Current vision on diagnosis and comprehensive care in hepatic encephalopathy.

The first clinical guidelines on hepatic encephalopathy were published in 2009. Almost 14 years since that first publication, numerous advances in the field of diagnosis, treatment, and special condition care have been made. Therefore, as an initiative of the Asociación Mexicana de Gastroenterología A.C., we present a current view of those aspects. The manuscript described herein was formulated by 24 experts that participated in six working groups, analyzing, discussing, and summarizing the following topics: Definition of hepatic encephalopathy; recommended classifications; epidemiologic panorama, worldwide and in Mexico; diagnostic tools; conditions that merit a differential diagnosis; treatment; and primary and secondary prophylaxis. Likewise, these guidelines emphasize the management of certain special conditions, such as hepatic encephalopathy in acute liver failure and acute-on-chronic liver failure, as well as specific care in patients with hepatic encephalopathy, such as the use of medications and types of sedation, describing those that are permitted or recommended, and those that are not.

Less liver fibrosis in metabolically healthy compared with metabolically unhealthy obese patients with non-alcoholic fatty liver disease.

AIM: This cross-sectional study evaluated liver fibrosis in patients with non-alcoholic fatty liver disease (NAFLD), and compared the characteristics of metabolically healthy obese (MHO) with metabolically unhealthy obese (MUHO) patients. METHODS: The study was nested within a randomized clinical trial (RCT) and included obese patients with NAFLD, as determined by liver ultrasonography. Fibrosis was assessed by transient elastography, and AST-to-platelet ratio index (APRI) and NAFLD score. Patients were compared according to obesity phenotype using various accepted criteria. RESULTS: The RCT included 1024 patients with NAFLD, of whom 428 (41.7%) were included in the present study. The prevalence of MHO ranged from 1.2% to 63%, depending on the criteria used. According to various criteria for metabolic health, obese patients had less liver fibrosis. MHO patients, as defined by all criteria, showed a significantly lower prevalence of advanced liver fibrosis (F3-F4) than MUHO on transient elastography (16.5% vs. 28%, respectively; P≤0.05). CONCLUSION: MUHO patients are at higher risk of liver fibrosis and, therefore, the identification of obese patients with 'healthy' characteristics is imperative as their entire clinical work-ups are likely to differ.

Role of oxidative stress and molecular changes in liver fibrosis: a review.

Liver fibrosis represents a health problem with significant morbidity and mortality that affects 100 million people worldwide. It is a final pathway to several chronic liver diseases and is characterized by excess collagen and accumulation of extracellular matrix in response to chronic hepatocellular damage. Clinical and experimental data suggest that oxidative stress (OS) mediates the progression of fibrosis, and that OS-related molecules may act as mediators of molecular and cellular events implicated in liver fibrosis. The generation of reactive oxygen species (ROS) plays an important role in producing liver damage and initiating hepatic fibrogenesis. OS disrupts lipids, proteins and DNA, induces necrosis and apoptosis of hepatocytes and amplifies the inflammatory response. ROS also stimulate the production of profibrogenic mediators from Kupffer cells and circulating inflammatory cells and directly activate hepatic stellate cells, resulting in the initiation of fibrosis. Advances in understanding the mechanisms involved in fibrosis have identified new molecular targets with therapeutic potential for more targeted and personalized control of this disease. This review will highlight recent concepts in OS, antioxidants and the molecular pathways involved in hepatic fibrosis.

Mechanisms involved in the protective effects of metformin against nonalcoholic fatty liver disease.

Metformin is an antidiabetic drug used widely in clinical practice. Its main clinical effect is to reduce blood glucose levels by improving insulin resistance. Nonalcoholic fatty liver disease is characterized by chronic liver damage and can develop into liver cirrhosis. Nonalcoholic fatty liver disease is associated with obesity and contributes to insulin resistance, and metformin is used to treat individuals with these conditions. The mechanisms underlying the clinical effects of metformin in treating nonalcoholic fatty liver disease are unclear. This article summarizes the literature on the mechanisms associated with liver glucose metabolism and the beneficial effects of metformin on this common liver disease.

Meta-analysis: antibiotic prophylaxis for cirrhotic patients with upper gastrointestinal bleeding - an updated Cochrane review.

BACKGROUND: Antibiotic prophylaxis seems to decrease the incidence of bacterial infections in patients with cirrhosis and upper gastrointestinal bleeding and is considered standard of care. However, there is no updated information regarding the effects of this intervention. AIM: To assess the benefits and harms of antibiotic prophylaxis in cirrhotic patients with gastrointestinal bleeding by performing a systematic review of randomised trials. METHODS: We searched The Cochrane Hepato-Biliary Group Controlled Trials Register, The Cochrane Central Register of Controlled Trials in The Cochrane Library, MEDLINE, EMBASE and Science Citation Index EXPANDED until June 2010. We statistically combined data calculating relative risk (RR) for dichotomous outcomes and mean difference (MD) for continuous outcomes. RESULTS: Twelve trials (1241 patients) evaluating antibiotic prophylaxis against placebo or no antibiotic prophylaxis were included. Antibiotic prophylaxis was associated with reduced mortality (RR 0.79, 95% CI 0.63-0.98), mortality from bacterial infections (RR 0.43, 95% CI 0.19-0.97), bacterial infections (RR 0.35, 95% CI 0.26-0.47), rebleeding (RR 0.53, 95% CI 0.38-0.74) and days of hospitalisation (MD -1.91, 95% CI -3.80-0.02). Trials analysing rebleeding rate and hospitalisation length are still scarce, thus, caution should be exerted when interpreting the results. CONCLUSIONS: Antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding significantly reduced bacterial infections, and reduce all-cause mortality, bacterial infection mortality, rebleeding events and hospitalisation length. Novel clinically significant outcomes were included in this meta-analysis. Some benefits are biased and the risks are not yet properly assessed, this encourages future research in this field.

In vitro models for the study of non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease is regarded as the hepatic manifestation of metabolic syndrome and is an important and common cause of chronic liver disease with a potential to develop end-stage liver disease. While important advances in the pathophysiology have been achieved using genetically modified and diet-induced animal models, in-vitro models have been only recently proposed. These models include primary culture and immortalized cell lines. Here we critically review the characteristics of the in vitro models described, the advantages and limitations of the in vitro approach, and the results derived.

Diagnostic yield, therapeutic impact, and complications of double-balloon enteroscopy in patients with small-bowel pathology.

BACKGROUND AND AIMS: Until recently the study of small bowel was limited to the radiographic approach. This paper describes experience with the first 86 procedures evaluated and treated with the new technique of double-balloon enteroscopy (DBE). PATIENTS AND METHODS: Between August 2005 and September 2006, DBE was conducted in consecutive patients. The characteristics of the patients, indications for the procedures, procedural parameters, and diagnostic yield are described here. All conventional treatment options were available. All the patients had previously undergone esophagogastroduodenoscopy and colonoscopy. RESULTS: Eighty-six procedures in sixty-eight patients were carried out (41 women, 27 men; mean age 48.5 years, range 20-82). The most common indications were gastrointestinal bleeding (n = 40) and iron deficiency anemia (n = 7). The mean duration of the procedure was 63 (range 20-194) mins and 80 (range 20-150) minutes for the oral and anal routes, respectively. The mean depth of small-bowel insertion was 250 and 200 cm for the oral and anal routes, respectively. Impact in diagnosis and/or treatment was obtained in 50 patients (73.5%). The commonest findings in the 68 patients were angiodysplasia (n = 11), polyps (n = 8), nodular lymphoid hyperplasia (n = 5) and normal (n = 20). No major complications were observed. CONCLUSION: DBE is a useful tool for the diagnosis and treatment of patients with small-bowel pathology in whom traditional methods have not been effective. In almost two-thirds of patients DBE was clinically useful for diagnosis and treatment. The complication rate with the procedure was very low.

Endoscopic ultrasound-guided celiac plexus neurolysis in patients with unresectable pancreatic cancer.

BACKGROUND: The treatment of pain in patients with pancreatic cancer is a difficult topic for the patients and their physicians. There are different treatment modalities with variable results. Celiac plexus neurolysis (CPN) is a technique with good previous results using fluoroscopy, CT guidance and recently, guided by endoscopic ultrasound (EUS). The aim of this study is to report the experience of EUS guided CPN (EUS CPN) for treatment of abdominal pain in patients with unresectable pancreatic cancer. METHODS: Patients with inoperable pancreatic cancer diagnosed by CT, MRI and/or EUS were included. The measurement of pain was made with a visual analog pain scale applied before and after the procedure. Follow up was made at weeks 2 and 4 after the procedure. The use of morphine before and after EUS CPN was evaluated. Complications related to the procedure were recorded. RESULTS: Eleven patients (five men and six women) underwent to the procedure, the mean age was 59 years (range 43-82). In follow-up at four weeks after the procedure, pain scores were reduced by at least 5 points of visual analog pain scale in 9 (72.2%) patients. At least a fifty percent reduction in pain or more was documented in 7 (63.6%) patients. Five patients substantially reduced their pain medication. No complications were seen in this study. CONCLUSIONS: The EUS NPC is an efficient and safe method for pain treatment in those patients with inoperable pancreatic cancer.

Endocannabinoid receptor CB2 in nonalcoholic fatty liver disease.

BACKGROUND AND AIM: Fatty infiltration and fibrosis are major issues in chronic liver disease. Recent reports suggest a role for the endocannabinoid system in these processes. AIM: To characterize localization and expression of CB2 in normal liver and nonalcoholic fatty liver. METHODS: We studied 64 liver biopsies: eight were considered normal; 56 had a diagnosis of nonalcoholic fatty liver disease (NAFLD); 32 with nonalcoholic steatosis and 24 nonalcoholic steatohepatitis (NASH). CB2 immunolocalization was studied in 38 samples in paraffin blocks using immunohistochemistry, and a computerized semiquantitative analysis was carried out. CB2 mRNA expression was assessed through RT-PCR in 26 frozen liver samples and the ratio CB2/beta-actin was used to evaluate differences between groups. Statistical analysis was performed with central tendency measures and the Mann-Whitney U-test. We considered as significant differences those with a P-value <0.05. RESULTS: Neither parenchymal nor nonparenchymal cells in normal liver tissue react towards anti-CB2 antibodies. All the samples from patients with steatosis and nonalcoholic steatohepatitis showed hepatocellular immunoreactivity. Cholangiocytes were positive only in the NAFLD group. Normal liver tissue showed a normalized CB2/beta-actin ratio of 0.001+/-0.01, steatosis 6.52+/-17.3 (P=0.05 vs normal) and NASH 6.49+/-12.2 (P=0.06 vs normal and P=0.6 vs steatosis). CONCLUSION: CB2 receptors are expressed by hepatocytes in nonalcoholic fatty liver disease but not in normal liver.

Adiponectin, structure, function and pathophysiological implications in non-alcoholic fatty liver disease.

Obesity is a major risk factor for the development of the metabolic syndrome, a cluster of diseases including insulin resistance, type 2 diabetes, dyslipidemia, hypertension, microalbuminuria, atherosclerosis, and non-alcoholic steatohepatitis. On the other hand, it is now generally accepted that adipose tissue acts as an endocrine organ producing a number of substances with an important role in the regulation of food intake, energy expenditure and a series of metabolic processes. Adiponectin is a recently discovered hormone produced exclusively by adipocytes. In fact, adiponectin is considered currently as a major factor in obesity-related insulin resistance and atherosclerosis. This new hormone differs from other adipocytokines in that its production and concentrations are actually decreased in insulin resistant subjects. The aim of this review is to summarize the current knowledge about the chemistry and physiology of adiponectin and to discuss its implications in the pathophysiology and potential treatment of insulin resistance and non-alcoholic fatty liver disease.