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Background Transjugular Intrahepatic Portosystemic Shunt (TIPS) is a well-established treatment for complications of portal hypertension. Aims To analyze the impact of TIPS on virologic response and safety profile in patients treated with direct-acting antivirals (DAAs). Methods We analyzed data from HCV-positive cirrhotic patients treated with DAAs. Twenty-one patients with previous TIPS placement were compared with 42 matched subjects without TIPS. Logistic regression was used to identify predictors of hepatic function worsening and adverse events. Results No differences were found between the two groups in particular regarding sustained virologic response (92.5 and 97.6% in TIPS vs no-TIPS, p = 0.559). Model for End-stage Liver Disease (MELD) of both TIPS and no-TIPS groups declined from baseline to week 24 of follow-up (from 12.5 ± 3.5 to 10.8 ± 3.4 and from 11.1 ± 3.5 to 10.3 ± 3.4, p = 0.044 and 0.025). There were no differences in adverse event rates. At univariate analysis, age was associated with MELD increase from baseline to week 24 (OR 1.111, 95% CI 1.019-1.211, p = 0.017), and patients with higher baseline MELD developed serious adverse events more frequently (OR 0.815, 95% CI 0.658–1.010, p = 0.062). Patients with or without TIPS did not show differences in transplant-free survival. Conclusion TIPS placement does not affect virologic response and clinical outcome of patients receiving DAAs.

As the clinical applications of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic ultrasound (EUS) take more and more root in everyday practice and these endoscopic procedures become increasingly more complex and interventional with a higher chance for complications, the demand for expert bilio-pancreatic endoscopists continues to increase. In response to this growing need, specific postgraduate fellowships have been developed, however the standardization of training programs and the assessment of the achieved competence still remains an open debate. ERCP and EUS competency often requires training beyond the scope of a standard GI fellowship program, which lasts at least 1-2 years, and there are some differences in the way to face the issues of advanced bilio-pancreatic endoscopy training between Europe, America and the Asian regions. Today there is no role for the self-teaching of ERCP and EUS through trial and error without supervision and, in the near future, it is necessary to critically revise current training guidelines, to establish a standardized curriculum for advanced bilio-pancreatic endoscopists and to implement universally validated skill assessment tools, able to ensure constant and targeted feedback to trainees.

Background & Aims: Surgery in cirrhosis is associated with a high morbidity and mortality. Retrospectively reported prognostic factors include emergency procedures, liver function (MELD/Child-Pugh scores) and portal hypertension (assessed by indirect markers). This study assessed the prognostic role of hepatic venous pressure gradient (HVPG) and other variables in elective extrahepatic surgery in patients with cirrhosis. Methods: A total of 140 patients with cirrhosis (Child-Pugh A/B/C: 59/37/4%), who were due to have elective extrahepatic surgery (121 abdominal; 9 cardiovascular/thoracic; 10 orthopedic and others), were prospectively included in 4 centers (2002–2011). Hepatic and systemic hemodynamics (HVPG, indocyanine green clearance, pulmonary artery catheterization) were assessed prior to surgery, and clinical and laboratory data were collected. Patients were followed-up for 1 year and mortality, transplantation, morbidity and post-surgical decompensation were studied. Results: Ninety-day and 1-year mortality rates were 8% and 17%, respectively. Variables independently associated with 1-year mortality were ASA class (American Society of Anesthesiologists), high-risk surgery (defined as open abdominal and cardiovascular/thoracic) and HVPG. These variables closely predicted 90-, 180- and 365-day mortality (C-statistic >0.8). HVPG values >16 mmHg were independently associated with mortality and values ≥20 mmHg identified a subgroup at very high risk of death (44%). Twenty-four patients presented persistent or de novo decompensation at 3 months. Low body mass index, Child-Pugh class and high-risk surgery were associated with death or decompensation. No patient with HVPG 0.63 developed decompensation. Conclusions: ASA class, HVPG and high-risk surgery were prognostic factors of 1-year mortality in cirrhotic patients undergoing elective extrahepatic surgery. HVPG values >16 mmHg, especially ≥20 mmHg, were associated with a high risk of post-surgical mortality. Lay summary: The hepatic venous pressure gradient is associated with outcomes in patients with cirrhosis undergoing elective extrahepatic surgery. It enables a better stratification of risk in these patients and provides the foundations for potential interventions to improve post-surgical outcomes.

Background/Aims Treatment of hepatorenal syndrome (HRS) is based on vasoconstrictors. Terlipressin is the one with the soundest evidence. Noradrenalin has been suggested as an effective alternative. The current study was aimed at assessing the efficacy and safety of noradrenalin vs terlipressin in patients with HRS. Methods Twenty-two consecutive cirrhotic patients with HRS (9 with HRS type 1; 13 with HRS type 2) were included. Patients were randomly assigned to be treated with noradrenalin (0.1–0.7μg/kg/min) and albumin (10 patients) or with terlipressin (1–2mg/4h) and albumin (12 patients). Treatment was administered until HRS reversal or for a maximum of two weeks. Patients were followed-up until liver transplantation or death. Results Reversal of HRS was observed in 7 of the 10 patients (70%) treated with noradrenalin and in 10 of the 12 patients (83%) treated with terlipressin, p =ns. Treatment led in both groups to a significant improvement in renal and circulatory function. No patient developed signs of myocardial ischemia. Conclusions Data from this unblinded, pilot study suggest that noradrenalin is as effective and safe as terlipressin in patients with HRS. These results would support the use of noradrenalin, a cheap and widely available drug, in the management of these patients.

Managing antiplatelet and anticoagulant drugs before endoscopy may be challenging.To assess whether the pre-endoscopic management of antiplatelet/anticoagulant drugs is adherent to current guidelines and the influence of patients' characteristics, referring physician's specialty, type of endoscopic procedure and therapeutic regimen on adherence.Two hundred and twenty patients taking aspirin, thienopyridines or warfarin and scheduled for upper endoscopy (± biopsies), variceal band ligation, colonoscopy (± biopsies or polypectomy), were prospectively analyzed.In 109 patients (49.5%) the management of antiplatelet/anticoagulant drugs was thoroughly compliant with guidelines. Neither demographic characteristics, nor in/outpatient status, nor type of endoscopic procedure, nor physician's specialty influenced the adherence but the therapeutic regimen had a significant impact (p0.0001) as compliance was less likely in patients on warfarin. Unwarranted drugs withholding was more frequent before colonoscopy than upper endoscopy (p = 0.0001). Warfarin was stopped longer than recommended more frequently than aspirin (p = 0.009). The International Normalized Ratio was properly checked before endoscopy in 47.7% of patients. Among the 55 patients who withheld warfarin, the decision about bridging to low molecular weight heparin was appropriate in 21 (38.2%).Compliance with guidelines is low especially in the management of warfarin, both among gastroenterologists and other physicians.

The use of angiotensin II antagonists in the treatment of portal hypertension remains controversial. Our aims were to assess the effect of Irbesartan on portal pressure and to evaluate its safety in cirrhotic patients with portal hypertension. Twenty-five cirrhotic patients were treated in a pilot study with Irbesartan 300 mg orally once daily for 60 days. Hemodynamic evaluations and biochemical tests were performed before therapy and after two months of treatment. Three patients (12%) discontinued treatment for symptomatic arterial hypotension (mean arterial pressure −26.% ± 3.1 versus basal). In the 18 responders, the hepatic venous pressure gradient diminished by a mean of 18.1% ± 10.5 from baseline (p = 0.02); the gradient decreased by 20% or more in only 5 patients (23%). The mean arterial pressure decreased significantly during therapy (92 ± 7 vs 109 ± 25 mm Hg, P < 0.001). In conclusions, Irbesartan induced a marginal reduction in portal pressure and its safety was limited by the pronounced effects on arterial pressure.

Portal venous aneurysm (PVA) is a rare condition characterized by dilatation of the portal venous system. PVA manifestation of symptoms is varied and depends on the aneurysm size, location and related-complications, such as thrombosis. While the majority of reported cases of PVA are attributed to portal hypertension, very little is known about the condition’s pathophysiology and clinical management remains a challenge. Here, we describe a 67-year-old woman who presented with complaint of dyspepsia and without a significant medical history, for whom PVA was incidentally diagnosed. The initial upper abdominal ultrasound revealed marked dilatation of the main portal vein, and subsequent contrast-enhanced computed tomography with angiography revealed a large aneurysm arising from the extrahepatic troncus portion of the portal vein, as well as gastroesophageal varices. A conservative approach using beta-blocker therapy was chosen. The patient was followed-up for 60 mo, during which time the asymptomatic status was unaltered and the PVA remained stable.

Background Hepatorenal syndrome is a severe complication of cirrhosis. Treatment with terlipressin has currently the best efficacy pedigree, inducing hepatorenal syndrome reversal in a high proportion of patients. However, hepatorenal syndrome recurrence after terlipressin withdrawal is very common, especially in type 2 hepatorenal syndrome. Midodrine, an oral adrenergic vasoconstrictor, has been suggested to be an effective therapy in hepatorenal syndrome. Aims To analyse the impact of treatment with midodrine after hepatorenal syndrome type 2 reversal induced by terlipressin on the prevention of hepatorenal syndrome recurrence. Patients and methods A case–control design was used. The outcome of 10 patients with hepatorenal syndrome type 2 treated successfully with terlipressin and then with midodrine (7.5–12.5 mg/tid) was compared with that of an historical control group of hepatorenal syndrome type 2 patients responders to treatment with terlipressin. Patients and controls were matched by age, plasma renin activity (PRA) levels and severity of renal and liver failure. Results Cases and controls were similar with respect to pre-treatment with terlipressin. The hepatorenal syndrome recurrence probability was the same in the two groups (cases and control: 9/10, 90%, p = ns). No significant differences were found between cases and controls with respect to serum creatinine (1.9 ± 0.1 mg/dl vs. 2 ± 0.2 mg/dl), blood creatinine clearance (28 ± 5 ml/min vs. 24 ± 5 ml/min), urinary sodium excretion (12 ± 6 mequiv./d vs. 19 ± 4 mequiv./d) and PRA levels (17 ± 3 ng/ml/h) vs. 20 ± 3 ng/ml/h) after terlipressin withdrawal ( p = ns). Conclusions These results show that in patients responders to terlipressin hepatorenal syndrome recurrence is not different between patients treated with midodrine and subjects who did not receive vasoconstrictor treatment after terlipressin withdrawal. These data suggest that midodrine is not effective in preventing hepatorenal syndrome type 2 recurrence.

Background/Aims The renin-angiotensin system plays an important role in hepatic fibrogenesis and in portal hypertension. To examine the long-term effects of Candesartan cilexetil, an angiotensin type 1 (AT1) receptor blocker, on portal-systemic haemodynamics and on liver fibrosis. Methods Forty-seven compensated Child A and Child B (⩽8) cirrhotic patients were randomly assigned to receive Candesartan cilexetil, 8mg/d (N.24) and no treatment (N.23) for 1 year. Portal-systemic haemodynamic parameters, serological levels of procollagen (PIIINP), hyaluronic acid (HA) and transforming growth factor beta 1 (TGFβ1) were assessed at baseline and after 12 months. Results No patients discontinued or decreased the drug. The hepatic venous pressure gradient (HVPG) decreased significantly in treated patients (−8.4%±2.4) with a reduction >20% in 25% of cases vs+5.6%±2.9 in the untreated group. HA plasma levels decreased significantly in Candesartan treated patients in whom HVPG diminished and rose in untreated patients in whom HVPG increased. Conclusions In selected cirrhotic patients, pharmacological inhibition of the AT1 receptor is well tolerated and induced a mild reduction of portal pressure. This haemodynamic effect might be related to liver fibrogenesis activity.

Lipohyperplasia or intestinal lipomatosis is an infrequent disease characterised by anomalous infiltration of adipose tissue in the intestinal submucosa. Localised forms are generally asymptomatic, whereas diffuse forms may lead to intestinal subocclusion, digestive hemorrhage or diarrhoea. Although benign, the differential diagnosis of intestinal lipomatosis with malignant pathologies of the colon or appendix often prompts the need for surgical exploration and the histological analysis of biopsy material. Surgical exeresis of the lesion is generally associated with the normalisation of clinical symptoms. The authors report the onset and clinical evolution of two cases of intestinal lipomatosis referred to their attention.

Hepatitis B virus (HBV) recurrence after liver transplantation is significantly reduced by prophylaxis with hepatitis B immune globulins (HBIG) or antiviral drugs in nonreplicating patients and by the combination of both drugs in replicating patients. However, the load of HBV DNA, which defines replicating status in patients undergoing liver transplantation, remains unclear. This study analyzes the correlation between the viral load, tested with a single amplified assay, at the time of liver transplantation, and the risk of hepatitis B recurrence in 177 HBV carriers who underwent transplantation in a single center from 1990 to 2002. Overall, HBV relapsed after surgery in 15 patients (8.5%) with a 5- and 8-year actuarial rate of recurrence of 8% and 21%, respectively. After liver transplantation hepatitis B recurred in 9% of 98 selected subjects treated only with immune globulins and in 8% of 79 viremic patients who received immune globulins and lamivudine (P = NS). A linear correlation was observed between recurrence and viral load at the time of surgery. In transplant patients with HBV DNA higher than 100,000 copies/mL, 200-99,999 copies/mL, and DNA undetectable by amplified assay, hepatitis B recurred in 50%, 7.5%, and 0% of patients, respectively. Overall, a viral load higher than 100,000 copies/mL at the time of liver transplantation was significantly associated with hepatitis B recurrence (P = .0003). In conclusion, spontaneous or antiviral-induced HBV DNA viral load at the time of surgery classifies the risk of HBV recurrence after liver transplantation and indicates the best prophylaxis strategy.

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.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.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%, P0.001). A clinically significant decrease was seen in one (7%) of the patients given Irb vs. five (33%) given Pro (P0.02). The fall in mean arterial pressure was significantly higher with Irb than with Pro (median -29%, range -15/-45% vs. -4.9%, +8/-19%, P0.02). Irb significantly modified the blood creatinine clearance (median -29 ml/m, range +9/-61 ml/m, -30, -24/-35% P0.0001 vs. basal).Irb offers no advantage over Pro in the control of portal hypertension. Moreover, its therapeutic profile is limited by important side effects.

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.

Background/Aims : Treatment with hepatitis B virus immune globulins (HBIG) or lamivudine has reduced the rate of hepatitis B recurrence after liver transplantation to approximately 50%. Methods : To further decrease hepatitis B recurrence, 33 hepatitis B virus (HBV)-related cirrhotic patients were treated with lamivudine before liver transplantation and with lamivudine together with low-dose HBIG (46 500 IU the first month followed by 5000 IU/monthly) after surgery. Results : While on lamivudine, serum HBV DNA level decreased significantly in all patients and in 11 (33%) the Child–Pugh score improved. Twenty-six patients were transplanted. Among the 25 who survived for longer than 12 months, only one (4%) experienced a hepatitis B recurrence over an average follow-up of 31 months, a rate significantly lower ( P =0.0002) than the 50% recurrence rate among a historical control group of 12 patients. However, low-level HBV replication was detected sporadically throughout the follow-up in 64% of patients. Conclusions : Over the medium-term, combined prophylaxis with lamivudine and HBIG significantly decreases the risk of hepatitis B recurrence after liver transplantation. Though low-level HBV infection recurred in two thirds of patients, the pathogenic expression of HBV was prevented.

The aim of this study was to investigate the role of portal hypertension determining the severity of bleeding in portal hypertensive rats. The effects of section of branches of the ileocolic vein were studied in sham-operated (SO), partial portal vein-ligated (PPVL), and common bile duct-ligated (CBDL) rats. The ensuing hemorrhage was compared with that caused by section of femoral vein, where the portal hypertensive factor is excluded. In PPVL rats, section of branches of increasing size (divided into fourth, third, second, and first order) resulted in increasingly severe bleeding (arterial pressure: / +/- 4%, / 6 +/- 12%, / /15 +/- 8%, and / 28 +/- 13%; P.005; hematocrit / 4 +/- 2%, / 6 +/- 1%, / 7 +/- 2%, and / 10 +/- 4%; P.005). Bleeding from first-order branches was mild in SO, moderate in PPVL, and severe in CBDL rats, as shown by increasing changes in arterial pressure (/ 3 +/- 3%, / 12 +/- 16% and, / 43 +/- 23%; P.01), hematocrit (/ 4 +/- 1%, / 12 +/- 2%, and / 32 +/- 19%; P.01), and mortality (0%, 0%, and 56%; P.001). Greater blood loss in CBDL rats was associated with higher portal pressure (16.6 +/- 2.7 vs. 13. 1 +/- 1.1 mm Hg in PPVL; P.01) and more prolonged bleeding time (70 +/- 4 vs. 35 +/- 3 seconds in PPVL; P.001). Vessels were similarly dilated in CBDL and PPVL (0.7 +/- 0.2 and 0.7 +/- 0.1 vs. 0.4 +/- 0.1 mm in SO; P.05). Section of femoral vein caused equal blood loss in SO, PPVL, and CBDL rats, assessed by falls in hematocrit (/ 8 +/- 2%, / 7 +/- 1%, / 8 +/- 1%, respectively; NS) and by the blood loss (3.6 +/- 0.7, 3.5 +/- 0.9, and 3.8 +/- 0.7 g; NS). The study shows that the degree of portal pressure elevation is a major determinant of the severity of portal hypertension-related bleeding in PPVL and CBDL rats.

BACKGROUND/AIMS/METHODS—During hepatic vein catheterisation, in addition to measurement of hepatic venous pressure gradient (HVPG), iodine wedged retrograde portography can be easily obtained. However, it rarely allows correct visualisation of the portal vein. Recently, CO2 has been suggested to allow better angiographic demonstration of the portal vein than iodine. In this study we investigated the efficacy of CO2 compared with iodinated contrast medium for portal vein imaging and its role in the evaluation of portal hypertension in a series of 100 patients undergoing hepatic vein catheterisation, 71 of whom had liver cirrhosis. RESULTS—In the overall series, CO2 venography was markedly superior to iodine, allowing correct visualisation of the different segments of the portal venous system. In addition, CO2, but not iodine, visualised portal-systemic collaterals in 34 patients. In cirrhosis, non-visualisation of the portal vein on CO2 venography occurred in 11 cases; four had portal vein thrombosis and five had communications between different hepatic veins. Among non-cirrhotics, lack of portal vein visualisation had a 90% sensitivity, 88% specificity, 94% negative predictive value, and 83% positive predictive value in the diagnosis of pre-sinusoidal portal hypertension. CONCLUSIONS—Visualisation of the venous portal system by CO2 venography is markedly superior to iodine. The use of CO2 wedged portography is a useful and safe complementary procedure during hepatic vein catheterisation which may help to detect portal thrombosis. Also, lack of demonstration of the portal vein in non-cirrhotic patients strongly suggests the presence of pre-sinusoidal portal hypertension. Keywords: portal thrombosis; liver cirrhosis; idiopathic portal hypertension; splanchnic haemodynamics

Many syndromes reflecting impaired metabolism have been described in association with primary neoplastic diseases. Hypercalcaemia secondary to malignancy without bone metastases and with normal parathyroid glands has been described as "pseudohyperparathyroidism". Differentiation from primary hyperparathyroidism is difficult and care should be taken to exclude an occult malignancy prior to surgical exploration for a parathyroid adenoma. Hypercalcaemia associated with hepatocellular carcinoma is not uncommon. Nevertheless, we describe a rare case of coma with persistent hypercalcaemia in a cirrhotic patient not previously known to have hepatocellular carcinoma.

A group of 24 patients underwent a 7-14-day course of continuously infused Cyclosporin A (2 mg.kg-1.day-1) to treat a severe attack of ulcerative colitis. In 19 of them, including eight treated with total parenteral nutrition, we retrospectively analyzed the serum aminotransferase (AST/ALT) levels at the beginning and at the end of Cyclosporin infusion. The baseline levels of AST/ALT in the group were 19.9 +/- 3.2 and 31.4 +/- 6.4; on stopping Cyclosporin infusion, they were 43 +/- 15.8 and 119 +/- 56, respectively. Six patients showed an ALT change above 1.5 times the upper limit of reference. They included five of the eight patients treated with total parenteral nutrition (62.5%). In one of six, ALT rose to 1000 U/l and was accompanied by full-blown febrile cholangitis (proven by liver biopsy). This episode was preceded by excessive accumulation of Cyclosporin in blood. The development of liver toxicity was independent of the length of Cyclosporin treatment, nor did it impair drug efficacy. Thus, in these patients total parenteral nutrition and Cyclosporin were synergistic, causing twice the frequency of liver damage (62.5%) reported for ulcerative colitis patients on total parenteral nutrition alone (37%). Total parenteral nutrition should not be used to support patients needing Cyclosporin for autoimmune disease. However, too high a dose of Cyclosporin may cause liver disease per se.

Wilson's disease is a hereditary disorder of biliary copper excretion. Most often the disease presents with hepatic and neurological involvement. In the hepatic forms, hypocerulo-plasminemia, the determination of eye copper and the dosage of copper in serum, urine and liver tissue are all leads to diagnosis. The presentation and the biochemistry may direct the diagnosis of the acute forms. Treatment differs according to the clinical patterns. Early diagnosis in the asymptomatic patient leads to chelating therapy to prevent copper overload. Chronic disease may benefit from chelation and liver transplant. Transplantation is the cure for fulminant forms. We report three young women with Wilson's disease; one had a fulminant form and was transplanted and the other two responded to chelation therapy. Family screening allowed the identification of an asymptomatic sibling.

Background: There are no formal guidelines regarding sedation for endoscopy in cirrhotic patients (CP). The use of propofol has been shown to be effective and safe for gastroscopy but its use for prolonged endoscopic procedure remains to be studied. Aim: To evaluate the efficacy and safety of propofol in CP undergoing prolonged endoscopic procedures compared with non-cirrhotic patients (NCP). Methods: Twenty-nine consecutively collected inpatients (mean age 58±SD7, M/F=18/11) with known liver cirrhosis (Child–Pugh class A=12, B=9, C=8) undergoing colonoscopy (21) or ERCP (8) received propofol by an anesthetist; the outcome measures studied (induction and recovery times, efficacy and safety of sedation, return to baseline function) were compared with those recorded among 68 consecutively collected NCP (mean age 61±SD8, M/F=41/27) undergoing the same endoscopic procedures (colonoscopy: 49, ERCP: 19). Results: The mean dose of propofol administered in CP was 242mg (SD±38, range 100–350) compared with 260mg (SD±8, range 120–380) in NCP (p = 0.2). The mean time to achieve sedation was 2.8min (SD±1.1) in CP and 3.1 (SD±1.2) in NCP (p = 0.9). The mean time to reach a maximal level of alertness on the Observer’S Assessment of Alertness and Sedation Scale (OAASS) in CP was 13.8min (SD±4.2) compared with 12.7 (SD±4) in NCP (p = 0.7). Time to full recovery was 28.6min (SD±9.1) in CP compared with 26.2min (SD±8) in NCP (p = 0.72). Procedures times between the groups were similar: 26min (SD±12) in CP vs 29min (SD±14) in NCP (p = 0.8). No significant complication related to sedation was observed in the 2 groups. Conclusions: Propofol sedation is efficacious, safe and well tolerated in CP undergoing prolonged endoscopic procedures.

Background. Transplantation for terminal hepatitis B virus (HBV) disease is aggravated by a high rate of reinfection and disease recurrence. Lamivudine, a new nucleoside analog, is a potent inhibitor of HBV synthesis, but its use may lead to the emergence of HBV-DNA polymerase mutants resistant to the drug. Methods and Results. We describe the case of a patient who developed an HBV recurrence after liver transplantation and was treated with lamivudine. An HBV-DNA breakthrough occurred 7 months after the start of therapy, and the drug was stopped after 9 months. The molecular state of HBV-DNA was analyzed, and a mutation in the YMDD (tyrosine, methionine, aspartate, aspartate) locus of HBV-DNA polymerase was identified. Nine months after the suspension of lamivudine the patient experienced a new hepatic attack accompanied by high HBV-DNA levels. Lamivudine was given again. Serum HBV-DNA levels normalized after 45 days of re-treatment, but lamivudine-resistant mutants were again the prevalent viral population after 3 months. Conclusions. The case described suggests that retherapy with lamivudine after a first emergence of YMDD mutants is temporarily effective in recontrolling HBV synthesis but ultimately induces the accelerated reemergence of a prevalently mutant population of HBV. This emphasizes the need for combined antiviral therapy.