Miriam J. Alter, PhD; Leonard B. Seeff, MD; Bruce R. Bacon, MD; David L. Thomas, MD; Michael O. Rigsby, MD; Adrian M. Di Bisceglie, MD
In the United States, chronic hepatitis C virus (HCV) infection affects an estimated 3 million persons, most younger than 50 years of age. It is one of the leading causes of chronic liver disease morbidity and mortality and the most common indication for liver transplantation. Effective treatment can eradicate the virus and eliminate or reduce liver inflammation and fibrosis, and counseling and immunization can modify or prevent the adverse effect of cofactors (for example, alcohol consumption or co-infections) on disease progression. However, controversy surrounds the need to routinely identify asymptomatic HCV-infected persons. Because no data currently demonstrate that treatment or other interventions will reduce future cases of HCV-related chronic disease and deaths, the U.S. Preventive Services Task Force found insufficient evidence to recommend for or against routine screening for HCV infection in adults at high risk. Chronic hepatitis C would require many years of follow-up to determine the incidence of complication after treatment of or other interventions in asymptomatic persons. It seems inappropriate to wait several decades to measure the impact of early identification of this viral infection when current data support a positive therapeutic effect that points to long-term benefits. In addition, treatment and other interventions must be provided before cirrhosis or liver failure occurs. Therefore, medical and public health professionals should continue the practice of screening persons for risk factors; offering testing to those at increased risk for HCV infection; and providing infected persons with appropriate counseling, medical evaluation, and treatment.
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Muhamad Aly Rifai
National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland
November 4, 2004
Hepatitis C patients with psychiatric illness: the forgotten
The clinical management of individuals with co-morbid hepatitis C virus (HCV) chronic infection and psychiatric illness is a substantial public health problem. The prevalence rates of psychiatric illness (affective, anxiety and psychotic disorders) in patients with HCV infection are at least double the rates of psychiatric illness in the US population (1-3). Furthermore, patients with psychiatric illness have significantly higher HCV infection rates when compared with the US population [10-20% vs. 1-2 %] (3). Despite such association, routine screening for HCV has not been recommended for patients with psychiatric illness. These patients are at high-risk for contracting HCV by engaging in high- risk behaviors and may not be forthcoming about risk factors for HCV infection.
The use of interferon-based therapies (IFN) has been problematic in HCV patients with psychiatric illness. Neuropsychiatric side effects occurred in at least half of those treated in HCV clinical trials reporting sustained virologic response (SVR) rates of 54- 56% (3). Fearing reduced SVR rates and the precipitation or worsening of pre-existing psychiatric illness with IFN, these trials excluded patients with histories of psychiatric or substance use disorders. In contrast to HCV-treatment trials, other reports (4, 5) detailing the clinical experience with IFN use describe little success in engaging patients with HCV treatment, and poorer SVR rates (10-15 %). These reports cite psychiatric illness and substance use as the main factors for HCV treatment ineligibility in at least half of the HCV patients being evaluated (4, 5).
The practice of excluding patients with HCV and psychiatric illness from IFN treatment is stigmatizing and can result in substantial morbidity and mortality for a vulnerable population no less deserving of treatment than HCV patients without psychiatric illness. The HCV-population with psychiatric illness is quite unique, as psychotropics (antidepressants, antipsychotics, mood stabilizers) are metabolized by the liver and are associated with significant hepatotoxicity. The combination of HCV-induced liver disease and psychotropics use (not to mention alcohol use) may hasten the progression to cirrhosis. Patients with HCV and psychiatric illness may also be less likely to receive a liver- transplant due to the perceived difficulties they might have in complying with the rigorous-post transplant regimen. In this context, the argument about the lack of data supporting the utility of IFN treatment in reducing morbidity and mortality from cirrhosis and primary liver cancer may not be applicable to the HCV population with psychiatric illness. In conclusion, there is a pressing need to develop recommendations on screening and treatment of HCV in patients with psychiatric illness.
1. Yovtcheva SP, Rifai MA, Moles JK, Van Der Linden BJ. Psychiatric Comorbidity Among Hepatitis C-Positive Patients. Psychosomatics. 2001;42(5):411-415.
2. el-Serag HB, Kunik M, Richardson P, Rabeneck L. Psychiatric disorders among veterans with hepatitis C infection. Gastroenterology. 2002;123(2):476-82.
3. Rosenberg SD, Swanson JW, Wolford GL, et al. Blood-Borne Infections and Persons With Mental Illness: The Five-Site Health and Risk Study of Blood-Borne Infections Among Persons With Severe Mental Illness. Psychiatric Services. 2003;54(6):827-835.
4. Cawthorne CH, Rudat KR, Burton MS, et al. Limited success of HCV antiviral therapy in United States veterans. The American Journal of Gastroenterology. 2002;97(1):149-155.
5. Falck-Ytter Y, Kale H, Mullen KD, Sarbah SA, Sorescu L, McCullough AJ. Surprisingly Small Effect of Antiviral Treatment in Patients with Hepatitis C. Ann Intern Med. 2002;136(4):288-292.
Consultant of Brazilian Ministry of Health; Post-grad. program in Med. Scien - UFRGS/Brazil
November 16, 2004
Lack of cost-effectiveness studies in hepatitis C screening programs
We agree with Alter MJ et al.(1) concerning their critical appraisal of literature, which resulted on lacking of evidence on clinical course of hepatitis C and the impact of treatment in the long run. As the authors declared, the two leading causes of liver diseases worldwide are hepatitis C and alcohol, for what educational programs and restriction of alcoholic beverages consumption might have impact in preventing liver diseases. A cost-effectiveness study (2) showed that the most beneficial effect of treatment, in terms of QALY, was the recovery of the quality of live lost with the HCV-positive status. It is our opinion that a non-selected screening strategy could be harmful instead of providing benefit. Even knowing the HCV-status might prevent from fulminant hepatitis A, this strategy has not been tested, as well as the theoretical risk reduction of transmission after testing. In our opinion, cost-effectiveness analysis is lacking in order to balance the evidence-based conclusions in this field. It seems particularly relevant when these are public health actions, which, in their turn, involve millions of dollars expended by the public health systems.
VA,,NY - HARBOR HEALTH CARE SYSTEM
December 22, 2004
Re: Lack of cost-effectiveness studies in hepatitis C screening programs
TESTING FOR HEPATITIS C VIRUS INFECTION OR TREATING IT
THE AUTHORS,ALTER AND ASSOCIATES DISCUSS THE ISSUES OF TESTING AND OF TREATING WHICH NEED TO BE CLEARLY SEPARATED.I WOULD HAVE LIKED TO SEE THE RISK/BENEFIT DATA FOR TESTING IN ORDER TO PREVENT TRANSMISSION OF THE VIRUS TO OTHERS. AS THE AUTHORS AGREE ABOUT THE LACK OF CONCLUSIVE DATA TO SUPPORT THE DELIVERY OF ANTIVIRAL THERAPY WITH IT'S PROVEN ASSOCIATED RISKS AND GARGANTUAN BURDEN FOR SOCIETY AS A WHOLE,THEIR CONCLUSIONS THAT "IT IS IMPERATIVE"..."OFFERING TESTING...AND TREATMENT" IS, I BELIEVE A CONTRADICTION. WOULD THE AUTHORS AGREE THAT ALL ANTIVIRAL TREATMENT OF THIS DISORDER SHOULD BE CATEGORIZED AS A VALUABLE EXPERIMENT AND ALSO TREATED AS SUCH?
Institute of Occupational Medicine, Catholic University School of Medicine, Rome, Italy
January 13, 2005
Testing and managing HCV-infected health care workers
I'm a physician charged of medical surveillance of hospital workers. I strongly agree with Alter's et al. and Rich's et al. warnings (1,2) against interruption of HCV testing practices of health care workers (HCWs). Testing HCWs for HCV proved to be cost-effective before performing exposure-prone procedures (EPPs), after needlestick or mucosal exposure, and if abnormal ALT levels are detected during a routine medical examination. Periodical testing might also be useful in detecting unapparent infections, specially in HCWs operating on high-risk populations, such as infectious disease departments, and prisons. To date, most European countries have no national policy for HCV infected HCWs, and existing guidelines are advisory in nature, and poorly enforced. A panel of European and American experts recently failed to reach a consensus statement as to how to manage HCV infected HCWs who perform EPPs, and concluded that screening for and restricting HCV infected HCWs is not justified, based on current published data (3). The worst option, however, is the "zero" policy, overlooking the problem. I recently witnessed the case of a university-teacher, who had been working as surgeon since 1969 in a university hospital. In 1972 he developed hepatitis B virus infection that subsequently healed. In 1974 he developed "nonA-nonB hepatitis", later diagnosed as chronic HCV-infection. In 1975 he was diagnosed at King's College Hospital in London as having hypersensitivity (toxic) hepatitis from halogenated anesthetics. The combined adverse effect of toxic factor and HCV infection was alarming. The surgeon signaled his health status to the university hospital management, but no appropriate preventive measure was taken. The surgeon tried to by-pass gas hazard, by using neuroleptoanalgesia; anesthetic gas, however, were used by neighboring surgeons. In subsequent years, when exposed to anesthetic gas, he showed recurrent increases of ALT. In 1998 he completely ceased surgical activity and suited the hospital. The court rejected his claim, on the consideration that the observed enzymatic changes could not be attributed without doubt to anesthetic gas hazard, owing the confounding effect of HCV chronic liver infection. No penal charge of university management was decided, notwithstanding the proved absence of preventive measures, both at individual and collective level. Given the fact that the surgeon remained HCV-RNA positive for 25 years of career, the risk of having transmitted HCV in at least one of the procedures performed, can be evaluated to be almost 88% (4). It is imperative that public health services effectively screen and manage infectious HCWs.
Nicola Magnavita, M.D. Institute of Occupational Medicine, Catholic University School of Medicine, Largo Gemelli 8, 00168 Rome, Italy.
References 1.Alter MJ, Seeff LB, Bacon BR, Thomas DL, Rigsby MO, Di Bisceglie AM. Testing for hepatitis C virus infection should be routine for persons at increased risk for infection. Ann Intern Med 2004; 141: 715-718 2.Rich JD, Taylor LE, Allen SA. Screening for hepatitis C virus infection in adults. Ann Intern Med 2004; 141: 575-576 3.Gunson RN, Shouval D, Roggendorf M, et al. Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in health care workers (HCWs): guidelines for prevention of transmission of HBV and HCV from HCW to patient. J Clin Virol 2003; 27: 213-230. 4.Ross RS, Viazov S, Roggendorf M. Risk of hepatitis C transmission from infected medical staff to patients. Arch Intern Med 2000; 160: 2313-2316
Alter MJ, Seeff LB, Bacon BR, Thomas DL, Rigsby MO, Di Bisceglie AM. Testing for Hepatitis C Virus Infection Should Be Routine for Persons at Increased Risk for Infection. Ann Intern Med. 2004;141:715-717. doi: 10.7326/0003-4819-141-9-200411020-00013
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Published: Ann Intern Med. 2004;141(9):715-717.
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