Letters to the Editor
Additional Letters to the Editor Available Online:
Influence of Video Games on Children's Health Adam Dimitrov, M.D.
Population-Based Strategy to Reverse the Obesity Epidemic Kathleen McAuliffe, M.D., M.P.H.
Benefit vs. Harm of Treatment of Chronic Hepatitis C
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 sprue-like 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.
REFERENCES
1. Ward RP, Kugelmas M, Libsch KD. Management of hepatitis C: evaluating suitability for drug therapy. Am Fam Physician 2004;69:1429-38.
2. NIH consensus statement on management of hepatitis C: 2002. NIH Consens State Sci Statements 2002;19:1-46.
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.
REFERENCES
1. Veldt BJ, Saracco G, Boyer N, Camma C, Bellobuono A, Hopf U, et al. Long term clinical outcome of chronic hepatitis C patients with sustained virological response to interferon monotherapy. Gut 2004;53:1504-8.
2. Abergel A, Darcha C, Chevallier M, Ughetto S, Henquell C, Pol S, et al; French Multicentre Study Group. Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis. Eur J Gastroenterol Hepatol 2004;16:1219-27.
3. Arif A, Levine RA, Sanderson SO, Bank L, Velu RP, Shah A, et al. Regression of fibrosis in chronic hepatitis C after therapy with interferon and ribavirin. Dig Dis Sci 2003;48:1425-30.
4. Shiratori Y, Ito Y, Yokosuka O, Imazeki F, Nakata R, Tanaka N, et al; Tokyo-Chiba Hepatitis Research Group. Antiviral therapy for cirrhotic hepatitis C: association with reduced hepatocellular carcinoma development and improved survival. Ann Intern Med 2005;142:105-14.
5. NIH consensus statement on management of hepatitis C: 2002. NIH Consens State Sci Statements 2002;19:1-46.
Treating Children with Obstructive Sleep Apnea
TO THE EDITOR: I would like to comment on a few points raised by the authors of "Obstructive Sleep Apnea in Children,”1 in American Family Physician. First, they state that "in children, an apnea-hypopnea index greater than 1…is considered abnormal.”1 This is incorrect: the study2 the authors cited clearly states that the recommended normal value of apnea index (not apnea-hypopnea index) is less than or equal to 1. The normal value of apnea-hypopnea index has not been established for children even though hypopnea is as important as apnea. Apnea-hypopnea index values of 5, 10, 15, 20, and 30 were used as definitions of obstructive sleep apnea in children.3 Using an apnea-hypopnea index greater than 1 as the definition of obstructive sleep apnea is not supported by the current evidence. The authors1 commented that adenotonsillectomy has been shown to improve weight problems. This is certainly true for failure to thrive, but not for obesity. It has been well documented that obesity often worsens after adenotonsillectomy.4,5 Hence, dietary and exercise advice is an essential component in managing children who are obese and have obstructive sleep apnea. One study6 reported resolution of sleep apnea after weight loss in five children who were morbidly obese.
REFERENCES
1. Chan J, Edman JC, Koltai PJ. Obstructive sleep apnea in children. Am Fam Physician 2004;69:1147-54.
2. Marcus CL, Omlin KJ, Basinki DJ, Bailey SL, Rachal AB, Von Pechmann WS, et al. Normal polysomnographic values for children and adolescents. Am Rev Respir Dis 1992;146(5 pt 1):1235-9.
3. Redline S, Sanders M. Hypopnea, a floating metric: implications for prevalence, morbidity estimates, and case findings. Sleep 1997;20:1209-17.
4. Marcus CL, Carroll JL, Koerner CB, Hamer A, Lutz J, Loughlin GM. Determinants of growth in children with the obstructive sleep apnea syndrome. J Pediatr 1994;125:556-62.
5. Soultan Z, Wadowski S, Rao M, Kravath RE. Effect of treating obstructive sleep apnea by tonsillectomy and/or adenoidectomy on obesity in children. Arch Pediatr Adolesc Med 1999;153:33-7.
6. Willi SM, Oexmann MJ, Wright NM, Collop NA, Key LL Jr. The effects of a high-protein, low-fat, ketogenic diet on adolescents with morbid obesity: body composition, blood chemistries, and sleep abnormalities. Pediatrics 1998;101(1 pt 1):61-7.
IN REPLY: As seen in previous studies,1,2 episodes of complete airway obstruction in children are relatively uncommon. Obstructive sleep apnea may manifest mainly as hypopneas and continuous hypoventilation with partial cessation of airflow. Therefore, incorporating information about hypopneas may be as important as data on apneas. Hopefully, further research in this area will lead to clearer guidelines regarding hypopneas and apneas.
We agree that adenotonsillectomy has been shown to be effective in improving weight in children with failure to thrive and not in children with obesity.3,4 It is stated in several places in our article5 that medical management of obesity may benefit the overweight child and potentially resolve their obstructive sleep apnea.5,6
REFERENCES
1. Marcus CL, Omlin KJ, Basinki DJ, Bailey SL, Rachal AB, Von Pechmann WS, et al. Normal polysomnographic values for children and adolescents. Am Rev Respir Dis 1992;146(5 pt 1):1235-9.
2. Uliel S, Tauman R, Greenfeld M, Sivan Y. Normal polysomnographic respiratory values in children and adolescents. Chest 2004;125:872-8.
3. Mitchell RB and Kelly J. Adenotonsillectomy for obstructive sleep apnea in obese children. Otolaryngol Head Neck Surg 2004;131:104-8.
4. Soultan Z, Wadowski S, Rao M, Kravath RE. Effect of treating obstructive sleep apnea by tonsillectomy and/or adenoidectomy on obesity in children. Arch Pediatr Adolesc Med 1999;153:33-7.
5. Chan J, Edman JC, Koltai PJ. Obstructive sleep apnea in children. Am Fam Physician 2004;69:1147-54.
6. Willi SM, Oexmann MJ, Wright NM, Collop NA, Key LL Jr. The effects of a high-protein, low-fat, ketogenic diet on adolescents with morbid obesity: body composition, blood chemistries, and sleep abnormalities. Pediatrics 1998;101(1 pt 1):61-7.
Send letters to Jay Siwek, M.D., Editor, American Family Physician, 11400 Tomahawk Creek Pkwy., Leawood, KS 66211-2672; fax: 913-906-6080; e-mail: afplet@aafp.org.
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