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Hepatitis C (HCV)

Level: Meta-analyses, Systematic reviews, Practice guidelines: 57 Abstracts

Legend: : Key Development,  : Very Important,  : Important, [no star]: Special Mention

 

Sofosbuvir and ledipasvir fixed-dose combination with and without ribavirin intreatment-naive and previously treated patients with genotype 1 hepatitis C virusinfection (LONESTAR): an open-label, randomised, phase 2 trial.
Lawitz E(1), Poordad FF(2), Pang PS(3), Hyland RH(3), Ding X(3), Mo H(3), SymondsWT(3), McHutchison JG(3), Membreno FE(2)., Lancet. 2014 Feb 8;383(9916):515-23. doi: 10.1016/S0140-6736(13)62121-2. Epub2013 Nov 5.

Comments: A fixed-dose combination of sofosbuvir (a nucleotide polymerase inhibitor, (400 mg) and the HCV NS5A inhibitor ledipasvir (90 mg), alone or with ribavirin can cure most patients with genotype-1 HCV, irrespective of treatment history or the presence of compensated cirrhosis.

 

New concepts of sofosbuvir-based treatment regimens in patients with hepatitis C.
Mariño Z(1), van Bömmel F, Forns X, Berg T., Gut. 2014 Feb;63(2):207-15. doi: 10.1136/gutjnl-2013-305771. Epub 2013 Nov 19.

 

Phase 2b trial of interferon-free therapy for hepatitis C virus genotype 1.
Kowdley KV(1), Lawitz E, Poordad F, Cohen DE, Nelson DR, Zeuzem S, Everson GT,Kwo P, Foster GR, Sulkowski MS, Xie W, Pilot-Matias T, Liossis G, Larsen L,Khatri A, Podsadecki T, Bernstein B., N Engl J Med. 2014 Jan 16;370(3):222-32. doi: 10.1056/NEJMoa1306227.

Comments: The protease inhibitor ABT-450 with ritonavir (ABT-450/r), the non-nucleoside polymerase inhibitor ABT-333, and ribavirin showed efficacy against the hepatitis C virus (HCV) in a pilot study involving patients with HCV genotype 1 infection.

 

Efficacy of an interferon- and ribavirin-free regimen of daclatasvir,asunaprevir, and BMS-791325 in treatment-naive patients with HCV genotype 1infection.
Everson GT(1), Sims KD(2), Rodriguez-Torres M(3), Hézode C(4), Lawitz E(5),Bourlière M(6), Loustaud-Ratti V(7), Rustgi V(8), Schwartz H(9), Tatum H(10),Marcellin P(11), Pol S(12), Thuluvath PJ(13), Eley T(2), Wang X(2), Huang SP(14),McPhee F(15), Wind-Rotolo M(14), Chung E(2), Pasquinelli C(2), Grasela DM(2),Gardiner DF(2)., Gastroenterology. 2014 Feb;146(2):420-9. doi: 10.1053/j.gastro.2013.10.057. Epub 2013 Oct 30.

Comments: The combination fo daclatasvir (NS5A replication complex inhibitor), asunaprevir (NS3 protease inhibitor), and BMS-791325 (a non-nucleoside NS5B inhibitor) all-oral, was well tolerated and achieved high rates of SVR12 in patients with HCV genotype 1 infection.

 

Daclatasvir plus sofosbuvir for previously treated or untreated chronic HCVinfection.
Sulkowski MS(1), Gardiner DF, Rodriguez-Torres M, Reddy KR, Hassanein T, JacobsonI, Lawitz E, Lok AS, Hinestrosa F, Thuluvath PJ, Schwartz H, Nelson DR, EversonGT, Eley T, Wind-Rotolo M, Huang SP, Gao M, Hernandez D, McPhee F, Sherman D,Hindes R, Symonds W, Pasquinelli C, Grasela DM; AI444040 Study Group., N Engl J Med. 2014 Jan 16;370(3):211-21. doi: 10.1056/NEJMoa1306218.

Comments: Daclatasvir (NS5A replication complex inhibitor) plus sofosbuvir (nucleotide analogue NS5B polymerase inhibitor) once-daily oral induced a 98% SVF at wk 12 patients infected with HCV genotype 1, 2, or 3.

 

Therapy for hepatitis C virus-related cryoglobulinemic vasculitis.
Dammacco F(1), Sansonno D., N Engl J Med. 2013 Sep 12;369(11):1035-45. doi: 10.1056/NEJMra1208642.

 

Sofosbuvir and ribavirin for hepatitis C genotype 1 in patients with unfavorable treatment characteristics: a randomized clinical trial.
Osinusi A(1), Meissner EG, Lee YJ, Bon D, Heytens L, Nelson A, Sneller M, KohliA, Barrett L, Proschan M, Herrmann E, Shivakumar B, Gu W, Kwan R, Teferi G,Talwani R, Silk R, Kotb C, Wroblewski S, Fishbein D, Dewar R, Highbarger H, ZhangX, Kleiner D, Wood BJ, Chavez J, Symonds WT, Subramanian M, McHutchison J, Polis MA, Fauci AS, Masur H, Kottilil S., JAMA. 2013 Aug 28;310(8):804-11. doi: 10.1001/jama.2013.109309.

Comments: Perspectives of interferon free treatment

 

Faldaprevir and deleobuvir for HCV genotype 1 infection.
Zeuzem S(1), Soriano V, Asselah T, Bronowicki JP, Lohse AW, Müllhaupt B,Schuchmann M, Bourlière M, Buti M, Roberts SK, Gane EJ, Stern JO, Vinisko R,Kukolj G, Gallivan JP, Böcher WO, Mensa FJ., N Engl J Med. 2013 Aug 15;369(7):630-9. doi: 10.1056/NEJMoa1213557.

Comments: idem

 

New horizons in hepatitis C antiviral therapy with direct-acting antivirals.
Aghemo A(1), De Francesco R., Hepatology. 2013 Jul;58(1):428-38. doi: 10.1002/hep.26371. Epub 2013 May 31.

Comments: Overview

 

Current and future therapies for hepatitis C virus infection.
Liang TJ, Ghany MG., N Engl J Med. 2013 May 16;368(20):1907-17. doi: 10.1056/NEJMra1213651.

Comments: Overview of treatment of HCV

 

Risk for immune-mediated graft dysfunction in liver transplant recipients withrecurrent HCV infection treated with pegylated interferon.
Levitsky J, Fiel MI, Norvell JP, Wang E, Watt KD, Curry MP, Tewani S, McCashland TM, Hoteit MA, Shaked A, Saab S, Chi AC, Tien A, Schiano TD., Gastroenterology. 2012 May;142(5):1132-1139.e1. doi:10.1053/j.gastro.2012.01.030. Epub 2012 Jan 25.

Comments: Patients with recurrent hepatitis C virus infection treated with PEG-IFN after liver transplantation can develop severe immune-mediated graft dysfunction (IGD) characterized by plasma cell hepatitis or rejection.It has a high morbidity and mortality and is not associated with increased rates of virologic response A high level of alkaline phosphatase at PEG initiation is a predictor.

 

The protease inhibitor, GS-9256, and non-nucleoside polymerase inhibitortegobuvir alone, with ribavirin, or pegylated interferon plus ribavirin inhepatitis C.
Zeuzem S, Buggisch P, Agarwal K, Marcellin P, Sereni D, Klinker H, Moreno C,Zarski JP, Horsmans Y, Mo H, Arterburn S, Knox S, Oldach D, McHutchison JG, MannsMP, Foster GR., Hepatology. 2012 Mar;55(3):749-58. doi: 10.1002/hep.24744.

Comments: In genotype 1 HCV, addition of RBV or RBV with Peg-IFN to combination therapy with tegobuvir (GS-9190), a non-nucleoside nonstructural protein (NS)5B polymerase inhibitor, and GS-9256, an NS3 serine protease inhibitorand GS-9256.provides additive antiviral activity.

 

Dual therapy with the nonstructural protein 5A inhibitor, daclatasvir, and thenonstructural protein 3 protease inhibitor, asunaprevir, in hepatitis C virusgenotype 1b-infected null responders.
Chayama K, Takahashi S, Toyota J, Karino Y, Ikeda K, Ishikawa H, Watanabe H,McPhee F, Hughes E, Kumada H., Hepatology. 2012 Mar;55(3):742-8. doi: 10.1002/hep.24724. Epub 2012 Jan 30.

Comments: Open-label, phase IIa study of 10 pts with chron HCV gt 1b and previous null response to Peg-IFN and RBV, received for 24 weeks combined the nonstructural protein 5A replication complex inhibitor, daclatasvir (60 mg once-daily), and the nonstructural protein 3 protease inhibitor, asunaprevir (initially 600 mg twice-daily, then reduced to 200 mg twice-daily). The 9 pts who completed 24 wks had HCV RNA undetectable at wk 8 and SVR( wk 12) and SVR(wk 24)

 

Treatment of chronic hepatitis C genotype 1 patients at an academic center inEurope involved in prospective, controlled trials: is there a selection bias?
Beinhardt S, Staettermayer AF, Rutter K, Maresch J, Scherzer TM, Steindl-Munda P,Hofer H, Ferenci P., Hepatology. 2012 Jan;55(1):30-8. doi: 10.1002/hep.24671. Epub 2011 Nov 30.

Comments: Study patients often show better baseline characteristics, but IL28B GT and treatment adherence were the most important factors determining outcome.

 

Serum ferritin levels are associated with a distinct phenotype of chronichepatitis C poorly responding to pegylated interferon-alpha and ribavirintherapy.
Lange CM, Kutalik Z, Morikawa K, Bibert S, Cerny A, Dollenmaier G, Dufour JF,Gerlach TJ, Heim MH, Malinverni R, Müllhaupt B, Negro F, Moradpour D, Bochud PY; Swiss Hepatitis C Cohort Study Group., Hepatology. 2012 Apr;55(4):1038-47. doi: 10.1002/hep.24787. Epub 2012 Feb 9.

Comments: In chronic HCV, elevated serum ferritin levels are independently associated with advanced liver fibrosis, hepatic steatosis, and poor response to interferon-alpha-based therapy.

  

Treatment for cryoglobulinemic and non-cryoglobulinemic peripheral neuropathy associated with hepatitis C virus infection.
Benstead TJ, Chalk CH, Parks NE., Cochrane Database Syst Rev. 2014 Dec 20;12:CD010404. doi: 10.1002/14651858.CD010404.pub2. Review.
Comments: About treatment of HCV related cryoglobulinemia

  

Relationship of vitamin D status with advanced liver fibrosis and response to hepatitis C virus therapy: a meta-analysis.
García-Álvarez M, Pineda-Tenor D, Jiménez-Sousa MA, Fernández-Rodríguez A, Guzmán-Fulgencio M, Resino S., Hepatology. 2014 Nov;60(5):1541-50. doi: 10.1002/hep.27281. Epub 2014 Sep 29.
Comments: Vitamin D in liver fibrosis and HCV

 

Eltrombopag increases platelet numbers in thrombocytopenic patients with HCVinfection and cirrhosis, allowing for effective antiviral therapy.
Afdhal NH(1), Dusheiko GM(2), Giannini EG(3), Chen PJ(4), Han KH(5), Mohsin A(6),Rodriguez-Torres M(7), Rugina S(8), Bakulin I(9), Lawitz E(10), Shiffman ML(11), Tayyab GU(12), Poordad F(10), Kamel YM(13), Brainsky A(14), Geib J(14), VaseySY(14), Patwardhan R(14), Campbell FM(13), Theodore D(15)., Gastroenterology. 2014 Feb;146(2):442-52.e1. doi: 10.1053/j.gastro.2013.10.012. Epub 2013 Oct 12.

Comments: Eltrombopag increases platelets in thrombocytopenic pts with HCV cirrhosis, allowing otherwise ineligible pts to begin and maintain antiviral therapy.

 

Effect of ribavirin on viral kinetics and liver gene expression in chronichepatitis C.
Rotman Y(1), Noureddin M, Feld JJ, Guedj J, Witthaus M, Han H, Park YJ, Park SH, Heller T, Ghany MG, Doo E, Koh C, Abdalla A, Gara N, Sarkar S, Thomas E,Ahlenstiel G, Edlich B, Titerence R, Hogdal L, Rehermann B, Dahari H, PerelsonAS, Hoofnagle JH, Liang TJ., Gut. 2014 Jan;63(1):161-9. doi: 10.1136/gutjnl-2012-303852. Epub 2013 Feb 8.

Comments: Ribavirin is a weak antiviral but its effect seems mediated by an indirect mechanism, which may act to reset IFN-responsiveness in HCV-infected liver.

 

Evaluation of liver disease progression in the German hepatitis C virus(1b)-contaminated anti-D cohort at 35 years after infection.
Wiese M(1), Fischer J, Löbermann M, Göbel U, Grüngreiff K, Güthoff W, Kullig U,Richter F, Schiefke I, Tenckhoff H, Zipprich A, Berg T, Müller T; East German HCVStudy Group., Hepatology. 2014 Jan;59(1):49-57. doi: 10.1002/hep.26644. Epub 2013 Nov 18.

Comments: The present study provides further evidence for a mild, but significant, disease progression at 35 yrs after infection in the German HCV (1b)-contaminated anti-D cohort.

 

The effects of female sex, viral genotype, and IL28B genotype on spontaneousclearance of acute hepatitis C virus infection.
Grebely J(1), Page K, Sacks-Davis R, van der Loeff MS, Rice TM, Bruneau J, MorrisMD, Hajarizadeh B, Amin J, Cox AL, Kim AY, McGovern BH, Schinkel J, George J,Shoukry NH, Lauer GM, Maher L, Lloyd AR, Hellard M, Dore GJ, Prins M; InC3 Study Group., Hepatology. 2014 Jan;59(1):109-20. doi: 10.1002/hep.26639. Epub 2013 Nov 22.

Comments: Female sex, favorable IL28B genotype, and HCV genotype 1 are independent predictors of spontaneous clearance of HCV.

 

Renal impairment is frequent in chronic hepatitis C patients under triple therapywith telaprevir or boceprevir.
Mauss S(1), Hueppe D, Alshuth U., Hepatology. 2014 Jan;59(1):46-8. doi: 10.1002/hep.26602. Epub 2013 Nov 11.

 

Cardiovascular diseases and HCV infection: a simple association or more?
Petta S(1), Macaluso FS, Craxì A., Gut. 2014 Mar;63(3):369-75. doi: 10.1136/gutjnl-2013-306102. Epub 2013 Dec 2.

 

The paradox of NKp46+ natural killer cells: drivers of severe hepatitis Cvirus-induced pathology but in-vivo resistance to interferon a treatment.
Pembroke T(1), Christian A, Jones E, Hills RK, Wang EC, Gallimore AM, Godkin A., Gut. 2014 Mar;63(3):515-24. doi: 10.1136/gutjnl-2013-304472. Epub 2013 May 11.

Comments: NKp46 marks out pathologically activated NK cells. Paradoxically these pathological NK cells do not appear to be involved in viral control in IFNa-treated individuals but predict slower rates of viral clearance.

 

Simeprevir increases rate of sustained virologic response amongtreatment-experienced patients with HCV genotype-1 infection: a phase IIb trial.
Zeuzem S(1), Berg T(2), Gane E(3), Ferenci P(4), Foster GR(5), Fried MW(6),Hezode C(7), Hirschfield GM(8), Jacobson I(9), Nikitin I(10), Pockros PJ(11),Poordad F(12), Scott J(13), Lenz O(14), Peeters M(14), Sekar V(15), De SmedtG(14), Sinha R(14), Beumont-Mauviel M(14)., Gastroenterology. 2014 Feb;146(2):430-41.e6. doi: 10.1053/j.gastro.2013.10.058.Epub 2013 Nov 1.

Comments: Simeprevir, an oral NS3/4 protease inhibitor in combination with peginterferon-a2a and ribavirin) significantly increased SVR at 24 wks in HCV genotype-1 previously treated with PegIFN and RBV.

 

Randomized controlled trial of danoprevir plus peginterferon alfa-2a andribavirin in treatment-naïve patients with hepatitis C virus genotype 1infection.
Marcellin P(1), Cooper C, Balart L, Larrey D, Box T, Yoshida E, Lawitz E,Buggisch P, Ferenci P, Weltman M, Labriola-Tompkins E, Le Pogam S, Nájera I,Thomas D, Hooper G, Shulman NS, Zhang Y, Navarro MT, Lim CY, Brunda M, TerraultNA, Yetzer ES., Gastroenterology. 2013 Oct;145(4):790-800.e3. doi: 10.1053/j.gastro.2013.06.051. Epub 2013 Jun 26.

Comments: Addition of danoprevir (a second-generation protease inhibitor) to PegIFN and RBV, led to increased viral eradication 85% with 600 mg vs. placebo (42%) but several pts had a reversible, grade 4 increase in alanine aminotransferase.

 

Optimizing ribavirin exposure by therapeutic drug monitoring improves treatmentresponse in patients with chronic hepatitis C genotype 1.
Stickel F, Worni M, Pache I, Moradpour D, Helbling B, Borovicka J, Gerlach TJ., Am J Gastroenterol. 2013 Jul;108(7):1176-8. doi: 10.1038/ajg.2013.140.

 

Liver stiffness is influenced by a standardized meal in patients with chronichepatitis C virus at different stages of fibrotic evolution.
Arena U(1), Lupsor Platon M, Stasi C, Moscarella S, Assarat A, Bedogni G,Piazzolla V, Badea R, Laffi G, Marra F, Mangia A, Pinzani M., Hepatology. 2013 Jul;58(1):65-72. doi: 10.1002/hep.26343. Epub 2013 May 27.

 

Sofosbuvir for previously untreated chronic hepatitis C infection.
Lawitz E, Mangia A, Wyles D, Rodriguez-Torres M, Hassanein T, Gordon SC, Schultz M, Davis MN, Kayali Z, Reddy KR, Jacobson IM, Kowdley KV, Nyberg L, Subramanian GM, Hyland RH, Arterburn S, Jiang D, McNally J, Brainard D, Symonds WT, McHutchison JG, Sheikh AM, Younossi Z, Gane EJ., N Engl J Med. 2013 May 16;368(20):1878-87. doi: 10.1056/NEJMoa1214853. Epub 2013 Apr 23.

Comments: Sofosbuvir combined with peginterferon-ribavirin in genotype 1 or 4 HCV: rate of sustained virologic response of 90% at 12 weeks

 

Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options.
Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, Nelson DR; POSITRON Study; FUSION Study., N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.

Comments: Sustained virologic response was 78% (95% confidence interval [CI], 72 to 83) with sofosbuvir and ribavirin in genotype 2 and 3,without interferon

 

HCV RNA viral load assessments in the era of direct-acting antivirals.
Cobb B, Pockros PJ, Vilchez RA, Vierling JM., Am J Gastroenterol. 2013 Apr;108(4):471-5. doi: 10.1038/ajg.2012.248.

Comments: Review of HCV RNA viral load results, analytical performance of the PCR assay and comparison of currently available commercial assays

 

Treatment of HCV infection by targeting microRNA.
Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, van derMeer AJ, Patick AK, Chen A, Zhou Y, Persson R, King BD, Kauppinen S, Levin AA, Hodges MR., N Engl J Med. 2013 May 2;368(18):1685-94. doi: 10.1056/NEJMoa1209026. Epub 2013Mar 27.

Comments: Miravirsen, a locked nucleic acid-modified DNA phosphorothioate antisense oligonucleotide that inhibits miR-122, showed prolonged dose-dependent reductions in HCV-RNA without evidence of viral resistance in genotype1

 

Effect of HCV infection on cause-specific mortality after HIV seroconversion,before and after 1997.
van der Helm J, Geskus R, Sabin C, Meyer L, Del Amo J, Chêne G, Dorrucci M, Muga R, Porter K, Prins M; CASCADE Collaboration in EuroCoord., Gastroenterology. 2013 Apr;144(4):751-760.e2. doi: 10.1053/j.gastro.2012.12.026. Epub 2012 Dec 22.

Comments: Individuals co-infected with HIV and HCV had a higher risk of death from HIV and/or AIDS, and from liver disease, than patients infected with only HIV

 

Vitamin B12 supplementation improves rates of sustained viral response inpatients chronically infected with hepatitis C virus.
Rocco A, Compare D, Coccoli P, Esposito C, Di Spirito A, Barbato A, Strazzullo P, Nardone G., Gut. 2013 May;62(5):766-73. doi: 10.1136/gutjnl-2012-302344. Epub 2012 Jul 17.

Comments: In vitro, vitamin B12 acts as a natural inhibitor of HCV replication.Vit B12 supplementation significantly improves SVR rates in HCV-infected patients naïve to antiviral therapy.

 

Hepatitis C virus testing of persons born during 1945-1965: recommendations from the Centers for Disease Control and Prevention.
Smith BD, Morgan RL, Beckett GA, Falck-Ytter Y, Holtzman D, Ward JW., Ann Intern Med. 2012 Dec 4;157(11):817-22.

Comments: 1: Adults born during 1945 to 1965 should receive 1-time testing for HCV 2: All persons identified with HCV infection should receive a brief alcohol screening and intervention, followed by referral to appropriate care and treatment services for HCV infection.

 

Genomics and HCV infection: progression of fibrosis and treatment response.
Estrabaud E, Vidaud M, Marcellin P, Asselah T., J Hepatol. 2012 Nov;57(5):1110-25. doi: 10.1016/j.jhep.2012.05.016. Epub 2012 May 30.

Comments: Review of the genomic factors (mRNAs, miRNAs, and SNPs) and of the IL-28B polymorphism that are implicated in the progression of fibrosis or treatment response in HCV are outlined.

 

Update on the management and treatment of hepatitis C virus infection:recommendations from the Department of Veterans Affairs Hepatitis C ResourceCenter Program and the National Hepatitis C Program Office.
Yee HS, Chang MF, Pocha C, Lim J, Ross D, Morgan TR, Monto A; Department ofVeterans Affairs Hepatitis C Resource Center Program; National Hepatitis CProgram Office., Am J Gastroenterol. 2012 May;107(5):669-89; quiz 690. doi: 10.1038/ajg.2012.48.

Comments: Recommendations from the Department of Veterans Affairs Hepatitis C Resource Center Program and the National Hepatitis C Program Office for the management of HCV.

 

Review and management of drug interactions with boceprevir and telaprevir.
Kiser JJ, Burton JR, Anderson PL, Everson GT., Hepatology. 2012 May;55(5):1620-8. doi: 10.1002/hep.25653.

Comments: Important review of the pharmacologic characteristics and drug-interaction potential of BOC and TPV and guidance on the management of drug interactions with these agents.

 

Preliminary study of two antiviral agents for hepatitis C genotype 1.
Lok AS, Gardiner DF, Lawitz E, Martorell C, Everson GT, Ghalib R, Reindollar R, Rustgi V, McPhee F, Wind-Rotolo M, Persson A, Zhu K, Dimitrova DI, Eley T, Guo T, Grasela DM, Pasquinelli C., N Engl J Med. 2012 Jan 19;366(3):216-24. doi: 10.1056/NEJMoa1104430.

 

Effect of IL28B genotype on early viral kinetics during interferon-free treatmentof patients with chronic hepatitis C.
Chu TW, Kulkarni R, Gane EJ, Roberts SK, Stedman C, Angus PW, Ritchie B, Lu XY, Ipe D, Lopatin U, Germer S, Iglesias VA, Elston R, Smith PF, Shulman NS., Gastroenterology. 2012 Apr;142(4):790-5. doi: 10.1053/j.gastro.2011.12.057. Epub 2012 Jan 13.

Comments: IL28B genotype appears to affect early Viral kinetics in patients with chronic hepatitis C receiving interferon-free treatment

 

Prediction of response to pegylated interferon plus ribavirin in HIV/hepatitis C virus (HCV)-coinfected patients using HCV genotype, IL28B variations, and HCV-RNAload.
Neukam K, Camacho A, Caruz A, Rallón N, Torres-Cornejo A, Rockstroh JK, Macías J, Rivero A, Benito JM, López-Cortés LF, Nattermann J, Gómez-Mateos J, Soriano V, Pineda JA., J Hepatol. 2012 Apr;56(4):788-94. doi: 10.1016/j.jhep.2011.11.008. Epub 2011 Dec 13.

Comments: The combination of IL28B genotype, HCV genotype, and HCV-RNA load enables to identify patients with a high and very low likelihood of SVR. HCV therapy could be deferred in the latter patients

 

Hepatitis C viral kinetics with the nucleoside polymerase inhibitor mericitabine (RG7128).
Guedj J, Dahari H, Shudo E, Smith P, Perelson AS., Hepatology. 2012 Apr;55(4):1030-7. doi: 10.1002/hep.24788. Epub 2012 Feb 15.

Comments: Mericitabine (RG7128) is a nucleoside polymerase inhibitor for HCV. Mathematical modeling has provided important insights for characterizing hepatitis C virus (HCV) RNA decline

 

Quantitative liver function tests improve the prediction of clinical outcomes in chronic hepatitis C: results from the Hepatitis C Antiviral Long-term TreatmentAgainst Cirrhosis Trial.
Everson GT, Shiffman ML, Hoefs JC, Morgan TR, Sterling RK, Wagner DA, Lauriski S, Curto TM, Stoddard A, Wright EC; HALT-C Trial Group., Hepatology. 2012 Apr;55(4):1019-29. doi: 10.1002/hep.24752. Epub 2012 Mar 1.

Comments: In HCV not responding to a classical treatment period, Peg-INF maintenance therapy failed to improve any of a battery of serially performed Quantitative Liver Function Tests. However of these QLFTs, cholate clearance and measurement of the perfused liver mass were able to predict the ultimate clinical outcome in 227 fibrotic/cirrhotic patients.

 

Effects of anti-viral therapy and HCV clearance on cerebral metabolism andcognition.
Byrnes V, Miller A, Lowry D, Hill E, Weinstein C, Alsop D, Lenkinski R, Afdhal NH., J Hepatol. 2012 Mar;56(3):549-56. doi: 10.1016/j.jhep.2011.09.015. Epub 2011 Oct 23.

Comments: HCV eradication showed a beneficial effect on cerebral metabolism as measured by Fifteen non-cirrhotic HCV positive subjects underwent (1)H MR spectroscopy in 15 non-cirrhotic HCV positive subjects.

 

Early changes in interferon signaling define natural killer cell response andrefractoriness to interferon-based therapy of hepatitis C patients.
Edlich B, Ahlenstiel G, Zabaleta Azpiroz A, Stoltzfus J, Noureddin M, Serti E, Feld JJ, Liang TJ, Rotman Y, Rehermann B., Hepatology. 2012 Jan;55(1):39-48. doi: 10.1002/hep.24628. Epub 2011 Nov 14.

Comments: IFN-a-induced modulation of STAT1/4 phosphorylation underlies the polarization of NK cells toward increased cytotoxicity and decreased IFN-? production in HCV infection, ashowing that NK cell responsiveness and refractoriness correlate to the antiviral effectiveness of IFN-a-based therapy.

 

Relative performances of FibroTest, Fibroscan, and biopsy for the assessment ofthe stage of liver fibrosis in patients with chronic hepatitis C: a step towardthe truth in the absence of a gold standard.
Poynard T, de Ledinghen V, Zarski JP, Stanciu C, Munteanu M, Vergniol J, France J, Trifan A, Le Naour G, Vaillant JC, Ratziu V, Charlotte F; Fibrosis-TAGS group., J Hepatol. 2012 Mar;56(3):541-8. doi: 10.1016/j.jhep.2011.08.007. Epub 2011 Sep1.

Comments: Liver fibrosis stage was assessed in1289 patients with CHC and 604 healthy volunteers: for advanced fibrosis, the specificity/sensitivity was for FibroTest 0.93/0.70, liver stiffness measurement (LSM) using Fibroscan 0.96/0.45, ALT 0.79/0.78 and biopsy 0.67/0.63, and for cirrhosis FibroTest 0.87/0.41, LSM 0.93/0.39, ALT 0.78/0.08 and biopsy 0.95/0.51

 

Viral clearance is associated with improved insulin resistance in genotype 1chronic hepatitis C but not genotype 2/3.
Thompson AJ, Patel K, Chuang WL, Lawitz EJ, Rodriguez-Torres M, Rustgi VK,Flisiak R, Pianko S, Diago M, Arora S, Foster GR, Torbenson M, Benhamou Y, NelsonDR, Sulkowski MS, Zeuzem S, Pulkstenis E, Subramanian GM, McHutchison JG;ACHIEVE-1 and ACHIEVE-2/3 Study Teams., Gut. 2012 Jan;61(1):128-34. doi: 10.1136/gut.2010.236158. Epub 2011 Aug 26.

Comments: SVR is associated with a reduction in HOMA-IR in patients with HCV genotype 1 but not in those with genotype 2/3. Genotype 1 may have a direct effect on the development of IR, independent of host metabolic factors, and may be partially reversed by viral eradication.

 

Interventions for dialysis patients with hepatitis C virus (HCV) infection.
Prabhu RA, Nair S, Pai G, Reddy NP, Suvarna D., Cochrane Database Syst Rev. 2015 Aug 19;8:CD007003. doi: 10.1002/14651858.CD007003.pub2. Review.

 

Hepatitis C genotype 1 virus with low viral load and rapid virologic response to peginterferon/ribavirin obviates a protease inhibitor.
Pearlman BL(1), Ehleben C., Hepatology. 2014 Jan;59(1):71-7. doi: 10.1002/hep.26624. Epub 2013 Nov 18.

Comments: Protease inhibitor therapy could be obviated in genotype 1-infected treatment-na?ve patients with low viral load at baseline who achieve undetectable viremia after 4 weeks of peginterferon/ribavirin.