Electronic letters to:

Review:
Tom Wong and Samuel S. Lee
Hepatitis C: a review for primary care physicians
CMAJ 2006; 174: 649-659 [Abstract] [Full text] [PDF]
*eLetters: Submit a response to this article

Electronic letters published:

[Read eLetter] Are liver biopsy and viral load measurement really unnecessary in HCV genotype 2 or 3?
Michal R. Pijak   (19 April 2006)
[Read eLetter] Hepatitis C and urticarial syndromes
Sujoy Khan   (6 April 2006)
[Read eLetter] Asia cannot ignore the dangers of the hidden epidemic- Hepatitis C
Prof. Govindasamy Agoramoorthy   (6 March 2006)

Are liver biopsy and viral load measurement really unnecessary in HCV genotype 2 or 3? 19 April 2006
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Michal R. Pijak
Department of Internal Medicine, University Hospital, 833 05 Bratislava, Slovakia

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Re: Are liver biopsy and viral load measurement really unnecessary in HCV genotype 2 or 3?

r.pijak{at}zutom.sk Michal R. Pijak

As Wong and Lee (1) mention in their article about hepatitis C, patients with genotype 2 or 3 (G-2/3) are, indeed, expected to have a high likelihood of treatment success (75-85%). However, the conclusion that these patients " ... therefore may not require a liver biopsy and do not require a baseline viral load measurement." seems premature.

Firstly, several clinical trials and one systematic review demonstrated decreased likelihood of a sustained virological response (SVR) in G-2/3 patients with advanced fibrosis.(2,3,4,5) Others, however, were unable to reproduce these findings, probably because such patients are often underrepresented in clinical trials.(6,7) Importantly, there are also evolving studies showing that steatosis is additional independent predictor of SVR in G-2/3 patients.(7,8,9) Interestingly, findings in G-3 patients indicate that only metabolic but not viral steatosis is associated with lower SVR.(10)

Secondly, current evidence suggests that among G-3 patients viral load is an important predictor of both SVR(4,7,11,12) and early virological response (EVR) (4). Moreover, patients with HCV G-2/3 and EVR at week 4 required shorter courses of therapy (12-16 weeks) which were as effective as the recommended course of 24 weeks. (4,11,12) Whether G-2/3 patients with high viral load and/or absence of EVR (with or without unfavourable histology ) may benefit from longer treatment should be investigated in further clinical trials.

Thus it appears that both baseline histology and viral load may be a useful guide to tailoring the treatment in certain subgroups of patients with HCV G-2/3 in whom standard therapy duration might be over- treatment.

References

1. Wong T, Lee SS. Hepatitis C: a review for primary care physicians. CMAJ 2006;174:649-59.

2. Gebo KA, Herlong HF, Torbenson MS, Jenckes MW, Chander G, Ghanem KG, et al. Role of liver biopsy in management of chronic hepatitis C: a systematic review. Hepatology 2002;36:S161-72.

3. Poynard T, McHutchison J, Goodman Z, Ling MH, Albrecht J. Is an "a la carte" combination interferon alfa-2b plus ribavirin regimen possible for the first line treatment in patients with chronic hepatitis C? The ALGOVIRC Project Group. Hepatology 2000;31:211-8. Erratum in: Hepatology 2000;32:446.

4. Dalgard O, Bjoro K, Hellum KB, Myrvang B, Ritland S, Skaug K, et al. Treatment with pegylated interferon and ribavarin in HCV infection with genotype 2 or 3 for 14 weeks: a pilot study. Hepatology 2004;40:1260 -5.

5. Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, et al. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet 2001;358:958-65.

6. Fried MW, Shiffman ML, Reddy KR, Smith C, Marinos G, Goncales FL Jr, et al. Peginterferon alfa-2a plus ribavirin for chronic hepatitis C virus infection. N Engl J Med 2002;347:975-82.

7. Zeuzem S, Hultcrantz R, Bourliere M, Goeser T, Marcellin P, Sanchez-Tapias J, et al. Peginterferon alfa-2b plus ribavirin for treatment of chronic hepatitis C in previously untreated patients with HCV genotypes 2 or 3. J Hepatol 2004; 40: 993-9.

8. Thomopoulos KC, Theocharis GJ, Tsamantas AC, Siagris D, Dimitropoulou D, Gogos CA, et al. Liver steatosis is an independent risk factor for treatment failure in patients with chronic hepatitis C. Eur J Gastroenterol Hepatol 2005;17:149-53.

9. Harrison SA, Brunt EM, Qazi RA, Oliver DA, Neuschwander-Tetri BA, Di Bisceglie AM, et al. Effect of significant histologic steatosis or steatohepatitis on response to antiviral therapy in patients with chronic hepatitis C. Clin Gastroenterol Hepatol 2005;3:604-9.

10. Poynard T, Ratziu V, McHutchison J, Manns M, Goodman Z, Zeuzem S, et al. Effect of treatment with peginterferon or interferon alfa-2b and ribavirin on steatosis in patients infected with hepatitis C. Hepatology 2003;38:75-85.

11. von Wagner M, Huber M, Berg T, Hinrichsen H, Rasenack J, Heintges T, et al. Peginterferon-alpha-2a (40KD) and ribavirin for 16 or 24 weeks in patients with genotype 2 or 3 chronic hepatitis C. Gastroenterology 2005;129:522-7.

12. Mangia A, Santoro R, Minerva N, Ricci GL, Carretta V, Persico M, et al. Peginterferon alfa-2b and ribavirin for 12 vs. 24 weeks in HCV genotype 2 or 3. N Engl J Med 2005;352:2609-17.

Conflict of Interest:

Dr. Pijak has received speaker fees and travel assistance from Hoffmann-La Roche and Schering-Plough.
Hepatitis C and urticarial syndromes 6 April 2006
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Sujoy Khan
Path Links Immunology

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Re: Hepatitis C and urticarial syndromes

sujoy.khan{at}nlg.nhs.uk Sujoy Khan

The review on hepatitis C by T Wong and S Lee 1 mentions some extrahepatic manifestations of HCV infection, but does not discuss the urticarias. However, internists and primary care physicians need to be aware that several forms of urticaria can be associated with asymptomatic hepatitis C virus (HCV) infection.

The link between HCV and urticaria is controversial2, since various studies have failed to differentiate between acute and chronic urticaria, and urticarial vasculitis, all of which have been proposed to be associated with HCV infection. The estimated prevalence of urticaria seems to vary in studies from 1.8-24% with a case-control study disputing the association altogether2. The association with other hepatitis viruses is more certain. Electron microscopy has identified hepatitis B surface antigen-antibody complexes in cryoprecipitates from patients during the acute urticarial episode3.

Immune-complex deposits of viral hepatitis can activate the complement system and result in a serum sickness-like syndrome with arthritis and headache (Caroli’s triad). Urticaria resolves on treatment with interferon, and more benefit is seen in urticarial vasculitis associated with mixed essential cryoglobulinaemia 4.

HCV testing should not be a routine screen for all urticarias, but it is good clinical practice to consider viral marker studies in an urticarial patient who presents with icterus and/or raised transaminase levels. The awareness that urticaria or urticarial vasculitis may be caused by hepatitis C is important as early anti-viral treatment can reduce significant morbidity and mortality.

S Khan (a) W A C Sewell (a, b)

a) Path Links Immunology, Scunthorpe General Hospital, Scunthorpe, North Lincolnshire, DN15 7BH b) University of Lincoln, Brayford Pool, Lincoln LN6 7TS

References:

1. Wong T, Lee SS. Hepatitis C: a review for primary care physicians. CMAJ. 2006; 174: 649-59.

2. Cribier B. Urticaria and hepatitis. Clin Rev Allergy Immunol. 2006; 30: 25-30.

3. Dienstag JL, Rhodes AR, Bhan AK, Dvorak AM, Mihm MC Jr, Wands JR. Urticaria associated with acute viral hepatitis type B: studies of pathogenesis. Ann Intern Med. 1978; 89: 34-40.

4. Hamid S, Cruz PD, Jr., Lee WM. Urticarial vasculitis caused by hepatitis C virus infection: Response to interferon alfa therapy. J Am Acad Dermatol 1998; 39(2 PT 1): 278-280.

Conflict of Interest:

None declared
Asia cannot ignore the dangers of the hidden epidemic- Hepatitis C 6 March 2006
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Prof. Govindasamy Agoramoorthy
Tajen University, Yanpu, Taiwan

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Re: Asia cannot ignore the dangers of the hidden epidemic- Hepatitis C

agoram{at}mail.nsysu.edu.tw Prof. Govindasamy Agoramoorthy

Asia cannot ignore the dangers of the hidden epidemic- Hepatitis C

Govindasamy Agoramoorthy + and Minna J. Hsu *

+Department of Pharmacy, Tajen University, Yanpu, Pingtung 907, Taiwan; *Department of Biological Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan; *Corresponding authour: email: hsumin@mail.nsysu.edu.tw

The review by Drs. Wong and Lee outlines an alarming reality that the Asia and the Pacific region harbor the most infected human population of Hepatitis C virus (HCV).1 The thorough review updates vital information pertaining to HCV and it will indeed serve as a valuable reference for primary care physicians who practice in rural areas in various developing countries in Asia.

There is no doubt that HCV infection is becoming a serious public health concern in Asia, especially the densely inhabited countries such as China and India. In China, the HCV prevalence has been reported at 3% while in India, it is about 1.5 to 2%.2-3 Although the Government of India has made it mandatory for blood banks nationwide to screen for HCV from 1 June 2001, some physicians doubt whether testing could be enforced due to the lack of efficient testing tools and equipments.4 China also faces problems to screen blood-borne viruses including HCV since several rural health facilities lack appropriate equipments and testing tools to carryout proper screening of patients.

According to recent studies in India, genotype 3 is the most prevalent in patients with chronic HCV in the Northern and Central parts of the country, and it is often associated with hepatic steatosis and fibrosis.5 However, two recent cases in India for the first time revealed an infection with genotype 6 strains, which have been previously reported only from Hong Kong and Southeast Asia.6 This further indicates that more screenings are crucial to clearly understand the prevalence of various strains of HCV.

The blood screening tests conducted in some rural hospitals in developing countries in Asia sometimes are not adequate enough to confirm the presence of viruses such as HCV and HIV. For example, the National AIDS Control Organization in India, a government agency responsible for AIDS prevention has reported a high incidence (8.2%) of blood donors who are HIV-positive among healthy blood donors in urban areas, which makes blood transfusion highly risky.7 To make the HCV screening successful in rural China and India, modern testing kits and equipments are urgently needed. Besides, appropriate training for healthcare personnel and related government officials at the grassroots level in the countryside must be done quickly so that enforcing the screening tests can succeed. If the HCV screening can be linked with the on-going HIV/AIDS screening projects across developing countries in Asia, it would achieve faster results since HIV/AIDS programs attract more media attention and eventual government response. Furthermore, it is also essential to bring pubic awareness on the precautions to avoid HCV infection among healthy people in Asia.

The review also cautions readers not to use hepatotoxins including herbal products such as kava and silymarin to treat HCV patients.1 Nonetheless we would like add that the use of herbal drugs in the treatment of liver diseases including HCV has long been a tradition in Asia countries. Of course scientific standardization has been a problem, and randomized clinical trials to support efficacy are often lacking when it comes to herbal medications to treat liver diseases. According to Schuppan et al, biologically active molecules derived from certain herbal extracts can indeed serve as suitable primary compounds for effective and targeted hepatotropic drugs.8 Future studies should look into this aspect that might lead to a cost-effective path for patients to treat complications related to hepatotropic viruses in developing countries in Asia.

References

1. Wong T & Lee SS. Hepatitis C: a review for primary care physicians. CMAJ February 28, 2006; 174(5). doi:10.1503/cmaj.1030034

2. Zhang ZW, Shimbo S, Qu JB, et al. Hepatitis B and C virus infection among adult women in Jilin Province, China: an urban-rural comparison in prevalence of infection markers. Southeast Asian Journal of Tropical Medicine & Public Health 2000;31:530–36.

3. Qu JB, Zhang ZW, Shimbo S, et al. Urban-rural comparison of HBV and HCV infection prevalence in eastern China. Biomedical & Environmental Sciences 2000; 13:243–53.

4. Sharma R. Unsuitable hepatitis C testing kit being used in India. BMJ 2001;323:955.

5. Hissar SS, Goyal A, Kumar M, et al. Hepatitis C virus genotype 3 predominates in North and Central India and is associated with significant histopathologic liver disease. Journal of Medical Virology 2006;78:452- 458.

6. Raghuraman S, Abraham P, Sridharan G, etal. Hepatitis C virus genotype 6 infection in India. Indian Journal of Gastroenterology 2005;24:72-73.

7. Choudhury N, Ayagiri A, Ray VL. True HIV seroprevalnce in Indian blood donors. Transfus Med 2000;10: 1–4.

8. Schuppan D, Jia JD, Brinkhaus B. et al. Herbal products for liver diseases: A therapeutic challenge for the new millennium. Hepatology 1999;30:1099:1104.

Conflict of Interest:

None declared