S. Caronna

Digestive Endoscopy Is Not a Major Risk Factor for Transmitting Hepatitis C Virus

Context Controversy persists regarding the risk for transmission of hepatitis C virus (HCV) as a result of digestive-tract endoscopy. Contribution This prospective study of HCV-negative patients who underwent gastroscopy with the same endoscopes as HCV-positive patients showed no transmission of infection on follow-up 6 months later. Biopsy with reusable or disposable forceps did not increase the risk for HCV infection. Blood donors who were HCV negative without endoscopic exposure showed a few conversions to infected status an average of 2.5 years later. Implications The risk for HCV transmission by endoscopy is extremely low when standard instrument-cleaning techniques are used. The Editors Health carerelated procedures have been implicated in the transmission of a consistent proportion of contemporary hepatitis C virus (HCV) infections. The role of major surgical operations, such as cardiovascular, gynecologic, and orthopedic procedures, is well established. However, the role of less invasive procedures, such as digestive endoscopy, remains a matter of debate. A claim from a retrospective French study (1) that digestive endoscopic procedures are a major cause of HCV transmission among blood donors has not been substantiated by other authors (2, 3); acquisition of HCV through endoscopy has in fact been rarely reported in recent years (4, 5). Nevertheless, endoscopy as a vehicle for HCV transmission has been suspected since 1996, when blood banks in France and Italy suspended donors who reported a history of recent digestive endoscopy from donating blood for 6 months and up to 1 year, respectively. It is therefore important to establish whether digestive endoscopy represents a real risk and, if so, to define its magnitude. We conducted a prospective study among outpatients referred to 3 endoscopic units in northwestern Italy from 1999 to 2002. The patients entering the study were tested for antibody to HCV (anti-HCV) at baseline and 6 months after endoscopy. The incidence of HCV infection in this cohort was compared with that in blood donors recruited in the same area and during the same time period; these donors had not undergone any digestive endoscopic procedure. Methods Endoscopy Cohort Between January 1999 and December 2002, all of the outpatients referred for upper digestive endoscopy to 3 endoscopic units in northwestern Italy (1 secondary referral center and 2 tertiary referral centers) were asked to participate in this study. Eligibility criteria were age older than 18 years and indication for gastroscopy. We restricted the procedure to gastroscopy in order to obtain a high rate of invasive procedures (for example, gastric biopsy). We excluded patients if they were hospitalized, had previously undergone endoscopic procedures, were known anti-HCV carriers, or had to undergo additional endoscopic procedures other than gastroscopy. However, to identify the potentially infective population, we retrospectively looked for known HCV carriers who underwent gastroscopy in the 3 centers between January 1999 and December 2002. Of 11348 patients fulfilling the inclusion criteria, 9188 (81.0%) agreed to participate and gave written consent. They completed a questionnaire about risk factors for HCV infection during the past 6 months, and a serum sample was obtained from each immediately before endoscopy. Mild sedation with midazolam and hyoscine butylbromide was administered to each patient by using disposable syringes and vials. Gastroscopies were done by using various types of endoscopes, including fiberscopes and video endoscopes (Olympus GIF-Q20, GIF-Q30, GIF-IT30, GIF-IT140, Olympus Europe, Hamburg, Germany). Biopsies were performed with disposable biopsy forceps (Radial Jaw 3, Boston Scientific Microvasive, Natick, Massachusetts) in one center and reusable biopsy forceps (FB-24U-1, Olympus Europe) in another center; the third center used reusable forceps (EN-62143, Pescetto, Genova, Italy) in 1999 and disposable forceps (Max Capacity, Boston Scientific Microvasive) after 1999. Each patient was invited to attend a follow-up visit 6 months after endoscopy in order to obtain a serum sample for determining anti-HCV; at this visit, the patient was asked to complete the HCV questionnaire again. To reduce the risk for false-negative results, potentially immunodeficient patients (those undergoing hemodialysis or receiving immunosuppressive treatment) were also tested for HCV RNA by polymerase chain reaction (PCR). All patients who did not attend the follow-up visit were recontacted by telephone. Among patients in the endoscopy cohort, we identified an at-risk subset of patients: Overall, 912 endoscopic procedures (732 gastroscopies performed on known HCV carriers and 180 gastroscopies performed on newly discovered HCV carriers) were considered potentially infective. When we considered that each endoscope was used 3 times during the endoscopic session and assumed that the anti-HCVpositive patient was the first, second, or third at random, the number of exposed patients per HCV-infectedpatient-day was 0, 1, or 2, with equal probability (the mean of those numbers is 1). Blood Donors Cohort Using a computerized database, we retrospectively identified all 51645 consecutive blood donors at 2 transfusion centers in Torino and Pinerolo between January 1999 and December 2002 who were negative for HCV. Of these, 415 (0.8%) reported previous digestive endoscopy; the blood bank database did not record invasive procedures performed during endoscopy (such as biopsy and polypectomy). These 415 donors were asked to repeat the serologic and virologic HCV tests: 329 (79.3%) agreed, and 86 declined. Of the 51230 blood donors who did not undergo endoscopic procedures during the observation period, 38 280 (74.7%) were tested again after a mean of 2.49 years (range, 6 months to 4 years); the remaining 12 950 blood donors could not be contacted by telephone for retesting or declined to be retested. Retested blood donors found to be newly positive for anti-HCV completed a structured questionnaire aimed at investigating risk factors for HCV infection, including endoscopic procedures, travel history, sexual activity, and potential parenteral exposures to blood or blood products (previous blood, platelet, or plasma transfusions; administration of coagulation factor concentrates; intravenous drug use; tattooing; acupuncture therapy; ear piercing; and major or minor surgery). Cleaning and Disinfection Method The instruments used for the known HCV carriers were not handled differently from those used for the HCV-negative patients; they were not removed from the general instrument pool, were disinfected in the same way as the others, and were then used promptly to perform endoscopy on the HCV-negative patients. Moreover, endoscopic procedures in known HCV carriers were not postponed at the end of the session but were performed according to the list of scheduled appointments. All units participating in this study adhered to the international guidelines for cleaning and disinfection practices in digestive endoscopy (6-10) and reprocessing endoscopic accessories (11); written protocols were available in each center. The staff involved in disinfection procedures consisted of trained nurses who were unaware of the ongoing study. At the end of the endoscopic procedure, the staff manually cleaned the instrument, including brushing the channels; each internal channel was flushed with detergent, rinsed with water, and blown through with air. The endoscopic units used 3 different automated washer-disinfectors (DSD-91E, Medivators, Minneapolis, Minnesota; Circlean MC-12, Shoei, Tokyo, Japan; and ETD2, Olympus Europe), but the reprocessing cycle was similar: 1) The units were immersed in 2% glutaraldehyde for 20 minutes, and internal channels were flushed with the same solution; 2) the units were rinsed internally and externally with drinking-quality water to remove all traces of disinfectant; and 3) the units were dried externally and each channel was flushed with air. Before the first endoscopy of each day, all endoscopes were disinfected in a washer-disinfector. After use, reusable biopsy forceps were immersed in enzymatic detergent solutions; next, they were cleaned first manually and then by a medical-grade ultrasonic cleaner. After rinsing and drying, the forceps were sterilized by autoclave at 134 C for at least 5 minutes. Finally, the sterilized devices were stored in sterile packaging in a closed cupboard where they were protected from dust, humidity, and temperature fluctuations. Laboratory Methods We tested for anti-HCV by using a third-generation enzyme immunoassay (Ortho HCV EIA-3, Ortho Diagnostic Systems, Raritan, New Jersey). Anti-HCV immunoreactivity was confirmed with a third-generation immunoblot assay (RIBA-3, Chiron Corp., Emeryville, California, and Ortho Diagnostic Systems). We measured HCV RNA by using PCR (Cobas Amplicor 2.0, Roche Diagnostic Systems, Branchburg, New Jersey); the sensitivity of this assay was 1000 copies/mL. Statistical Analysis We estimated person-years of observation and incidence rates of anti-HCV seroconversion for both cohorts. We used the difference between the incidence rates to compare the 2 cohorts. For the endoscopy cohort, we also measured the risk for anti-HCV seroconversion 6 months after the procedure, using the number of persons as denominators. Further analyses were limited to subgroups of the endoscopy cohort: 1) 6132 patients who underwent biopsy (biopsy cohort) and 2) 912 patients who underwent endoscopy later in the same day as and with the same instruments used in HCV-positive patients (at-risk cohort). Because we could not identify with certainty each patient in the at-risk cohort, we estimated that number with a rough but conservative approach. If we assume that each endoscope was used approximately 3 times during an ordinary endoscopic session and that at least 1 HCV carrier would be seen at

Adrenaline plus cyanoacrylate injection for treatment of bleeding peptic ulcers after failure of conventional endoscopic haemostasis

BACKGROUND Endoscopic therapy is a safe and effective method for treating non-variceal upper gastrointestinal bleeding. However failure of therapy, in terms of continuing bleeding or rebleeding, is seen in up to 20%. Cyanoacrylate is a tissue glue used for variceal bleeding that has occasionally been reported as an alternative haemostatic technique in non-variceal haemorrhage. AIM To retrospectively describe personal experience using cyanoacrylate injection in the management of bleeding ulcers after failure of first-line endoscopic modalities. PATIENTS AND METHODS Between January 1995 and March 1998, 18 [12 M/6 F, mean age 68.1 years) out of 176 patients, referred to our Unit for non-variceal upper gastrointestinal bleeding, were treated with intralesional injection of adrenaline plus undiluted cyanoacrylate. Persistent bleeding after endoscopic haemostasis or early rebleeding were the indications for cyanoacrylate treatment. RESULTS Definitive haemostasis was achieved in 17 out of 18 patients treated with cyanoacrylate. One patient needed surgery. No early or late rebleeding occurred during the follow-up. No complications or instrument lesions related to cyanoacrylate were recorded. CONCLUSIONS In our retrospective series, cyanoacrylate plus adrenaline injection was found to be a potentially safe and effective alternative to endoscopic haemostasis when conventional treatment modalities fail in controlling bleeding from gastroduodenal ulcers.

Etiology of and risk factors for transient and persistent aminotransferase elevation in a population of virus-free blood donors: a multicentre study.

AIM We evaluated the etiology and risk factors for transient and persistently elevated aspartate and/or alanine aminotransferase levels in virus-free blood donors. METHODS INCLUSION CRITERIA HBsAg/HBV-DNA and anti-HCV/HCV-RNA negative blood donors with elevated aspartate aminotransferase and/or alanine aminotransferase, observed in 5 blood transfusion centres in Italy from 2004 to 2005. Aspartate aminotransferase/alanine aminotransferase levels were measured at entry and every 2 months during a period of 6 months. RESULTS 291 individuals were evaluated (144 with persistent and 147 with transient abnormal aminotransferases). High body mass index was the most frequent (75.5%) etiological factor and was more common in the persistent elevated levels group, compared to the transient elevated levels group (82.0% vs 65.3%; p<0.01). Excessive alcohol intake (>2 units/day) was reported in 23.6%, with no differences between the two groups. Instead, recent use of medication or paint exposure were most frequently associated with transient elevated levels than persistent elevated levels (61.6% vs 23.3% for drugs and 13.7% vs 4.3% for paint, p<0.001). Considering the participants with transient elevated levels as controls, the multivariate analysis showed that high body mass index was the only independent predictor of persistent elevated aminotransferase levels (OR=5.3; 95%CI=1.88-13.42 for those with body mass index>29.9). CONCLUSIONS In virus-free blood donors, excessive body mass index is the most frequent etiological factor of abnormal aminotransferases and it is the sole risk factor associated with persistently elevated aminotransferases.