Raffaella Lionetti

A new highly effective short-term therapy schedule for Helicobacter pylori eradication

Although triple therapy regimens suggested in the Current European guidelines give fairly good results, several studies have reported an unsatisfactory Helicobacter pylori eradication rate (< 80%).

Modification of cardiac function in cirrhotic patients with and without ascites

OBJECTIVES: Abnormalities in cardiac function have been reported in liver cirrhosis, suggesting a latent cardiomyopathy in these patients. In this study we investigated cardiac function in cirrhotic patients and in controls. METHODS: A total of 20 cirrhotic patients without previous or ongoing ascites, 20 cirrhotic patients with moderate-to-severe ascites, and 10 healthy controls were studied by two-dimensional Doppler echocardiography. Cardiac dimensions and left and right ventricular function were evaluated. The left ventricular geometric pattern was calculated according to Ganau’s criteria. Diastolic function was evaluated by the peak filling velocity of E wave and A wave, E/A ratio, and deceleration time of E wave. The pulmonary systolic arterial pressure was also estimated in patients with tricuspid insufficiency. RESULTS: Right and left atrium and right ventricle diameters were significantly enlarged in cirrhotic patients versus controls. E/A ratio was decreased (p < 0.05) in patients with ascites (0.9 ± 0.2) versus those without ascites (1.3 ± 0.4) and controls (1.3 ± 1). The estimated pulmonary systolic arterial pressure was slightly elevated in patients with ascites (35 ± 5 mm Hg, six patients) versus those with no ascites (28 ± 5, 10 patients) and controls (27 ± 8, 6 controls, analysis of variance, p < 0.05). The pattern of left ventricular geometry was normal in the majority of patients. Nitrite and nitrate levels were increased in cirrhotics irrespective of the presence of ascites. CONCLUSIONS: Liver cirrhosis is associated with enlarged right cardiac chambers. Diastolic dysfunction and mild pulmonary hypertension are evident in cirrhotic patients with ascites. These changes do not depend on variations in the left ventricular geometry.

Hepatic encephalopathy after transjugular intrahepatic portosystemic shunt. Incidence and risk factors

Forty-seven consecutive patients were prospectively evaluated to study the incidence of hepatic encephalopathy as well as modifications in the PSE index after TIPS. Various clinical, laboratory, and angiographic parameters were also recorded to identify risk factors for the development of post-TIPS hepatic encephalopathy (HE). Mean follow-up was 17±7 months. During follow-up, six patients died and one underwent transplantation. All other patients were followed for at least a year. Fifteen patients (32%) experienced 20 acute episodes of precipitated HE (hospitalization was necessary in 10 instances), and five patients (11%) presented a continuous alteration in mental status with frequent spontaneous exacerbation during follow-up. Both precipitated and spontaneous HE occurred more frequently during the first three months of follow-up. Moreover the PSE index was significantly worse than basal values one month after TIPS, thereafter returning to near basal values. HE was successfully treated in all patients but one who required a reduction in the stent/shunt diameter. Increasing age (>65 years) and low portacaval gradient (<10 mm Hg) were predictors of HE after TIPS. A gradual dilation of the stent/shunt should be performed to obtain a portacaval gradient >10 mm Hg to avoid an unacceptable rate of HE after TIPS.

Sofosbuvir plus daclatasvir for post-transplant recurrent hepatitis C: Potent antiviral activity but no clinical benefit if treatment is given late

BACKGROUND We evaluated efficacy and safety of sofosbuvir and daclatasvir±ribavirin in liver transplant recipients with severe recurrent hepatitis C. METHODS Patients included in an international compassionate use programme for treatment with sofosbuvir and daclatasvir±ribavirin for 24 weeks were prospectively studied. Serum hepatitis C virus RNA was measured at treatment weeks 4, 12, and 24 and during follow-up at weeks 4, 8, and 12. RESULTS Twelve patients (3 with fibrosing cholestatic hepatitis and 9 with cirrhosis; median model for end-stage liver disease score 20) received sofosbuvir 400mg/day+daclatasvir 60mg/day, and 6 patients (50%) also received ribavirin 200-800mg/day. Nine patients completed 24 weeks of treatment (75%), and all had undetectable hepatitis C virus RNA at week 24; 3 patients died (25%, liver failure, gastrointestinal bleeding and sepsis); 4 patients experienced severe liver disease-related adverse events. Post-treatment hepatitis C virus RNA was available for 5 patients (week 8, n=2; week 4, n=3) and was undetectable in all cases. Mean Child-Pugh score and albumin level improved significantly at week 24. No changes in immunosuppressant doses were needed. CONCLUSION All-oral sofosbuvir plus daclatasvir combination shows high virological efficacy in liver transplant recipients and does not interact with immunosuppressants. All adverse events were unrelated to study drugs. These data strongly suggest that this combination must be initiated before decompensation.

Ten and eight-day sequential therapy in comparison to standard triple therapy for eradicating Helicobacter pylori infection: a randomized controlled study on efficacy and tolerability.

Background Sequential therapy (SQT) is effective in the eradication of Helicobacter pylori and could become an alternative to standard triple therapy (STT). Aim To compare the efficacy and tolerability of SQT, for either 8 or 10 days, with a 7-day STT. Methods A total of 270 naive H. pylori-positive patients were randomized to receive: SQT for 8 days (SQT-8, n=90) or 10 days (SQT-10, n=90) including esomeprazole 20 mg twice daily (bid) associated with amoxicillin 1000 mg bid (early 4 and 5 d, respectively), followed by esomeprazole 20 mg bid associated with clarithromycin 500 mg bid plus tinidazole 500 mg bid (last 4 and 5 d, respectively); STT (n=90) including esomeprazole 20 mg bid plus amoxicillin 1000 mg bid and clarithromycin 500 mg bid for 7 days. Tolerability was assessed by scoring the severity of symptoms. Results Eradication rates after SQT-8 and SQT-10 were higher than that of after STT at both intention-to-treat (83% and 86% vs. 66%, P<0.02) and per-protocol analysis (90% and 88% vs. 75%, P<0.05), whereas no difference was found between the 2 SQTs. Conclusions This study shows that SQT, for 8 or 10 days, is well tolerated and highly effective in H. pylori eradication and could represent a valid alternative to STT. Further studies, with more power, on larger populations and from other countries are necessary to validate the present findings.

Daclatasvir combined with sofosbuvir or simeprevir in liver transplant recipients with severe recurrent hepatitis C infection

Daclatasvir (DCV) is a potent, pangenotypic nonstructural protein 5A inhibitor with demonstrated antiviral efficacy when combined with sofosbuvir (SOF) or simeprevir (SMV) with or without ribavirin (RBV) in patients with chronic hepatitis C virus (HCV) infection. Herein, we report efficacy and safety data for DCV‐based all‐oral antiviral therapy in liver transplantation (LT) recipients with severe recurrent HCV. DCV at 60 mg/day was administered for up to 24 weeks as part of a compassionate use protocol. The study included 97 LT recipients with a mean age of 59.3 ± 8.2 years; 93% had genotype 1 HCV and 31% had biopsy‐proven cirrhosis between the time of LT and the initiation of DCV. The mean Model for End‐Stage Liver Disease (MELD) score was 13.0 ± 6.0, and the proportion with Child‐Turcotte‐Pugh (CTP) A/B/C was 51%/31%/12%, respectively. Mean HCV RNA at DCV initiation was 14.3 × 6 log10 IU/mL, and 37% had severe cholestatic HCV infection. Antiviral regimens were selected by the local investigator and included DCV+SOF (n = 77), DCV+SMV (n = 18), and DCV+SMV+SOF (n = 2); 35% overall received RBV. At the end of treatment (EOT) and 12 weeks after EOT, 88 (91%) and 84 (87%) patients, respectively, were HCV RNA negative or had levels <43 IU/mL. CTP and MELD scores significantly improved between DCV‐based treatment initiation and last contact. Three virological breakthroughs and 2 relapses occurred in patients treated with DCV+SMV with or without RBV. None of the 8 patient deaths (6 during and 2 after therapy) were attributed to therapy. In conclusion, DCV‐based all‐oral antiviral therapy was well tolerated and resulted in a high sustained virological response in LT recipients with severe recurrent HCV infection. Most treated patients experienced stabilization or improvement in their clinical status. Liver Transplantation 22 446‐458 2016 AASLD

Whole body and regional body composition analysis by dual-energy X-ray absorptiometry in cirrhotic patients

Objectives: To compare whole body and regional (arms, legs and trunk) fat mass, fat-free mineral-free mass, bone mineral content and bone mineral density, measured by DXA, in cirrhotic patients and age, sex and BMI matched healthy volunteers.Design: Cross-sectional study.Setting: Two medical research institutions.Subjects: Twenty-two non ascitic cirrhotic patients and 16 age, sex and BMI matched healthy volunteers.Interventions: The Lunar DPX whole-body X-ray densitometer with Lunar software version 3.6z (Lunar Radiation Corp., Madison WI, USA) was used. Regional analysis was performed on the arms, legs, trunk and head.Results: Compared to controls, cirrhotic patients showed a significant reduction in percentage body fat. When differentiated by gender, however, the reduction in percentage body fat was evident in female cirrhotics only, particularly in the trunk. In male cirrhotic patients fat-free mineral-free mass was reduced in absolute terms in the whole body and the limbs. For both genders and in each body segment bone mineral content and density were reduced in cirrhotics compared to controls. In cirrhotic patients bone mineral density was significantly correlated to both fat-free, mineral-free mass (r=0.85; P<0.001) and to the Physical Activity Index (r=0.52; P<0.01).Conclusions: Two different patterns of soft tissue loss may be found in cirrhotic patients: in women lean tissue is maintained while fat stores are reduced, as in early starvation; in men lean tissue is reduced, as seen under conditions of stress. Moreover, factors influencing lean body mass, such as nutritional depletion and physical inactivity, may contribute to the reduction of bone density frequently observed in cirrhotic patients.Sponsorship: This work has been funded by the University of Rome, ‘La Sapienza’ research grant MURST 60%, 1995.

Portal vein aneurysm: What to know.

Portal vein aneurysm is an unusual vascular dilatation of the portal vein, which was first described by Barzilai and Kleckner in 1956 and since then less than 200 cases have been reported. The aim of this article is to provide an overview of the international literature to better clarify various aspects of this rare nosological entity and provide clear evidence-based summary, when available, of the clinical and surgical management. A systematic literature search of the Pubmed database was performed for all articles related to portal vein aneurysm. All articles published from 1956 to 2014 were examined for a total of 96 reports, including 190 patients. Portal vein aneurysm is defined as a portal vein diameter exceeding 1.9 cm in cirrhotic patients and 1.5 cm in normal livers. It can be congenital or acquired and portal hypertension represents the main cause of the acquired version. Surgical indication is considered in case of rupture, thrombosis or symptomatic aneurysms. Aneurysmectomy and aneurysmorrhaphy are considered in patients with normal liver, while shunt procedures or liver transplantation are the treatment of choice in case of portal hypertension. Being such a rare vascular entity its management should be reserved to high-volume tertiary hepato-biliary centres.

Laparoscopic liver resections in normal and cirrhotic livers: a retrospective analysis in a tertiary hepato-biliary unit.

BACKGROUND Liver surgery in patients with underlying liver disease results in higher mortality and morbidity rates compared to patients without underlying liver disease. Laparoscopy seems to have good results in patients with normal liver in terms of postoperative outcomes, but is more challenging in cirrhotic patients. Aim of this study was to evaluate the feasibility of laparoscopic liver resection both in normal and cirrhotic livers, and secondary endpoint was to compare the surgical results. METHODS We retrospectively evaluated 105 patients who underwent laparoscopic liver resection between November 2001 and January 2012. Candidates for laparoscopic liver resection were divided into two groups according to the presence or absence of an underlying liver disease. RESULTS 105 patients (52.4% males, median age 56.1 years) were enrolled, and 37.1% had liver cirrhosis. Hepatocellular carcinoma in hepatitis C virus-related cirrhosis (89.7%) and liver metastases (57.6%) were the main indications for surgery in patients with cirrhosis and non-cirrhotic livers, respectively. None of the patients died post-operatively. Cirrhotic patients had greater blood loss (100 vs 50 ml; p<0.012) and longer hospital stays (6 vs 4 days; p<0.031) compared to non-cirrhotics. CONCLUSIONS Laparoscopic liver resections are safe and feasible procedures in both patients with cirrhotic and non-cirrhotic livers.

Endoscopic management with multiple plastic stents of anastomotic biliary stricture following liver transplantation: long-term results

BACKGROUND AND AIMS Anastomotic biliary stricture (ABS) is the most common biliary complication after orthotopic liver transplantation (OLT) and can be successfully managed endoscopically. The long-term results of a protocol using placement of multiple plastic stents to treat ABS following OLT were analyzed. METHODS All patients who underwent endoscopic retrograde cholangiopancreatography (ERCP) for OLT-related biliary complications at our Endoscopy Unit between July 1994 and March 2012 were retrospectively identified from the ERCP database. Patients with an ABS treated with an increasing number of plastic stents were included in the study. Follow-up after stent removal was obtained by telephone contact with the patient and/or referring physician and by liver function tests (LFTs) evaluation. RESULTS 56 patients, treated with an increasing number of plastic stents until resolution of the stricture, were included. Five patients were then excluded (unrelated death during treatment, n = 3; incomplete treatment because of poor compliance, n = 2), and 51/56 patients reached study end points and were included in the analysis. Resolution of ABS was obtained in 50/51 patients; 1 patient required hepaticojejunostomy because of failure to pass the stricture with the guidewire (per protocol resolution, 98 %). Mean duration of endoscopic treatment was 11.5 months, with a median 4 ERCPs per patient. Immediate ERCP-related adverse events occurred in 3/56 patients (5.4 %). After a median follow-up of 5.8 years from stent removal, 3/50 patients (6 %) had recurrence of ABS. These 3 patients were successfully treated again endoscopically and are asymptomatic after a further median follow-up of 5.6 years. CONCLUSIONS At long-term follow-up, endoscopic treatment with multiple plastic stents of ABS following OLT appeared to be effective in most patients. Stricture recurrence is rare and can be successfully treated again endoscopically.