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Challenges and priorities in the management of HIV/HBV and HIV/HCV coinfection in resource-limited settings.
Seminars In Liver Disease. 2012 May; 32(2):147-57.Liver disease due to chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infection is now emerging as an increasing cause of morbidity and mortality in human immunodeficiency virus- (HIV-) infected persons in resource-limited settings (RLS). Existing management guidelines have generally focused on care in tertiary level facilities in developed countries. Less than half of low-income countries have guidance, and in those that do, there are important omissions or disparities in recommendations. There are multiple challenges to delivery of effective hepatitis care in RLS, but the most important remains the limited access to antiviral drugs and diagnostic tests. In 2010, the World Health Assembly adopted a resolution calling for a comprehensive approach for the prevention, control, and management of viral hepatitis. We describe activities at the World Health Organization (WHO) in three key areas: the establishment of a global hepatitis Program and interim strategy; steps toward the development of global guidance on management of coinfection for RLS; and the WHO prequalification program of HBV and HCV diagnostic assays. We highlight key research gaps and the importance of applying the lessons learned from the public health scale-up of ART to hepatitis care. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
Contraception. 2009 Oct; 80(4):325-6.This commentary discusses women with liver diseases and the considerations that are necessary when choosing the appropriate contraceptive method due to the effect of hormones on the liver. It provides recommendations provided by the World Health Organization expert Working Group on family planning guidance to assist those women with their contraceptive options.
Safety of switching to nevirapine-based highly active antiretroviral therapy at elevated CD4 cell counts in a resource-constrained setting [letter]
Journal of Acquired Immune Deficiency Syndromes. 2007 Aug 15; 45(5):598-600.The World Health Organization recommends the use of generic nevirapine (NVP)/efavirenz (EFV)-based highly active antiretroviral therapy (HAART) regimens as first-line therapy in the management of HIV in resource-limited settings. Initiating NVP-based HAART at elevated CD4 cell counts can lead to liver toxicity. Short-term risk of liver toxicity has been reported in men with CD4 counts greater than 400 cells/mL and in women with CD4 counts greater than 250 cells/mL. Hence, clinicians are advised to monitor the results of liver chemistry tests closely in the first 18 weeks of therapy because of the potential to develop life-threatening hepatic events. Mocroft et al showed that initiating NVP therapy at elevated CD4 levels may be safe for use in antiretroviral-experienced patients. Little is known about short-term adverse consequences and clinical outcome at elevated CD4 cell counts in a resource-limited setting. (author's)
Geneva, Switzerland, WHO, 1978. (World Health Organization Technical Report Series No. 619) 54 pStudies on steroid contraception (SC) and risk of neoplasia are reviewed. Methodological issues in neoplasia etiology studies include: 1) possibility of a latent period between exposure to cause and disease development; 2) cumulative effects of prolonged or repeated SC exposure; 3) discontinued drugs or dosage schedules; 4) time of exposure (adolescence or prenatal, e.g.); 5) isolation of specific causes among multiple risks; and 6) variations in neoplasma diagnoses. The 4 epidemiological approaches to SC-associated neoplasia studies have inherent shortcomings, but cohorts yield significant associations. Relative risk (ratio of disease incidence among exposed vs. nonexposed persons) is an index of association only, not evidence of cause and effect. Benign breast neoplasia risk was reduced by current SC use of >2 years, and weak evidence points to a residual protective effect, apparently associated with progestogen dose. Aggregated breast cancer data show no clear adverse or beneficial effect of SC use; however, evidence suggests SCs may increase breast cancer risk in population subgroups (e.g., young women). Only short-term evidence is available; hence, no inference of long-term SC breast cancer effects is possible. No beneficial effect of SCs on uterine fibroids is evident, but sequential SCs, no longer marketed, may have increased risk to endometrial carcinoma. Inconclusive data suggest SCs may decrease ovarian cancer risk. Increased risk of cervical dysplasia and carcinoma in situ is associated with SC use, especially long-term use by women with predisposing factors. Risk of hepatocellular adenoma of the liver increases with prolonged SC exposure, especially high dose. Relevance of existing data from more developed countries to disease risk in less developed ones is discussed, and recommendations made.
LAKARTIDNINGEN. 1979 Apr 25; 76(17):1625-7.An overview of the risk of developing cancer related to oral contraceptive (o.c.) use is presented. A committee of experts affiliated with WHO studied the problem of developing cancer related to o.c. use. O.c. use for more than 2 years prevents the formation of benign breast tumors, even after discontinuing o.c. use. The effect is due to the progestin component. There is no clear indication that o.c. use increases the risk of breast cancer. A higher risk of endometrial cancer is associated with sequential preparation use, but not with the use of combination preparations. Cervical neoplasms and pituitary adenoma may be more frequent among predisposed women who use o.c.s. Studies show a reduced risk of ovarian cancer with o.c. use, but more studies are necessary. There is a marked increase in the relative risk of developing hepatocellular adenoma among women who use o.c.s for longer than 3 years. The risk increases with the hormone dosage, the duration of treatment, and the age of the patient. There is no reliable data to indicate that the risk of malignant melanoma increases with o.c. use. More study is needed to determine the possible cancer risks of injection preparations. Combination preparations can cause an increased risk of vaginal epithelial metaplasia. Diethylstilbestrol taken during early pregnancy can cause vaginal neoplasms in the offspring. More epidemiological studies and clinical and laboratory studies on the carcinogenic effects of o.c.s and the endocrinological effects of o.c.s on younger women should be undertaken. It is recommended that o.c.s with the lowest possible hormone dosages be used. O.c.s should not be prescribed to women with vaginal adenosis. (Summary in ENG)
In: Diczfalusy, E., ed. Regulation of human fertility. (Proceedings of the WHO Symposium on Advances in Fertility Regulation, Moscow, USSR, November 16-19, 1976) Copenhagen, Denmark, Scriptor, 1977. p. 283-321This review of low-dose gestagen contraception emphasizes the variety of findings from different studies. For example, studies of chlormadinone acetate have found pregnancy rates of 1.1-12/100 woman-years. Results of trials of megestrol acetate suggested that a 500-mcg dose level yielded unacceptable pregnancy rates. No significant difference between various doses of norgestrel which have been studied were found (e.g., 50 and 75 mcg daily of dl-norgestrel or 30 mcg daily of the d-isomer). Pregnancy rate reported for most trials with this gestagen and also norethisterone and quingestanol were within an acceptable range. With 1 exception, pregnancy rates reported in trials of lynestrenol were remarkable low. Cumulative results of trials with various gestagens show Pearl Index rates between 2 and 3, except for lynestrenol. Dose level was the critical variable; i.e., it must be sufficiently high to exert antifertility action and low enough to avoid a high incidence of irregular bleeding. Apart from menstrual irregularities, other side effects from the minipill seem minor and in general less severe than those encountered with combined oral contraceptives.
Medical Journal of Australia. November 18, 1978; 2(11):531.The report of the World Health Organization's (WHO's) Scientific Group on the subject of the risk of neoplasia associated with the use of steroid contraception was published in 1978. Regarding the association between liver tumors and the use of OCs, the Scientific Group reached the following conclusions: 1) current evidence demonstrates a marked increase in the relative risk of hepatocellular adenoma of the liver among women who have used OCs for longer than 3 years; 2) the magnitude of the risk increases with the dose of steroid, the duration of use, and the age of the user; 3) preliminary calculations based upon the results of 2 recent studies suggest that, despite the extremely large relative risk estimate, the attributable risk of hepatocellular adenoma among women under 30 years of age is no more than 3/100,000 OC users per year, regardless of length of use; and 4) these data apply more to OCs containing high doses of steroids.
Contraception. 1970 Jun; 1(6):409-445.This article reviews the validity of previously published material linking oral contraceptive usage to health hazards. The statistical methods involved in such studies are thoroughly examined, particularly those studies relating oral contraceptive usage to thromboembolic disease incidence. Problems inherent to the basic designs of such studies are discussed. Some relationship between thromembolic disease and oral contraceptive usage has been established. Studies on animals relating oral contraceptive usage with carcinogenesis are inconclusive due to the different metabolic rates obtained for different animals and different strains and the high dosage used to produce tumors. Review of the data relating oral contraceptives with alterations in carbohydrate metabolism, serum lipids, etc., show pure speculation of conclusion. Endrocrine effects persisting after discontinuation of oral contraceptives were rare; apparently both types of steroids play some part. It was suggested that most data on this subject is faulty and filled with fixed opinions which should be avoided.
Bulletin of the Pan American Health Organization. 1983; 17(3):323.A World Health Organization (WHO) Consultative Group on Hepatitis met during July 1983 to draft a global program for viral hepatitis control. At this time, hepatitis viruses infects tens of millions of people every year. These viruses can be transmitted by the fecal-oral route, in blood or certain blood products, and through intimate personal contact. Of the various forms (heptitis A, hepatitis B, and hepatitis non-A, non-B) hepatitis B arouses particular concern because it can produce chronic liver disease and premature death. Currently, there are over 200 million persistent carriers of this virus, many of whom will die of chronic liver damage. Firm evidence recently shows a clear cause and effect relationship between infection with hepatitis B virus and primary liver cancer, a common cancer that claims hundreds of thousands of lives a year. The July meeting made recommendations to improve the situation. One of the most important recommendations was to strengthen national capabilities to control viral hepatitis. The group also reviewed available diagnosis and control methods and suggested areas where action by the WHO would be most effective. The group agreed that the availability of safe and effective vaccines against hepatitis B provides a unique opportunity to break the chain of transmission and to prevent acute and chronic liver disease, including primary liver cancer. There has been concern that the plasma-derived hepatitis B vaccines could contain transmissible agents that might be implicated in the acquired immune deficiency syndrome (AIDS). It was felt that much care needs to be taken in selecting plasma donors and in purifying the immunizing component of the vaccine, known as hepatitis B surface antigen, so as to ensure a very high degree of purity and freedom from all infectious agencts. No evidence exists at this time of AIDS transmission by any hepatitis B vaccine.
Bulletin of the Pan American Health Organization. 1983; 17(2):212.A World Health Organization (WHO) sponsored scientific meeting concludes that hepatitis B vaccine presents unique opportunities for preventing a common type of human cancer by vaccination. Should these prospects be realized, it would be the 1st time an important human cancer has been prevented in this way. The 5-day meeting, held in February 1983, brought together specialists in biostatistics, epidemiology, molecular biology, pathology, virology, and vaccine development and production from 16 countries. The topic at the meeting was liver cancer, one of the 10 most common cancers in the world and one of the most prevalent cancers in developing countries. The evidence for the implication of hepatitis B virus in the etiology of primary liver cancer is based upon epidemiologic and geographic observations of a strong association between hepatitis B infection and this form of cancer and also upon recent results of molecular biology studies showing integration of hepatitis B viral DNA into the host's genetic material. About 80% of all liver cancers are thought to occur as a result of infection with hepatitis B virus. Actual development of such cancers is believed to proceed through a series of intermediate stages, including establishment of a persistent infection with the virus, the hepatitis B carrier stage, and integration of the virus into the host genome. Worldwide, survival, and persistence of the hepatitis B virus depends on a huge reservoir of human carriers, estimated conservatively to number over 200 million. Prolonged "shedding" of the virus by a portion of these carriers and its transmission to others by various routes helps to account for the high incidence of the disease. In many parts of the world perinatal infection and infection in early life play a very important role in transmission and often lead to continuing infection. Feasibility studies conducted in recent years in several countries with 2 newly developed hepatitis B vaccines demonstrated that immunization of babies can prevent natural infection with hepatitis B virus and also can prevent development of a persistent hepatitis B infection. It seems an appropriate time to take international action to plan and initiate a number of field intervention trials with the new vaccines among populations known to have high prevalence of hepatitis B infection, the hepatitis C carrier state, and liver cancer.