to the editor: I am quite apprehensive that your article1 on hepatitis C by Dr. Ward and colleagues will cause misconceptions for family physicians and may cause harm to our patients.
The article1 trumpets the efficaciousness of treatment of chronic hepatitis C. However, no justification for the repeated assertion of treatment effectiveness is offered. Treatment of hepatitis C does lower viral RNA loads, but I fear there is no evidence showing that treatment prevents cirrhosis, cancer, disability, and death. In lieu of outcomes evidence, what do experts say? The authors cited the consensus statement from the National Institutes of Health,2 which discusses only disease-oriented evidence regarding the benefit of hepatitis C treatment. My local gastroenterology colleagues have no patient-oriented outcome evidence to report either. Real patient benefit, such as reduced incidence of cancer, cirrhosis, disability, and death remains speculative and the topic of ongoing research.
Yet, we have plenty of patient-oriented outcome evidence showing how this supposedly effective treatment is toxic. In my own practice, I have several patients who have been harmed significantly by treatment for hepatitis C, with outcomes such as chronic spruelike enteropathy, myopathy, and depression.
No patient would tolerate cancer chemotherapy without the confidence that it improved their chance for better health. Yet, we are poisoning thousands of our patients who have hepatitis with just such a situation of known harm and uncertain benefits from treatment.
I have stopped referring my patients who have hepatitis C to gastroenterologists unless they enter a research protocol to help achieve patient-oriented outcome evidence. Until we have patient-oriented evidence that rates of cirrhosis and cancer are reduced with treatment, I do not feel that clear harm and no clear outcome benefit is acceptable.
in reply: While I agree with Dr. Steinberg that the pegylated interferon and ribavirin used in the treatment of patients with chronic hepatitis C are difficult agents to use, I disagree with his assertion that there is no evidence for improved patient outcomes with treatment.
Treatment not only “lowers viral RNA loads,” but, when successful, appears to eliminate viral RNA entirely. The published treatment response rate of approximately 50 percent is not measured at the end of treatment, but represents the percentage of patients in whom hepatitis C viral RNA continues to be undetectable six months after finishing medication. Follow-up of patients who are RNA negative at six months shows that only 5 to 10 percent of them have had a virologic relapse at five years, with virtually none of those recurrences occurring after year 4.1
Other studies2,3 have shown slowing and even regression of hepatic fibrosis, and a few of the patients in these studies actually regressed from cirrhosis to an earlier stage of fibrosis. Furthermore, among patients receiving treatment, even those who failed to achieve viral elimination showed a cessation of progression of fibrosis while being treated. Among patients who already have cirrhosis at the time of treatment initiation, therapy has been shown to improve survival (risk reduction [RR], 0.54; confidence interval [CI], 0.33 to 0.89) and to reduce the occurrence of hepatocellular carcinoma (RR, 0.65; CI, 0.43 to 0.97]).4
The National Institutes of Health consensus statement on the management of hepatitis C does not recommend that all patients with hepatitis C receive treatment, but rather states: “All patients with chronic hepatitis C are potential candidates for antiviral therapy. Treatment is recommended for patients with an increased risk of developing cirrhosis.”5 The decision to treat a patient with hepatitis C frequently is not an easy one and involves balancing the possibilities of cirrhosis, liver cancer, and death against the known side effects of the medications—side effects that, as Dr. Steinberg points out, occasionally may include serious toxicities. My own patient base includes those who have had substantial difficulties in tolerating pegylated interferon and ribavirin and those who have died from hepatitis C and its complications.
These medications are important advances in our ability to treat this illness, and I suspect that the data regarding their benefits are likely to continue to accumulate as longer-term outcome studies become available.