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Elizabeth E Powell - One of the best experts on this subject based on the ideXlab platform.

  • effeCt of weight reduCtion on liver histology and bioChemistry in patients with ChroniC Hepatitis C
    Gut, 2002
    Co-Authors: Ingrid J Hickman, David M Purdie, Andrew D Clouston, Graeme A. Macdonald, Johannes B Prins, Susan Ash, J R Jonsson, Elizabeth E Powell
    Abstract:

    BaCkground: Steatosis oCCurs in more than 50% of patients with ChroniC Hepatitis C and is assoCiated with inCreased hepatiC fibrosis. In many of these patients the pathogenesis of steatosis appears to be the same as for patients with non-alCoholiC fatty liver disease—that is, related to visCeral adiposity and obesity. Methods: The effeCt of a three month weight reduCtion programme on liver bioChemistry and metaboliC parameters was examined in 19 subjeCts with steatosis and ChroniC Hepatitis C. Paired liver biopsies were performed in 10 subjeCts, prior to and 3–6 months following the intervention, to determine the effeCt of weight loss on liver histology. Results: There was a mean weight loss of 5.9 (3.2) kg and a mean reduCtion in waist CirCumferenCe of 9.0 (5.0) Cm. In 16 of the 19 patients, serum alanine aminotransferase levels fell progressively with weight loss. Mean fasting insulin fell from 16 (7) to 11 (4) mmol/l (p<0.002). Nine of 10 patients with paired liver biopsies had a reduCtion in steatosis irrespeCtive of viral genotype. In these subjeCts the median modified Knodell fibrosis sCore deCreased from 3 to 1 (p=0.04) and aCtivated stellate Cells signifiCantly deCreased (p<0.004). ConClusions: Weight loss in patients with ChroniC Hepatitis C may be assoCiated with a reduCtion in steatosis and abnormal liver enzymes and an improvement in fibrosis, despite the persistenCe of the virus. Weight reduCtion may provide an important adjunCt treatment strategy for patients with ChroniC Hepatitis C.

  • steatosis and ChroniC Hepatitis C analysis of fibrosis and stellate Cell aCtivation
    Journal of Hepatology, 2001
    Co-Authors: Andrew D Clouston, David M Purdie, Claudia Shorthouse, Elizabeth E Powell, Graeme A. Macdonald, Julie R Jonsson, Nirmala Pandeya
    Abstract:

    AbstraCt BaCkground/Aims : Steatosis is a frequent histologiCal finding in ChroniC Hepatitis C and is assoCiated with inCreased hepatiC fibrosis. Methods : We studied 80 patients with untreated ChroniC Hepatitis C to determine whether steatosis Contributes to fibrosis through a steatoHepatitis-like pathway. Results : Fine sinusoidal and/or Central vein fibrosis was present in 52 patients (65%). This was typiCally loCated in aCinar zone 3 and had a ChiCken-wire appearanCe similar to that seen in steatoHepatitis. A statistiCally signifiCant relationship was found between subsinusoidal fibrosis and age ( r s =0.33, P =0.003) and grade of steatosis ( r s =0.35, P =0.001). Mean body mass index was higher in patients with foCal (28.4±4.7 kg/m 2 ) or extensive (29.6±5.9 kg/m 2 ) subsinusoidal fibrosis than in those patients with no subsinusoidal fibrosis (25.5±3.7 kg/m 2 ). The extent of α -smooth musCle aCtin staining (as a marker of stellate Cell aCtivation) Correlated with the degree of portal inflammation and the stage of portal fibrosis, but not with the grade of hepatiC steatosis. ConClusions : These findings suggest that in Hepatitis C infeCtion, host faCtors, partiCularly adiposity, Contribute to both steatosis and aCinar fibrosis. The impliCation of these observations is that weight reduCtion may provide an important therapeutiC strategy for patients with ChroniC Hepatitis C.

  • interleukin 10 promoter polymorphism prediCts initial response of ChroniC Hepatitis C to interferon alfa
    Hepatology, 1999
    Co-Authors: Catherine Edwardssmith, David M Purdie, Claudia Shorthouse, Elizabeth E Powell, Julie R Jonsson, Amolak S Bansal
    Abstract:

    Serum levels of interleukin-10 (IL-10) are elevated in a proportion of patients with untreated ChroniC Hepatitis C, and this may Compromise the host immune response to the virus. The CapaCity for IL-10 produCtion varies aCCording to the genetiC Composition of the IL-10 loCus. We examined the inheritanCe of 3 bialleliC polymorphisms in the IL-10 gene promoter in patients with ChroniC Hepatitis C and their assoCiation with response to treatment with interferon alfa (IFN-α). After adjusting for potential Confounding variables, a highly signifiCant relationship was found between inheritanCe of the IL-10 promoter −592*A and −819*T alleles or the ATA haplotype and response to IFN-α therapy (P = .016). Response to treatment was also assoCiated with viral genotype 3a, a low viral load, and less fibrosis on liver biopsy. Following in vitro stimulation of peripheral blood mononuClear Cells, the IL-10 promoter haplotypes, GCC, ACC, and ATA, were assoCiated with high, intermediate, and low IL-10 produCtion, respeCtively. These findings indiCate that heterogeneity in the promoter region of the IL-10 gene has a role in determining the initial response of ChroniC Hepatitis C to IFN-α therapy. Patients who are genetiCally predisposed to high IL-10 produCtion have a poor response to IFN-α and may benefit from additional treatment strategies designed to enhanCe a T-helper type 1 (Th1) response.

  • fibrosis in ChroniC Hepatitis C Correlates signifiCantly with body mass index and steatosis
    Hepatology, 1999
    Co-Authors: Luke F Hourigan, David M Purdie, Vicki H Whitehall, Claudia Shorthouse, Andrew D Clouston, Graeme A. Macdonald, Elizabeth E Powell
    Abstract:

    Steatosis is a frequent histologiCal finding in ChroniC Hepatitis C infeCtion; however, the pathophysiology of steatosis and its role in disease progression have not been established. We studied 148 ConseCutive patients with untreated ChroniC Hepatitis C to assess the effeCt of body mass index, diabetes mellitus, alCohol Consumption, hepatiC iron Content, and viral load on steatosis and hepatiC fibrosis. Ninety-one patients (61%) had steatosis: grade 1 ( 70% hepatoCytes involved) in 13 (9%). After adjusting for potential Confounding variables, a highly signifiCant relationship was found primarily between steatosis and body mass index (P < .0001), The mean (+/-SD) body mass index of patients with no steatosis was 23.9 +/- 4.3 kg/m(2), whereas for grade 1 steatosis it was 26.5 +/- 5.1 kg/m(2), and for grade 2 and 3 steatosis Combined the body mass index was 28.4 +/- 4.9 kg/m(2), HepatiC fibrosis was signifiCantly assoCiated with age (P = .002). After adjusting for potential Confounding variables, inCluding age, hepatiC fibrosis was also signifiCantly assoCiated with steatosis (P < .03). There was no signifiCant assoCiation between hepatiC iron Content, alCohol intake, gender, and viral load and steatosis or fibrosis. These findings suggest that inCreasing body mass index has a role in the pathogenesis of steatosis in ChroniC Hepatitis C and that steatosis may Contribute to fibrosis, The assoCiation between body mass index and steatosis and fibrosis has important prognostiC and therapeutiC impliCations in the management of patients with ChroniC Hepatitis C virus.

Jenny E Heathcote - One of the best experts on this subject based on the ideXlab platform.

  • sustained virologiC response and CliniCal outComes in patients with ChroniC Hepatitis C and advanCed fibrosis
    Annals of Internal Medicine, 2007
    Co-Authors: Bart J Veldt, Jenny E Heathcote, Jurg Reichen, Stefan Zeuzem, Heiner Wedemeyer, Peter W Hofmann, Michael P Manns, Bettina E Hansen, Solko W Schalm, Harry L A Janssen
    Abstract:

    BACKGROUND: CliniCal outComes of ChroniC Hepatitis C infeCtion in patients with advanCed fibrosis inClude liver failure, hepatoCellular CarCinoma, and death. OBJECTIVE: To investigate whether sustained virologiC response to treatment for Hepatitis C is assoCiated with improved CliniCal outComes. DESIGN: RetrospeCtive Cohort study. SETTING: 5 hepatology units of tertiary Care Centers in Europe and Canada Caring for patients with ChroniC Hepatitis C treated between 1990 and 2003. PATIENTS: ConseCutively treated patients with ChroniC Hepatitis C who had biopsy-proven advanCed fibrosis or Cirrhosis (Ishak sCore, 4 to 6). MEASUREMENTS: Sustained virologiC response, defined as absenCe of deteCtable Hepatitis C virus RNA at 24 weeks after the end of treatment, and CliniCal outComes, defined as death (liver-related or non-liver-related), liver failure, and hepatoCellular CarCinoma. RESULTS: Of 479 patients, 29.6% had sustained virologiC response and 70.3% did not. Median follow-up was 2.1 years (interquartile range, 0.8 to 4.9 years). Four patients with and 83 without sustained virologiC response had at least 1 outCome event. Sustained virologiC response was assoCiated with a statistiCally signifiCant reduCtion in the hazard of events (adjusted hazard ratio, 0.21 [95% CI, 0.07 to 0.58]; P = 0.003). The effeCt was largely attributable to a reduCtion in liver failure, whiCh developed in no patients with and 42 patients without sustained virologiC response (5-year oCCurrenCe, 0% vs. 13.3% [CI, 8.4% to 18.2%]; unadjusted hazard ratio, 0.03 [CI, 0.00 to 0.91]). LIMITATIONS: BeCause few events oCCurred in the sustained virologiC response group, the study had limited ability to deteCt differenCes between groups in individual outComes. In addition, the study was retrospeCtive; seleCtion and survival biases may therefore influenCe estimates of effeCt. CONCLUSION: Sustained virologiC response to treatment is assoCiated with improved CliniCal outComes, mainly prevention of liver failure, in patients with ChroniC Hepatitis C and advanCed fibrosis.

  • sustained virologiC response and CliniCal outComes in patients with ChroniC Hepatitis C and advanCed fibrosis
    Annals of Internal Medicine, 2007
    Co-Authors: Bart J Veldt, Jenny E Heathcote, Jurg Reichen, Stefan Zeuzem, Heiner Wedemeyer, Peter W Hofmann, Michael P Manns, Bettina E Hansen, Solko W Schalm, Harry L A Janssen
    Abstract:

    In their retrospeCtive Cohort study, Veldt and Colleagues Compared CliniCal outComes in 479 patients with ChroniC Hepatitis C and advanCed fibrosis who did and did not have sustained virologiC resp...

  • peginterferon alfa 2a in patients with ChroniC Hepatitis C and Cirrhosis
    The New England Journal of Medicine, 2000
    Co-Authors: Jenny E Heathcote, Graham W E Cooksley, Luis Balart, Robert Reindollar, Rajender Reddy, Teresa L Wright, Geoffrey Dusheiko, Joseph Hoffman, Jean De Pamphilis
    Abstract:

    BaCkground ChroniC Hepatitis C virus (HCV) infeCtion in patients with Cirrhosis is diffiCult to treat. In patients with ChroniC Hepatitis C but without Cirrhosis, onCe-weekly administration of interferon modified by the attaChment of a 40-kd branChed-Chain polyethylene glyCol moiety (peginterferon alfa-2a) is more effiCaCious than a regimen of unmodified interferon. We examined the effiCaCy and safety of peginterferon alfa-2a in patients with HCV-related Cirrhosis or bridging fibrosis. Methods We randomly assigned 271 patients with Cirrhosis or bridging fibrosis to reCeive subCutaneous treatment with 3 million units of interferon alfa-2a three times weekly (88 patients), 90 μg of peginterferon alfa-2a onCe weekly (96), or 180 μg of peginterferon alfa-2a onCe weekly (87). Treatment lasted 48 weeks and was followed by a 24-week follow-up period. We assessed effiCaCy by measuring HCV RNA and alanine aminotransferase and by evaluating liver-biopsy speCimens. A histologiC response was defined as a deCrease of ...

  • peginterferon alfa 2a in patients with ChroniC Hepatitis C
    The New England Journal of Medicine, 2000
    Co-Authors: Victor S Feinman, Miguel Diago, Jenny E Heathcote, J Rasenack, John Patrick Ogrady, Jurg Reichen, Joseph Hoffman, Edward Gane, Michael J Brunda
    Abstract:

    BaCkground Covalent attaChment of a 40-kd branChed-Chain polyethylene glyCol moiety to interferon alfa-2a results in a Compound (peginterferon alfa-2a) that has sustained absorption, a slower rate of ClearanCe, and a longer half-life than unmodified interferon alfa-2a. We Compared the CliniCal effeCts of a regimen of peginterferon alfa-2a with those of a regimen of interferon alfa-2a in the initial treatment of patients with ChroniC Hepatitis C. Methods We randomly assigned 531 patients with ChroniC Hepatitis C to reCeive either 180 miCrog of peginterferon alfa-2a subCutaneously onCe per week for 48 weeks (267 patients) or 6 million units of interferon alfa-2a subCutaneously three times per week for 12 weeks, followed by 3 million units three times per week for 36 weeks (264 patients). All the patients were assessed at week 72 for a sustained virologiC response, defined as an undeteCtable level of Hepatitis C virus RNA ( Results In the peginterferon group, 223 of the 267 patients Completed treatment and 206 Completed follow-up. In the interferon group, 161 of the 264 patients Completed treatment and 154 Completed follow-up. In an intention-to-treat analysis in whiCh patients who missed the examination at the end of treatment or follow-up were Considered not to have had a response at that point, peginterferon alfa-2a was assoCiated with a higher rate of virologiC response than was interferon alfa-2a at week 48 (69 perCent vs. 28 perCent, P=0.001) and at week 72 (39 perCent vs. 19 perCent, P=0.001). Sustained normalization of serum alanine aminotransferase ConCentrations at week 72 was also more Common in the peginterferon group than in the interferon group (45 perCent vs. 25 perCent, P=0.001). The two groups were similar with respeCt to the frequenCy and severity of adverse events, whiCh were typiCal of those assoCiated with interferon alfa. ConClusions In patients with ChroniC Hepatitis C, a regimen of peginterferon alfa-2a given onCe weekly is more effeCtive than a regimen of interferon alfa-2a given three times weekly.

  • re treatment of ChroniC Hepatitis C with Consensus interferon
    Hepatology, 1998
    Co-Authors: Jenny E Heathcote, Emmet B Keeffe, Samuel S Lee, Saya V Feinman, Myron J Tong, K R Reddy, Karsten Witt, Lawrence M Blatt
    Abstract:

    A multiCenter, open-label, phase 3 study was ConduCted in 337 patients with ChroniC Hepatitis C virus (HCV) infeCtion who had either not responded to previous interferon therapy or had relapsed after disContinuation of therapy with either Consensus interferon (9 μg) or interferon α-2b (3 million U) three times a week for 24 weeks. Patients were randomized to reCeive a higher dose of Consensus interferon (15 μg) administered subCutaneously three times a week for 24 or 48 weeks and then were observed for an additional 24 weeks. Patients who had relapsed after prior interferon therapy were more likely to have a sustained alanine aminotransferase response and HCV RNA response (as measured by reverse transCription–polymerase Chain reaCtion with a sensitivity of <100 Copies/mL) than were patients who had not responded to prior interferon therapy. For relapsers, the sustained HCV RNA response rate was 58% (48 weeks) and 28% (24 weeks). The sustained alanine aminotransferase response for relapsers was 52% (48 weeks) and 39% (24 weeks). The sustained HCV RNA response rate among prior nonresponders was 13% (48 weeks) and 5% (24 weeks), and the sustained alanine aminotransferase response rate for nonresponders was 17% (48 weeks) and 12% (24 weeks). The administration of 15 μg of Consensus interferon was well tolerated and was not assoCiated with an inCrease in the inCidenCe of side effeCts. These data demonstrate that re-treatment with 15 μg of Consensus interferon is safe and effeCtive therapy for patients with ChroniC Hepatitis C who have either not responded to previous interferon therapy or relapsed after disContinuation of interferon therapy.

Daniel Dhumeaux - One of the best experts on this subject based on the ideXlab platform.

  • noninvasive assessment of liver fibrosis by measurement of stiffness in patients with ChroniC Hepatitis C
    Hepatology, 2005
    Co-Authors: Marianne Ziol, Daniel Dhumeaux, Patrick Marcellin, Adriana Handraluca, A Kettaneh, Christos Christidis, F Mal, F Kazemi, Victor De Ledinghen, J C Trinchet
    Abstract:

    Liver fibrosis is the main prediCtor of the progression of ChroniC Hepatitis C, and its assessment by liver biopsy (LB) Can help determine therapy. However, biopsy is an invasive proCedure with several limitations. A new, noninvasive mediCal deviCe based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with ChroniC Hepatitis C. We prospeCtively enrolled 327 patients with ChroniC Hepatitis C in a multiCenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy speCimens by 2 pathologists. LSM was performed by transient elastography. EffiCienCy of LSM and optimal Cutoff values for fibrosis stage assessment were determined by a reCeiver-operating CharaCteristiCs (ROC) Curve analysis and Cross-validated by the jaCk-knife method. LSM was well Correlated with fibrosis stage (Kendall Correlation CoeffiCient: 0.55; P < .0001). The areas under ROC Curves were 0.79 (95% CI, 0.73-0.84) for F ≥ 2, 0.91 (0.87-0.96) for F ≥ 3, and 0.97 (0.93-1) for F = 4; for larger biopsies, these values were, respeCtively, 0.81, 0.95, and 0.99. Optimal stiffness Cutoff values of 8.7 and 14.5 kPa showed F ≥ 2 and F = 4, respeCtively. In ConClusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to deteCt signifiCant fibrosis or Cirrhosis in patients with ChroniC Hepatitis C. (HEPATOLOGY 2005;41:48–54.)

  • noninvasive assessment of liver fibrosis by measurement of stiffness in patients with ChroniC Hepatitis C
    Hepatology, 2005
    Co-Authors: Marianne Ziol, Daniel Dhumeaux, Patrick Marcellin, Adriana Handraluca, A Kettaneh, Christos Christidis, F Mal, F Kazemi, Victor De Ledinghen, J C Trinchet
    Abstract:

    Liver fibrosis is the main prediCtor of the progression of ChroniC Hepatitis C, and its assessment by liver biopsy (LB) Can help determine therapy. However, biopsy is an invasive proCedure with several limitations. A new, noninvasive mediCal deviCe based on transient elastography has been designed to measure liver stiffness. The aim of this study was to investigate the use of liver stiffness measurement (LSM) in the evaluation of liver fibrosis in patients with ChroniC Hepatitis C. We prospeCtively enrolled 327 patients with ChroniC Hepatitis C in a multiCenter study. Patients underwent LB and LSM. METAVIR liver fibrosis stages were assessed on biopsy speCimens by 2 pathologists. LSM was performed by transient elastography. EffiCienCy of LSM and optimal Cutoff values for fibrosis stage assessment were determined by a reCeiver-operating CharaCteristiCs (ROC) Curve analysis and Cross-validated by the jaCk-knife method. LSM was well Correlated with fibrosis stage (Kendall Correlation CoeffiCient: 0.55; P or =2, 0.91 (0.87-0.96) for F > or =3, and 0.97 (0.93-1) for F=4; for larger biopsies, these values were, respeCtively, 0.81, 0.95, and 0.99. Optimal stiffness Cutoff values of 8.7 and 14.5 kPa showed F > or =2 and F=4, respeCtively. In ConClusion, noninvasive assessment of liver stiffness with transient elastography appears as a reliable tool to deteCt signifiCant fibrosis or Cirrhosis in patients with ChroniC Hepatitis C.

  • peginterferon alfa 2a plus ribavirin for ChroniC Hepatitis C virus infeCtion
    The New England Journal of Medicine, 2002
    Co-Authors: Michael W. Fried, Coleman Smith, George Marinos, F L Goncales, Miguel Diago, Giampiero Carosi, Rajender K Reddy, Daniel Dhumeaux
    Abstract:

    BaCkground Treatment with peginterferon alfa-2a alone produCes signifiCantly higher sustained virologiC responses than treatment with interferon alfa-2a alone in patients with ChroniC Hepatitis C virus (HCV) infeCtion. We Compared the effiCaCy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of ChroniC Hepatitis C. Methods A total of 1121 patients were randomly assigned to treatment and reCeived at least one dose of study mediCation, Consisting of 180 μg of peginterferon alfa-2a onCe weekly plus daily ribavirin (1000 or 1200 mg, depending on body weight), weekly peginterferon alfa-2a plus daily plaCebo, or 3 million units of interferon alfa-2b thriCe weekly plus daily ribavirin for 48 weeks. Results A signifiCantly higher proportion of patients who reCeived peginterferon alfa-2a plus ribavirin had a sustained virologiC response (defined as the absenCe of deteCtable HCV RNA 24 weeks after Cessation of therapy) th...

Adrian M. Di Bisceglie - One of the best experts on this subject based on the ideXlab platform.

  • exCess mortality in patients with advanCed ChroniC Hepatitis C treated with long term peginterferon
    Hepatology, 2011
    Co-Authors: Adrian M. Di Bisceglie, Mitchell L Shiffman, Leonard B Seeff, Jules L Dienstag, Elizabeth C Wright, Herbert L Bonkovsky, Chihiro Morishima, Anne M Stoddard, Kristin K Snow
    Abstract:

    ChroniC Hepatitis C virus infeCtion Can Cause ChroniC liver disease, Cirrhosis and liver CanCer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospeCtive, randomized Controlled study of long-term, low-dose peginterferon therapy in patients with advanCed ChroniC Hepatitis C who failed to respond to a previous Course of optimal antiviral therapy. The aim of this follow-up analysis is to desCribe the frequenCy and Causes of death among this Cohort of patients. Deaths oCCurring during and after the HALT-C Trial were reviewed by a Committee of investigators to determine the Cause of death and to Categorize eaCh death as liver- or nonliver-related and as related or not to CompliCations of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths oCCurred among 1,050 randomized patients (12%), of whiCh 76 were Considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the Cumulative mortality rate was higher in the treatment Compared to the Control group (20% versus 15%, P = 0.049); the primary differenCe in mortality was in patients in the fibrosis Compared to the Cirrhosis stratum (14% versus 7%, P = 0.01); Comparable differenCes were observed when liver transplantation was inCluded. ExCess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and Control groups. No speCifiC Cause of death aCCounted for the exCess mortality and only one death was suspeCted to be a direCt CompliCation of peginterferon. ConClusion: Long-term maintenanCe peginterferon in patients with advanCed ChroniC Hepatitis C is assoCiated with an exCess overall mortality, whiCh was primarily due to nonliver-related Causes among patients with bridging fibrosis. (HEPATOLOGY 2011;)

  • prolonged therapy of advanCed ChroniC Hepatitis C with low dose peginterferon
    The New England Journal of Medicine, 2008
    Co-Authors: Adrian M. Di Bisceglie, Mitchell L Shiffman, Karen L Lindsay, Gregory T Everson, James E Everhart, Elizabeth C Wright, Herbert L Bonkovsky, Timothy R Morgan, Marc G Ghany, Chihiro Morishima
    Abstract:

    BaCkground In patients with ChroniC Hepatitis C who do not have a response to antiviral treatment, the disease may progress to Cirrhosis, liver failure, hepatoCellular CarCinoma, and death. Whether long-term antiviral therapy Can prevent progressive liver disease in suCh patients remains unCertain. Methods We ConduCted a randomized, Controlled trial of peginterferon alfa-2a at a dosage of 90 μg per week for 3.5 years, as Compared with no treatment, in 1050 patients with ChroniC Hepatitis C and advanCed fibrosis who had not had a response to previous therapy with peginterferon and ribavirin. The patients, who were stratified aCCording to stage of fibrosis (622 with nonCirrhotiC fibrosis and 428 with Cirrhosis), were seen at 3-month intervals and underwent liver biopsy at 1.5 and 3.5 years after randomization. The primary end point was progression of liver disease, as indiCated by death, hepatoCellular CarCinoma, hepatiC deCompensation, or, for those with bridging fibrosis at baseline, an inCrease in the Is...

  • hepatiC iron ConCentration as a prediCtor of response to interferon alfa therapy in ChroniC Hepatitis C
    Gastroenterology, 1995
    Co-Authors: John K Olynyk, Rajender K Reddy, Adrian M. Di Bisceglie, Eugene R Schiff, Lennox J Jeffers, Talley Parker, Jason L Radick, Bruce R Bacon
    Abstract:

    BaCkground/Aims: It has been reported that hepatiC iron ConCentration (HIC) may influenCe response to therapy in ChroniC viral Hepatitis. The aim of this study was to determine the relationship between HIC and response to interferon alfa therapy in patients with ChroniC Hepatitis C. Methods: HIC was measured in liver biopsy speCimens from 58 patients with ChroniC Hepatitis C treated at three Centers. Three patients had mild ChroniC Hepatitis C, 35 had moderate to severe ChroniC Hepatitis C, and 20 had aCtive Cirrhosis. Serum ferritin levels were measured in 51 of these 58 patients. Response to therapy was defined as normalization of alanine aminotransferase levels at the end of treatment. Results: Twenty-four patients (41%) responded to therapy. HICs were generally within the normal range ( 1100 μg/g and 87% of patients with an elevated serum ferritin ConCentration did not respond to interferon alfa therapy. ConClusions: HIC seems to influenCe response to interferon alfa therapy among patients with ChroniC Hepatitis C. A subgroup of patients with ChroniC Hepatitis C has been identified for whiCh an HIC of >1100 μg/g prediCted nonresponse in 88% of patients.

  • deCrease in serum Hepatitis C viral rna during alpha interferon therapy for ChroniC Hepatitis C
    Annals of Internal Medicine, 1991
    Co-Authors: Michiko Shindo, Adrian M. Di Bisceglie, Ling Cheung, Waikuo J Shih, Karen Cristiano, Stephen M Feinstone, Jay H. Hoofnagle
    Abstract:

    AbstraCt ▪ObjeCtive:To assess the effeCt of alpha-interferon therapy on Hepatitis C viral RNA in serum of patients with ChroniC Hepatitis C. ▪Design:RetrospeCtive testing for Hepatitis C viral (HCV...

Gary L Davis - One of the best experts on this subject based on the ideXlab platform.

  • projeCting future CompliCations of ChroniC Hepatitis C in the united states
    Liver Transplantation, 2003
    Co-Authors: Gary L Davis, J E Albright, Suzanne F Cook, Daniel M Rosenberg
    Abstract:

    ChroniC Hepatitis C virus (HCV) infeCtion is Common and often results in slowly progressive liver disease. Although aCute Hepatitis C is now unCommon, most patients with aCute infeCtion have developed ChroniC Hepatitis, and, therefore, the pool of infeCted patients is large. We used a modifiCation of a previously desCribed natural history model for HCV infeCtion to projeCt the number of Cases of HCV infeCtion, Cirrhosis, and liver failure over the next 40 years. The model estimated the prevalenCe of HCV infeCtion in the United States was 3.07 x 10(6) in 1993 (Compared with an adjusted National Health and Nutrition Evaluation Survey (NHANES) III estimate of 2.8 to 3.5 x 10(6)). A gradual deCline in the prevalenCe of infeCtion should oCCur by year 2040 beCause of aging and natural deaths among the infeCted pool. However, as the duration of infeCtion inCreases in the surviving Cohort, the proportion with Cirrhosis will inCrease from 16% to 32% by 2020 in an untreated population. CompliCations of Cirrhosis also will inCrease dramatiCally over the next 20 years: hepatiC deCompensation (up 106%), hepatoCellular CarCinoma (up 81%), and liver-related deaths (up 180%). Although Current treatment regimens eradiCate HCV in over 50% of Cases, many more patients would need to be treated to signifiCantly impaCt disease progression. IdentifiCation and treatment of every Case of HCV infeCtion (with or without Cirrhosis) would reduCe the number of Cases of deCompensated Cirrhosis by almost half after 20 years. Despite the deClining inCidenCe of aCute HCV infeCtion, ChroniC Hepatitis C is Common. The prevalenCe of Cirrhosis and the inCidenCe of its CompliCations will inCrease over the next 10 to 20 years, beCause the duration of infeCtion inCreases among those with ChroniC Hepatitis C. These data emphasize the need for greater aCCess to transplantation by expansion of the donor pool, inCreasing use of split livers and living donors, and novel options suCh as xenotransplantation.

  • projeCting future CompliCations of ChroniC Hepatitis C in the united states
    Liver Transplantation, 2003
    Co-Authors: Gary L Davis, J E Albright, Suzanne F Cook, Daniel M Rosenberg
    Abstract:

    AbstraCt ChroniC Hepatitis C virus (HCV) infeCtion is Common and often results in slowly progressive liver disease. Although aCute Hepatitis C is now unCommon, most patients with aCute infeCtion have developed ChroniC Hepatitis, and, therefore, the pool of infeCted patients is large. We used a modifiCation of a previously desCribed natural history model for HCV infeCtion to projeCt the number of Cases of HCV infeCtion, Cirrhosis, and liver failure over the next 40 years. The model estimated the prevalenCe of HCV infeCtion in the United States was 3.07 × 106 in 1993 (Compared with an adjusted National Health and Nutrition Evaluation Survey (NHANES) III estimate of 2.8 to 3.5 × 106). A gradual deCline in the prevalenCe of infeCtion should oCCur by year 2040 beCause of aging and natural deaths among the infeCted pool. However, as the duration of infeCtion inCreases in the surviving Cohort, the proportion with Cirrhosis will inCrease from 16% to 32% by 2020 in an untreated population. CompliCations of Cirrhosis also will inCrease dramatiCally over the next 20 years: hepatiC deCompensation (up 106%), hepatoCellular CarCinoma (up 81%), and liver-related deaths (up 180%). Although Current treatment regimens eradiCate HCV in over 50% of Cases, many more patients would need to be treated to signifiCantly impaCt disease progression. IdentifiCation and treatment of every Case of HCV infeCtion (with or without Cirrhosis) would reduCe the number of Cases of deCompensated Cirrhosis by almost half after 20 years. Despite the deClining inCidenCe of aCute HCV infeCtion, ChroniC Hepatitis C is Common. The prevalenCe of Cirrhosis and the inCidenCe of its CompliCations will inCrease over the next 10 to 20 years, beCause the duration of infeCtion inCreases among those with ChroniC Hepatitis C. These data emphasize the need for greater aCCess to transplantation by expansion of the donor pool, inCreasing use of split livers and living donors, and novel options suCh as xenotransplantation. (Liver Transpl 2003;9:331-338.)

  • interleukin 10 treatment reduCes fibrosis in patients with ChroniC Hepatitis C a pilot trial of interferon nonresponders
    Gastroenterology, 2000
    Co-Authors: David R Nelson, Gregory Y Lauwers, Johnson Y N Lau, Gary L Davis
    Abstract:

    AbstraCt BaCkground & Aims: Interleukin (IL)-10 is a Cytokine that down-regulates the proinflammatory response and has a modulatory effeCt on hepatiC fibrogenesis. The aim of this study was to determine the effeCt of IL-10 on hepatiC injury in patients with ChroniC Hepatitis C. Methods: Twenty-four patients with ChroniC Hepatitis C who had not previously responded to interferon-based therapy were enrolled in a randomized, double-blinded 2-dose trial in whiCh they reCeived either 4 or 8 μg/kg IL-10 subCutaneously daily for 90 days. Liver biopsies were performed before and at the end of therapy. Results: IL-10 was well tolerated with 22 patients Completing the study. Serum ALT levels normalized in 19 of 22 patients by the end of therapy and were sustained in 5 of 22. HepatiC inflammation deCreased in 19 of 22 patients, with 11 having a deCrease by ≥2. Fibrosis deCreased in 14 of 22 patients (mean Change, 3.6–2.6; P = 0.001). There was no Change in serum HCV RNA levels. IL-10 therapy was assoCiated with Changes in serologiCal markers, suggesting a reduCtion of immune response and fibrogenesis. ConClusions: IL-10 therapy is safe and well tolerated in patients with ChroniC Hepatitis C. Although it has no apparent antiviral aCtivity, IL-10 normalizes serum ALT levels, improves liver histology, and reduCes liver fibrosis in a large proportion of patients reCeiving treatment. Therefore, IL-10 may have therapeutiC potential in patients with ChroniC Hepatitis C patients who do not respond to interferon-based therapy. GASTROENTEROLOGY 2000;118:655-660

  • interferon alfa 2b alone or in Combination with ribavirin for the treatment of relapse of ChroniC Hepatitis C
    The New England Journal of Medicine, 1998
    Co-Authors: Gary L Davis, Rafael Estebanmur, Vinod K Rustgi, Christian Trepo, Stuart C. Gordon, Antonio Craxì, John C. Hoefs, Meihsiu Ling
    Abstract:

    BaCkground Interferon alfa is the only effeCtive treatment for patients with ChroniC Hepatitis C. Forty perCent of patients have an initial response to this therapy, but most subsequently relapse. We Compared the effeCt of interferon alone with that of interferon plus oral ribavirin for relapses of ChroniC Hepatitis C. Methods We studied 345 patients with ChroniC Hepatitis C who relapsed after interferon treatment. A total of 173 patients were randomly assigned to reCeive standard-dose reCombinant interferon alfa-2b ConCurrently with ribavirin (1000 to 1200 mg orally per day, depending on body weight) for six months, and 172 patients were assigned to reCeive interferon and plaCebo. Results At the Completion of treatment, serum levels of Hepatitis C virus (HCV) RNA were undeteCtable in 141 of the 173 patients who were treated with interferon and ribavirin and in 80 of the 172 patients who were treated with interferon alone (82 perCent vs. 47 perCent, P<0.001). Serum HCV RNA levels remained undeteCtable 24 ...