Why a new oral therapy for hepatitis C may be a game changer

May 1, 2014

The looming promise of a well-tolerated and extremely effective oral agent to eradicate HCV infection is exciting, as it offers the possibility of eliminating this disease as a significant public health problem, as well as the albeit uncommon ophthalmic manifestations.

By Peter J. McDonnell, MD

A recent study-conducted in Spain, England, Germany and the United States-has reported remarkable success with an oral therapy for hepatitis C.1 The study included more than 200 people with infection severe enough to cause cirrhosis of the liver. After 12 weeks of treatment, 191 of 208 (92%) recipients were found to be free of infection, and the success rate after 24 weeks of treatment increased to 165 of 172 (96%) subjects. Reported side effects were fatigue, headache, and nausea.

This is a game changer. Hepatitis C is remarkably prevalent in the United States, with close to 4 million people infected. According to the Centers for Disease Control, infection is most prevalent among Americans born between 1945 and 1965. About 20,000 people are estimated to be newly infected each year, with 75% to 85% of those infections becoming chronic. Patients suffer from both hepatic and extra-hepatic manifestations, and the risk of transmission via bodily fluids, caregivers via needle sticks, and contamination of the blood supply have been problems.

Current therapies have been limited by the combination of unimpressive efficacy and impressive side effects, as well as very high cost. About 1% to 5% of people with chronic HVC infection will die from either the cirrhosis or liver cancer.

 

Hepatitis C can have ophthalmic manifestations, although they are either very rare or not always recognized (or both). Zegans et al2 report that “the ocular manifestations of HCV infections best supported by the literature include a dry eye syndrome similar to Sjögren’s syndrome, and ischemic retinopathy.”

Whether the ischemic retinopathy occurs as the consequence of HCV-induced micro vascular pathology or the interferon used to treat the infection is uncertain; some have found evidence that both mechanisms may be operative.3

Diabetics are reportedly more susceptible to interferon retinopathy and to subsequent permanent visual loss. There have been no cases of HCV transmission via corneal transplantation, suggesting that protocols requiring the screening of potential donors are effective in preventing this route of transmission or that the avascular cornea is not a preferred site for the virus to take up residence. HCV RNA can be found in only about one-fourth of corneas from sero-positive cadavers.4

 

Zegan and colleagues recommend consideration of screening for HCV in patients with risk factors for HCV infection who suffer from unexplained ischemic retinopathy or dry eyes. While the recommendation related to the retinopathy makes sense to me, the prevalence of “unexplained dry eyes” is so high in our population that the cost-effectiveness of such a recommendation is unclear.

The looming promise of a well-tolerated and extremely effective oral agent to eradicate HCV infection is exciting, as it offers the possibility of eliminating this disease as a significant public health problem, as well as the albeit uncommon ophthalmic manifestations.

References

1.      Afdhal N, et al. N Engl J Med. 2014 April 11 [epub ahead of print].

2.     Zegans ME, et al. Curr Opinion Ophthalmol. 2002;13:423-427.

3.     Pazienza Z. Biomed Pharmacother. 2011;65:317-318.

4.     Lee HM et al. Cornea. 2001;20:37-40.

 

 

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