Wilma Debernardi Venon

Renal failure in cirrhotic patients: role of terlipressin in clinical approach to hepatorenal syndrome type 2

Objectives Renal failure secondary to hepatorenal syndrome or to organic renal disease occurs frequently in cirrhotic patients with portal hypertension. The present prospective study investigates the usefulness of terlipressin in both the diagnostic and the therapeutic approach to cirrhotics with renal failure. Patients and methods Sixteen patients were studied: 11 with hepatorenal syndrome type 2 (group 1) and five with organic renal disease (group 2). All received terlipressin (1 mg/4 h intravenously) for 7 days. Subsequently, 12 patients (nine from group 1 and three from group 2) underwent a transjugular intrahepatic portosystemic shunt. Results Terlipressin significantly improved renal function (serum creatinine, 1.8 ± 0.8 versus 2.4 ± 0.9 mg/dl; blood creatinine clearance, 53 ± 8 versus 21.3 ± 8.7 ml/min; P < 0.05) in group 1 [8/11 patients (73%) versus 1/5 (20%) of group 2; P < 0.05]. The only patient in group 2 who responded to terlipressin had a mixed renal dysfunction. Renal function improved significantly after transjugular portosystemic shunt in all patients who responded to terlipressin. Conclusions Terlipressin administration significantly improves renal function in cirrhotic patients with hepatorenal syndrome type 2 but not in organic kidney failure. By providing the critical information that a patients kidney function is (or is not) reversible, a trial with terlipressin may be useful when selecting cirrhotic patients with renal failure as candidates for a transjugular intrahepatic portosystemic shunt or liver transplantation.

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

Effects of long-term Irbesartan in reducing portal pressure in cirrhotic patients: comparison with propranolol in a randomised controlled study

BACKGROUND/AIMS The role of angiotensin II (AT-II) type I receptor antagonists in the treatment of portal hypertension remains controversial. We tested the efficacy of Irbesartan (Irb) vs. Propranolol (Pro) in reducing portal pressure and evaluated its systemic haemodynamic effects. METHODS Thirty-four patients were randomly assigned to receive either Irb 300 mg/day (19 patients) or Pro 40-120 mg/day (15 patients) for 2 months. RESULTS Irb was discontinued in five patients (26%). No major side effect occurred in the Pro group. On an average, the portal pressure gradient decreased significantly more in the Pro than in the Irb group (median -19.5%, range -11/-31% vs. -4.8%, +2.5/-10%, P<0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P<0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P<0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P<0.0001 vs. basal). CONCLUSIONS Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.

Consensus conference on TIPS management: Techniques, indications, contraindications

The trans jugular intrahepatic Porto systemic shunt (TIPS) is no longer viewed as a salvage therapy or a bridge to liver transplantation and is currently indicated for a number of conditions related to portal hypertension with positive results in survival. Moreover, the availability of self-expandable polytetrafluoroethylene (PTFE)-covered endoprostheses has dramatically improved the long-term patency of TIPS. However, since the last updated International guidelines have been published (year 2009) new evidence have come, which have open the field to new indications and solved areas of uncertainty. On this basis, the Italian Association of the Study of the Liver (AISF), the Italian College of Interventional Radiology-Italian Society of Medical Radiology (ICIR-SIRM), and the Italian Society of Anesthesia, Analgesia and Intensive Care (SIAARTI) promoted a Consensus Conference on TIPS. Under the auspices of the three scientific societies, the consensus process started with the review of the literature by a scientific board of experts and ended with a formal consensus meeting in Bergamo on June 4th and 5th, 2015. The final statements presented here were graded according to quality of evidence and strength of recommendations and were approved by an independent jury. By highlighting strengths and weaknesses of current indications to TIPS, the recommendations of AISF-ICIR-SIRM-SIAARTI may represent the starting point for further studies.

Safety of propofol in cirrhotic patients undergoing colonoscopy and endoscopic retrograde cholangiography: results of a prospective controlled study

Background and aims Safety of propofol sedation in patients with liver cirrhosis undergoing colonoscopy or endoscopic retrograde cholangiopancreatography (ERCP) remains to be studied. The aim of this study was to investigate whether the use of propofol is safe for endoscopic procedures more complex than gastroscopy in patients with liver cirrhosis in a prospective controlled study. Methods Two hundred and fourteen consecutive patients, with or without cirrhosis, who underwent colonoscopy or ERCP with propofol sedation were recruited between January and June 2009. Administration of sedation was performed by anesthesiologists and outcome measures were recorded. Main outcomes were complication rates and recovery times. Results Sixty-one (28.5%) cirrhotic patients and 153 (71.5%) noncirrhotic patients were included. The incidence of sedation-related complications did not significantly differ between the two populations (11.5 vs. 17.0%, respectively, P=0.31). The mean (±SD) dose of propofol administered (213±86 vs. 239±100 mg, P=0.07), the mean time to achieve adequate sedation (3.3±1.1 vs. 3.0±1.2 min, P=0.21), the mean total duration of the endoscopic procedure (24.5±10.6 vs. 27.4±11.8 min, P=0.08), the mean time to reach Observer’s Assessment of Alertness and Sedation Scale 5 (17.2±4.4 vs. 18.4±5.6 min, P=0.15), the mean time from completion of the procedure to release (9.0±2.5 vs. 9.1±3.2 min, P=0.86), and the mean time to full recovery (42.2±7.3 vs. 42.3±7.8 min, P=0.88) were very similar between the two groups. The limitation of this study was lack of randomization, and a control group of cirrhotic patients using standard sedation with benzodiazepines and opioids. Conclusion Propofol deep sedation administered by an anesthesiologist with appropriate monitorings seems to be a safe procedure during colonoscopy or ERCP in cirrhotic patients.

Application of the model for end-stage liver disease score for transjugular intrahepatic portosystemic shunt in cirrhotic patients with refractory ascites and renal impairment.

Background and aims Transjugular intrahepatic portosystemic shunt (TIPS) can manage severe complications of portal hypertension. The Mayo Clinic group proposed a so-called model for end-stage liver disease (MELD) to predict survival in cirrhotic patients. High creatinine levels determine a decrease in calculated survival chances with MELD but functional renal disease can be reversed by TIPS. The aim of this study was to evaluate the efficacy of MELD in predicting survival after TIPS, particularly in patients with refractory ascites associated with functional renal failure. Methods This retrospective analysis examines 68 cirrhotic patients who underwent elective TIPS: 48 patients had refractory ascites and 20 patients had recurrent variceal bleeding. Multivariate analysis was used to establish predictive parameters of survival after TIPS. Kaplan–Meier and log-rank tests were used to compare survival rates observed in our patients with those evaluated with the MELD score. Results The age of patients was the only variable shown to have an independent value in predicting survival after TIPS. In patients undergoing shunting for refractory ascites, the survival rates at 6, 12 and 24 months after the procedure were significantly higher than expected with the MELD score. Conclusions The MELD scale may underestimate the efficacy of TIPS in end-stage cirrhotic patients with refractory ascites and functional kidney dysfunction. Further studies are needed to confirm this finding and ultimately to assess a correction factor to better predict survival after TIPS in patients with functional renal impairment.

Transcatheter arterial chemoembolization for hepatocellular carcinoma in cirrhosis: influence on portal hypertension.

Background Transcatheter arterial chemoembolization (TACE) is a routine treatment for hepatocellular carcinoma in cirrhotic patients. Whether TACE influences the degree of portal hypertension remains uncertain. Aim and Patients We retrospectively analyzed the clinical course of 283 TACE to investigate the incidence of variceal bleeding and ascites after the procedure. We also prospectively evaluated portal pressure by hepatic venous portal gradient (HVPG) before and within 3 days by TACE in a group of 15 patients. Results Before TACE, esophageal varices were present in 125 patients. Variceal bleeding occurred in three (1.5%) and ascites in two (1%) patients during the follow-up post-TACE. Patients with variceal bleeding were significantly older (P=0.019). In 15 patients who underwent portal pressure measurement before and within 3 days by TACE, HVPG was unchanged (mean 13.1 vs. 12.8 mmHg, P>0.05). Conclusion In our series portal hypertension-related complications after TACE were rare and did not result in higher mortality. As TACE did not influence HVPG, the preventive ligation of esophageal varices before TACE does not seem justified.

Prospective randomized trial: endoscopic follow up 3 vs 6 months after esophageal variceal eradication by band ligation in cirrhosis.

BACKGROUND AND OBJECTIVES Endoscopic variceal ligation (EVL) is recommended to treat esophageal varices (EV) in cirrhosis and portal hypertension. A program of endoscopic surveillance is not clearly established. The aim of this prospective randomized trial was to assess the most effective timing of endoscopic monitoring after variceal eradication and its impact on the patients outcome and on the costs. METHODS A hundred and two cirrhotic patients with esophageal varices treated by EVL were evaluated. After variceal eradication patients were randomized to receive first endoscopic control at 3 (Group 1) and 6 (Group 2) months respectively. RESULTS Variceal obliteration was achieved in all patients. Variceal recurrence was observed in 28 cases at the first control (29.1%) without difference between the two groups (32% vs 29% in group 1 and 2 respectively, p=0.75). The incidence of large varices is similar in the two groups (33% vs 38% respectively). Using a multivariate analysis, medical therapy with B blockers was the only independent predictor of lowest risk of variceal recurrence [OR 2.30, 95% CI (1.68-3.26)]. Bleeding related to recurrent varices occurred in 3.1% of cases and was associated with portal thrombosis. Child Pugh score ≥8 was the only predictor of mortality (p=0.0002). CONCLUSIONS Recurrence of varices after banding ligation is not rare but it is associated with a low risk of variceal progression and bleeding. Accordingly, a first endoscopic control at 6 months after variceal eradication associated with a good risk stratification might be a cost-effective strategy of monitoring.

⁎4532 Clinical application of endoscopic ultrasound in portal hypertension: eus can predict variceal recurrence in endoscopically treated patients.

BACKGROUND AND AIM: 210 After endoscopic eradication of oesophageal varices by means of sclerotherapy or rubber-band ligation, varices recurrence remains a maior problem. Some studies suggested that in patients with endoscopic signs of varices obliteration, EUS may demostrate still patent residual lumina in the esophageal wall. The aim of our study was to assess if EUS can supply usefull information in the evaluation of endoscopic varices eradication in order to predict variceal recurrence and rebleeding.MATERIAL AND METHODS: 107 patients (74 men, mean age 56±11 years) bleeding from gastroesophageal varices underwent endoscopic treatment by means of sclerotherapy or rubber-band ligation until obtaining endoscopic eradication of oesophageal varices in 104 of them. Then they underwent EUS with a rotating sector scanner (Olympus GF-UM3/UMQ130) within 1 month from the treatment. Eighty-six of the 104 eradicated patients had an endoscopic follow-up (8.8 ± 7.1 months) to evaluate the recurrence of oesophageal varices. RESULTS: 56 of the endoscopically eradicated patients (65%) were not judged completely eradicated by EUS, because it made possible to identify still patent variceal lumina or just partially thrombosed vessels or some small residual anechoic structures in the oesophageal wall. Forty-one of them (73%) developed recurrence of oesophageal varices, while just 8 out of the remaining 30 patients (27%), judged eradicated by both endoscopy and EUS, showed oesophageal varices in the follow-up (Chi-square P=0.02). CONCLUSIONS: EUS detects more patent residual vessels in the esophageal wall than endoscopy after endoscopic variceal eradication by means of sclerotherapy or rubber-band ligation. These EUS findings may have a precise clinical impact: predicting variceal recurrence they can indicate the need of further endoscopic therapy.

4756 Eus can supply information of clinical usefulness and prognostic value in evaluating patients with portal hypertension (ph).

Purpose: EUS can be of value in evaluating gastroesophageal signs of PH. The aim of our study was to show that EUS may add usefull information to the endoscopic diagnosis of gastroesophageal complications of PH and it can be more sensitive than endoscopy at gastric level. Methods: 149 patients (pts) (105 men, mean age 55±12 years) with endoscopic signs of PH underwent EUS with a rotating sector scanner (Olympus GFUM3/UMQ130). 107 pts were endoscopically treated after bleeding until obtaining oesophageal eradication in 104. Afterward they underwent EUS within 1 month. 109 pts were followed up by endoscopy. Results: gastric varices were diagnosed in 14 of the 109 followed up pts (13%) by endoscopy and in 32 (29%) by EUS. Of the 95 pts without gastric varices at endoscopy 21 (22%) were positive at EUS and 2/21 (9%) developed them during the follow-up. Conversely 3/74 pts without gastric varices at endoscopy and EUS developed them successively (4%). About junctional varices 18/109 (16%) pts were positive at endoscopy, 54/109 (50%) at EUS. Of the 91 pts without junctional varices at endoscopy 43 resulted positive at EUS (47%) and 11/43 (26%) developed them during the follow-up versus 2/48 pts (4%) without junctional varices at EUS (Fisher exact test P=0.026). 111/148 showed EUS features described as typical for congestive gastropathy (CG), while only 61/148 were positive at endoscopy (Chi-square P=0.023). Conversely 37/148 pts did not show any typical signs of CG at EUS versus 87/148 at endoscopy (Chi-square P=0.001). Conclusion: according to the literature in our study EUS detected more gastric and junctional varices than endoscopy. EUS supplied usefull information to predict the development of new junctional varices during the follow-up of pts previously endoscopically negative. Unluckily the number of pts is still too small for any statistically significant meaning of EUS in predicting the development of new gastric varices. Furthermore EUS seems to have a very high positive and an even higher negative predictive value in detecting CG compared to endoscopy.