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Biomedical subjects

R S Koff

Publications and source records attributed to R S Koff.

At least 19 recordsLinked to original sources
PubMed2001

Hepatitis vaccines.

The development of highly effective and safe inactivated HAV vaccines and highly effective and safe recombinant HBsAg subunit HBV vaccines represents major advances in the control of viral hepatitis, but many challenges remain. Because current HAV immunization recommendations target high-risk groups only, infection rates are unlikely to fall dramatically until universal childhood immunization programs are implemented. Routine HBV vaccination of infants, children, adolescents, and individuals at high risk will reduce the incidence of infection, but vaccine nonresponsiveness and escape mutants are important potential challenges. Whether either HAV or HBV vaccine provide lifelong protection remains to be determined. Vaccines for HDV, HEV, and HCV are not yet available.

Adult↗
PubMed2001

Risks associated with hepatitis A and hepatitis B in patients with hepatitis C.

Individuals with hepatitis C virus (HCV) are at risk for acquiring hepatitis A virus (HAV) or hepatitis B virus (HBV) because of shared risk factors. A number of organizations recommend vaccination against HAV and HBV for patients with HCV. The rationale for vaccinating these patients is to prevent hepatic superinfections. Acute HAV superinfection causes more severe disease, acute hepatic failure, and higher fatality rates in patients with underlying chronic liver disease, specifically chronic HBV infection and chronic HCV infection. Available data, although limited, suggest that HBV coinfection with HAV and HCV causes more severe hepatic injury than infection with HAV or HCV alone. At standard doses, hepatitis A and hepatitis B vaccines are safe and immunogenic in patients with mild-to-moderate hepatitis C or chronic liver disease. Regardless of disease severity, vaccination should be routinely administered to patients upon diagnosis of HCV infection. Early vaccination is important because response to vaccination is reduced as liver disease progresses. Prevaccination and postvaccination serology testing is recommended in specific populations. A new combination hepatitis A and hepatitis B vaccine has been shown to be as safe and effective as monovalent hepatitis A and B vaccines and is currently under review by the United States Food and Drug Administration. A combination vaccine would offer ease of administration and convenience and could increase compliance in patients with hepatitis C or other chronic liver disease: two groups that should be more aggressively targeted by healthcare professionals.

Adult↗
PubMed2000

Watchful waiting with periodic liver biopsy versus immediate empirical therapy for histologically mild chronic hepatitis C. A cost-effectiveness analysis.

BACKGROUND: Not all patients with histologically mild chronic hepatitis C progress to cirrhosis. OBJECTIVE: To compare no antiviral treatment, periodic liver biopsy with subsequent antiviral treatment for moderate hepatitis or cirrhosis, and immediate antiviral therapy. DESIGN: Cost-effectiveness analysis. DATA SOURCES: Clinical trial data and published studies. TARGET POPULATION: Hepatitis C virus-infected patients with histologically mild hepatitis. TIME HORIZON: Lifetime. PERSPECTIVE: Societal. INTERVENTION: Immediate combination antiviral treatment or biopsy every 3 years plus combination antiviral therapy for moderate hepatitis or cirrhosis. OUTCOME MEASURES: Life expectancy, quality-adjusted life expectancy, and costs. RESULTS OF BASE-CASE ANALYSIS: Over 20 years, biopsy every 3 years with treatment of moderate hepatitis would avoid treatment in 50% of the cohort and would result in an 18% likelihood of cirrhosis compared with 16% for immediate treatment and 27% for no antiviral therapy. Immediate antiviral treatment should increase life expectancy by 1.0 quality-adjusted life-year compared with biopsy management. Over an average lifetime, biopsy management would lead to six liver biopsies costing $6200; immediate antiviral treatment would cost $5100 less than biopsy management because of savings related to biopsy and prevention of future hepatitis C-related morbidity. Immediate therapy was cost-effective compared with biopsy management and had a cost-effectiveness ratio of $7000 compared with no antiviral therapy. RESULTS OF SENSITIVITY ANALYSIS: When age, sex, genotype, and estimates of histologic progression or compliance with follow-up are varied, immediate therapy should result in an increase of at least 0. 8 quality-adjusted life-year compared with biopsy management. CONCLUSION: For histologically mild chronic hepatitis C, initial combination treatment compared with periodic liver biopsy should reduce the future risk for cirrhosis, prolong life, and be cost-effective.

Adult↗
PubMed2000

Hepatitis B school-based vaccination programmes in the USA: a model for hepatitis A and B.

Following the recommendation for routine vaccination against hepatitis B virus for newborns, many states have started school-based catch-up vaccination of 11- to 12-year-olds. Implementation of these programmes requires educational and promotional initiatives to increase awareness among parents, children, teachers, school nurses, school boards and administration. Experience in Framingham, Massachusetts, suggests that over 90% of targeted hepatitis B vaccine coverage can be achieved. Because hepatitis B vaccination targeted at high-risk groups in the USA was largely unsuccessful, this suggests that the initial similar targeted approach with hepatitis A vaccination will also fail. Only about 50% of hepatitis A cases have a known risk factor, and multiple high-risk areas exist throughout the USA. However, the geographical clustering of these high-risk areas and the occurrence of periodic outbreaks, suggest that school-based hepatitis A vaccination programmes may be effective in reducing the risk of infection. A voluntary programme in San Antonio achieved 43% of the targeted coverage in its first year, and a compulsory programme is due to start in Oklahoma. The effectiveness of this programme is not yet known, but future recommendations are likely to include hepatitis A vaccination as a school entry requirement in areas with high incidence of hepatitis A.

Child↗
PubMed2000

Diagnosis and monitoring of hepatic injury. I. Performance characteristics of laboratory tests.

PURPOSE: To review information on performance characteristics for tests that are commonly used to identify acute and chronic hepatic injury. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed for key words related to hepatic tests, including quality specifications, aminotransferases, alkaline phosphatase, gamma-glutamyltransferase, bilirubin, albumin, ammonia, and viral markers. Abstracts were reviewed, and articles discussing performance of laboratory tests were selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. The drafts were also reviewed by the Practice Guidelines Committee of the American Association for the Study of Liver Diseases and approved by the committee and the Association's Council. RECOMMENDATIONS: Although many specific recommendations are made in the guidelines, some summary recommendations are discussed here. Alanine aminotransferase is the most important test for recognition of acute and chronic hepatic injury. Performance goals should aim for total error of <10% at the upper reference limit to meet clinical needs in monitoring patients with chronic hepatic injury. Laboratories should have age-adjusted reference limits for enzymes in children, and gender-adjusted reference limits for aminotransferases, gamma-glutamyltransferase, and total bilirubin in adults. The international normalized ratio should not be the sole method for reporting results of prothrombin time in liver disease; additional research is needed to determine the reporting mechanism that best correlates with functional impairment. Harmonization is needed for alanine aminotransferase activity, and improved standardization for hepatitis C viral RNA measurements.

Acute Disease↗
PubMed2000

Diagnosis and monitoring of hepatic injury. II. Recommendations for use of laboratory tests in screening, diagnosis, and monitoring.

PURPOSE: To review information on the use of laboratory tests in screening, diagnosis, and monitoring of acute and chronic hepatic injury. DATA SOURCES AND STUDY SELECTION: A MEDLINE search was performed for key words related to hepatic diseases, including acute hepatitis, chronic hepatitis, alcoholic hepatitis, cirrhosis, hepatocellular carcinoma, and etiologic causes. Abstracts were reviewed, and articles discussing use of laboratory tests selected for review. Additional articles were selected from the references. Guideline Preparation and Review: Drafts of the guidelines were posted on the Internet, presented at the AACC Annual Meeting in 1999, and reviewed by experts. Areas requiring further amplification or literature review were identified for further analysis. Specific recommendations were made based on analysis of published data and evaluated for strength of evidence and clinical impact. RECOMMENDATIONS: Although many specific recommendations are made in the guidelines, only some summary recommendations are listed here. In acute hepatic injury, prothrombin time and, to a lesser extent, total bilirubin are the best indicators of severity of disease. Although ALT is useful for detecting acute and chronic hepatic injury, it is not related to severity of acute hepatic injury and only weakly related to severity of chronic hepatic injury. Specific tests of viral markers should be the initial differential tests in both acute and chronic hepatic injury; when positive, they are also useful for monitoring recovery from hepatitis B and C.

Acute Disease↗
PubMed1999

A phase I/II study of recombinant human interleukin-12 in patients with chronic hepatitis C.

Interleukin-12 (IL-12) plays a central role in mounting an effective cellular immune response directed towards elimination of intracellular pathogens. The present open-label, multicenter, dose-escalation phase I/II study was designed to assess tolerability, pharmacokinetics, pharmacodynamics, and efficacy of subcutaneously administered recombinant human interleukin-12 (rHuIL-12) in the treatment of chronic hepatitis C. Sixty patients (42 men, 18 women, aged 24-60) were treated with 0.03 microgram/kg (n = 16), 0.1 microgram/kg (n = 14), 0.25 microgram/kg (n = 15), or 0.5 microgram/kg rHuIL-12 (n = 15) for 10 consecutive weeks. rHuIL-12 was generally well tolerated, with 2 patients (3.3%) being withdrawn from treatment for adverse events. Treatment was associated with temporary decreases in neutrophils and lymphocyte counts and with elevations in serum transaminases and bilirubin. Serum IL-12 levels observed were higher at 0.5 microgram/kg compared with 0.25 microgram/kg doses, suggesting a dose-related increase in systemic exposure of IL-12. Measurable levels of interferon gamma (IFN-gamma) were also observed at the highest dose of 0.5 microgram/kg. At the end of treatment hepatitis C virus (HCV) RNA was detectable in all patients. A more than 50% decrease in pretreatment HCV RNA levels was observed in 3 of 16 patients of the 0.03-microgram/kg dose group, in 3 of 14 of the 0.10-microgram/kg dose group, in 6 of 15 of the 0.25-microgram/kg dose group, and in 8 of 15 patients of the 0.5-microgram/kg dose group. Although in several cases serum alanine transaminase (ALT) levels decreased either during or after treatment, ALT normalization was observed in only 4 patients at the end of treatment and in 5 patients at the end of follow-up. Significant anti-rHuIL-12 antibody titers were not detectable in any patient. In conclusion, antiviral activity of rHuIL-12 in patients with chronic hepatitis C does not appear advantageous in comparison with other currently available treatments.

Adolescent↗
PubMed1999

Cost-effectiveness of treatment for chronic hepatitis C.

Concerns about the variable natural history of untreated chronic hepatitis C and the costs and benefits of current therapy for this disease have been addressed by the techniques of cost-effectiveness analysis. The methodologies of decision analysis and Markov computer simulation, and available data on natural history, costs of care, and response to treatment, have been utilized to project the long-term costs and benefits of treatment. These models indicate that interferon monotherapy and combination therapy (interferon plus ribavirin) for previously untreated patients, for retreatment of patients who relapse after interferon treatment, and for retreatment of those who are non-responders to interferon monotherapy have calculated cost-effectiveness ratios that fall within the bounds of other widely accepted therapies or are cost-saving. Even empirical treatment, without liver biopsy, HCV RNA quantitation, or HCV genotyping, has an acceptable cost-effectiveness.

Antiviral Agents↗
PubMed1999

Cost-effectiveness of combined interferon and ribavirin versus interferon alone.

Several decision analysis, computer-generated models developed to study the cost effectiveness of current treatment for chronic hepatitis C appear to have produced similar results. They indicate that IFN monotherapy and the combination of IFN plus ribavirin treatment have calculated cost-effectiveness ratios that either fall within the bounds of other widely accepted current therapies in medicine or are cost-saving. This cost effectiveness has been shown for the treatment of previously untreated patients, for the re-treatment of patients who experience relapse after an initial course of IFN monotherapy, and for the re-treatment of those patients who did not respond to IFN monotherapy. Although targeting treatment to patients most likely to respond will improve cost effectiveness, the benefits of treatment are such that even empiric IFN monotherapy, without liver biopsy, HCV RNA quantitation, or HCV genotyping, has an acceptable cost effectiveness. Although not studied, empiric combination therapy might result in even further cost efficiencies.

Antiviral Agents↗