Rapid Responses to:

CLINICAL REVIEW: Paul J Gow and David Mutimer Regular review: Treatment of chronic hepatitis BMJ 2001; 323: 1164-1167 [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

Hepatitis C -- to tret or not to treat?

Mikhaylo Nabatoff   (18 November 2001)

Treatment of hepaitis-B: inaccuracies

Stephen Malnick   (25 November 2001)

Competing interest

Abbas Zagnoon   (26 November 2001)

ECONOMIC APPROPRIATENESS OF THE EXPENDITURE FOR LAMIVUDINE IN HEPATITIS B: ANALYSIS OF NATIONAL PRESCRIPTION DATA IN ITALY

Cecilia Orsi, Franca Vacca   (20 May 2004)

Hepatitis C -- to tret or not to treat? 18 November 2001
Mikhaylo Nabatoff, Head of the CCU Kherson Infectious Hospital, ul.Begmy 1A, Kherson, 73000, Ukraine Send response to journal: Re: Hepatitis C -- to tret or not to treat?	EDITOR -- The excellent review by Paul J Gow and David Mutimer was published In this number of BMJ about treatment of chronic hepatitis 1. By coincidence, The New England Journal of Medicine printed the paper about treatment of viral hepatitis C (VH C) this week too (there was early release on www.nejm.org a while ago) and editorial on this subject 2,3. There are some discrepancies concerning the natural history of viral hepatitis C infections in this articles. Author in New England Journal of Medicine argues, that the rate of progression of VH C to chronic infection may be artificially high, that in some populations lower rates of chronic infections are reported and long term follow up of young adults with acute hepatitis C demonstrated little morbidity and virtually no deaths from chronic liver disease during the first two decades of infections. In contrast, the paper in BMJ states, that natural history of VH C is well studied (?) and the rate of chronic infection and terminal liver disease is quite high. Paul J Gow and David Mutimer state: All patients with evidence of chronic infection who are likely to be compliant with 6­12 months of intense medical therapy should be referred to an appropriate specialist for consideration of treatment. Is their statement evidence-based? Should the compliance with the treatment be the main predictor to interferon/ribavirin therapy? We in Ukraine already got most important criterion for electing the patients with VH C infection to treat — the personal wealth of the infected. Not many infected people can afford interferon, and almost nobody — ribavirin. May be substantial proportion of VH C infected patients will get the benefits of no treatment — in terms of cost effectiveness and the absence of complications. Should there be some more definite criteria to elect HCV patients for treatment. Mikhaylo S. Nabatoff 1. Treatment of chronic hepatitis Paul J Gow, David Mutimer BMJ2001;323:1164–7 2. Treatment of Acute Hepatitis C with Interferon Alfa-2b E. Jaeckel and Others N Engl J Med 2001;345:1452-7. 3. Therapy for Acute Hepatitis C Therapy for Acute Hepatitis C J. H. Hoofnagle N Engl J Med 2001;345: 1495
Treatment of hepaitis-B: inaccuracies 25 November 2001
Stephen Malnick, Head, Department of Internal Medicine C Kaplan Medical Center, Rehovot 76100, Israel Send response to journal: Re: Treatment of hepaitis-B: inaccuracies	Sir, We found several disagreements between the recommendations of the authors and current recommendations for the treatment of chronic HBV hepatitis in the review by Gow and Mutimer (BMJ 17th November). The dose of interferon recommended by the authors is 5 million units 3 times per week for four to 6 months. They state that "response rates are increased by higher doses but the safety and tolerability of high dose interferon are a concern". The management of hepatitis B was reviewed last year in a 3 day workshop at the NIH and has recently been published 1. The recommendations for treatment of HBV hepatitis is 5 MU daily or 10 MU 3 times per week for 16 weeks. The impression we got from the article was that the treatment of choice for chronic HBV hepatitis is lamivudine whereas the recommendation from the NIH workshop is "lamivudine monotherapy should be reserved for patients with moderate-to-severe disease". The review article is also inaccurate regarding the combination of lamivudine and interferon. The statement that "initial studies… suggest that this treatment has greater efficacy than either drug alone" is at a complete disagreement with the recommendation from the workshop "thus, the 3 published trials of combination therapy provide little support for the use of interferon- lamivudine combination instead of monotherapy". We feel that the review of Gow and Mutimer is inaccurate regarding the current recommendations for chronic HBV hepatitis and that physicians who are not specialists in this field should receive a more balanced set of guidelines. Stephen DH Malnick MA(Oxon) MSc MBBS(Lond) Dept. Internal Medicine C Marc Beergabel MD. Institute of Gastroenterology and Hepatology 1 Lok AS, Heathcote EJ, Hoofnagle JH. Management of Hepatitis B: 2000. Summary of a workshop. Gastroenterology 2001;120:1828-53.
Competing interest 26 November 2001
Abbas Zagnoon, Consultant Gastroenterologist/Hepatologist King faisal specialist Hospital and research center, Jeddah, saudi arabia Send response to journal: Re: Competing interest	I am glad that BMJ does request declaration of competing interest. The first author of the article; PJG is honest enough to declare such competing interest. This may have influenced his strong favor of lamivudine for the treatment of hepatitis B. I would have looked at his recommendation with greater respect had he mentioned the advantages and disadvanteges of both options; lamivudine Vs Interferon. Also the recommended dose of Interferon for Hep B is either 5 million daily OR 10 million thrice weekly.
ECONOMIC APPROPRIATENESS OF THE EXPENDITURE FOR LAMIVUDINE IN HEPATITIS B: ANALYSIS OF NATIONAL PRESCRIPTION DATA IN ITALY 20 May 2004
Cecilia Orsi, researcher Laboratorio SIFO di Farmacoeconomia, c/o Azienda Ospedaliera Careggi, 50132 Firenze, Italy, Franca Vacca Send response to journal: Re: ECONOMIC APPROPRIATENESS OF THE EXPENDITURE FOR LAMIVUDINE IN HEPATITIS B: ANALYSIS OF NATIONAL PRESCRIPTION DATA IN ITALY	In reviewing the treatments for hepatits B, Gow and Mutimer (1) have examined the data that support the effectiveness of lamivudine (given alone or in combination with interferon). Since Gow's review is focused on clinical effects, in this Rapid Response we have evaluated the cost- effectiveness of this drug. In patients with chronic hepatitis B, lamivudine (at the oral dosage of 100 mg once daily) has been shown to improve liver istology, suppress replication of HBV and reduce serum viral load (1-3).The results of controlled clinical trials indicate that one year of lamivudine therapy in patients with HBeAg-positive chronic hepatitis B results in HBeAg seroconversion rates similar to those obtained with a standard course of interferon-a. Moreover, results after two or three years of lamivudine therapy show that the cumulative HBeAg seroconversion rate continues to increase with extended lamivudine therapy (3,4), even though a prolonged treatment increases the probability of drug resistance. To interpret the data of yearly Italian expenditure (EXPEND) of lamivudine prescribed to adult patients with chronic hepatitis B, we have used the method previously used by Messori et al. (5-14) that assigns an index of "economic appropriateness" to the treatment under examination. This method is based on the comparison between the health gain theoretically expected from EXPEND (according to current cost effectiveness benchmarks, EHG) and the amount of health that is estimated to be gained in the real patients (real health gain, RHG). The final index is calculated as RHG/EHG. In Italy, a total of 7,288,632 Euros have been spent in 2003 on lamivudine for the treatment of chronic hepatitis B. Using the benchmark of 10,000 euros per life year gained the EHG is 729 life years (729 years = 7,288,632 years /10,000 Euros per life year). The value of quality-adjusted survival gain per patient resulting from lamivudine therapy is estimated from the unadjusted survival gain of 3.02 years per patient (age = 30 years) calculated by Orlewska (15) and from the utility value of 0.611 reported by Crowley et al. (16). The quality-adjusted gain is therefore equal to 1.84 quality-adjusted life years (QALYs) per patient (1.84 = 3.02 x 0.611). The same figure for a patient aged 50 is 0.98 QALYs per patient (survival gain =1.6 years per patient; 0.98 = 1.6 x 0.611). The number of Italian patients who have been started on lamivudine therapy in 2003 is estimated to be 6,166 (assumptions used for this estimation: EXPEND = 7,288,632 Euros; average treatment duration = 1 year; yearly cost of lamivudine therapy = 1182 Euros per patient; 50% discount of lamivudine price for hospitals according to the Italian regulation; total consumption of lamivudine as 86.1% for outpatients plus 13.9% for inpatients and subjects referred to day-hospitals). Hence, RHG is 11,345 or 6,043 QALYs in individuals aged 30 or 50, respectively (where: 11,345 = 6,166 x 1.84 and 6,043 = 6,166 x 0.98). Comparing EHG with RHG gives a favourable ratio (ratio of RHG/EHG = 15.6 or 8.3 in patients aged 30 or 50, respectively). Therefore, our analysis produces a favourable pharmacoeconomic profile of lamivudine because RHG is, in both cases, greater than EHG. Our method has several limitations. For example, the value of utility reported by Crowley et al. (16) (and obtained within a sponsored study) is extremely favourable, and this has probably contributed to overestimating the value of RHG. Anyhow, our study has determined the "economic appropriateness” of lamivudine alone given to patients with chronic hepatitis B using the best scientific information presently available. This information is original because the only pharmacoeconomic study conducted so far on this subject (16) (using common currencies such as dollars or Euros), evaluated interferon alone as well as the combination of interferon plus lamivudine, but not the treatment with lamivudine alone. REFERENCES 1 Gow PJ, Mutimer D. Treatment of chronic hepatitis. BMJ 2001;323:1164-7. 2 Lai C-L, Leung NW, et.al. A one-year trial of lamivudine for chronic hepatitis B. N Engl J Med 1998; 339:61-8. 3 Ganem D, Prince AM. Hepatitis B virus infection-natural history and linacal consequences. N Engl J >Med. 2004 Mar 11;350(11):1118-29. 4 Dixon JS, Boeheme RE. Lamivudine of chronic hepatitis B. Acta Gastroenterol Belg. 2000 Oct-Dec;63(4):348-56. 5 Messori A, Pelagotti F, Vacca F, Pascal M. Clinical-economic appropriateness of trastuzumab in the treatment of breast cancer with her2 overexpression: analysis of national prescription data in Italy http://bmj.com/cgi/eletters/321/7261/644#54155. 6 Messori A et al. Economic appropriateness of the expenditure for lendronate: cost-effectiveness analysis of national prescription data in Italy. http://bmj.com/cgi/eletters/327/7406/89#40333. 7 Santarlasci B, Trippoli S, Messori A. Economic appropriateness of the >expenditure for beta-interferon in multiple sclerosis: analysis of national >prescription data in Italy. http://bmj.bmjjournals.com/cgi/eletters/326/7388/522#46835. 8 Cecchi M, Pelagotti F, Santarlasci B, Trippoli S, Brutti C, Messori A. Economic appropriateness of the expenditure for infliximab in rheumatoid arthritis: analysis of national prescription data in Italy. http://bmj.com/cgi/eletters/324/7333/312#44561. 9 Santarlasci B, Brutti C, Messori A. Economic appropriateness of the expenditure for aromatase inhibitors: analysis of national prescription data in Italy. http://bmj.com/cgi/eletters/327/7420/885#47864. 10 Messori A et al. Economic appropriateness of the expenditure for coxibs: cost-effectiveness analysis of national prescription data in Italy. http://bmj.com/cgi/eletters/327/7420/933-b#39700. 11 Santarlasci B. Economic appropriateness of national drug expenditures: improved estimation of cost-effectiveness ranking for coxibs. http://bmj.com/cgi/eletters/327/7420/933-b#42273. 12 Messori A et al. Spending on statins. http://bmj.com/cgi/eletters/327/7420/933-b#38400. 13 Messori A et al. Questionable cost-effectiveness of statins for primary prevention of cardiovascular events. http://bmj.com/cgi/eletters/326/7404/1407#34612. 14 Vacca F et al. Cost effectiveness of statins in men vs women. http://bmj.com/cgi/eletters/327/7420/933-b#39209. 15 Orlewska E. The cost-effectiveness of alternative therapeutic strategies for the management of chronic hepatitis B in Poland. Value Healt. 2002 Sept-Oct; 5(5):404-20 16 Crowley SJ, Tognarini D, Desmond PV, Lees M. Cost-effectiveness analysis of lamivudine for the treatment of chronic hepatitis B. Pharmacoeconomics 2000 May;17(5):409-427 Competing interests: None declared