Consensus document of the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis on massive nonvariceal gastrointestinal bleeding and direct-acting oral anticoagulants.

INTRODUCTION: there is limited experience and understanding of massive nonvariceal gastrointestinal bleeding during therapy with direct-acting oral anticoagulants. OBJECTIVES: to provide evidenced-based definitions and recommendations. METHODS: a consensus document developed by the Spanish Society of Digestives Diseases and the Spanish Society of Thrombosis and Haemostasis using modified Delphi methodology. A panel was set up of 24 gastroenterologists with experience in gastrointestinal bleeding, and consensus building was assessed over three rounds. Final recommendations are based on a systematic review of the literature using the GRADE system. RESULTS: panelist agreement was 91.53 % for all 30 items as a group, a percentage that was improved during rounds 2 and 3 for items where clinical experience is lower. Explicit disagreement was only 1.25 %. A definition of massive nonvariceal gastrointestinal bleeding in patients on direct-acting oral anticoagulants was established, and recommendations to optimize this condition's management were developed. CONCLUSION: the approach to these critically ill patients must be multidisciplinary and protocolized, optimizing decisions for an early identification of the condition and patient stabilization according to the tenets of damage control resuscitation. Thus, consideration must be given to immediate anticoagulation reversal, preferentially with specific antidotes (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors); hemostatic resuscitation, and bleeding point identification and management.

Author's reply: "A question on dyspeptic patients analyzed by psychometric scores".

First of all, we want to thank Pellicano et al. for their comments on our article "New psychometric data from the Spanish versions of the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health scale measures". The aim is always the scientific improvement of the manuscript.

New psychometric data from the Spanish versions of the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health Scale measures.

BACKGROUND AND OBJECTIVE: There are no structural abnormalities in functional dyspepsia, therefore it is essential to have a viable questionnaire to measure treatment outcome according to patient perception. The aim of the study was to extensively document psychometric characteristics of the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health Scale that are currently available in Spanish. METHODS: Patients with functional dyspepsia (n = 158) were recruited from a randomized trial that assessed standard vs. standard and psychological treatment. Participants had completed the validation questionnaires and the Medical Outcome Study Short-form 36. Reliability (Cronbach's alpha), validity (Confirmatory Factor Analysis, convergent and known group validity) and responsiveness (minimal clinically important difference) were analyzed. RESULTS: A Confirmatory Factor Analysis of the Glasgow Dyspepsia Severity Score showed a one-factor solution model, but a low Cronbach's alpha (0.61). With regard to the Dyspepsia-Related Health Scale, the Cronbach's alpha (0.80-0.97) and Confirmatory Factor Analysis supported a model with four inter-correlated dimensions and suggested a need to improve the "Satisfaction with dyspepsia-related health" dimension (Cronbach's alpha < 20). Finally, the global scores for both the Glasgow Dyspepsia Severity Score and the Dyspepsia-Related Health Scale were responsive at six months post-treatment, with a minimal clinically important difference of 4 and 6, respectively. CONCLUSIONS: Our findings support the continued application of the Dyspepsia-Related Health Scale and the need to improve the "Satisfaction with dyspepsia-related health" dimension. Although the Glasgow Dyspepsia Severity Score is a promising questionnaire, further review of the content is required to eliminate and add items in order to provide greater consistency to the evaluated construct.

[Comparison of esophageal stenoses produced by endoscopic sclerotherapy versus variceal ligation]. / Comparación de las estenosis esofágicas producidas por escleroterapia o ligadura de varices.

INTRODUCTION: Variceal ligation (VL) eradicates esophageal varices faster than endoscopic sclerotherapy (ES) with a lower rebleeding rate and fewer secondary effects. However, most studies have evaluated the short-term effects of these treatments and some late complications may be overlooked. PATIENTS AND METHODS: To determine the incidence and the characteristics of stenosis, we included 253 cirrhotic patients treated endoscopically for variceal bleeding from 1988 to 2004 in our hospital. ES was carried out with ethanolamine 5% and polidocanol 1.5%. ES and VL were carried out every 15 days until varices were eradicated and then at 3-, 6- and 12-month intervals; if varices reappeared, the initial treatment was repeated. Stenosis was considered mild when esophageal size was more than 10 mm and severe when the endoscope could not be passed through the stricture. RESULTS: We found stenosis in seven out of 105 (6.7%) ES-treated patients and in 10 out of 148 (6.7%) VL-treated patients. The clinical characteristics of the patients and the previous number of endoscopic sessions were similar in both groups. Four out of seven ES patients developed stenosis during the first eradication process (mean: 11 months, 1-60), but this early stenosis was observed in one out of 10 VL patients (mean: 20 months, 1-72). Stenosis was severe in three out of seven ES patients (43%) but in only two out of ten VL patients (20%) (NS). CONCLUSIONS: The incidence of esophageal stenosis was similar after treatment of esophageal varices with ES and VL, although VL had a tendency to produce later stenosis.

Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.

Osteoprotegerin and receptor activator of nuclear factor-kappaB ligand system in the early post-operative period of liver transplantation.

BACKGROUND: The precise mechanism that leads to accelerated bone resorption in the early post-transplant period remains unclear. Recent data suggest that osteoprotegerin (OPG) and its ligand receptor activator of nuclear factor-kappaB ligand (RANKL) constitute a novel cytokine system that can influence the function of both bone and immune cells. The aim of our study was to assess OPG and RANKL concentrations in the early post-operative period of liver transplantation. METHODS: Serum OPG and RANKL levels were measured in 30 patients who underwent liver transplantation at 1, 7 and 14 d post-operatively. These values were compared with 22 age- and sex-matched healthy controls. Plasma sodium, creatinine, aspartate-aminotransferase, alanine-amino transferase, gamma-glutamyl transferase, alkaline phosphatase, bilirubin, albumin, prothrombin time, tacrolimus and cyclosporine levels were measured in each patient. RESULTS: We found a significant increase in OPG levels in the early post-operative period compared with the control group: day 1 (10.42 pmol/L, range 3.80-17.50 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.0001), day 7 (6.90 pmol/L, range 3.00-15.30 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.0001) and day 14 (5.76 pmol/L, range 2.60-10.70 vs. 3.91 pmol/L, range 1.20-6.60; p = 0.001). Similarly, serum RANKL levels were significantly higher than in the control group in this period, day 1 (0.123 pmol/L, range 0.010-0.420 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.02), day 7 (0.236 pmol/L, range 0.010-0.720 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.0004) and day 14 (0.137 pmol/L, range 0.010-0.520 vs. 0.054 pmol/L, range 0.010-0.300; p = 0.007). No correlation was found between OPG levels and RANKL, ischemic times, liver function tests, albumin, sodium or creatinine concentrations and tacrolimus or cyclosporine levels. CONCLUSIONS: A significant amount of OPG and RANKL is released in the early post-transplant period of liver transplantation. This might be explained by an activation of the immune system caused by the allograft. Therefore, the RANKL/OPG system may be involved in the pathophysiological evolution of transplantation osteoporosis.

Osteoprotegerin and RANKL in alcoholic liver cirrhosis.

BACKGROUND/AIMS: The mechanisms leading to osteoporosis in alcoholic liver disease remain poorly understood. Recently identified soluble circulating osteoprotegerin (OPG), is the osteoclastogenesis inhibitory factor. It acts as a decoy receptor for osteoclast activating factor, receptor activator of nuclear factor-kappaB ligand (RANKL), and impairs osteoclast function. The aim of our study was to investigate the OPG/RANKL system in alcoholic cirrhotic patients and their correlation with biochemical marker of bone turnover. PATIENTS AND METHODS: Serum OPG, RANKL, osteocalcin (OC), C-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase activity (bALP), and urinary hydroxyproline were measured in 30 patients with alcoholic cirrhosis, and in 20 age- and sex-matched healthy controls. RESULTS: OPG levels were significantly increased in patients with alcoholic cirrhosis compared with healthy subjects (5.9 pmol/l, range 2.7-9.0 vs 4.1 pmol/l, range 1.2-6.6; P < 0.001). RANKL levels were significantly higher in patients with cirrhosis (0.48 pmol/l, range 0.01-1.34) than in healthy subjects (0.11 pmol/l, range 0.01-0.90). There was a positive correlation between serum OPG and RANKL (r = 0.37; P < 0.001), bALP (r = 0.66; P < 0.001) and urinary hydroxyproline (r = 0.51; P < 0.05) but not with OC and CTX-I. CONCLUSIONS: OPG might partly represent a compensating mechanism to the negative balance of bone remodelling in patients with alcoholic cirrhosis.

Liver transplantation with allografts from hepatitis B core antibody-positive donors: a new approach.

The enduring shortfall of organ donors has inspired the widespread utilization of hepatic allografts from donors with hepatitis B core antibodies in spite of the potential risk of transmitting hepatitis B virus (HBV) infection to the recipient. Here we report a protocol of naive recipients receiving livers from hepatitis B core antibody-positive donors. From November, 1999 to March, 2002, 77 liver transplantations were performed in 73 patients at our institution, 7 of whom received livers from hepatitis B core antibody-positive donors. All recipients received 10,000 U/d of intravenous HBIg for 7 days and 100 mg/d of lamivudine until we could obtain the HBV-DNA from the donor samples (serum and liver tissue). If the results of the HBV-DNA from the donor samples were positive, the patient would continue with prophylaxis and if they were negative we would finish the combined prophylaxis. After transplantation, HBV serologic markers and HBV-DNA by polymerase chain reaction (PCR) in serum and lymphocytes were tested in the recipients on the seventh, fifteenth, thirtieth, and ninetieth days as well as every 3 months after transplantation. All seven donor organs were negative for HBV-DNA in serum and liver tissue. Thus, we stopped the combined prophylaxis in all recipients (range, 7 to 10 days). None of the 7 patients developed de novo HBV infection over the 3-year study period (range, 9 to 36 months). Our approach is reasonably safe, and it appears to be very effective in the prevention of de novo HBV infection after liver transplantation.