Permanent loss of anti-HBc after reactivation of hepatitis B virus infection in an anti-HBs and anti-HBc-positive patient after allogeneic stem cell transplantation.

BACKGROUND: Reactivation of a hepatitis B virus (HBV) infection after transplantation is associated with a high morbidity and mortality. HBV infections generally result in anti-HBc persisting lifelong. CASE REPORT: A 44-year-old female presented 10 years after allogeneic stem cell transplantation with a chronic hepatitis B. The infection was reactivated from a resolved (anti-HBs and anti-HBc positive) HBV infection acquired some years prior to transplantation. Interestingly, she lost all antibodies to HBV including anti-HBc and is upto now anti-HBc negative. The sequence of the surface and the core gene did not reveal any escape mutations. Thus, the loss of anti-HBc might suggest an immunotolerance of the donor's immune system against HBcAg. CONCLUSION: This data illustrate that an HBV infection might be reactivated despite high anti-HBs levels prior to transplantation. Furthermore, this is the first patient in which a complete loss of anti-HBc could be documented. Moreover, since anti-HBc is often used as a screening marker for HBV it should be kept in mind that anti-HBc negative patients with high viremic HBV infection may occur.

Cost-benefit analysis of screening colonoscopy in 40- to 50-year-old first-degree relatives of patients with colorectal cancer.

BACKGROUND AND AIMS: As shown previously, 40- to 50-year-old first-degree relatives of patients with colorectal cancer (CRC) have significantly more colorectal adenomas than controls of the same age. Screening colonoscopy of these persons at risk between 40 and 50 years might be cost beneficial. METHODS: We prepared a detailed cost-benefit analysis of screening colonoscopy and possible repeat endoscopies according to current expenditures for endoscopic procedures in Germany. Since screening colonoscopy is generally offered and reimbursed from 55 years on in Germany, we analysed the period between 45 and 55 years, taking an annual interest rate of 5% into account. Costs were analysed based on the results of a former study [11] depending on various participation rates in a general screening programme. FINDINGS: Based on the available 1994 figure of about 20,000 euros for diagnosis and treatment of one cancer case, screening colonoscopy is cost beneficial when participation is high. Under a more realistic assumption of currently about 40,000 euros per cancer case, screening colonoscopy is cost beneficial in any case. INTERPRETATION: Our data support that systematic screening colonoscopy in first-degree relatives of patients with CRC by the age of 45 years most likely demonstrates an economic benefit.

Screening colonoscopy in 40- to 50-year-old first-degree relatives of patients with colorectal cancer is efficient: a controlled multicentre study.

BACKGROUND AND AIMS: Persons with a familial risk of colorectal cancer (CRC) account for about 25% of all CRC cases. The adenoma prevalence in relatives of CRC patients 50-60 years of age is 17-34%; data on younger individuals are scarce. Our aim was to prospectively define the adenoma prevalence in 40- to 50-year-old first-degree relatives of CRC patients compared to controls. PATIENTS AND METHODS: CRC patients were identified via the regional cancer registry, and their 40- to 50-year-old first-degree relatives (risk group) were invited for screening colonoscopy. Additional probands and controls of the same age were recruited by newspaper articles and radio or television broadcastings. Using high-resolution video colonoscopy, each detected polyp was removed and histopathologically assessed. Each participant completed demographic and epidemiological questionnaires. RESULTS: Of 228 subjects in the risk group 36.4% had polypoid lesions compared to 20.9% of 220 controls (p<0.001). Forty-three (18.9%) subjects in the risk group had adenomas compared to 18 (8.2%) in the control group (p=0.001). High-risk adenomas (>10 mm and/or of villous type) were found in 12 persons in the risk group compared to 5 controls (not significant). In the risk group most lesions (52%) were located proximal to the sigmoid colon compared to 29% in controls. CONCLUSIONS: Subjects between 40-50 years with first-degree relatives with CRC demonstrate a significantly higher prevalence of adenomas than controls, with a tendency towards a more proximal location. These data support a screening colonoscopy in persons with familial risk already between 40 and 50 years.

High-dose interferon-alpha2b induction therapy in combination with ribavirin for treatment of chronic hepatitis C in patients with non-response or relapse after interferon-alpha monotherapy.

AIM: To evaluate the daily high-dose induction therapy with interferon-alpha2b (IFN-alpha2b) in combination with ribavirin for the treatment of patients who failed with interferon monotherapy and had a relapse, based on the assumption that the viral burden would decline faster, thus increasing the likelihood of higher response rates in this difficult-to-treat patient group. METHODS: Seventy patients were enrolled in this study. Treatment was started with 10 MU IFN-alpha2b daily for 3 wk, followed by IFN-alpha2b 5 MU/TIW in combination with ribavirin (1 000-1 200 mg/d) for 21 wk. In case of a negative HCV RNA PCR, treatment was continued until wk 48 (IFN-alpha2b 3 MU/TIW+1 000-1 200 mg ribavirin/daily). RESULTS: The dose of IFN-alpha2b or ribavirin was reduced in 16% of patients because of hematologic side effects, and treatment was discontinued in 7% of patients. An early viral response (EVR) was achieved in 60% of patients. Fifty percent of all patients achieved an end-of-treatment response (EOT) and 40% obtained a sustained viral response (SVR). Patients with no response had a significantly lower response rate than those with a former relapse (SVR 30% vs 53%; P = 0.049). Furthermore, lower response rates were observed in patients infected with genotype 1a/b than in patients with non-1-genotype (SVR 28% vs 74%; P = 0.001). As a significant predictive factor for a sustained response, a rapid initial decline of HCV RNA could be identified. No patient achieving a negative HCV-RNA PCR at wk 18 or later eventually eliminated the virus. CONCLUSION: Daily high-dose induction therapy with interferon-alpha2b is well tolerated and effective for the treatment of non-responders and relapsers, when interferon monotherapy fails. A fast decline of viral load during the first 12 wk is strongly associated with a sustained viral response.

Evaluation of a new automated, standardized generic nucleic acid extraction method (total nucleic acid isolation kit) used in combination with cytomegalovirus DNA quantification by COBAS AMPLICOR CMV MONITOR.

The new generic Total Nucleic Acid Isolation kit improved the detection limit of a cytomegalovirus (CMV) PCR from 400 to 200 copies/ml. Sensitivity and specificity in 30 CMV-positive and 100 negative samples were 100%. Analytical performance was excellent. The kit provides a reliable, standardized, and time-saving tool for DNA extraction.

Epstein-Barr viral load as a tool to diagnose and monitor post-transplant lymphoproliferative disease.

Epstein-Barr virus (EBV)-induced post-transplant lymphoproliferative disease (PTLD) continues to be a rare but severe complication following transplantation. EBV viral load is used as a tool to identify patients at risk for developing PTLD. However, studies on EBV viral load are hard to compare since study design as well as EBV detection method and calculation of results are highly variable. In the majority of cases EBV viral load is increased in patients with PTLD compared to patients without disease. There is, however, some overlap. Some individual patients with only low viral load show PTLD while others show the opposite. The major future goals will be to standardize EBV-DNA detection in order to generate comparable data in different centers and to establish cut-off values to distinguish patients with PTLD from patients without with a high precision.