) M) induced a 3-fold and 1.7-fold increase in HSC migration, respectively. Bile duct segments isolated from cholestatic rats triggered a 3-fold increase in migration. This stimulation was significantly more potent than that observed in the presence of normal bile ducts. It was inhibited by neutralizing anti-PDGF antibodies and by STI571 PDGF receptor tyrosine kinase inhibitor, by 60% and 85%, respectively, whereas Bosentan, an endothelin receptor antagonist, had no significant inhibiting effect. In bile duct segments from cholestatic rats PDGF-B chain mRNA was detected at higher levels than in controls, whereas PDGF-BB was immunolocalized in bile duct epithelial cells. The results indicate that chemotaxis of HSC towards bile duct structures may contribute to the development of periductular fibrosis in cholestatic disorders, and that PDGF-BB is the major mediator in this process. In addition, anti-liver fibrogenic properties of STI571 are suggested by potent inhibition of myofibroblastic HSC function.

Animals↗
PubMed2000

Prevention of proteolysis in cold-stored rat liver by addition of amino acids to the preservation solution.

BACKGROUND: One process identified as detrimental in liver preservation is proteolysis. METHODS: We tested the effects of adding antiproteolytic amino acids (L-alanine, L-glutamine, L-histidine, L-leucine, L-methionine, L-phenylalanine, L-proline, L-tryptophan) to the preservation medium, in a model of reperfusion of 24 h cold-stored rat livers. RESULTS: During the preservation period, antiproteolytic amino acids inhibited the proteolysis observed in stored livers as shown by branched-chain amino acid fluxes, which switched from release to uptake. During reperfusion, cold storage of lives without the addition of antiproteolytic amino acids resulted in a decrease in the total amino acid and branched-chain amino acid uptake and a lower perfusion flow rate. The addition of antiproteolytic amino acids during liver storage resulted in the maintenance of total amino acid and branched-chain amino acid uptake and a significant improvement in the perfusion flow rate during reperfusion. CONCLUSIONS: The presence of antiproteolytic amino acids in the preservation medium might be of interest in improving hepatic graft viability in transplantation.

Amino Acids↗
PubMed2000

Treatment of primary biliary cirrhosis.

Although primary biliary cirrhosis (PBC) is generally a progressive disease, the rate of progression varies greatly from one patient to another. The terminal phase is characterized by hyperbilirubinaemia (>100 micromol/l), a major decrease in the number of intrahepatic bile ducts, and extensive fibrosis or cirrhosis. It is now well established that orthotopic liver transplantation is the treatment of choice for patients entering the terminal phase of the disease.A variety of therapeutic agents have been proposed for treatment of patients with PBC. However, most have been found ineffective or too toxic to be widely used. In contrast, there is accumulating evidence from large therapeutic trials that long-term administration of ursodeoxycholic acid (UDCA) is safe and prolongs survival free of liver transplantation. Treatment with UDCA slows the histological progression and delays the onset of cirrhosis. In patients who have a sub-optimal response to UDCA therapy alone, the combination of colchicine or methotrexate with UDCA has minimal or no additional benefit, whereas that with corticosteroids is more promising but not yet demonstrated. Among causes of non-response to UDCA therapy, the most common is the PBC-autoimmune hepatitis overlap syndrome. The benefit from the combination of corticosteroids and UDCA in this setting is obvious.Further studies are needed to define the patients who are most likely to respond to UDCA therapy and to assess the benefit of combined medical treatments.

Cholagogues and Choleretics↗
PubMed2000

Differential HFE allele expression in hemochromatosis heterozygotes.

BACKGROUND & AIMS: Hereditary hemochromatosis is associated with C282Y homozygosity. Some heterozygotes may also present with abnormal iron parameters. However, the precise role of H63D and C282Y mutations in iron overload is poorly understood. We investigated the level of expression of the mutated and unmutated HFE alleles in these heterozygous patients. METHODS: We studied the expression of HFE messenger RNAs in peripheral blood mononuclear cells from 34 heterozygotes using reverse-transcription polymerase chain reaction (PCR) followed by enzymatic digestion or sequence analysis of the PCR products, which allows relative quantification of mutated and unmutated transcripts. HFE proteins were quantified by Western blotting in Epstein-Barr virus-immortalized lymphocyte extracts from 2 C282Y and H63D homozygotes and a compound heterozygote. RESULTS: (187C > G; H63D) mutated transcripts predominated in H63D and compound heterozygotes and the normal transcripts in C282Y heterozygotes. The amount of HFE protein was increased in the H63D homozygotes and the compound heterozygote compared with the C282Y homozygotes. In addition, we found a new mutation at codon 282 (C282S) associated with severe iron overload. CONCLUSIONS: We demonstrate the existence of differential allelic expression of the HFE alleles, suggesting that the (187C > G; H63D) mutation plays a role in the disease expression in H63D heterozygotes, in particular when associated with environmental or host factors.

Adult↗
PubMed2000

The effect of ursodeoxycholic acid therapy on liver fibrosis progression in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) is the only approved treatment for primary biliary cirrhosis (PBC). However, the benefit from UDCA therapy on the progression of PBC from its early stage towards extensive fibrosis and cirrhosis has not been clearly shown. The aim of this study was to assess the effect of UDCA therapy on liver fibrosis progression in PBC. A Markov model was used to analyze the progression rates between early and late histologic stages in 103 patients with PBC enrolled in a randomized, double-blind, placebo-controlled trial of UDCA. Early stage was defined by the presence of portal and periportal lesions without extensive fibrosis, whereas late stage was defined by the presence of numerous septa, bridging fibrosis, or cirrhosis. A total of 162 pairs of liver biopsy specimens were studied. The model accurately described the observed data. UDCA therapy was associated with a 5-fold lower progression rate from early stage disease to extensive fibrosis or cirrhosis (7% per year under UDCA vs. 34% per year under placebo, P <.002), but was not associated with a significant difference in regression rates (3% per year under both UDCA and placebo). At 4 years, the probability of UDCA-treated patients to remain in early stage disease is 76% (95% confidence interval: 58%-88%), as compared with 29% (15%-52%) in placebo-treated patients. In conclusion, UDCA therapy significantly delays the progression of liver fibrosis in PBC. Markov modeling should prove useful in assessing the efficacy of future medical treatments in clinical trials involving histologic endpoints.

Disease Progression↗
PubMed2000

Randomized trial of interferon-alpha plus ursodeoxycholic acid versus interferon plus placebo in patients with chronic hepatitis C resistant to interferon.

BACKGROUND: Ursodeoxycholic acid (UDCA) could potentiate the effect of interferon (IFN) in patients with chronic hepatitis C resistant to IFN. We compared the efficacy of IFN with that of a combination of IFN and UDCA. METHODS: Patients were randomized to receive UDCA (13-15 mg/kg/day) (n = 47) or placebo (n = 44) plus interferon (3 MU three times weekly) for 6 months and were then followed up for 6 additional months. RESULTS: At entry 30% of patients had cirrhosis, and 70% had HCV genotype 1. Five and four patients withdrew from the combination and the monotherapy groups, respectively. At 6 months alanine aminotransferase (ALAT) and gamma-glutamyl transferase (GGT) activities were significantly lower (P < 0.001) in the combination group than in the monotherapy group; the differences were no longer significant at 1 year. At 6 months ALAT activities normalized in 10 and 8 patients in the combination and the monotherapy groups, respectively (P = 0.67). In 10 of them (5 in each group) HCV RNA levels became undetectable. At 1 year four versus one patient had a sustained normalization of ALAT, and in one patient the HCV RNA became negative. There was no difference in the histologic progression. In this setting, in contrast to chronic cholestasis, UDCA administration induced an increase in total serum bile acids and did not change primary bile acids. CONCLUSIONS: An IFN plus UDCA combination is more effective than IFN alone in terms of ALAT but not in terms of the virologic response. These results favor the hypothesis that UDCA has an effect on the biochemical indices of cellular injury independent of a change in primary bile acids.

Adult↗
PubMed2000

Comparison of a new method for the direct and simultaneous assessment of LDL- and HDL-cholesterol with ultracentrifugation and established methods.

BACKGROUND: Automated electrophoresis combined with enzymatic cholesterol staining might improve routine assessment of LDL- and HDL-cholesterol (LDLC and HDLC), as an alternative to the Friedewald equation and precipitation. A new method (Hydrasys; SEBIA) that adapts the cholesterol esterase/cholesterol oxidase reaction within urea-free gels was evaluated. METHODS: Fresh sera from 725 subjects (512 dyslipidemics) were analyzed by electrophoresis, in parallel with sequential ultracentrifugation, beta-quantification, calculation, and precipitation. RESULTS: Electrophoresis was linear up to 4 g/L cholesterol, with a detection limit of 0.042 g/L cholesterol/band. Within-run, between-run, between-batch, and between-operator imprecision (CVs) were 1.6%, 2.0%, 1.5%, and 2.7% for LDLC, and 3.9%, 4.3%, 5.5%, and 4.9% for HDLC, and remained unchanged up to 6.3 g/L plasma triglycerides (TGs). Precision decreased with very low HDLC (<0.25 g/L). Serum storage for 3-7 days at +4 or -80 degrees C did not interfere significantly with the assay. Agreement with beta-quantification was stable for LDLC up to 5.07 g/L (r = 0.94), even at TG concentrations >4 g/L (r = 0.91). Bias (2.88% +/- 12%) and total error (7.84%) were unchanged at TG concentrations up to 18.5 g/L. Electrophoresis predicted National Cholesterol Education Program cut-points with <0.04 g/L error, exactly and appropriately classified 79% and 96% of the subjects, and divided by 2.4 (all subjects) and 5.8 (TGs >1.5 g/L) the percentage of subjects underestimated by calculation. One-half of the patients with TGs >4 g/L had LDLC >1.30 g/L. For HDLC, correlation was better with precipitation (r = 0.87) than ultracentrifugation (r = 0.76). Error (-0.10% +/- 26%) increased when HDLC decreased (<0.35 g/L). Direct assessment of the LDLC/HDLC ratio detected 45% more high-risk subjects than the calculation/precipitation combination. CONCLUSIONS: Electrophoresis provides reliable quantification of LDLC, improving precision, accuracy, and concordance over calculation, particularly with increasing plasma TGs. Implementation of methods to detect low cholesterol concentrations could extend the applications for HDLC assessment.

Adolescent↗
PubMed1999

Histopathological study of primary biliary cirrhosis and the effect of ursodeoxycholic acid treatment on histology progression.

The semiquantitative histopathological analysis of the liver biopsies obtained before and after 4 years of ursodeoxycholic acid (UDCA) therapy in a cohort of primary biliary cirrhosis (PBC) patients is reported. The relationships between elementary histological lesions before treatment and their progression under therapy were assessed. At baseline, two independent groups of lesions, each of which participate in the development of fibrosis, were individualized, i.e., florid bile duct lesions and ductopenia on one hand and lymphocytic piecemeal necrosis, ductular proliferation, and lobular necroinflammatory changes on the other hand. Four years of UDCA therapy were associated with a significant decrease in the prevalence of florid interlobular bile duct (ILBD) lesions, of epithelioid granuloma (P <.001) without any aggravation in the severity of bile duct paucity. Lobular inflammation and necrosis markedly improved (P <.001) whereas the degree of severity of the lymphocytic piecemeal necrosis and ductular proliferation at entry and at 4 years were similar. Worsening of fibrosis was observed in 14 patients (12 of them had a one grade progression) whereas stabilization was noted in 30 of the remaining patients. Severity of both the lymphocytic piecemeal necrosis and lobular inflammation and necrosis at entry was significantly associated with the progression of fibrosis. The results suggest that UDCA therapy influences the process leading to bile duct destruction. Patients with severe lymphocytic piecemeal necrosis and lobular inflammation may need additional therapeutic intervention because they have increased risk of fibrosis progression.

Bile Ducts↗
PubMed1999

Ten-year survival in ursodeoxycholic acid-treated patients with primary biliary cirrhosis. The UDCA-PBC Study Group.

Ursodeoxycholic acid (UDCA) treatment has been shown to increase survival without orthotopic liver transplantation (OLT) in patients with primary biliary cirrhosis (PBC) at 4 years. Whether this beneficial effect was maintained over the long term remained to be established. In a large cohort of UDCA-treated patients with PBC, we aimed to determine the 10-year outcome of these patients using two endpoints: (1) survival without OLT, and (2) survival. The cohort was comprised of 225 patients with PBC treated with UDCA (13-15 mg/kg/d) monitored from the beginning of treatment until time of last follow-up, OLT, or death. Because of the absence of a control group, survival without OLT was compared with survival predicted by the Mayo model (first 7 years), and observed 10-year survival with an estimation of survival of a standardized control cohort of the French population. Observed survival without OLT of UDCA-treated patients was significantly higher (P <.04) than survival predicted by the Mayo model. Observed survival was significantly lower (P <. 01) than survival predicted from the French population. Observed survival of noncirrhotic patients was not different (P >.9) from that of the French control population but survival of cirrhotic patients was significantly lower (P <.0001). Twenty-two patients died; 13 patients died of hepatic causes and 4 patients died after OLT. In conclusion, survival without OLT among patients treated with UDCA for PBC is higher than that of untreated patients, as predicted by the Mayo model. Ten-year survival among UDCA-treated patients is slightly lower than that of an age- and sex-matched general population, the difference mainly being explained by mortality among cirrhotic patients.

Bilirubin↗
PubMed1999

Bile acids modulate the interferon signalling pathway.

We have previously shown that cholestasis and bile acids inhibit 2', 5' oligoadenylate synthetase (OAS) activity in the liver and in primary hepatocyte cultures. Here, we assessed the influence of bile acids on interferon (IFN) pathway activation in three hepatoma cell lines. In HepG2 cells, bile acids (100-200 micromol/L) inhibited IFN-induced 2',5' OAS activity to an extent depending on their surface activity index. In Western blot analysis, IFN-induced expression of two major antiviral proteins, MxA and OAS p100, was reduced by 54% +/- 8% and 44% +/- 12%, respectively, when cells were preincubated for 4 hours with 100 micromol/L chenodeoxycholic acid (CDCA). In the same conditions, CDCA did not modify the IFN-induced signal transducers and activators of transcription (STAT)s tyrosine phosphorylation. In contrast, it reduced IFN-induced MxA promoter activity by 60%. The inhibitory effect of CDCA was not mediated by a 4beta-phorbol 12beta-myristate 13alpha-acetate (PMA)-sensitive protein kinase C (PKC)-dependent pathway. Finally, using CHO cells stably expressing a functional human bile acid carrier (Na+-dependent taurocholate cotransporting polypeptide [NTCP]), we found that bile acid inhibition of the IFN pathway occurred in the range of more physiological concentrations (12-50 micromol/L). In summary, our results provide strong evidence that bile acids inhibit the induction of proteins involved in the antiviral activity of IFN. This might partly explain the lack of responsiveness to IFN therapy in some patients with advanced chronic viral liver diseases.

2',5'-Oligoadenylate Synthetase↗