Daniel M. Rosenberg

World-wide epidemiology of HBeAg-negative chronic hepatitis B and associated precore and core promoter variants

Hepatitis B is a serious disease that is endemic in many parts of the world. A significant proportion of patients with chronic hepatitis B (CHB) are infected with a variant form of the hepatitis B virus (HBV) which decreases or abolishes the production of hepatitis B e‐antigen (HBeAg). The purpose of this literature review is to describe the epidemiology of HBeAg‐negative CHB (e‐CHB) worldwide. A literature search was conducted to identify studies pertaining to e‐CHB and underlying variants (precore and core promoter). Fifty studies were included in our analysis. The median prevalence of e‐CHB among patients with chronic HBV infection was 33% in the Mediterranean, 15% in Asia Pacific, and 14% in the USA and Northern Europe. The pre core stop codon variant was detected in a median of 60% (range 0–100%) of HBeAg‐negative patients overall, 92% in the Mediterranean, 50% in Asia Pacific and 24% in the USA and Northern Europe. There were very few data on the prevalence of core promoter variants outside Asia where the median prevalence among HBeAg‐negative patients was 77%. This literature review revealed that e‐CHB is more common than previously suspected and that it is present worldwide with marked variations in the prevalence of associated HBV variants across different geographical regions. Additional research using population based samples of adequate size based on a consensus definition of e‐CHB and using standardized HBV DNA assays is needed to better estimate the true prevalence of e‐CHB and its associated HBV variants.

Chronic hepatitis B virus infection in the Asia–Pacific region and Africa: Review of disease progression

Abstract  Countries in the the Asia–Pacific region and Africa tend to have the highest prevalence of hepatitis B infection worldwide. Hepatitis B infection progresses from an asymptomatic persistently infected status to chronic hepatitis B, cirrhosis, decompensated liver disease and/or hepatocellular carcinoma. The aim of this review was to summarize rates and risk factors for progression between disease states in the Asia–Pacific region and Africa. A literature search was conducted employing MEDLINE and EMBASE (1975–2003) using the following key words: hepatitis B, natural history, disease progression, cirrhosis, hepatocellular carcinoma, mortality, Africa and the Asia–Pacific region. Bibliographies of articles reviewed were also searched. Ranges for annual progression rates were: (i) asymptomatic persistent infection to chronic hepatitis B, 0.84–2.7%; (ii) chronic hepatitis B to cirrhosis, 1.0–2.4%; and (iii) cirrhosis to hepatocellular carcinoma, 3.0–6.6%. Patients with asymptomatic persistent infection and chronic hepatitis B had relatively low 5‐year mortality rates (<4%); rates (>50%) were much higher in patients with decompensated liver disease and hepatocellular carcinoma. No data were found for progression rates in African populations. Hepatitis B e antigen was a risk factor for chronic hepatitis B, and bridging hepatic necrosis in chronic hepatitis B increased the risk of cirrhosis. Risk factors for hepatocellular carcinoma included cirrhosis, co‐infection with hepatitis C virus, and genetic and environmental factors. In this review, wide ranges of disease progression estimates are documented, emphasizing the need for further studies, particularly in Africa, where progression rates are largely not available. Summarizing information on factors associated with disease progression should assist in focusing efforts to arrest the disease process in those at most risk.

Impact of patient characteristics on the risk of influenza/ILI-related complications

BackgroundWe sought to quantify the impact of patient characteristics on complications and health care costs associated with influenza and influenza-like illness (ILI) in a nonelderly population.MethodsPatients with medical reimbursement claims for influenza in the 1996–1997 season were identified from the automated database of a large private New England Insurer (NEI). Influenza care during the 21- day follow-up period was characterized according to age, gender, vaccine status, co-morbidities, prior influenza/ILI episodes, treatments, and recent health care costs and related diagnoses.ResultsThere were 6,241 patients. Approximately 20% had preexisting chronic lung disease. Overall, 23% had health care services for possible complications, among which respiratory diagnoses were the most common (13%). Two percent of the influenza/ILI episodes involved hospitalization, with a median stay of five days. Factors most strongly predictive of hospitalizations and complications were preexisting malignancy (hospitalizations OR = 3.7 and complications OR = 2.4), chronic heart disease (OR = 3.2 and OR = 1.8), diabetes (OR = 2.2 and OR = 1.7) and recent illnesses that would have counted as complications had they occurred during an influenza/ILI episode (hospitalizations OR = 3.2 and complications OR = 1.5). The same factors affected influenza-related costs and total costs of care as dramatically as they affected complication rates.ConclusionsInfluenza/ILI-related costs are driven by the characteristics that predict complications of influenza. Patients with chronic illness and those with recent acute respiratory events are the most likely to experience complications and hospitalizations.

The Current Status of Asthma in Korea

A systematic review of English and Korean articles published between 1990 and 2004 and a search of database and various online resources was conducted to determine the prevalences, mortality rates, socioeconomic burden, quality of life, and treatment pattern of asthma in Korean adults and children. Asthma morbidity and mortality in Korea are steadily increasing. The prevalence of asthma in Korea is estimated to be 3.9% and its severity is often underestimated by both physicians and patients. Mortality resulting from chronic lower respiratory diseases including asthma increased from 12.9 to 22.6 deaths per 100,000 of the population between 1992 and 2002. Disease severity, level of control, and symptom state were all found to negatively impact the quality of life of asthmatics. Although international and Korean asthma management guidelines are available, familiarity with and implementation of these guidelines by primary care physicians remain poor.

Chronic hepatitis B: A long-term retrospective cohort study of disease progression in Shanghai, China

Background and Aims:  The present study aimed to describe the disease progression of chronic hepatitis B patients without or with compensated cirrhosis at baseline, to estimate the risk of progression to decompensated cirrhosis, hepatocellular carcinoma and death, and to determine prognostic factors of disease progression in patients in Shanghai, China.

The effect of zanamivir treatment on influenza complications: A retrospective cohort study

BACKGROUND Complications of influenza are a major cause of morbidity and mortality during the influenza season. Clinical trials of zanamivir have reported a reduced incidence of influenza complications among high-risk patients. OBJECTIVES This retrospective study sought to determine whether the use of zanamivir lowers the risk of acute influenza complications in a broader population, based on an analysis of claims data from a large managed care organization. METHODS Medical and pharmacy health insurance claims data from October 1, 1999, through April 30, 2000, were compiled for UnitedHealthcare members in 19 states. All patients with a diagnosis of influenza (International Classification of Diseases, Ninth Revision, Clinical Modification diagnostic code 487.xx) associated with a physician visit were identified. From these, all patients were selected who had received zanamivir on the same day as the diagnosis of influenza. The propensity score matching technique was used to identify a comparison group with similar health service utilization and comorbidities who received a diagnosis of influenza but no antiviral therapy. Follow-up started the day after the influenza diagnosis and continued for 21 days. RESULTS From the 43,741 patients originally identified, 2341 were selected who received a simultaneous diagnosis of influenza and a prescription for zanamivir. The untreated comparator group numbered 2337. Fewer zanamivir patients than untreated patients were hospitalized for complications, and the absolute risks were low (0.6% and 1.0%, respectively; risk ratio [RR], 0.58; 95% CI, 0.30-1.12). Zanamivir-treated patients had an excess of outpatient visits (16.9% vs 14.5%; RR, 1.16; 95% CI, 1.02-1.33) and antibiotic use (16.3% vs 14.8%; RR, 1.10; 95% CI, 0.97-1.26), although the RRs were modest. CONCLUSIONS In the setting of a large managed care plan, patterns of influenza complications were similar in zanamivir-treated and untreated patients with a diagnosis of influenza. The results of this study are in contrast to those of published clinical trials reporting a reduction in the risk of influenza complications in zanamivir-treated patients.

The Prevalence of Anxiety Symptoms and Depressive Symptoms in Patients with Somatic Disorders in Urban China: A Multi-Center Cross-Sectional Study

Objective: To assess the prevalence of anxiety and depressive symptoms among patients with somatic diseases in urban China. Method: A hospital-based cross-sectional study was carried out in four major cities of China from June to August in 2004. There were 2111 eligible subjects with Stroke, Parkinsons Disease, Epilepsy, Irritable Bowel Syndrome, Functional Dyspepsia, and Menopausal Syndrome, and 317 Post-natal women were recruited from general hospitals. Self-completed hospital anxiety and depression scale (HAD) questionnaire was used for screening anxiety and/or depressive symptoms. Subjects with a HAD score of >=9 were further assessed with Hamilton anxiety scale (HAMA) and Hamilton depression scale (HAMD) by certified psychologists or psychiatrists. Results: The prevalence of “screened” depressive and anxiety symptoms using HAD were 11 ∼ 19% and 11 ∼ 22% respectively in patients with above somatic diseases and post-natal women. Assessed by HAMA/HAMD scale, the prevalence of “definite” depressive symptoms was 30% ∼ 59% in subjects with “screened” depressive symptoms, and 44% ∼ 84% in subjects with “screened” anxiety symptoms. About half of the subjects had co-morbidity depressive and anxiety symptoms. Less than one-fourth of these subjects had ever been diagnosed as depressive/anxiety disorders and been treated prior to the investigation. Conclusion: There is a high prevalence and low diagnosis and treatment rate of depressive and anxiety symptoms in patients with these somatic diseases in China.

Risk for respiratory events in a cohort of patients receiving inhaled zanamivir: A retrospective study

BACKGROUND Inhaled zanamivir is indicated for treatment of uncomplicated acute illness due to influenza A and B viruses in patients aged > or = 12 years who have been symptomatic for no more than 2 days. OBJECTIVE The primary objective of this study was to estimate the incidence of adverse respiratory events among zanamivir-treated patients under conditions of usual care. METHODS The Ingenix research database includes insurance claims for all dispensations, inpatient and outpatient services, and procedures including the associated diagnoses and costs for a subset of all enrolled UnitedHealthcare members. We identified all persons with a dispensation of zanamivir recorded between October 1, 1999, and April 30, 2000. We captured medical and pharmaceutical claims data for the 6 months before the dispensation to obtain information about comorbidities, overall health status, and respiratory events. Medical and hospital record abstraction and clinical review served to confirm inpatient/emergency department (ED) events. We also examined the records of an approximately 10% random sample of patients treated for a potential respiratory event in an outpatient/ physician office visit during the 10-day follow-up period. Respiratory events not sufficiently severe to result in medical care were not captured in this study. RESULTS A total of 5498 eligible zanamivir dispensations contributed by 5450 patients (2911 females, 2539 males; mean age, 38.8 years), with 40 confirmed inpatient/ED respiratory events, were included in the study. Of these 40 events, 31 were pneumonia, bronchitis, or exacerbations of existing chronic respiratory disease; none required intubation or ventilation. No events occurred on the dispensation date. The overall risk for an inpatient/ ED respiratory event was 0.7 per 100 episodes (95% CI, 0.5-1.0). Seven events of wheezing or shortness of breath were not an obvious extension of the original influenza-like illness or of a complicating bronchitis (risk = 0.13 per 100 episodes; 95% CI, 0.06-0.26). CONCLUSIONS No immediate or severe bronchoconstrictive responses occurred among 5498 zanamivir dispensations. The overall risk for any respiratory event was low, and none was sufficiently severe to suggest respiratory failure.

Demographic behavioral and knowledge factors associated with herpes simplex virus type 2 infection among men whose current female partner has genital herpes.

Objective/Goal: The objective of this study was to evaluate risk factors for herpes simplex virus type 2 (HSV-2) infection among men whose female partners have genital herpes (GH). Study: Between 1998 and 2001, 717 men in heterosexual monogamous relationships, without a history of GH, completed a cross-sectional questionnaire on demographic, behavioral, and knowledge factors for GH. Their female partners were symptomatic and HSV-2-seropositive. Risk factors for HSV-2 seropositivity were assessed using logistic regression. Results: On laboratory confirmation, 25% of the men were HSV-2-seropositive. Factors significantly (P <0.01) associated with HSV-2 infection included: never using condoms (adjusted odds ratio [aOR], 1.84; 95% confidence interval [CI], 1.15–2.95), prior sexually transmitted disease (STD) (aOR, 1.80; CI, 1.27–2.58), vaginal intercourse during symptomatic episodes (aOR, 1.77; CI, 1.19–2.62), longer partnership (for each additional year aOR, 1.07; CI, 1.03–1.09), and lower knowledge of GH (aOR, 1.14; CI, 1.05–1.23). Conclusion: Potentially modifiable risk factors for HSV-2 infection included engaging in vaginal sex during symptomatic episodes, never using condoms, and lower knowledge of GH.

Factors associated with response to lamivudine: Retrospective study in a tertiary care clinic serving patients with chronic hepatitis B

Background and Aims: Chronic hepatitis B (CHB) is an important cause of end stage liver disease and hepatocellular carcinoma. Controlled clinical trials indicate treatment with lamivudine results in positive clinical responses. The study goal was to determine if the response to lamivudine treatment (HBeAg loss, HBV DNA loss and alanine aminotransferase [ALT] reduction) differs according to pretherapy (pre‐tx) ALT levels.