NIH consensus development statement on management of hepatitis B.

OBJECTIVE: To provide health care providers, patients, and the general public with a responsible assessment of currently available data on the management of hepatitis B. PARTICIPANTS: A non-DHHS, nonadvocate 12-member panel representing the fields of hepatology and liver transplantation, gastroenterology, public health and epidemiology, infectious diseases, pathology, oncology, family practice, internal medicine, and a public representative. In addition, 22 experts from pertinent fields presented data to the panel and conference audience. EVIDENCE: Presentations by experts and a systematic review of the literature prepared by the Minnesota Evidence-based Practice Center, through the Agency for Healthcare Research and Quality. Scientific evidence was given precedence over anecdotal experience. CONFERENCE PROCESS: The panel drafted its statement based on scientific evidence presented in open forum and on published scientific literature. The draft statement was presented on the final day of the conference and circulated to the audience for comment. The panel released a revised statement later that day at http://consensus.nih.gov. This statement is an independent report of the panel and is not a policy statement of the NIH or the Federal Government. CONCLUSIONS: The most important predictors of cirrhosis or hepatocellular carcinoma in persons who have chronic HBV are persistently elevated HBV DNA and ALT levels in blood. Other risk factors include HBV genotype C infection, male sex, older age, family history of hepatocellular carcinoma, and co-infection with HCV or HIV. The major goals of anti-HBV therapy are to prevent the development of progressive disease, specifically cirrhosis and liver failure, as well as hepatocellular carcinoma development and subsequent death. To date, no RCTs of anti-HBV therapies have demonstrated a beneficial impact on overall mortality, liver-specific mortality, or development of hepatocellular carcinoma. Most published reports of hepatitis therapy use changes in short-term virologic, biochemical, and histologic parameters to infer likelihood of long-term benefit. Approved therapies are associated with improvements in intermediate biomarkers, including HBV DNA, HBeAg loss or seroconversion, decreases in ALT levels, and improvement in liver histology (Table). Although various monitoring practices have been recommended, no clear evidence exists for an optimal approach. The most important research needs include representative prospective cohort studies to define the natural history of the disease and large RCTs of monotherapy and combined therapies, including placebo-controlled trials, that measure the effects on clinical health outcomes. Table. Criteria Useful in Determining for Whom Therapy is Indicated: Patients for whom therapy is indicated: Patients who have acute liver failure, cirrhosis and clinical complications, cirrhosis or advanced fibrosis and HBV DNA in serum, or reactivation of chronic HBV after chemotherapy or immunosuppression; Infants born to women who are HBsAg-positive (immunoglobulin and vaccination). Patients for whom therapy may be indicated: Patients in the immune-active phase who do not have advanced fibrosis or cirrhosis. Patients for whom immediate therapy is not routinely indicated: Patients with chronic hepatitis B in the immune-tolerant phase (with high levels of serum HBV DNA but normal serum ALT levels or little activity on liver biopsy); Patients in the inactive carrier or low replicative phase (with low levels of or no detectable HBV DNA in serum and normal serum ALT levels); Patients who have latent HBV infection (HBV DNA without HBsAg). We recommend routine screening for hepatitis B of newly arrived immigrants to the United States from countries where the HBV prevalence rate is greater than 2%. Screening will facilitate the provision of medical and public health services for infected patients and their families and provide public health data on the burden of disease in immigrant populations. The screening test should not be used to prohibit immigration.

Intrauterine devices and pelvic inflammatory disease: meta-analyses of published studies, 1974-1990.

We conducted a meta-analysis of 36 papers published between 1974 and 1990 to estimate the effects of intrauterine device (IUD) use and Dalkon Shield use, in particular, on pelvic inflammatory disease (PID). The number of women studied in each report ranged from 50 to 26,507. For general IUD use, analyses were separated by type of PID (symptomatic or asymptomatic) because of extreme rate-ratio heterogeneity across studies. Dalkon Shield rate ratios were more homogeneous and were considered in a single meta-regression. There was substantial heterogeneity, however, in all three meta-regressions; the rate-ratio estimates ranged from 0.51 to 12 for IUD use and symptomatic PID, from 1.0 to 132 for IUD use and asymptomatic PID, and from 0.32 to 28 for Dalkon-Shield use and PID. This heterogeneity appeared to be due to differences in reference groups, study populations, and characteristics of study design. We observed consistent, positive associations of IUD use with both symptomatic and asymptomatic PID. These associations were largest for the Dalkon Shield.

Diagnostic quality of mammograms obtained with a new low-radiation-dose dual-screen and dual-emulsion film combination.

We evaluated the image quality of mammograms made by using a new dual-screen, dual-emulsion film combination (Kodak Min-R Fast screen, T-Mat Mll film) that permits reduction of radiation exposure by approximately 50% when compared with a standard single-screen, single-emulsion film system (Kodak Min-R screen, OM-1 film). This new film has been improved when compared with earlier T-Mat M film, including the introduction of an inert dye to reduce light crossover to essentially 0%. Mammogram pairs made with the dual-emulsion film combination and the standard single-emulsion film combination were obtained in 50 patients otherwise undergoing routine mammography. The image pairs were randomized and evaluated by three radiologists who used a three-point scale (better, same, or worse). Each pair was evaluated with regard to parenchymal contrast, sharpness, and latitude, as well as the number and sharpness of calcifications (n = 19) and sharpness of masses (n = 12) when present. All three observers found the dual-emulsion film combination to be better than or the same as the standard with regard to parenchymal sharpness (94-100%), the number and sharpness of calcifications (98-100%), and sharpness of masses (100%). Two observers found the dual-emulsion film combination to be significantly worse (p less than .05) than the standard with respect to parenchymal contrast (72%, 86%), and all three observers rated it significantly worse for film latitude (14 to 42%). Our results suggest that this new dual-emulsion film combination that allows mammography to be performed with less radiation exposure can be used without loss of image quality.

DNA content of rectal scrapings from individuals at low and high risk for the development of colorectal cancer. A feasibility study.

Scrapings of superficial rectal mucosa were collected from 31 patients with colorectal carcinoma, 66 patients with sporadic adenoma, and 53 control subjects with no personal or family history of colorectal cancer. The DNA ploidy level and proliferative patterns of each specimen were analyzed by flow cytometry (FCM). A GMS index, calculated as the ratio of G2 + M:S, was found to be significantly lower in control subjects than in any of the high-risk groups studied. Aneuploidy was more prevalent in rectal scrapings from cancer patients and adenoma patients than in those from control subjects. Aneuploid cell populations were detected in apparently normal rectal scrapings from two control subjects. Some high-risk individuals (i.e., cancer patients and patients with adenomas and a family history of cancer) exhibited higher proportions of tetraploid (designated G2/M) cells and a higher G2/M:S phase ratio than control subjects. The results accumulated thus far show that the rectal scraping procedure is safe and easy to perform. Our limited findings give hope that the DNA content analysis of cells obtained by rectal scraping may eventually prove useful in mass screening for colorectal cancer risk. However, definitive evaluation will require further refinement and elaboration of analytic technique and testing on more patients at various levels of predetermined risk.