SIFACT - The current evidence on newest direct acting antivirals for hepatitis C:
a selection of primary references
By Chiumente M, De Rosa M.
(updated: 30 June 2015)
TOPIC: Achieving SVR predicts long-term survival benefits. ..................................................................... 1
TOPIC: Achieving SVR reduces the risk of hepatocellular carcinoma on the long term........................... 1
TOPIC: Delaying treatment determines unfavourable effects on extra-hepatic disease manifestations.2
TOPIC: Screening and epidemiology.......................................................................................................... 2
TOPIC: Effectiveness of the newest agents ............................................................................................... 3
TOPIC: Cost/effectiveness, cost of illness, criteria for patients’ prioritization to treatment .................... 3
TOPIC: Effectiveness of the newest agents in the real-world .................................................................. 4
TOPIC: Monitoring of real-life patients .................................................................................................... 5
TOPIC: Achieving SVR predicts long-term survival benefits.
Simmons B, Saleem J, Heath K, Cooke GS, Hill A. Long-term treatment outcomes of patients infected with Hepatitis C
virus: a systematic review and meta-analysis of the survival benefit of achieving a Sustained Virological Response. Clin
Infect Dis. 2015 May 17. pii: civ396. [Epub ahead of print]
TOPIC: Achieving SVR reduces the risk of hepatocellular carcinoma on the
long term.
Dohmen K, Kawano A, Takahashi K, Shigematsu H, Tanaka H, Haruno M, Yanagita K, Ichiki Y, Mori T, Hayashida K,
Shimoda S, Ishibashi H, Nomura H. The incidence and risk factors for the development of hepatocellular carcinoma
after peginterferon plus ribavirin therapy for chronic hepatitis C. Hepatogastroenterology. 2013 Nov-Dec;60(128):2034-
1
Morgan RL, Baack B, Smith BD, Yartel A, Pitasi M, Falck-Ytter Y. Eradication of hepatitis C virus infection and the
development of hepatocellular carcinoma: a meta-analysis of observational studies. Ann Intern Med. 2013 Mar 5;158(5
Pt 1):329-37.
TOPIC: Delaying treatment determines unfavourable effects on extra-hepatic
disease manifestations.
Gragnani L, Fognani E,1Alessia Piluso A, Boldrini B, Urraro T, Fabbrizzi A, Stasi C, Ranieri J, Monti M, Arena U,
Iannacone C, Laffi G, Zignego AL for the MaSVE Study Group. Long-Term Effect of HCV Eradication in Patients
With Mixed Cryoglobulinemia: A Prospective, Controlled, Open-Label, Cohort Study. Hepatology 2015;61:1145-1153.
Innes HA, McDonald SA, Dillon JF, Allen S, Hayes PC, Goldberg D, Mills PR, Barclay ST, Wilks D, Valerio H, Fox
R, Bhattacharyya D, Kennedy N, Morris J, Fraser A, Stanley AJ, Bramley P, Hutchinson SJ. Toward a more complete
understanding of the association between a hepatitis C sustained viral response and cause-specific outcomes.
Hepatology. 2015 Feb 26. doi: 10.1002/hep.27766. [Epub ahead of print] PubMed PMID: 25716707.
Lee MH, Yang HI, Lu SN, Jen CL, You SL, Wang LY, Wang CH, Chen WJ, Chen CJ; R.E.V.E.A.L.-HCV Study
Group. Chronic hepatitis C virus infection increases mortality from hepatic and extrahepatic diseases: a communitybased long-term prospective study. J Infect Dis. 2012 Aug 15;206(4):469-77.
van der Meer AJ. Association between antiviral treatment and extrahepatic outcomes in patients with hepatitis C virus
infection. Gut. 2015 Mar;64(3):364-6.
TOPIC: Screening and epidemiology
Ansaldi F, Bruzzone B, Salmaso S, Rota MC, Durando P, Gasparini R, Icardi G. Different seroprevalence and
molecular epidemiology patterns of hepatitis C virus infection in Italy. J Med Virol. 2005 Jul;76(3):327-32. PubMed
PMID: 15902713.
Cazzagon N, Trevisani F, Maddalo G, Giacomin A, Vanin V, Pozzan C, Poggio PD, Rapaccini G, Nolfo AM,
Benvegnù L, Zoli M, Borzio F, Giannini EG, Caturelli E, Chiaramonte M, Foschi FG, Cabibbo G, Felder M, Ciccarese
F, Missale G, Baroni GS, Morisco F, Pecorelli A, Farinati F; Italian Liver Cancer (ITA.LI.CA) Group. Rise and fall of
HCV-related hepatocellular carcinoma in Italy: a long-term survey from the ITA.LI.CA centres. Liver Int. 2013
Oct;33(9):1420-7. doi: 10.1111/liv.12208. Epub 2013 Jun 12. PubMed PMID: 23758775.
Crispo A, Barba M, Malvezzi M, Ciliberto G, Montella M. Mortality trend for liver cancer in a hyperendemic area of
hepatitis C virus infection in southern Italy: join-point analysis and comparison with European and Italian data. Eur J
Gastroenterol Hepatol. 2014 Feb;26(2):245-6. doi: 10.1097/MEG.0b013e32836506f1. PubMed PMID: 24366455.
Fabris P, Baldo V, Baldovin T, Bellotto E, Rassu M, Trivello R, Tramarin A, Tositti G, Floreani A. Changing
epidemiology of HCV and HBV infections in Northern Italy: a survey in the general population. J Clin Gastroenterol.
2008 May-Jun;42(5):527-32. doi:10.1097/MCG.0b013e318030e3ab. PubMed PMID: 18277889.
Fedeli U, Schievano E, Lisiero M, Avossa F, Mastrangelo G, Saugo M. Descriptive epidemiology of chronic liver
disease in northeastern Italy: an analysis of multiple causes of death. Popul Health Metr. 2013 Oct 10;11(1):20. doi:
10.1186/1478-7954-11-20. PubMed PMID: 24112320; PubMed Central PMCID:PMC3852117.
Guadagnino V, Stroffolini T, Caroleo B, Menniti Ippolito F, Rapicetta M, Ciccaglione AR, Chionne P, Madonna E,
Costantino A, De Sarro G, Focà A, Lentini M, Staltari O; Sersale's Study Group. Hepatitis C virus infection in an
endemic area of Southern Italy 14 years later: evidence for a vanishing infection. Dig Liver Dis. 2013 May;45(5):403-7.
doi:10.1016/j.dld.2012.10.014. Epub 2012 Nov PubMed PMID: 23199596.
Haley SJ, Kreek MJ. A window of opportunity: maximizing the effectiveness of new HCV regimens in the United
States with the expansion of the Affordable Care Act. Am J Public Health. 2015 Mar;105(3):457-63. doi:
10.2105/AJPH.2014.302327. Epub 2015 Jan 20. PubMed PMID: 25602859.
Ieluzzi D, Covolo L, Donato F, Fattovich G. Progression to cirrhosis, hepatocellular carcinoma and liver-related
mortality in chronic hepatitis B patients in Italy. Dig Liver Dis. 2014 May;46(5):427-32. doi:
10.1016/j.dld.2014.01.003. Epub 2014 Feb 16. PubMed PMID: 24548819.
2
Koretz RL, Lin KW, Ioannidis JP, Lenzer J. Is widespread screening for hepatitis C justified? BMJ. 2015 Jan
13;350:g7809. doi: 10.1136/bmj.g7809. PubMed, PMID: 25587052.
Marascio N, Liberto M, Barreca G, Zicca E, Quirino A, Lamberti A, Bianco G, Matera G, Surace L, Berardelli G,
Surace L, De Maria V, Giancotti F, Leone R, Villella V, Nisticò S, Borelli A, Caruso V, Calderazzo M, Griffo G,
Masciari R, Minchella P, Cosco L, Laganà C, Oliva A, Foti G, Fiorillo M, Bocchiaro G, Surace P, Ciccaglione A,
Ciccozzi M, Cesario F, Torti C, Focà A. Update on epidemiology of HCV in Italy: focus on the Calabria Region. BMC
Infect Dis. 2014;14 Suppl 5:S2. doi: 10.1186/1471-2334-14-S5-S2. Epub 2014 Sep 5. Review
Mariano A, Scalia Tomba G, Tosti ME, Spada E, Mele A. Estimating the incidence, prevalence and clinical burden of
hepatitis C over time in Italy. Scand J Infect Dis. 2009;41(9):689-99. doi: 10.1080/00365540903095358. PubMed
PMID: 19579149.
Montella M, Crispo A, Grimaldi M, Angeletti C, Amore A, Ronga D, Sabbatini M, Pisani A, Spiteri D, Serraino D.
Prevalence of hepatitis C virus infection in different population groups in southern Italy. Infection. 2005 Feb;33(1):912.
Puoti M, Girardi E. Chronic hepatitis C in Italy: the vanishing of the first and most consistent epidemic wave. Dig Liver
Dis. 2013 May;45(5):369-70. doi:10.1016/j.dld.2013.02.012. Epub 2013 Apr 6. PubMed PMID: 23567493.
Santantonio T, Medda E, Ferrari C, Fabris P, Cariti G, Massari M, Babudieri S, Toti M, Francavilla R, Ancarani F,
Antonucci G, Scotto G, Di Marco V, Pastore G, Stroffolini T. Risk factors and outcome among a large patient cohort
with community-acquired acute hepatitis C in Italy. Clin Infect Dis. 2006 Nov 1;43(9):1154-9. Epub 2006 Sep 27.
PubMed PMID: 17029134.
Stroffolini T, Sagnelli E, Mariano A, Craxí A, Almasio P; Italian Hospitals Collaborating Group. Characteristics of
HCV positive subjects referring to hospitals in Italy: a multicentre prevalence study on 6,999 cases. J Viral Hepat. 2006
May;13(5):351-4. PubMed PMID: 16637867.
Wray CM, Davis AM. Screening for hepatitis C. JAMA. 2015 May12;313(18):1855-6. doi: 10.1001/jama.2015.2833.
PubMed PMID: 25965235.
.
TOPIC: Effectiveness of the newest agents
European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J
Hepatol. 2015 Apr 21. pii: S0168-8278(15)00208-1. doi:10.1016/j.jhep.2015.03.025. [Epub ahead of print]
TOPIC: Cost/effectiveness, cost of illness, criteria for patients’ prioritization
to treatment
Chhatwal J, Kanwal F, Roberts MS, Dunn MA. Cost-effectiveness and budget impact of hepatitis C virus treatment
with sofosbuvir and ledipasvir in the United States. Ann Intern Med. 2015 Mar 17;162(6):397-406. doi: 10.7326/M141336.PubMed PMID: 25775312; PubMed Central PMCID: PMC4435698.
Colombo M. Interferon-free therapy for hepatitis C: The hurdles amid a golden era. Dig Liver Dis. 2015 Apr 11.
Etzion O, Ghany MG. A cure for the high cost of hepatitis C virus treatment. Ann Intern Med. 2015 May 5;162(9):6601.
Ghany MG. The ongoing debate of who to treat for chronic hepatitis C virus.
JAMA Intern Med. 2015 Feb;175(2):169-70
Lawson A; Trent Hepatitis C Study Group. Hepatitis C virus-infected patients with a persistently normal alanine
aminotransferase: do they exist and is this really a group with mild disease? J Viral Hepat. 2010 Jan;17(1):51-8. doi:
10.1111/j.1365-2893.2009.01148.x. Epub 2009 Jul 28. PubMed PMID: 19656289.
Leidner AJ, Chesson HW, Xu F, Ward JW, Spradling PR, Holmberg SD. Cost-effectiveness of hepatitis C treatment for
patients in early stages of liver disease. Hepatology 2015 Vol: 61 (6) :1860-1869. doi: 10.1002/hep.27736
3
Linas BP, Barter DM, Morgan JR, Pho MT, Leff JA, Schackman BR, Horsburgh CR, Assoumou SA, Salomon JA,
Weinstein MC, Freedberg KA, Kim AY. The cost-effectiveness of sofosbuvir-based regimens for treatment of hepatitis
C virus genotype 2 or 3 infection. Ann Intern Med. 2015 May 5;162(9):619-29.
Marcolongo M, Young B, Dal Pero F, Fattovich G, Peraro L, Guido M, Sebastiani G, Palù G, Alberti A. A seven-gene
signature (cirrhosis risk score) predicts liver fibrosis progression in patients with initially mild chronic hepatitis C.
Hepatology. 2009 Oct;50(4):1038-44. doi: 10.1002/hep.23111. PubMed PMID: 19676127.
Mennini FS. Health policy model: long term predictive results associated with the management of hepatitis C virus
induced diseases in Italy. Clinico Economics and Outcomes Research 2014;6:303–310.
Messori A. Letter: Estimating the cost-neutral price of sofosbuvir-based triple therapy for the treatment of naıve patients
with genotype 1 HCV infection in Italy Aliment Pharmacol Ther 2014;40:213-220
Najafzadeh M, Andersson K, Shrank WH, Krumme AA, Matlin OS, Brennan T, Avorn J, Choudhry NK. Costeffectiveness of novel regimens for the treatment of hepatitis C virus. Ann Intern Med. 2015 Mar 17;162(6):407-19.
doi:10.7326/M14-1152. PubMed PMID: 25775313.
Rein DB, Wittenborn JS, Smith BD, Liffmann DK, Ward JW. The Cost-effectiveness, Health Benefits, and Financial
Costs of New Antiviral Treatments for Hepatitis C Virus. Clin Infect Dis. 2015 Mar 16. pii: civ220.[Epub ahead of
print] 4 2.
Torres HA, Mahale P. Most patients with HCV-associated lymphoma present with mild liver disease: a call to revise
antiviral treatment prioritization. Liver Int. 2015 Jun;35(6):1661-4. doi: 10.1111/liv.12825. Epub 2015 Apr 5. PubMed
PMID:25779000.
Williams MJ, Lang-Lenton M; Trent HCV Study Group. Progression of initially mild hepatic fibrosis in patients with
chronic hepatitis C infection. J Viral Hepat. 2011 Jan;18(1):17-22. doi: 10.1111/j.1365-2893.2009.01262.x. PubMed
PMID:20088889.
TOPIC: To what extent are the newest treatments equi-effective with one
another?
European Association for the Study of the Liver. EASL Recommendations on Treatment of Hepatitis C 2015. J
Hepatol. 2015 Apr 21. pii: S0168-8278(15)00208-1. doi:10.1016/j.jhep.2015.03.025. [Epub ahead of print]
Feeney ER, Chung RT. Antiviral treatment of hepatitis C. BMJ. 2014 Jul 7;348:g3308. doi: 10.1136/bmj.g3308.
Review. PubMed PMID: 25002352.
Graham CS. Hepatitis C and HIV co-infection: closing the gaps. JAMA. 2015 Mar 24-31;313(12):1217-8. doi:
10.1001/jama.2015.1111. PubMed PMID: 25705993
Keating GM. Ledipasvir/Sofosbuvir: a review of its use in chronic hepatitis C.Drugs. 2015 Apr;75(6):675-85. doi:
10.1007/s40265-015-0381-2. PubMed PMID:25837989.
Kohli A, Shaffer A, Sherman A, Kottilil S. Treatment of hepatitis C: a systematic review. JAMA. 2014 Aug
13;312(6):631-40. doi: 10.1001/jama.2014.7085. Review. PubMed PMID: 25117132.
Pawlotsky JM. New hepatitis C therapies: the toolbox, strategies, and challenges. Gastroenterology. 2014
May;146(5):1176-92. doi:10.1053/j.gastro.2014.03.003. Epub 2014 Mar 12. Review. PubMed PMID: 24631495.
Trippoli S, Fadda V, Maratea D, Messori A. Bayesian network meta-analysis to evaluate interferon-free treatments in
naïve patients with genotype 1 HCV infection. Eur J Gastroenterol Hepatol. 2015 Aug;27(8):983-984.
TOPIC: Effectiveness of the newest agents in the real-world
4
Backus LI, Belperio PS, Shahoumian TA, Loomis TP, Mole LA. Effectiveness of sofosbuvir-based regimens in
genotype 1 and 2 hepatitis C virus infection in 4026 U.S. Veterans. Aliment Pharmacol Ther. 2015 Jun 26. doi:
10.1111/apt.13300. [Epub ahead of print] PubMed PMID: 26113432.
TOPIC: Monitoring of real-life patients
Messori A. Newest treatments for hepatitis C: how can we manage sustainability? Clinical Infectious Diseases 2015 (in
press), http://www.osservatorioinnovazione.net/papers/cid2015pricing.pdf
Messori A, Brunetto MR, De Luca A, Zignego AL Direct antiviral agents for treatment-naïve patients with genotype 1
hepatitis C: a statistical model for comparing outcomes between real world and clinical trials. Digestive Liver Disease
2015 (in press), available at www.osservatorioinnovazione.net/papers/dld-2015-bayes.pdf
NOTE – To ensure the scientific quality of these references, we have exclusively considered papers that met the
criterion of being published in peer-reviewed journal indexed in PubMed. Non sono stati presi in considerazione
i contributi/articoli autoreferenziali, privi di questi requisiti.
5
