1. new WHO guidelines on screening, care, treatment of hep c (see here).
not much new, but reviews epidemiology, reinforces importance of testing and goes through some of the newer regimens (though these seem to change on a daily basis — see next 3 reviews below). they do add a nice global health perspective, including treatment in resource-poor countries. a few points:
–estimated 185M people worldwide with hep c (!!), 350,000 die each year. largest # people infected (>50M each) are in east asia and south asia
–(although i never thought i’d be able to say it) hep c differs from other chronic hepatitis infections because it can be cured, over 90% of the time!!!
–they suggest screening all people with high HCV prevalence or hx of possible exposure (note USPSTF suggests one-time screening of everyone born between 1945-65, since HCV prevalence in this age group is relatively high
–screen for alcohol use and advise reduction
–screen for liver fibrosis and cirrhosis. they give 2 pathways: for resource-limited settings, screen with APRI ((AST/ALT)/platelet ratio). or FIB4 (age x AST/plt). their Table 6.4 has the cutpoints for signficant cirrhosis and fibrosis (low quality evidence, conditional recommendation). some tests require special and expensive equipment (eg ultrasound-based transient elastography). still, liver bx does best.
–everyone (adults/kids) should be assessed for antiviral treatment.
–treatment with telaprevir or boceprevir, in combo with peg-interferon/ribivirin in genotype 1 over interferon/ribiv
–treat with sofosbuvir in combo with ribivirin +/- interferon depending on genotype,
–treat with simeprevir in combo with peg-interferon/ribivirin with genotype 1b or in those with genotype 1a but without Q80K polymorphism (these last 2 recommendations do not take resources into account, since pricing info internationally not available)
–hard to recommend one of the new therapies over another, since studies so far are from drug registration trials and no comparative outcome trials. and many of the prices for these new meds are not fixed yet.
–in terms of prioritizing this very expensive treatment: those with less advanced fibrosis respond to treatment best, BUT if treatment availability is limited, priority should be given to those with advanced fibrosis and cirrhosis [METAVIR stages F3 (numerous septa without cirrhosis) and F4 (cirrhosis)], since highest risk of developing cirrhosis and hepatocellular ca (ie, they respond somewhat less well but achieve the greatest benefit)
–their table 8.3 has drug-drug interactions between HIV and hep C meds. chapter 9 is for specific populations, with long section on HIV/hep c co-infection
2. shorter course treatment of genotype 1 infection in people without cirrhosis (see DOI: 10.1056/NEJMoa1402355). 647 treatment naive pts randomized to ledipasivir and sofosbuvir for 8 weeks, that combo plus ribivirin for 8 weeks, or the 3 drugs for 12 weeks. looked at sustained viral response (SVR) 12 weeks after completion of therapy. results:
–ledipasivir and sofosbuvir for 8 weeks: 94%
–ledipasivir and sofosbuvir with ribivirin for 8 weeks: 93%
–ledipasivir and sofosbuvir with ribivirin for 1 weeks: 95%
–more adverse effects (not shockingly) with ribivirin. no one in the first group stopped therapy because of adverse effects
3. treatment naive patients without cirrhosis, with genotype 1 and another interferon-free regimen, using ABT-450/ritonivir plus ombitasvir (ABT-267), plus dasabuvir (ABT-333) with ribivirin for 12 weeks (see DOI: 10.1056/NEJMoa1315722). 632 patients given the above regimen (a grand total of 3 pills/d!!) vs placebo. results:
–SVR of 96.2%. genotype 1a with 95.3% and genotype 1b with 98%
–rate of discontinuation 0.6% in each group. major adverse effects nausea, pruritus, insomnia, diarrhea, asthenia
4. same as the previous study, but in genotype 1 patients without cirrhosis who failed prior peginterferon/ribivirin treatment (see DOI: 10.1056/NEJMoa1401561). 394 pts randomized to above for 12 weeks, or placebo
–SVR 96.3% (which they compared to historical control of pts with genotype 1, no cirrhosis, failed peg-interferon/ribiv, and given telaprevir and peginterferon/ribivirin, who had 65% SVR)
–SVR was 100% in pts with partial response to prior peginterferon/ribivirin, and 95.2% in those with no response to that treatment
so, as an observer over time (as in, decades) and with lots of patients with hepatitis c, these results are really, really shocking. genotype 1 response before was in the 20+% range. seeing mid 90% with a couple of pills and almost no significant side-effects is awesome, in the strict sense of the word. the cost, availability, and actually showing this therapy works in larger populations (different ethnicities, co-infections, degrees of hepatic impairment) is still to come, however these are the advances we have been waiting for….