Imaging features of microvascular invasion in hepatocellular carcinoma developed after direct-acting antiviral therapy in HCV-related cirrhosis.

OBJECTIVES: To evaluate imaging features of microvascular invasion (MVI) in hepatocellular carcinoma (HCC) developed after direct-acting antiviral (DAA) therapy in HCV-related cirrhosis. METHODS: Retrospective cohort study on 344 consecutive patients with HCV-related cirrhosis treated with DAA and followed for 48-74 weeks. Using established imaging criteria for MVI, HCC features were analysed and compared with those in nodules not occurring after DAA. RESULTS: After DAA, HCC developed in 29 patients (single nodule, 18 and multinodular, 11). Median interval between therapy end and HCC diagnosis was 82 days (0-318). Forty-one HCC nodules were detected (14 de novo, 27 recurrent): maximum diameter was 10-20 mm in 27, 20-50 mm in 13, and > 50 mm in 1. Imaging features of MVI were present in 29/41 nodules (70.7%, CI: 54-84), even in 17/29 nodules with 10-20 mm diameter (58.6%, CI: 39-76). MVI was present in only 17/51 HCC nodules that occurred before DAA treatment (33.3%, CI: 22-47) (p= 0.0007). MVI did not correlate with history of previous HCC. CONCLUSIONS: HCC occurs rapidly after DAA therapy, and aggressive features of MVI characterise most neoplastic nodules. Close imaging evaluations are needed after DAA in cirrhotic patients. KEY POINTS: • In HCV cirrhosis, hepatocellular carcinoma develops soon after direct-acting antiviral therapy. • HCC presents imaging features of microvascular invasion, predictive of more aggressive progression. • Cirrhotic patients need aggressive and close monitoring after direct-acting antiviral therapy.

Early occurrence and recurrence of hepatocellular carcinoma in HCV-related cirrhosis treated with direct-acting antivirals.

BACKGROUND & AIMS: Hepatocellular carcinoma (HCC) represents a serious complication of HCV-related cirrhosis. New direct-acting antivirals (DAA) cure HCV infection in over 90% of patients. The aim of this study was to evaluate the early occurrence and recurrence of HCC in cirrhotic patients treated with DAA. METHODS: We analysed 344 consecutive cirrhotic patients, without HCC, who were treated with DAA, and followed for 24weeks. Fifty-nine patients had previous HCC. RESULTS: DAA therapy induced sustained virological response in 91% of patients. During 24-week follow-up, HCC was detected in 26 patients (7.6%, 95% CI: 4.99-10.84): 17 of 59 patients (28.81%, 95% CI: 17.76-42.07) with previous HCC and 9 of 285 patients (3.16%, 95% CI: 1.45-5.90) without previous HCC. Child-Pugh Class B, more severe liver fibrosis, lower platelet count, and previous HCC were significantly associated with HCC development, at univariate analysis. At multivariate analysis, Child-Pugh class (p=0.03, OR: 4.18, 95% CI: 1.17-14.8) and history of HCC (p<0.0001, OR: 12.0, 95% CI: 4.02-35.74) resulted independently associated with HCC development. Among the 59 patients with previous HCC, younger age and more severe liver fibrosis were significantly associated with HCC recurrence, both at univariate and at multivariate analysis. CONCLUSIONS: In patients with HCV-related cirrhosis, DAA-induced resolution of HCV infection does not seem to reduce occurrence of HCC, and patients previously treated for HCC have still a high risk of tumour recurrence, in the short term. For these reasons, all cirrhotic patients should be closely monitored and followed during and after antiviral therapy. LAY SUMMARY: New direct-acting antivirals are able to eradicate HCV infection in over 90% of patients with advanced liver disease. Unfortunately, the occurrence of liver cancer is not reduced in effectively treated cirrhotic patients. In addition, patients previously treated for HCC have still a high risk of tumour recurrence in the short term, despite DAA treatment.

Relationship between indocyanine green retention test, decompensation and survival in patients with Child-Pugh A cirrhosis and portal hypertension.

BACKGROUND & AIMS: Indocyanine green retention test (ICG-r15) is a non-invasive marker of functional hepatic reserve. Among patients with compensated cirrhosis, ICG-r15 correlates to the degree of portal hypertension (PH); however, its prognostic relationship with the occurrence of decompensation events still requires clarification. METHODS: ICG-r15 was prospectively measured in 154 patients with compensated cirrhosis. Patients with hepatocellular carcinoma (HCC), Child-Pugh B-C, MELD>15, bilirubin > 2 mg/dl, INR > 1.5 or portal vein thrombosis were excluded. All patients underwent laboratory tests, upper endoscopy and hepatic venous pressure gradient (HVPG). Decompensation, development of HCC, liver transplant and death were recorded and analysed through competing-risk analysis. RESULTS: The study group was composed of 134 patients who were followed for a median of 39 months. During follow-up, 46 patients (34.3%) developed liver decompensation. Hepatocellular carcinoma occurred in 18 patients and two patients died from non-liver-related causes. The 1-, 2- and 3-year cumulative incidences of decompensation were 9.7%, 28.4% and 33.4% respectively. Patients with ICG-r15 < 10% did not experience any decompensation events during follow-up, while the 3-year cumulative incidence of decompensation of patients with ICG-r15 between 10% and 22.9% was 29.2% and that of patients with ICG-r15 ≥ 23% was 70.0% (P < 0.001). ICG-r15 gave the lowest pseudo-log-likelihood value, in comparison to oesophageal varices present, MELD, low platelet count and HVPG. CONCLUSIONS: ICG-r15 appears to be strictly related to liver decompensation, longitudinally confirming the preliminary findings of its correlation with PH among patients with compensated cirrhosis, and can be used for patient prognostication.

Indocyanine green retention test as a noninvasive marker of portal hypertension and esophageal varices in compensated liver cirrhosis.

UNLABELLED: Noninvasive markers would be useful for the assessment of portal hypertension (PH) and esophageal varices (EV) in patients with cirrhosis. The aim of our study was to evaluate the performance of the indocyanine green (ICG) retention test as a noninvasive marker of PH and EV, measured against the gold standards (hepatic venous pressure gradient [HVPG] measurement and upper endoscopy). We prospectively enrolled patients with compensated cirrhosis referral to our unit. All patients underwent laboratory tests, abdominal ultrasound, upper gastrointestinal endoscopy, HVPG measurement, and the ICG 15-minute retention (ICG-r15) test. We evaluated the sensitivity and specificity of the ICG retention test and other noninvasive tools for the diagnosis of PH and EV. Ninety-six consecutive Child-Pugh A patients (67 male and 29 female; 60.3 ± 11.8 years of age) were enrolled. Seventy-four patients had clinically significant portal hypertension (CSPH), of whom 59 had severe portal hypertension (SPH). ICG-r15 and Lok index were independently related to the presence of both CSPH and SPH, whereas ICG-r15 and INR were related to EV. ICG-r15 values (<6.7% and <6.9%, respectively) were able to rule out the presence of CSPH and SPH (LR(-) 0.15 and 0.14); ICG-r15 <10% provided a 97.8% sensitivity (LR(-) 0.042) for the exclusion of EV and a 100% sensitivity (LR(-) 0.0) for large EV. CONCLUSION: The ICG-r15 test is an effective tool for assessment of PH in patients with compensated cirrhosis. Although this would not replace endoscopy, the ICG-r15 appears able to identify patients with advanced liver disease in which endoscopy is mandatory as well as rule out the presence of EV in patients with compensated cirrhosis.

Extracorporeal shock wave lithotripsy for difficult common bile duct stones: a comparison between 2 different lithotripters in a large cohort of patients.

BACKGROUND: Extracorporeal shock wave lithotripsy (ESWL) for difficult common bile duct (CBD) stones is a safe and effective treatment strategy allowing for bile duct clearance in approximately 90% of patients with a low incidence of mild adverse events. OBJECTIVE: To compare the CBD clearance rates achieved after ESWL performed with 2 different lithotripters (Siemens Lithostar Plus and Storz Modulith SLX-F2) in a large cohort of patients with difficult CBD stones. DESIGN: A retrospective analysis of a prospectively collected database. SETTING: Tertiary care center. PATIENTS: All of the consecutive patients who underwent ESWL because of difficult CBD stones between 1990 and 2012 were considered suitable for inclusion. INTERVENTIONS: ESWL with Lithostar Plus or with Modulith SLX-F2. MAIN OUTCOME MEASUREMENTS: CBD clearance. RESULTS: Three hundred ninety-two patients with difficult CBD stones were treated; 199 patients were treated with the Lithostar Plus and 193 patients with the Modulith SLX-F2. CBD clearance was achieved in 349 patients (89.0%) with no significant difference between the patients treated with Lithostar Plus and those treated with Modulith SLX-F2 (90.5% vs 87.6%; P = .45). Patients treated with Modulith SLX-F2 underwent a significantly lower number of ESWL sessions (3 [range, 2 to 4] vs 3 [range, 2 to 4]; P = .0015), had a lower incidence of ESWL-related adverse events (5.2% vs 13.6%; P = .009), and never required opioid analgesia (P < .001). LIMITATIONS: Retrospective design. CONCLUSIONS: The Modulith SLX-F2 allows the same clearance rate as the Lithostar Plus but has a significantly lower incidence of adverse events and requires fewer ESWL sessions.

Four-year follow-up of psychiatric and psychosomatic profile in patients with Inflammatory Bowel Disease (IBD).

Psychological characterization of patients affected by Inflammatory Bowel Disease (IBD) focuses on comorbidity with psychiatric disorders, somatization or alexithymia. Whereas IBD patients had higher risk of stable anxiety and depression for many years after the diagnosis of the disease, there is a lack of studies reporting a comprehensive psychosomatic assessment addressing factors of disease vulnerability, also in the long-term. The objective of this investigation is to fill this gap in the current literature. The aims were thus to assess: a) changes between baseline and a 4-year follow-up in psychiatric diagnoses (SCID), psychosomatic syndromes (DCPR), psychological well-being (PWB-I), lifestyle, gastrointestinal symptoms related to IBD and Irritable Bowel Syndrome (IBS)-like symptoms b) stability of psychiatric and psychosomatic syndromes at 4-year follow-up. A total of 111 IBD outpatients were enrolled; 59.5% of them participated at the follow-up. A comprehensive assessment, including both interviews and self-report questionnaires, was provided at baseline and follow-up. Results showed increased psychiatric diagnoses, physical activity, consumption of vegetables and IBS-like symptoms at follow-up. Additionally, whereas psychiatric diagnoses were no longer present and new psychopathological pictures ensued at follow-up, more than half of the sample maintained psychosomatic syndromes (particularly allostatic overload, type A behavior, demoralization) from baseline to follow-up. Long-term presence/persistence of such psychosocial burden indicates the need for integrating a comprehensive psychosomatic evaluation beyond traditional psychiatric nosography in IBD patients. Moreover, since psychosomatic syndromes represent vulnerability factors of diseases, further studies should target subgroups of patients presenting with persistent psychosomatic syndromes and worse course of the disease.

The Gastropack Access System as a Model to Access Gastroenterology Services for Gastroscopy Appropriateness in Patients with Upper Gastrointestinal Symptoms: A Comparison with the Open Access System.

Esophagogastroduodenoscopy (EGD) appropriateness in Open-Access System (OAS) is a relevant issue. The Gastropack Access System (GAS) is a new system to access gastroenterological services, based on the partnership between Gastroenterologists and GPs. This study aims to evaluate if GAS is superior to OAS in terms of EGDS appropriateness. Secondarily, we evaluated the diagnostic yield of EGDS according to ASGE guidelines. The GAS was developed in an area of Bologna where General Practitioners (GPs) could decide to directly prescribe EGDS through OAS or referring to GAS, where EGDS can be scheduled after contact between GPs and specialists sharing a patient's clinical information. Between 2016 and 2019, 2179 cases (M:F = 861:1318, median age 61, IQR 47.72) were referred to GAS and 1467 patients (65%) had a prescription for EGDS; conversely, 874 EGDS were prescribed through OAS (M:F = 383:491; median age 58 yrs, IQR 45.68). Indication was appropriate in 92% in GAS (1312/1424) versus 71% in OAS (618/874), p < 0.001. The rate of clinically significant endoscopic findings (CSEF) was significantly higher in GAS (49% vs. 34.8%, p < 0.001). Adherence to ASGE guidelines was not related to CSEF; however, surveillance for pre-malignant conditions was independently related to CSEF. All neoplasm were observed in appropriate EGD. GAS is an innovative method showing extremely high rates of appropriateness. ASGE guidelines confirmed their validity for cancer detection, but their performance for the detection of other conditions needs to be refined.

Transjugular intrahepatic portosystemic shunt placement for refractory ascites: a single-centre experience.

BACKGROUND: The presence of refractory ascites is a common indication for transjugular intrahepatic portosystemic shunt (TIPS). Different models have been proposed for the prediction of survival after TIPS. The aim of this study was to evaluate the predictive factors associated with patients' survival after TIPS placement for refractory ascites. METHODS: Data from all consecutive patients undergoing TIPS placement in our center for refractory ascites between February 2003 and January 2008 were prospectively recorded. RESULTS: Seventy-three patients (52M/21F; 57 ± 10 years) met the inclusion criteria; mean follow-up was 17 ± 2 months. Mean MELD value, before TIPS placement, was 15.7 ± 5.3. TIPS placement led to an effective resolution of refractory ascites in 54% of patients (n = 40) with no significant increase in severe portosystemic encephalopathy. The 1-year survival rate observed was 65.7%, while the overall mortality was 23.3% (n = 17) with a mean survival of 17 ± 14 months. MELD score (B = 0.161, p = 0.042), basal AST (B = 0.020, p = 0.090), and pre-TIPS HVPG (B = 0.016, p = 0.093) were independent predictors of overall mortality, while MELD (B = 0.419, p = 0.018) and HVPG (B = 0.223, p = 0.060) independently predicted 1-year survival. ROC curves identified MELD ≥ 19 and HVPG ≥ 25 mmHg as the best cut-off points for the prediction of 1-year mortality. CONCLUSIONS: TIPS is an effective treatment for refractory ascites in cirrhotic patients, leading to an effective ascites control in more than half patients. Improvement in patients' selection criteria could lead to better outcome and survival after this procedure. Liver function (MELD), presence of active necroinflammation (AST), and portal hypertension (HVPG) are independent predictors of patients' outcome after TIPS.

High dose lamivudine in HBV-related cirrhotic patients with unsatisfactory response after adefovir add-on.

BACKGROUND: Before tenofovir approval for chronic hepatitis B therapy, the clinical management of patients with suboptimal response or virological breakthrough during combination treatment with lamivudine and adefovir dipivoxil was a difficult clinical challenge. AIMS: In order to improve virologic response and reduce the risk of decompensation, we evaluate the efficacy of a high dose of lamivudine on chronic HBV patients who have previously presented an unsatisfactory response during treatment with lamivudine 100mg/day and adefovir 10mg/day. METHODS: Six patients with HBV-related liver cirrhosis were prospectively enrolled. All were HBeAg-negative and presented a suboptimal response or virological breakthrough after "adefovir add-on" because of development of clinical breakthrough during Lamivudine treatment. Lamivudine dose was increased to 200 or 300 mg, depending on viral load. After 12 months of follow-up, virological and biochemical response were evaluated. RESULTS: After 12 months of high-dose lamivudine, all patients (6/6, 100%) achieved a significant decrease of serum HBV DNA (mean reduction 2,62 ± 1,15 Log10 UI/ml, P = 0.03) and normalized ALT. In three patients (3/6, 50%), HBV DNA became undetectable within 6 months. No patient developed liver decompensation and no significant changes occurred in serum creatinine, serum and urinary electrolytes. No adverse events were registered. CONCLUSIONS: In our experience, rescue strategy with high-dose lamivudine inhibited viral replication leading to undetectability of serum HBVDNA. This rescue treatment presented a good safety profile, without adverse events during the study period. Customized increase of nucleos(t)ide analogues dose in difficult-to-treat patients may be a proficient approach in challenging clinical setting.

Immune inflammation indicators and ALBI score to predict liver cancer in HCV-patients treated with direct-acting antivirals.

BACKGROUND: Unexpectedly high occurrence or recurrence rate of hepatocellular carcinoma (HCC) has been observed in patients with chronic hepatitis C receiving direct-acting antivirals (DAAs) therapy. AIMS: We evaluated the predictive value of albumin-bilirubin (ALBI) score and immune-inflammation indicators to identify the risk of occurrence or recurrence of HCC in patients treated with DAAs in a real life setting. METHODS: In this retrospective cohort study, we analysed data from 514 patients with cirrhosis who were prospectively enrolled for treatment with DAAs. We assessed baseline neutrophil to lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet to lymphocyte ratio (PLR), aspartate aminotransferase-lymphocyte ratio (ALRI) index and ALBI score. RESULTS: In patients with no history of HCC (N = 416), increased AST, bilirubin, ALRI, and ALBI score, and decreased albumin and platelets were significantly associated with an increased risk of HCC development, at univariate analysis. At multivariate analysis, increase in ALBI grade (p = 0.038, HR: 2.35, 95% CI: 1.05-5.25) and decrease in platelets (p = 0.048, HR: 0.92, 95% CI: 0.85-1.0) were independently associated with HCC development. In patients with previous HCC (N = 98), adjusting for the time from HCC treatment, increased ALRI (p = 0.008, HR: 1.05, 95% CI: 1.01-1.09) was significantly associated with a risk of recurrence. CONCLUSION: ALBI score, platelet count and ALRI are promising, easy to perform and inexpensive tools for identifying patients with higher risk of HCC after treatment with DAAs.

Lamivudine treatment for severe acute HBV hepatitis.

Treatment for acute hepatitis B is recommended in order to reduce the risk of progression to fulminant hepatitis and the need of OLT. We report our experience on treatment with high dose lamivudine, in patients with severe acute HBV infection. The diagnosis was based on clinical and virological findings and exclusion of other known causes of liver damage. The decision to treat was based on the prolongation of INR together with increasing values of bilirubin and ALT. Four patients received Lamivudine 200 mg/daily until clearance of serum HBV-DNA and then 100 mg/daily until clearance of HBsAg and appearance of anti-HBs antibodies. One patient received 100 mg/daily because of chronic renal impairment. The median period of hospitalization was 13 days, and none of the patients had complications, related either to underlying disease or to therapy. The complete normalization of serum transaminases and bilirubin occurred on average after 5.5 weeks and 3 weeks respectively. All patients cleared serum HBV-DNA within three months, lost HBeAg and HBsAg and seroconverted to anti-HBe; four patients developed anti-HBs at a protective titre. Early antiviral treatment attenuates the clinical and biochemical impairment leading to fast healing and promoting complete recovery.

Hepatocellular carcinoma risk assessment by the measurement of liver stiffness variations in HCV cirrhotics treated with direct acting antivirals.

BACKGROUND: Direct-acting antivirals (DAA) are an effective treatment for hepatitis C virus infection. However, sustained virologic response (SVR) after DAA treatment does not seem to reduce the risk of hepatocellular carcinoma (HCC) development in these patients. Liver stiffness measurement (LSM) may predict the risk of developing HCC in liver cirrhosis patients. AIMS: The aim of our study was to evaluate the role of LSM variation as predictor of HCC development in patients treated with DAA. METHODS: In 139 HCV-related cirrhotic patients, LSM and laboratory tests were carried out at baseline (BL) and at the end of DAA treatment (EOT). Patients were followed for at least 6 months after the EOT. LSM reduction was expressed as Delta LS (∆LS). Cox regression analysis was used to identify prognostic factors for HCC development after DAA. RESULTS: Median LSM values were significantly reduced from BL to EOT (from 18.6 to 13.8 kPa; p < 0.001). The median ∆LS was -26.7% (IQR: -38.4% -13.6%). During a median follow-up of 15 months after DAA treatment, 20 (14.4%) patients developed HCC. Significant LSM reduction was observed both in patients who developed HCC and in those who did not, but this was significantly lower in the patients who developed HCC (-18.0% vs -28.9% p = 0.005). At multivariate analysis, ∆LS lower than -30%, Child-Turcotte-Pugh-B and history of HCC were independently associated with HCC development. CONCLUSION: Our results indicate that ∆LS is a useful non-invasive marker for predicting HCC development after DAA treatment.

Severe immune thrombocytopenia after peg-interferon-alpha2a, ribavirin and telaprevir treatment completion: A case report and systematic review of literature.

Mild to moderate autoimmune thrombocytopenia (AITP) is a common finding in patients receiving interferon-based antiviral treatment, due to bone marrow suppression. Here we report the case of a patient with chronic genotype 1b hepatitis C virus (HCV) infection treated with pegylated-interferon alpha-2a, ribavirin and telaprevir for 24 wk; the patient developed severe AITP three weeks after treatment withdrawal. We performed a systematic literature search in order to review all published cases of AITP related to HCV antiviral treatment. To our knowledge, this is the second case of AITP observed after antiviral treatment withdrawal. In most published cases AITP occurred during treatment; in fact, among 24 cases of AITP related to interferon-based antiviral treatment, only one occurred after discontinuation. Early diagnosis of AITP is a key factor in order to achieve an early interferon discontinuation; in the era of new direct antiviral agents those patients have to be considered for interferon-free treatment regimens. Prompt prescription of immuno-suppressant treatment (i.e., corticosteroids, immunoglobulin infusion and even rituximab for unresponsive cases) leads to favourable prognosis in most of cases. Physicians using interferon-based treatments should be aware that AITP can occur both during and after treatment, specially in the new era of interferon-free antiviral treatment. Finally, in the case of suspected AITP, presence of anti-platelet antibodies should be checked not only during treatment but also after discontinuation.

Long-term leukocyte natural α-interferon and ribavirin treatment in hepatitis C virus recurrence after liver transplantation.

AIM: To evaluate the effect of long-term treatment with leukocyte natural α-interferon (ln-α-IFN) plus ribavirin (RBV). METHODS: Forty-six patients with hepatitis C virus (HCV) recurrence received 3 MU three times a week of ln-α-IFN plus RBV for 1 mo; then, patients with good tolerability (n = 30) were switched to daily IFN administration, while the remaining were treated with the same schedule. Patients have been treated for 12 mo after viral clearance while non-responders (NR) entered in the long-term treatment group. Liver biopsies were planned at baseline, 1 year after sustained virological response (SVR) and at 36 mo after start of therapy in NR. MedCalc software package was used for statistical analysis. RESULTS: About 16.7% of genotype 1-4 and 70% of genotype 2-3 patients achieved SVR. Nine patients withdrew therapy because of non-tolerance or non-compliance. A significant improvement in serum biochemistry and histological activity was observed in all SVR patients and long-term treated; 100% of patients with SVR achieved a histological response (fibrosis stabilization or improvement) with a significant reduction in mean staging value (from 2.1 to 1.0; P = 0.0031); histological response was observed in 84% of long-term treated patients compared to 57% of drop-out. Six patients died during the entire study period (follow-up 40.6 ± 7.7 mo); of them, 5 presented with severe HCV recurrence on enrollment. Diabetes (OR = 0.38, 95%CI: 0.08-0.59, P = 0.01), leukopenia (OR = 0.54, 95%CI: 0.03-0.57, P = 0.03) and severe HCV recurrence (OR = 0.51, 95%CI: 0.25-0.69, P = 0.0003) were variables associated to survival. Long-term treatment was well tolerated; no patients developed rejection or autoimmune disease. CONCLUSION: Long-term treatment improves histology in SVR patients and slows disease progression also in NR, leading to a reduction in liver decompensation, graft failure and liver-related death.

Pneumatosis cystoides intestinalis.

Pneumatosis cystoides intestinalis (PCI) is a rare condition that may be associated with a variety of diseases. The presenting clinical picture may be very heterogeneous and represent a challenge for the clinician. In the present paper we describe both a common and an uncommon clinical presentation of PCI and review the pertaining literature. Our cases confirm that, apart from asymptomatic cases, the clinical presentation of PCI may be widely different and suggest that a new onset of stipsis might be the presenting symptom. Diagnosis might be suggested by a simple X-ray of the digestive tract showing a change in the characteristics of the intestinal wall in two-thirds of these patients. However, one third of the patients do not have a suggestive X-ray and require a computed tomography (CT) scan/nuclear magnetic resonance that may reveal a thickened bowel wall containing gas to confirm the diagnosis and distinguish PCI from intraluminal air or submucosal fat. CT also allows the detection of additional findings that may suggest an underlying, potentially worrisome cause of PCI such as bowel wall thickening, altered contrast mucosal enhancement, dilated bowel, soft tissue stranding, ascites and the presence of portal air. Our results also point out that clinicians and endoscopists should be aware of the possible presentations of PCI in order to correctly manage the patients affected with this disease and avoid unnecessary surgeries. The increasing number of colonoscopies performed for colon cancer screening makes PCI more frequently casually encountered and/or provoked, therefore the possible endoscopic appearances of this disease should be well known by endoscopists.

Adverse effects of proton pump inhibitors.

Proton pump inhibitors (PPI) are very effective drugs used largely in acid related disorders. During the last years concern have been raised regarding their overutilisation in benign condition, such as gastroesophageal reflux disease. The debate focussed also on the risk of adverse events related to long term use of PPI. Apart of the case of Helicobacter Pylori (H. Pylori) positive patients, in whose long term acid suppression lead to the development of corpus predominant atrophic gastritis, precursor of cancer; the other assumed adverse events, have never been demonstrated in prospective studies. The attention should move towards the appropriate prescription of PPI, rather than the fear adverse effects of PPI. In fact, in clinical practise, PPI are often prescribed in patients without a specific acid related disease and continued long term based on their safety profile. This review focus on the main adverse events related to long term PPI use.

ESWL for difficult bile duct stones: a 15-year single centre experience.

AIM: To evaluate the efficacy of extracorporeal shock wave lithotripsy (ESWL) for the management of refractory bile duct cholelithiasis in a third level referral centre. METHODS: The clinical records of all patients treated with a second generation electromagnetic lithotripter (Lithostar Plus, SIEMENS) from October 1990 to April 2005 were evaluated. All patients were monitored during the procedure and antibiotics were administered in case of cholangitis. The chi(2) test and logistic regression analysis were performed as appropriate. RESULTS: Two hundred and fourteen patients (102 males, 112 females; mean age 74.8 +/- 0.84 years--single stone 97, multiple stones 117) underwent ESWL. The mean number of sessions and shock waves were 3.5 +/- 0.13 and 3477.06 +/- 66.17, respectively. The maximum stone size was 5 cm. Complete stone clearance was achieved in 192 (89.7%) patients. Of the remaining patients 15 required surgery, 2 a palliative stent and in 5 patients stone fragmentation led to effective bile drainage with clinical resolution despite incomplete clearance. Age, sex and stone characteristics were not related to treatment outcome. Major complications occurred in two patients (haemobilia and rectal bleeding) and minor complications in 25 (3 vomiting, 22 arrhythmias). No procedure-related deaths occurred. CONCLUSION: ESWL is a safe and effective technique for clearance of refractory bile duct stones.

G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence.

AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN alpha-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response. METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled. All patients developing neutropenia received G-CSF. RESULTS: Twenty three (34%) received G-CSF. Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) (P < 0.0001). Three patients did not respond to G-CSF. Treatment duration was similar in neutropenic and non-neutropenic patients. No differences in the rate of discontinuation, infections or virological response were observed between the two groups. G-CSF was protective for the onset of de novo autoimmune hepatitis (P < 0.003). CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients. It prevents the occurrence of de novo autoimmune hepatitis.