Sofosbuvir with pegylated interferon alfa-2a and ribavirin for treatment-naive patients with hepatitis C genotype-1 infection (ATOMIC): an open-label, randomised, multicentre phase 2 trial.
Kowdley KV, Lawitz E, Crespo I, Hassanein T, Davis MN, Demicco M, Bernstein DE, ...
Lancet. 2013 Mar 14. [Epub ahead of print]
Rating & Commentary
** Results from the largest randomized phase 2 in 316 HCV genotype 1 and 16 genotype 4 or 6 patients confirm the high efficacy (85-90% SVR) with 12 weeks of sofosbuvir containing regimens as well as the good tolerability of sofosbuvir.

Treatment of HCV Infection by Targeting MicroRNA.
Janssen HL, Reesink HW, Lawitz EJ, Zeuzem S, Rodriguez-Torres M, Patel K, ...
N Engl J Med. 2013 Mar 27. [Epub ahead of print]
Rating & Commentary
** The propagation of HCV is dependent on an interaction between the virus and liver-expressed microRNA-122 (miR-122).This study assesses the safety and efficacy of miravirsen, the first antisense oligonucleotide against miR-122 to enter clinical development. Thirty-six treatment-naïve chronic HCV genotype 1 infected patients were randomly assigned to receive five weekly s.c. injections of miravirsen at 3 different doses or placebo over a 29-day period. The mean maximum HCV RNA reduction from baseline was 1.2 log IU/mL in the 3mg group, 2.9 in the 5 mg group and 3.0 in the 7 mg group (P<0.01 compared to 0.4 in the placebo group). HCV RNA negativity was occurred in 5 miravirsen-treated patients. There were no dose-limiting adverse events. This study shows the potential of miRNA targeted therapy, not only for patients with chronic HCV infection but also for other disease in which miRNAs play a role.

A phase 2a trial of 12-week interferon-free therapy with two direct-acting antivirals (ABT-450/r, ABT-072) and ribavirin in IL28B C/C patients with chronic hepatitis C genotype 1.
Lawitz E, Poordad F, Kowdley KV, Cohen DE, Podsadecki T, Siggelkow S, Larsen L, ...
J Hepatol. 2013 Feb 22. [Epub ahead of print]
Rating & Commentary
** This phase 2a study evaluated the safety and efficacy of an interferon-free antiviral regimen containing ABT-450 (an HCV NS3 protease inhibitor), ABT-072 (a NS5B polymerase inhibitor) and ribavirin. Eleven treatment-naïve HCV genotype 1 patients were included; ten patients (91%) achieved SVR 24 post-treatment. Adverse events were mild. This study confirms that interferon-free regimens have the potential to cure a large proportion of HCV genotype 1 infected patients.

Long-term outcome of chronic hepatitis C after sustained virological response to interferon-based therapy.
Koh C, Heller T, Haynes-Williams V, Hara K, Zhao X, Feld JJ, Kleiner DE, Rotman Y, ...
Aliment Pharmacol Ther. 2013 May;37:887-94.
Rating & Commentary
* This single center study in 103 patients with SVR followed from 1984 to 2003 confirms a more than 95% durability of SVR, and no evidence of disease progression although a low risk for hepatocellular carcinoma persists.

Comparative effectiveness of antiviral treatment for hepatitis C virus infection in adults: a systematic review.
Chou R, Hartung D, Rahman B, Wasson N, Cottrell EB, Fu R.
Ann Intern Med. 2013 Jan 15;158:114-23.
Rating & Commentary
* This systematic review confirms that SVR rates for genotype 1 infection are higher with triple therapy that includes a protease inhibitor than with standard dual therapy, and that SVR after antiviral therapy is associated with improved clinical outcomes.

Lack of clinical and histological progression of chronic hepatitis C in individuals with true persistently normal ALT: the result of a 17-year follow-up.
Nunnari G, Pinzone MR, Cacopardo B.
J Viral Hepat. 2013 Apr;20:e131-7.
Rating & Commentary
* Thirty to 40% of patients with chronic hepatitis C have persistently normal alanine aminotransferase (PNALT). Some experts consider them as healthy people, but others disagree since most PNALT carriers actually have some degree of histological liver damage. This study carried out between 1994 and 2011 followed 70 PNALTs and 55 HCV infected patients with elevated alanine aminotransferase (H-ALT). In the PNALT group, none of the patients developed hepatic decompensation, while 14% of ALTs were affected by decompensated cirrhosis. No significant variation of the Metavir scores was observed among PNALTs; on the contrary, a significant increase in Metavir scores was noticed within the H-ALT group.

Screening for hepatitis B and C in first-generation Egyptian migrants living in the Netherlands.
Zuure FR, Bouman J, Martens M, Vanhommerig JW, Urbanus AT, Davidovich U, ...
Liver Int. 2013 May;33:727-38.
Rating & Commentary
* This Dutch study evaluated an HCV- and HBV-screening program to identify  infections among asymptomatic first-generation Egyptian migrants in Amsterdam. Screening sessions held at Egyptian meeting places detected HCV antibodies in 11/465 (2%) migrants had; 10/11 were HCV RNA positive, all with HCV genotype 4. 9/10 chronic HCV infections were newly diagnosed.

Earlier Sustained Virologic Response Endpoints for Regulatory Approval and Dose Selection of Hepatitis C Therapies.
Chen J, Florian J, Carter W, Fleischer RD, Hammerstrom TS, Jadhav PR, Zeng W, ...
Gastroenterology. 2013 Mar 4. [Epub ahead of print]
Rating & Commentary
* This study combined data from 15 phase II and III trials assessing interferon-based antiviral therapy to determine the concordance between HCV RNA negativity at 24 weeks and 12 weeks after cessation of antiviral therapy (SVR24 and SVR12 respectively). Overall, the positive predictive value of SVR12 was 98% and the negative predictive value (NPV) was 99% for SVR24.

Liver injury and disease pathogenesis in chronic hepatitis C.
Yamane D, McGivern DR, Masaki T, Lemon SM.
Curr Top Microbiol Immunol. 2013;369:263-88.
Rating & Commentary
* Review of chronic hepatitis C infection with regard to molecular mechanisms responsible for virus-induced changes affecting both the liver and other organs, including those of the endocrine, hematopoietic, and nervous systems.

Regression of Hodgkin lymphoma in response to antiviral therapy for hepatitis C virus infection.
Takahashi K, Nishida N, Kawabata H, Haga H, Chiba T.
Intern Med. 2012;51:2745-7.
Rating & Commentary
* Report of the first documented case of a patient with HCV-associated Hodgkin lymphoma who showed a marked regression following interferon-based antiviral therapy.