Maurizio Fadda

Treatment of recurrent hepatitis C in liver transplants: efficacy of a six versus a twelve month course of interferon alfa 2b with ribavirin ☆

BACKGROUND/AIMS Interferon (IFN) with ribavirin combination therapy (CT) was proposed for the treatment of hepatitis C recurring in liver transplants. We assessed the efficacy of two protocols of CT in transplanted patients with recurrent severe hepatitis C virus (HCV) hepatitis. METHODS Fifty-seven patients (68% genotype 1b) were treated with IFN alfa-2b 3 million units three times weekly and oral ribavirin 800mg/die for 6 or 12 months. Study end-points were the end of treatment (ETVR) and the 12-month post-therapy sustained virologic response (SVR; negative HCV-RNA). RESULTS ETVR was induced in 9/27 (33%) and in 7/30 patients (23%) treated, respectively, for 6 and 12 months (P=0.4); a SVR was induced in six (22%) of the former and five (17%) of the latter (P=0.4). HCV genotype non-1 patients responded better than genotype 1 (SVR: 43% in genotype non-1 versus 12% in genotype 1, P: 0.02). In ETV responders the hepatitis activity index improved by >2 points in biopsies taken after therapy compared to pre-therapy biopsies. Anemia and leukopenia required reduction of therapy in 51% of the patients. CONCLUSIONS CT is efficacious in controlling HCV disease in about 20% of transplants with recurrent hepatitis C. Six months of therapy are as efficacious as 12 months.

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.

Colectomy rate in steroid-refractory colitis initially responsive to cyclosporin: a long-term retrospective cohort study

BackgroundThere is consistent evidence that 50% of patients with acute, steroid-resistant flare of ulcerative colitis (UC) may achieve remission and avoid colectomy if treated with cyclosporin (CsA). However, follow-up of the responders has shown that most of them relapse and need surgery shortly after the response. We compared the records of our CsA-treated patients with those of other groups in order to help clarify this matter.MethodsAll patients admitted consecutively to our Unit with an attack of UC and treated with CsA between January 1991 and December 1999 were studied. Patients were begun on continuously-infused CsA at 2 mg/kg/day (1991–1996), or on NEORAL at an initial dose of 5 mg/kg/day (1996–1999). The maintenance treatment included oral CsA for 3–6 months with or without azathioprine (AZA). CsA failure was defined as a relapse requiring steroids with or without progression to colectomy; the cumulative probability of relapse/colectomy was assessed by Fishers exact tests and Kaplan-Meier analysis.ResultsAmong the patients, 39/61 (63%) initially responded. These 39 included a fatality and 4 drop-outs (unrelated to the side-effects of CsA), leaving 34 patients for the study. Of these, 61% and 35% were colectomy-free at 1 and 7 years, respectively; the corresponding figures were 80 and 60% respectively in the subset treated with AZA, but 47% and 15% in the AZA-untreated subgroup (p= 0.0007 at 7 years). Among the 34 patients, 44% were relapse-free at 1 year, but all had relapsed at 7 years (p = 0.0635). The overall resort to colectomy was 72%, while 19% of the patients remained colectomy-free.ConclusionSixty percent of a cohort of patients with steroid-refractory colitis responded to CsA and 60% of these responders retained the colon after 1 year. These figures fell to 35% at 7 years but improved to 60% on AZA. The overall need for colectomy remains high in these patients and toxicity must be monitored.

Preliminary experience with a new cytology brush in EUS-guided FNA

BACKGROUND Despite the high diagnostic yield of EUS-guided FNA, room for technical improvements remains. Recently, the EchoBrush (Cook Endoscopy, Winston-Salem, NC), a disposable cytologic brush, was introduced to the market. To date, only 1 study, limited to 10 pancreatic cyst cases, using this device has been published. OBJECTIVE To assess the diagnostic yield of the EchoBrush in a cohort of consecutive patients, irrespective of the target lesion. DESIGN Case series. SETTING Tertiary care university hospital (Molinette Hospital, Turin, Italy). PATIENTS Thirty-nine consecutive patients (12 with solid pancreatic masses, 12 with pancreatic cysts, 7 with enlarged lymph nodes, and 8 with submucosal masses) were enrolled. INTERVENTIONS The material collected with the EchoBrush and with a standard FNA needle was double-blind evaluated by 2 cytopathologists. MAIN OUTCOME MEASUREMENTS Adequacy of the sample and sensitivity and specificity of the EchoBrush method. RESULTS Adequate material for cytologic analysis was collected in 17 of 39 patients (43.6%) with a single pass of the EchoBrush. Results were better for pancreatic lesions (for solid and cystic lesions, the adequacy was 58.3% and 50%, respectively); adequacy was low (28.6% and 25%, respectively) for lymph nodes and submucosal masses. The overall sensitivity and specificity were 57.9% and 31.2%, respectively. There were no adverse events with the procedure. LIMITATION Preliminary study. CONCLUSIONS This report suggests that the EchoBrush may provide adequate cellularity to diagnose solid and cystic pancreatic lesions. More extensive studies are needed to compare the EchoBrush and standard needles.

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.

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.

The 17-year single-center experience with the use of azathioprine to maintain remission in ulcerative colitis.

Despite the accumulation of positive data, the role of azathioprine (AZA) in the maintenance of remission of ulcerative colitis is still controversial. We looked at the follow-up of the ulcerative colitis patients who, after responding to either steroids or cyclosporin (CsA), received AZA at our referral center for over a decade. The 39 patients (29 m/10f) were treated between 1991 and 2007. Twenty-five of them had responded to CsA, the remaining 14 to corticosteroids. AZA was usually overlapped with either of the two agents at the initial dose of 2mg/kg/day. The definitions of remission, relapse, and AZA toxicity followed commonly agreed criteria. The median duration of the AZA treatment was 14 months (<1-201). Fifty-two percent and 14%, respectively, of the CsA and the steroid responders needed surgery (overall rate=38%). The figures were 32 and 15 at the first year. The majority of the patients had 1-2 relapses often in connection with withdrawal of AZA; only 3 of these relapsers needed hospitalization. AZA caused toxicity in 16/39 (41%) patients, requiring withdrawal in 23% of the cases; leukopenia (17%) and hepatitis/cholestasis (10%) ranked first and second for frequency. All of the patients in whom AZA was stopped (or reduced) relapsed. In conclusion, the 1-year colectomy rates compare favorably with the figures reported by the literature. By contrast, the toxicity rates were higher than expected. Failure to genotype or to use escalating AZA doses can only be hypothesized as causes.

Longitudinal study of quality of life in advanced cancer patients on home parenteral nutrition

Since there is little knowledge regarding the quality of life (QoL) of cancer patients on home parenteral nutrition (HPN), we planned a prospective, longitudinal, double‐center study to investigate the changes of QoL in these patients. One hundred and eleven adult cancer patients who were candidates for HPN following the indications of the European guidelines were consecutively enrolled. For QoL analysis, EORTC QLQ‐C30 questionnaires were filled at the HPN start and after 1, 2, 3, and 4 months, and scores changes over time were analyzed according to the univariate mixed‐effects linear model for repeated measures. Most patients had gastrointestinal cancers, were severely malnourished, and were in stage IV; two‐thirds were still receiving oncologic treatments. Median weight loss over 3 months and body mass index were 11.7% and 20.7, respectively. Median survival was 4.7 (1–42) months; 67 and 34% of patients survived 3 and 6 months, respectively. Global QoL, physical functioning, role functioning, emotional functioning, appetite loss, and fatigue scores had a statistically significant trend over time (P < 0.001, P < 0.001, P = 0.007, P < 0.001, P = 0.004, P = 0.022, respectively). At the univariate analyses, the determinants significantly associated with changes in trend over time for physical, role, and emotional functioning were oncologic treatments (P < 0.001, P = 0.014, P = 0.040, respectively) and for appetite loss they were weight loss and Karnofsky performance status (P = 0.003, P = 0.023, respectively). Global QoL, physical, role, and emotional functioning improved during HPN even in advanced cancer patients on oncologic treatments.

Antibiotics and Non-Steroidal Anti-Inflammatory Drugs in Outpatient Practice: Indications and Unwanted Effects in a Gastroenterological Setting

OBJECTIVE To explore the type and frequency of the unwanted effects following use of non-steroidal antiinflammatory drugs (NSAIDs) and antibiotics in a gastroenterological out-patient setting. METHODS We analyzed a gastroenterological database which includes 151 inflammatory bowel disease (IBD) patients followed between January 2008 and December 2009. The key-words included NSAIDs and antibiotics. RESULTS Of 19 cases treated with NSAIDs, 8 displayed convincing evidence linking them with the subsequent development of IBD. Of 44 antibiotic mentions, 7 documents alluded to macrolide prescriptions, which were followed by induction or relapse of IBD in 5; all of the newly diagnosed cases of IBD were endoscopically proven, and one ran a fulminant course requiring emergency colectomy; 4 of 5 prescriptions of amoxycillin/clavulanic acid were accompanied by toxicity (three hepatitides and one reactivated IBD). Overall, the frequency of unwanted effects was 36% for both NSAIDs and antibiotics. CONCLUSION We suggest that NSAIDs and antibiotics (specifically of the macrolide structure) can induce gut and hepatic damage, significantly enhancing co-morbidities in gastroenterologic out-patients, with break of cost-containment guidelines. Therefore, caution is advisable in prescribing NSAIDs and antibiotics in this setting. Though retrospective and possibly biased, the current data coincide with both bench work and epidemiological evidence.

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.