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.

The Mexican consensus on nonalcoholic fatty liver disease. / Consenso mexicano de la enfermedad por hígado graso no alcohólico.

Nonalcoholic fatty liver disease (NAFLD) affects nearly one third of the population worldwide. Mexico is one of the countries whose population has several risk factors for the disease and its prevalence could surpass 50%. If immediate action is not taken to counteract what is now considered a national health problem, the medium-term panorama will be very bleak. This serious situation prompted the Asociación Mexicana de Gastroenterología and the Asociación Mexicana de Hepatología to produce the Mexican Consensus on Fatty Liver Disease. It is an up-to-date and detailed review of the epidemiology, pathophysiology, clinical forms, diagnosis, and treatment of the disease, whose aim is to provide the Mexican physician with a useful tool for the prevention and management of nonalcoholic fatty liver disease.

Consenso Mexicano para el Tratamiento de la Hepatitis C / The Mexican consensus on the treatment of Hepatitis C

El objetivo del Consenso Mexicano para el Tratamiento de la Hepatitis C fue el de desarrollar un documento como guía en la práctica clínica con aplicabilidad en México. Se tomó en cuenta la opinión de expertos en el tema con especialidad en: gastroenterología, infectología y hepatología. Se realizó una revisión de la bibliografía en MEDLINE, EMBASE y CENTRAL mediante palabras claves referentes al tratamiento de la hepatitis C. Posteriormente se evaluó la calidad de la evidencia mediante el sistema GRADE y se redactaron enunciados, los cuales fueron sometidos a voto mediante un sistema modificado Delphi, y posteriormente se realizó revisión y corrección de los enunciados por un panel de 34 votantes. Finalmente se clasificó el nivel de acuerdo para cada oración. Esta guía busca dar recomendaciones con énfasis en los nuevos antivirales de acción directa y de esta manera facilitar su uso en la práctica clínica. Cada caso debe ser individualizado según sus comorbilidades y el manejo de estos pacientes siempre debe ser multidisciplinario.

The aim of the Mexican Consensus on the Treatment of Hepatitis C was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitis C treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.

The Mexican consensus on the treatment of hepatitis C. / Consenso Mexicano para el Tratamiento de la Hepatitis C.

The aim of the Mexican Consensus on the Treatment of HepatitisC was to develop clinical practice guidelines applicable to Mexico. The expert opinion of specialists in the following areas was taken into account: gastroenterology, infectious diseases, and hepatology. A search of the medical literature was carried out on the MEDLINE, EMBASE, and CENTRAL databases through keywords related to hepatitisC treatment. The quality of evidence was subsequently evaluated using the GRADE system and the consensus statements were formulated. The statements were then voted upon, using the modified Delphi system, and reviewed and corrected by a panel of 34 voting participants. Finally, the level of agreement was classified for each statement. The present guidelines provide recommendations with an emphasis on the new direct-acting antivirals, to facilitate their use in clinical practice. Each case must be individualized according to the comorbidities involved and patient management must always be multidisciplinary.

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.

Risk of non-alcoholic fatty liver disease in patients with psoriasis: a systematic review and meta-analysis.

BACKGROUND: Psoriasis has been linked to an increased risk of metabolic syndrome (MetS). Non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of MetS, is now the commonest liver disease worldwide and can evolve into cirrhosis in a subgroup of patients. Psoriasis has been reported to be associated to NAFLD. AIM: The aim of this study was to evaluate the strength of the association between psoriasis and NAFLD. METHODS: A systematic review of the literature was conducted in six databases (Medline, CINAHL, Scopus, LILACS, Cochrane Library and EMBASE). Data from studies assessing frequency of NAFLD in psoriatic and non-psoriatic patients were extracted and meta-analysed using the Mantel-Haenszel method. Subgroups analysis of patients with psoriatic arthritis and moderate to severe psoriasis was also performed. RESULTS: Seven case-control studies were included, all of them of low or moderate quality. Psoriatic patients exhibited an increased risk of NAFLD compared to non-psoriatic controls (six studies; n = 267,761 patients; odds ratio (OR): 2.15, 95% CI: 1.57-2.94). The association remained significant (OR: 2.07, 95% CI: 1.62-2.64) when only high/moderate quality studies were analysed (three studies; n = 3345 patients). The risk of NAFLD was significantly greater in patients with psoriatic arthritis (three studies; n = 505 patients; OR: 2.25, 95% IC: 1.37-3.71) and in patients with moderate to severe psoriasis compared to those with mild psoriasis (two studies; 51,930 patients, OR: 2.07, 95% CI: 1.59-2.71). LIMITATIONS: Data quality and heterogeneity may restrict the interpretation of the pooled risk estimates. CONCLUSION: Case-control studies support an association between psoriasis and NAFLD. Screening of NAFLD in this group of patients may be warranted.

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.

[Usefulness of chewing gum for the resolution of postoperative ileus in left colon resections]. / Utilidad de la goma de mascar para la resolución del íleo posoperatorio en resecciones de colon izquierdo.

BACKGROUND AND AIM: Disturbances in intestinal motility have been described since XIX century, with a not very well understood pathogenesis and few therapeutic approaches. Considering chewing as an important stimulus to promote intestinal motility we designed this study to assess the efficacy of chewing gum to improve the postoperative ileus, and the clinical relevance of this intervention. METHODS: Were included patients who underwent for elective left hemicolectomy during January 2007 to December 2008. The patients were randomly assigned to receive chewing gum or nothing during the post-surgery period. The main outcomes assessed were duration of postoperative ileus, and reduction in hospitalization days. RESULTS: During the period of the study were included 32 patients, were included mainly men (11 and 9 in treated and control patients, respectively). The first defecation after surgery procedure occurs at (44.2 ± 17.6 h) in the treated group and (55.5 ± 14.8 h) in the control group (p = 0.05). In the same way oral tolerance was achieved faster in the treated group (p= 0.05). The hospital stay duration was not different among treated and not treated patients. CONCLUSIONS: The use of chewing gum in patients after elective left hemicolectomy, reduce the duration of the postoperative ileus. However, this does not reduce the hospital stay duration.

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.

[Comparative study of the clinical presentation and complications of acute colonic diverticulitis in patients older and younger than 65 years.]. / Estudio comparativo de la presentación clínica y complicaciones de la diverticulitis aguda colónicaen pacientes mayores y menores de 65 años.

BACKGROUND AND AIM: Colonic diverticular disease has an incidence from 66 to 85% in population older than 65 years. Most of them remain asymptomatic;20% will be symptomatic and about 35%will present an episode of Acute Colonic Diverticulitis(ACD). To date, there are not studies to compare its presentation in elderly patients. The aim of this study was to compare the clinical presentation, diagnostic procedures, treatment and complications of acute colonic diverticulitis (ACD)in patients older and younger than 65 years. MATERIAL AND METHODS: A retrospective review of patients diagnosed with ACD from January 2003 to May 2006. Exclusion criteria included patients with incomplete medical records and those who didn't complete the in hospital treatment. Demographic,clinical, laboratory, and radiological,prognostic variables as well as chosen treatment,presence of complications were evaluated. Descriptive and comparative statistic analysis was performed by the Fisher Exact Test for categorical variables and Student t-Test for continual variables considering a statistically significant difference for p <0.05. The analysis was made with SPSS/PC v12.0 software. RESULTS: Of 126 patients, 69 were men and 57 women; 93 younger than 65 years and 33 older than 65 years. 20 patients were excluded by previously defined criteria. Significant statistical differences were found for presence of pain in the left inferior quadrant (73.2% vs. 48.5% p <0.01); mean hemoglobin level (14.6 vs. 13.2 g/dL p<0.01), presence of anemia (10.8% vs. 27.3% p <0.05) use of ultrasonography (24.7% vs. 6.1%,p < 0.05) and presence of hemorrhage (3.3% vs.21.3% p < 0.01) respectively. There was not mortality in the series. CONCLUSION: This series demonstrates that elderly patients with ACD have a greater rate of lower gastrointestinal bleeding and greater degree of anemia than younger patients.

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.