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Background: Kidney transplant (KT) recipients have a high rate of hepatitis C virus (HCV) infection, which can impact long-term graft and patient survival rates. Although direct-acting antivirals (DAAs) are effective for treating HCV, there is limited data on their use in post-KT patients with HCV genotype 4 infection. Objectives: To evaluate the effectiveness and occurrence of adverse events with grazoprevir/elbasvir combination treatment without ribavirin in post-KT patients with HCV genotype 4 infection. Methods: In this case series, nine therapy-naïve adult post-KT patients with HCV genotype 4 infection were recruited. They had stable graft function and received a fixed dose of grazoprevir/elbasvir (50 mg/100 mg) combination without ribavirin daily for 12 weeks. Patients co-infected with hepatitis B virus, HIV, or with evidence of decompensated liver disease were excluded from the study. Patients were monitored for viral load, laboratory values, and adverse events associated with drug treatment. The response was defined by the sustained virologic response at 12 weeks (SVR12) after the end of treatment. Results: All nine patients completed the treatment period and achieved SVR12 with no treatment failure or relapse. Of them, six patients had HCV genotype 4 infection alone, and three had HCV of mixed genotypes 1 and 4. Two (22%) patients showed a rapid HCV clearance at four weeks. No adverse events or serious adverse events were reported. The patients’ renal function was stable during and after the treatment with no deterioration of graft function, and no adjustments to the immunosuppressive therapy were required. Conclusions: Grazoprevir/elbasvir combination without ribavirin is an effective and safe treatment option for post-KT patients with genotype 4 HCV infection.

Organ transplantation is still the treatment of choice for end-stage organ failure. Despite the establishment of the Saudi Center for Organ Transplantation (SCOT), the organ supply still does not meet the increasing demand. This study aims to assess the knowledge of Saudis about organ donation both among the public and the medical staff and to assess the trend in the change from 1996 until now. A cross-sectional study was conducted among Saudis above the age of 18 years. A self-administered, 25-item, questionnaire was completed by participants including both outpatients and medical staff at King Abdulaziz Medical City using a convenient sampling technique. A total of 376 individuals answered the questionnaire; 238 (63.1%) heard about SCOT, of whom 124 (70.5%) were males. Health-care professionals had better attitude and knowledge on organ donation (P

Summary Limited clinical trial data has shown high efficacy of co-formulated ledipasvir/sofosbuvir (LDV/SOF) in the treatment of hepatitis C virus (HCV) genotype (GT)-4 infected cirrhotic patients. We assessed real-world safety and efficacy of LDV/SOF with or without ribavirin (RBV) in GT4-infected patients with compensated and decompensated cirrhosis. Patients & Methods This observational cohort (n = 213) included GT4 treatment-naive (59.6%) and -experienced (40.4%) patients with advanced fibrosis (F3, Metavir; n = 30), compensated (F4, n = 135) and decompensated cirrhosis (n = 48) treated for 12 (n = 202) or 24 weeks (n = 11) with LDV/SOF. RBV was dosed by physician discretion between 600–1200 mg daily. Patients with prior DAA failure were excluded from the analysis. The primary efficacy endpoint was sustained virologic response 12 weeks after treatment (SVR12) on an intention-to-treat analysis, and occurrence of serious adverse events (SAEs). Results The mean age of the overall cohort was 59.6 ± 12.1 years and 125 (58.7) were female. Overall, 197 (92.5%) of the patients achieved SVR12, including 93.3% of F3 fibrosis, 93.3% of compensated cirrhotics and 89.6% of the decompensated cirrhotics ( P = 0.686). Addition of RBV (68.5%) did not enhance efficacy (91.8% vs. 94.0% without RBV, P = 0.563), including in F3 fibrosis, compensated and decompensated cirrhosis ( P > 0.05, for all). There was no difference in SVR12 rates with 24 and 12 weeks therapy (90.9% and 92.6%, respectively; P = 0.586). Treatment failure (n = 16) was mostly related to relapse (n = 11), while on-treatment death (n = 3) and breakthrough (n = 2) comprised a minority. SAEs occurred in 9 (4.2%) patients requiring early treatment discontinuation in 4 (3 on-treatment deaths and 1 pregnancy). Conclusion LDV/SOF therapy yielded high SVR12 rates in both compensated and decompensated cirrhotic GT4 patients. The addition of RBV to this regimen did not improve efficacy. The safety profile of this regimen was comparable with that reported for other HCV genotypes.

In chronic hepatitis B virus (HBV) patients, fluctuations in HBV DNA serve as a "gray area" and impede the accurate identification of inactive carriers. We aimed to assess if such fluctuations impact the presence of significant hepatic fibrosis (Metavir F2-4) in chronic HBV patients.Consecutive, untreated HBeAg-negative carriers (n = 234) with fluctuating HBV DNA (n = 73) above or below a level of 2000 IU/mL were included and compared to those without fluctuations (n = 161). Patients without fluctuating HBV DNA were further analyzed based on those with persistently low (2,000 IU/mL, n = 137) and higher HBV DNA (2,000-20,000 IU/mL, n = 24). Hepatic fibrosis (assessed by transient elastography) was correlated with virologic and biochemical profiles.The mean age of the overall cohort was 47.8 ± 11.1 years, of whom 107 (45.7%) were male. During a median of 60 months (interquartile range [IQR] 34-82) of follow-up, 73 (31.2%) patients had a mean of 1.6 ± 0.9 fluctuations in HBV DNA. The median time to the first fluctuation was at 14.5 (IQR 5.0-33.7) months. Patients with fluctuating viremia had higher logFluctuating HBV DNA levels occur frequently but are not associated with significant fibrosis. Minor fluctuations in HBV DNA levels are unlikely to be of clinical relevance.

Optimal doses of Ribavirin (RBV) for hepatitis C virus (HCV) treatment are not known. To assess the safety and efficacy of PegIFNalfa-2a in combination with an adjusted (ADJ) RBV dose based on early pharmacokinetics versus a fixed standard (STD) dose of RBV in chronic HCV genotype (GT) 4-naive patients in a randomized trial. One hundred eighty-one patients were randomized. The baseline variables were similar in both arms and females were 50.3% of the patients, 76.5% had minimal-moderate fibrosis (F0-2). Sustained virologic response (SVR) was achieved in 99 (54.7%) subjects. SVR was seen in 50/90 (55.6%) of ADJ dose of RBV and 49/91 (53.9%) of STD dose subjects. Prematurely withdrawal or discontinuation of treatment prematurely in the ADJ RBV arm occurred in 11/90 patients (12.2%) compared with 6/91 subjects (6.6%) in the STD arm (P = 0.214). Similarly, virologic relapse was seen in 14/90 (15.6%) patients of the ADJ arm and 12/91 (13.2%) of the STD arm. Anemia grade 3-4 was seen in 36.7% in ADJ versus 17.6% in STD arm (P = 0.003). Occurrence of rapid virologic response and absences of F4 fibrosis predicted SVR in a univariate analysis. However, age, gender, weight, presence of diabetes, baseline alanine aminotransferase, and vitamin D levels were not significantly different in patients achieving SVR. ADJ higher doses of RBV based on its early pharmacokinetics-based RBV do not improve SVR rates in HCV GT4 treated in combination with peg-IFN alpha-2-a versus STD therapy. Patients on ADJ higher doses of RBV experienced higher rates of anemia and require more erythropoietin without increasing SVR.

Hepatic artery pseudoaneurysm (HAA) is a rare vascular complication of liver transplantation. Minimally invasive radiological interventions are generally considered before seeking surgical treatment of HAA. Coil embolization of the aneurysmal sac and or exclusion of pseudoaneurysm by deploying a stent over the aneurysm are effective interventions to control hemobilia arising from the HAA. Migration of coils inside the bile duct is a rarely reported complication in post-hepatic transplantation. Treatment options remain largely unexplored due to the rarity of its occurrence. Endoscopic retrograde cholangiographic removal of migrated vascular coils in the common bile duct following embolization of HAA has not been described in a liver transplant setting. We report a liver transplant recipient who underwent uneventful and successful endoscopic removal of migrated coils into the bile duct.

The prevalence of the hepatitis B e antigen (HBeAg)-negative form of chronic hepatitis B (CHB) has increased over the years and is generally more difficult to treat. Pegylated interferon (PEG-IFN) offers a durable response, finite treatment duration and absence of viral resistance. On the other hand, the risk of viral relapse for patients discontinuing nucleos(t)ide analogues remains a major concern for this form of treatment, raising the spectre of drug resistance and safety with long-term use. PEG-IFN remains one of the first-line drugs for a select group of CHB patients, and with its dual immunomodulatory and antiviral effect offers a realistic chance of durable off-treatment response and HBsAg clearance. PEG-IFN could be offered to patients with a high pre-treatment likelihood of response. In this article we aim to discuss the indications and goals of antiviral therapy in HBeAg-negative patients, the safety and efficacy of IFN-based therapy, the predictors of response, and its potential future directions.

Background: The hepatitis C pandemic has been systematically studied and characterized in North America and Europe, but this important public health problem has not received equivalent attention in other regions. Aim: The objective of this systematic review was to characterize hepatitis C virus (HCV) epidemiology in selected countries of Asia, Australia and Egypt, i.e. in a geographical area inhabited by over 40% of the global population. Methodology: Data references were identified through indexed journals and non-indexed sources. In this work, 7770 articles were reviewed and 690 were selected based on their relevance. Results: We estimated that 49.3‐64.0 million adults in Asia, Australia and Egypt are anti-HCV positive. China alone has more HCV infections than all of Europe or the Americas. While most countries had prevalence rates from 1 to 2% we documented several with relatively high prevalence rates, including Egypt (15%), Pakistan (4.7%) and Taiwan (4.4%). Nosocomial infection, blood transfusion (before screening) and injection drug use were identified as common risk factors in the region. Genotype 1 was common in Australia, China, Taiwan and other countries in North Asia, while genotype 6 was found in Vietnam and other Southeast Asian countries. In India and Pakistan genotype 3 was predominant, while genotype 4w as found in Middle Eastern countries such as Egypt, Saudi Arabia and Syria. Conclusion: We recommend implementation of surveillance systems to guide effective public health policy that may lead to the eventual curtailment of the spread of this pandemic infection.

Background/Aims: Middle Eastern countries, including Saudi Arabia to some extent, are endemic for chronic hepatitis B (CHB) infection which could be associated with high mortality and comorbidities risk. However, limited data characterizing this CHB population exists. Our aim was to characterize and compare CHB patients in 2015 with those in 2010 and 2012 in Saudi Arabia. Patients and Methods: We conducted and compared three cross-sectional analyses of adult patients with CHB defined as either positive hepatitis B surface antigen or documented CHB history in 2010, 2012, and 2015. Data were accessed from the multicenter Systematic Observatory Liver Disease Registry (SOLID). Results: A total of 765 CHB patients were identified in 2010 (n = 274), 2012 (n = 256), and 2015 (n = 235). Median age was significantly higher in 2015 (47 years) compared to 2010 and 2012 (42 years;P < 0.05). The proportions of patients with hepatocellular carcinoma (range 1–12%) and cirrhosis (range 5–23%) were significantly higher in 2015 compared to 2010 and 2012 (P < 0.05). Compared to 2010, patients in 2015 had significantly (P < 0.05) higher prevalence of coronary artery disease (10% vs. 4%) and hyperbilirubinemia (18% vs. 9%). Although not significant, there was a numerical increase in 2015 in chronic kidney disease (9% vs. 7% in 2010;P= 0.559) and hepatic steatosis (32% vs. 25% in 2010;P= 0.074). Significantly more patients in 2015 (P < 0.05) were treatment experienced (23% vs. 5% in 2010/2012) and switched treatment (17% vs. 1–2% in 2010/2012). Conclusions: Between 2010 and 2015, the CHB population in Saudi Arabia had significantly aged and was more likely to develop liver disease sequelae and other comorbidities.

Although systemic amyloidosis of amyloid-associated protein (AA) type (secondary or reactive amyloidosis) frequently involves the liver, it rarely causes clinically apparent liver disease. Mild elevation of alkaline phosphatase and hepatomegaly are the most common biochemical and clinical findings, respectively. We report a case of systemic amyloidosis of AA type, which clinically presented as subacute hepatic failure and resulted in a fatal clinical course in a 69-year-old man. To the best of our knowledge, this is the fifth case of hepatic amyloidosis of AA type that clinically presented as fatal subacute hepatic failure, an unusual clinical presentation for hepatic involvement by systemic AA-type amyloid.

Objective: Measurement of ribavirin (RBV) is important for therapeutic drug monitoring in hepatitis C patient. A simple and fast high performance liquid chromatography (HPLC) method developed and validated to measure ribavirin concentration in serum samples without an evaporation step. Design and method: About 500 μl serum sample, 50 μl internal standard and 20 mM ammonium acetate buffer (pH=8.5) were mixed for 30 seconds and centrifuged. The supernatant was transferred into preconditioned phenyl boronic acid cartridges for solid phase extraction. All cartridges were washed two times with 1 mL of 20 mM ammonium acetate buffer under vacuum not exceeding 10 psi. Ribavirin and internal standard were eluted with 300 μl of 3% formic acid. An aliquot of 100 μl was injected into HPLC system. Results: The method was linear in the range of 0.1-8.0 mg/l with 0.05 mg/l as limit of detection. The correlation coefficient of method comparison was 0.975 with p value of 0.116 showing a good reproducibility of results. The mean accuracy was checked at three different concentrations and found to be between 107-110% for all three levels. The extraction efficiency was 65.5% for ribavirin in the range of 0.1-8.0 mg/l and 71.2% for internal standard at 50 mg/l. The intra assay precisions were determined at 0.5, 2.5, and 5.0 mg/l and % CV were found to be 2.2%, 5.0%, 4.5% respectively. The injection reproducibility at three levels was 5.5%, 6.1% and 3.3%. Removal of gravity flow and evaporation step made this method faster and easy for routine analysis of ribavirin samples. Conclusion: The newly developed HPLC method was faster, accurate and sensitive. It applied for determining serum ribavirin level in hepatitis C patient in our hospital.

The hepatitis C virus (HCV) epidemic was forecasted through 2030 for 15 countries in Europe, the Middle East and Asia, and the relative impact of two scenarios was considered: increased treatment efficacy while holding the annual number of treated patients constant and increased treatment efficacy and an increased annual number of treated patients. Increasing levels of diagnosis and treatment, in combination with improved treatment efficacy, were critical for achieving substantial reductions in disease burden. A 90% reduction in total HCV infections within 15 years is feasible in most countries studied, but it required a coordinated effort to introduce harm reduction programmes to reduce new infections, screening to identify those already infected and treatment with high cure rate therapies. This suggests that increased capacity for screening and treatment will be critical in many countries. Birth cohort screening is a helpful tool for maximizing resources. Among European countries, the majority of patients were born between 1940 and 1985. A wider range of birth cohorts was seen in the Middle East and Asia (between 1925 and 1995).

Blood in the stomach and esophagus in patients with variceal bleeding often obscures the endoscopic view and makes endoscopic intervention difficult to perform. Erythromycin, a motilin agonist, induces gastric emptying.To assess the effect of erythromycin on endoscopic visibility and its outcome in patients with variceal bleeding.Randomized, double-blind, placebo-controlled trial.Tertiary care hospital.Adult patients with liver cirrhosis presenting with hematemesis within the previous 12 hours.Either 125 mg erythromycin or placebo administered intravenously 30 minutes before endoscopy.Endoscopic visibility during index endoscopy and mean duration of procedure. SECONDARY OUTCOME MEASUREMENTS: Need for repeat endoscopy and blood transfusions within 24 hours, endoscopy-related complications, and length of hospital stay.A total of 102 patients received either erythromycin or placebo (53 erythromycin and 49 placebo). Forty-seven patients in the erythromycin group and 43 in the placebo group had variceal bleeding and were considered for final analysis. A completely empty stomach was seen in 48.9% of the erythromycin group versus 23.3% of the placebo group (P.01). Mean endoscopy duration was significantly shorter in the erythromycin group than in the placebo group (19.0 minutes vs 26.0 minutes, respectively; P.005). Length of hospital stay was significantly shorter in the erythromycin group than in the placebo group (3.4 days vs 5.1 days, respectively; P.002). The need for repeat endoscopy and the mean number of units of blood transfused did not differ significantly in the 2 groups. No adverse events were observed with erythromycin.Sample size not sufficient to measure the need for repeat endoscopy and survival benefit.Erythromycin infusion before endoscopy in patients with variceal bleeding significantly improves endoscopic visibility and shortens the duration of the index endoscopy. (NCT01060267.).

While the role of endoscopic retrograde cholangiopancreatography (ERCP) and endoscopic sphincterotomy (EST) in the diagnosis and management of choledocholithiasis is well established, this study evaluates the usefulness of ERCP and EST in patients with symptomatic cholecystolithiasis and suspected choledocholithiasis before undergoing laparoscopic cholecystectomy (LC), and the role of ERCP-EST in the management of complications resulting from LC.This paper reviews retrospectively our experience from 1992 to 1995. A total of 1221 LCs and 717 ERCPs were performed, out of which 257 ERCPs were performed on 225 patients who underwent LC (230 ERCPs before and 27 after). The age range was 10-85 years (mean 43.5). The study group comprised 148 females (66%) and 77 males (34%).The overall success rate for ERCP was 92% (96% for diagnostic and 88% for therapeutic). Choledocholithiasis was found at preoperative ERCP in 45% of cases. Prediction of choledocholithiasis was accurate in 46%, based on abnormal liver chemistry, and 70% when based on a combination of abnormal liver tests and dilated main bile duct (7 mm) by ultrasound. In 40 cases of acute biliary pancreatitis, choledocholithiasis was found at ERCP in eight cases (20%). In the post-LC group, all eight cases with residual stones and seven of eight cases with bile leaks were successfully treated endoscopically. There were four cases with major duct injuries that required surgical management. The complications related to ERCP-EST included two cases of bleeding post-EST (one was controlled with injection therapy and the second one was managed surgically), and three cases of mild pancreatitis.ERCP and EST are effective and safe in the diagnosis and management of choledocholithiasis, and facilitate LC for symptomatic cholelithiasis. The procedures are also valuable in the diagnosis and management of most complications resulting from LC.

There are a paucity of data available on the exact prevalence of delta hepatitis among HBsAg positive carriers in Saudi Arabia. The aim of this study was to determine the exact prevalence of delta antibody in HBsAg positive carriers in Saudi Arabia.Between January 1996 and January 1997 the serum of 19,250 patients was tested for HBsAg. HBsAg positive sera were subsequently tested for delta antibody. In addition, 3147 healthy blood donors underwent HBsAg testing. Those who were HBsAg positive had delta antibody testing using the ELISA method.Among 19,250 patients, 780 (4.1 %) were HBsAg positive, of which 67 (8.6%) patients were anti-delta positive and 2 (0.25%) were anti-delta borderline. Among 3147 healthy donors, 60 (1.9%) were HBsAg positive with 2 (3.3%) being delta antibody positive.The prevalence of delta antibody among hospital- and clinic-based HBsAg positive patients was 8.6% and among healthy blood donors who were HBsAg positive, the prevalence was 3.3%. Furthermore, delta antibody prevalence was 0.06% for "all comers", i.e., healthy blood donors. With decreasing hepatitis B prevalence as a result of universal vaccination, it is expected that delta hepatitis infection among Saudis will decrease with time.

Background & Aims Differing threshold levels of hepatitis B virus (HBV) DNA and alanine aminotransferase (ALT) are recommended by international guidelines for commencement of antiviral therapy. These guidelines advocate therapy for patients with significant fibrosis (METAVIR score ≥F2); we assessed the accuracy of these guideline-defined thresholds in identifying patients with ≥F2 fibrosis. Methods We applied the European (European Association for the Study of the Liver [EASL] 2012), Asian-Pacific (Asian-Pacific Association for the Study of the Liver [APASL] 2012), American (American Association for the Study of Liver Diseases [AASLD] 2009), and United States Panel Algorithm (USPA 2008) criteria to 366 consecutive hepatitis B e antigen–negative patients with liver biopsy samples: EASL, ALT >laboratory-defined upper limit of normal (ULN) and HBV DNA ≥2000 IU/mL (n = 171); APASL, ALT >2-fold laboratory-defined ULN and HBV DNA ≥2000 IU/mL (n = 87); AASLD, ALT >2-fold the updated ULN (0.5-fold ULN [corresponding to ≤19 U/L] for women and 0.75-fold the ULN [corresponding to ≤30 U/L] for men) and HBV DNA ≥20,000 IU/mL (n = 53); and USPA, ALT >updated ULN (>0.5-fold ULN for women and >0.75-fold ULN for men) and HBV DNA ≥2000 IU/mL (n = 173). Results Overall, 113 patients (30.9%) had ≥F2 fibrosis, which was more frequent among patients who fulfilled any guideline criteria (45.7% vs 17.9% for those who did not fulfill any criteria, P P = .145) and 82.1%, 73.8%, 77.1%, and 82.4% ( P = .366), respectively. The EASL criteria (area under the receiver operating characteristic [AUROC] curve, 0.66; 95% confidence interval [CI], 0.61–0.71) and USPA criteria (AUROC, 0.66; 95% CI, 0.58–0.73) performed better than APASL (AUROC, 0.64; 95% CI, 0.59–0.69; P = .421) and significantly better than the AASLD criteria (AUROC, 0.59; 95% CI, 0.54–0.64; P = .013). Conclusions In hepatitis B e antigen–negative patients with chronic hepatitis, the EASL, AASLD, APASL, and USPA criteria identify patients with ≥F2 fibrosis with low levels of accuracy. However, the EASL and USPA criteria are the most accurate for identification of these patients.

Trough concentrations of cyclosporine can be highly variable because of its poor bioavailability in current oral formulations, Sandimmune (SIM). Neoral (N-SIM) a new microemulsion of cyclosporine is more readily absorbed than SIM in healthy controls. The present study compared the pharmacokinetic profiles of SIM and N-SIM following orthotopic liver transplantation. In 16 patients with partial biliary diversion, 1 week after transplantation, the bioavailability and peak concentration of a single 300 mg dose of N-SIM were greater than SIM by 724% (p = 0.0019) and 800% (p = 0.0001), respectively. In 39 patients who were on stable doses of cyclosporine 1 month after transplantation, the bioavailability of N-SIM was higher than that of SIM under both fasting (+64%, p = 0.001) and fed (+37%, p = 0.004) conditions. Trough concentrations were similar for the two formulations. However, peak concentrations were higher for N-SIM in both fasting (+119%, p = 0.003) and fed (+53%, p = 0.003) patients. Also, time to peak was shorter for N-SIM in both fasting (-21%, p = 0.027) and fed (-59%, p = 0.0001) patients. The correlation between trough concentrations and bioavailability was greater for N-SIM than for SIM in fasted (r = 0.80, p = 0.0001 versus r = 0.75, p = 0.0001) and fed patients (r = 0.65; p = 0.002 versus r = 0.55; p = 0.012). We conclude that the rate of absorption and the bioavailability of N-SIM is significantly and consistently better than SIM and may, therefore, improve the therapeutic index of cyclosporine after liver transplantation.

This guideline has been approved by the Saudi Association for the Study of Liver diseases and Transplantation and represents the position of the Association. These practice guidelines have been written to assist physicians and other health care providers to aid in the recognition, diagnosis, and management of chronically infected hepatitis C virus (HCV) patients. They are based on a formal review and analysis of published literature on the topic that impact the management of chronic HCV infection, and the experience of the authors in hepatitis C. In addition, various international practice guidelines and consensus documents on management of chronic hepatitis C were considered in the development of these guidelines. The recommendations contained herein suggest preferred approaches to the diagnostic, therapeutic, and preventive aspects of care related to the disease. Our understanding of the natural history of HCV infection and the potential for therapy of the resultant disease is continuously improving. However, despite the increasing knowledge, areas of uncertainty still exist and therefore clinicians, patients, and public health authorities must continue to make choices on the basis of the evolving evidence. Therefore, these guidelines are intended to be flexible and may be updated periodically as new information becomes available.

Variceal bleeding is a life-threatening complication of portal hypertension with a high probability of recurrence. Treatment to prevent first bleeding or rebleeding is mandatory. The study has been aimed at investigating the effectiveness of endoscopic band ligation in preventing upper gastrointestinal bleeding in patients with portal hypertension and to establish the clinical outcome of patients.We analyzed in a multicenter trial, the efficacy and side effects of endoscopic band ligation for the primary and secondary prophylaxis of esophageal variceal bleeding. We assigned 603 patients with portal hypertension who were hospitalized to receive treatment with endoscopic ligation. Sessions of ligation were repeated every two to three weeks until the varices were eradicated. The primary end point was recurrent bleeding.The median follow-up period was 32 months. A total of 126 patients had recurrent bleeding. All episodes were related to portal hypertension and 79 to recurrent variceal bleeding. There were major complications in 51 patients (30 had bleeding esophageal ulcers). Seventy-eight patients died, 26 deaths were related to variceal bleeding and 1 to bleeding esophageal ulcers.A great improvement in the prevention of variceal bleeding has emerged over the last years. However, further therapeutic options that combine higher efficacy, better tolerance and fewer side effects are needed.