Hepatitis C: What Therapy this Week?

“We really have entered this new era of direct acting antivirals, and as of this fall, we’ve finally laid to rest Interferon in the grave that we’ve all been wanting to put it in, for more than 2 decades,” said Jacqueline G. O’Leary, MD, MPH, AGAF, during her presentation at the 2015 AGA Clinical Congress of Gastroenterology & Hepatology.

According to O’Leary, sofosbuvir changed everything — a truly pangenotypic polymerase inhibitor (NSSB) prescribed as 400 mg daily, never modified with no significant food effect reported. It had recently been co-formulated with ledipasvir, the first-in-class NSSA inhibitor, once-daily dose, and also with no existing food effect.

In a key randomized controlled trial, patients receive sof/ledipasvir for 12 weeks versus 24 weeks, so you can treat patients, off-label, with 12 weeks, or on-label for 24 weeks.

Switching gears, O’Leary discussed the other FDA approved all oral regiment of paritapevir with ombitasvir and dasabuvir, for their genotype 1 patients. “This is a trick from HIV that allows lower dosing in medication, a dramatic increase in half-life, which adds an additional protection. This is binding against the thumb blood site, which definitely gets two thumbs up, because it allows you to give the finger to hepatitis C.”

“One dose keeps the ‘Hep C’ away,” quipped O’Leary.

Two key decisions to consider regarding paritapevir regiment were addressed:

1. How long do you treat patients? The vast majority of people get 12 weeks, except for genotype 1a cirrhotics, who can receive 24 weeks.

2. Whether or not you should require ribavirin, for everyone but non- cirrhotics.

In this regiment, research had reported the cure rate within a 12-week period was 95-98%. A series of trials conducted indicated that in their 1b patients, the cure rate was equivalent, which determined ribavirin was unnecessary. O’Leary noted the adverse effects to be insomnia, fatigue, headache, and diarrhea. But in general, this regiment was well tolerated.

Most physicians forayed into the Interferon free land prior to the FDA approval for all the regiments of genotype 1. Looking at sofosbuvir with second wave inhibitor, both dose once daily, regardless of ribavirin use, treatment history, and baseline cirrhosis, the results produced an 85% cure rate, which led to the FDA approval of this regiment.

Through physicians’ experiences with sofosbuvir, they were able to realize the difference between the varied genotypes, so they altered on-label treatment.

“So,” O’Leardy, asked, “what’s next?” She mused that it’d be nice if there were only one pill a day and experts didn’t have to cross-reference the genotype.

“Certainly it’s very exciting that these days we can achieve cure rates north 90%, in almost everyone which may leave us wondering if we’re all going to be in business in Hepatology anymore. But some of the dietary modifications as well as the behavioral modifications that are happening in the community certainly allow us to stay in business, forever,“ concluded O’Leary.