Myostatin is associated with the presence and development of acute-on-chronic liver failure.

Background & Aims: Acute-on-chronic liver failure (ACLF) has been linked to different pathophysiological mechanisms, including systemic inflammation and mitochondrial dysfunction. Sarcopenia has also been proposed as a potential mechanism; myostatin is a key factor inducing sarcopenia. Therefore, this study aimed to evaluate the association of myostatin levels with the development of ACLF and mortality in patients with cirrhosis. Methods: We performed a prospective cohort study, including both outpatient and hospitalized patients with cirrhosis. Clinical, biochemical, and nutritional parameters were evaluated, and the development of acute decompensation (AD) or ACLF during follow-up was recorded. ACLF was defined according to the EASL-CLIF criteria. Receiver-operating characteristic, Kaplan-Meier and Cox regression analyses were performed. Results: A total of 186 patients with the whole spectrum of cirrhosis were included; mean age was 53.4 ± 14 years, mean Child-Pugh score was 8 ± 2.5 and mean MELD score was 15 ± 8. There was a stepwise decrease in myostatin levels from a compensated stage to AD and ACLF. Myostatin correlated positively with nutritional markers and negatively with severity scores. The prevalence of sarcopenia was 73.6%. During follow-up, 27.9% of patients developed AD and 25.8% developed ACLF. Most episodes were grade 2-3, mainly (62.5%) precipitated by infections. The most common organ failures observed were in the liver (63.3%) and the kidney (64.6%). Receiver-operating characteristic analysis yielded <1,280 pg/ml as the best serum myostatin cut-off for the prediction of ACLF. In Kaplan-Meier curves and multivariate analysis, myostatin levels remained independently associated with the incidence of ACLF and survival. Conclusions: There is a progressive decrease in myostatin levels as cirrhosis progresses, demonstrating an association of sarcopenia with the development of ACLF and increased mortality. Impact and implications: Myostatin is a muscle hormone, it is decreased in patients with muscle loss and is a marker of impaired muscle function. In this study we show that myostatin levels are decreased in patients with cirrhosis, with lower levels in patients with acute decompensation and acute-on chronic liver failure (ACLF). Low myostatin levels in cirrhosis predict the development of ACLF and mortality independently of liver disease severity and sex.

Production and activity of matrix metalloproteinases during liver fibrosis progression of chronic hepatitis C patients.

BACKGROUND: Matrix metalloproteinases (MMPs) participate in the degradation of extracellular matrix compounds, maintaining the homeostasis between fibrogenesis and fibrolytic processes in the liver. However, there are few studies on the regulation of liver MMPs in fibrosis progression in humans. AIM: To assess the production activity and regulation of matrix metalloproteinases in liver fibrosis stages in chronic hepatitis C (CHC). METHODS: A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized in fibrosis grades through FibroTest ® and/or FibroScan ® . Serum MMP-2, -7, and -9 were determined by western blot and multiplex suspension array assays. Differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. The Spearman correlation coefficient and area under the receiver operating characteristic curve were calculated. Collagenolytic and gelatinase activity was determined through the Azocoll substrate and zymogram test, whereas tissue inhibitor of metalloproteinase-1 production was determined by dot blot assays. RESULTS: Serum concentrations of the MMPs evaluated were higher in CHC patients than in healthy subjects. MMP-7 distinguished early and advanced stages, with a correlation of 0.32 (P < 0.001), and the area under the receiver operating characteristic displayed moderate sensitivity and specificity for MMP-7 in F4 (area under the receiver operating characteristic, 0.705; 95% confidence interval: 0.605-0.805; P < 0.001). Collagenolytic activity was detected at F0 and F1, whereas gelatinase activity was not detected at any fibrosis stage. Tissue inhibitor of metalloproteinase-1 determination showed upregulation in F0 and F1 but downregulation in F2 (P < 0.001). CONCLUSION: High concentrations of inactive MMPs were present in the serum of CHC patients, reflecting the impossibility to restrain liver fibrosis progression. MMPs could be good diagnostic candidates and therapeutic targets for improving novel strategies to reverse liver fibrosis in CHC.

Bacterial infections in cirrhosis: Current treatment.

Bacterial infections frequently cause decompensating events in cirrhotic patients and are also the most common factor identified for the development of acute-on-chronic liver failure (ACLF). The increase in the prevalence of infections caused by multidrug-resistant (MDR) microorganisms has resulted in the reduced effectiveness of empiric antimicrobial treatment. We conducted a PubMed search from the last 20 years using the Keywords cirrhosis; multidrug-resistant; infections; diagnosis; treatment; prophylaxis; monitoring; sepsis; nutrition and antibiotic resistant. We made a review about bacterial infections among cirrhotic patients; we mainly focus on the description of diagnostic tools; biomarkers; clinical scores for diagnosis and prognosis also; we made an analysis concerning the monitoring of cirrhotic patients with sepsis and finally made some recommendations about the treatment; prophylaxis and prevention.

Heading Toward the Elimination of Hepatitis C Virus.

Chronic hepatitis C is often asymptomatic and may progress over the years to cirrhosis and hepatocellular carcinoma. Although the prevalence and incident cases are decreasing, the peak mortality of hepatitis C virus (HCV)-related complications is ahead of us in most countries. The economic impact of this burden is enormous. Scaling up the identification of new opportunities to facilitate the road toward HCV elimination includes increasing screening, awareness, and the number of prescribing physicians. Screening should occur within the context of linkage-to-care and patient retention across the care continuum. Awareness and access to treatment in different countries are not systematic as countries have diverse healthcare organizations so that treatment eligibility and availability criteria vary significantly. The simplicity of oral regimens with direct-acting antiviral drugs that are effective across HCV genotypes expands the number of physicians who can prescribe them with accessible treatment models. The ultimate aim is the elimination of HCV by 2030.

Portopulmonary hypertension and hepatopulmonary syndrome: a clinician-oriented overview.

Liver disease and portal hypertension can be associated with pulmonary vascular complications, including portopulmonary hypertension (POPH), characterised by an elevated mean pulmonary artery pressure secondary to an increased pulmonary vascular resistance, and hepatopulmonary syndrome (HPS), characterised by hypoxaemia due to pulmonary vasodilatation and shunting. Although clear diagnostic guidelines exist for both conditions on the basis of echocardiography, right heart catheterisation and arterial blood gases, there is considerable variation between centres regarding diagnosis and management of these conditions. Awareness of evaluation and management algorithms for POPH and HPS are critical for optimisation of outcomes in patients with these conditions. Key aspects of management of POPH and HPS include identification of patients likely to benefit from liver transplantation (LTx) and management before and after LTx. Although both disorders may improve after LTx, severe forms of POPH represent a contraindication to LTx. Novel approaches to the treatment of POPH and HPS offer new management options that may expand the pool of transplantable patients and improve overall outcomes.

Minimal hepatic encephalopathy.

The term minimal hepatic encephalopathy (MHE) refers to the subtle changes in cognitive function, electrophysiological parameters, cerebral neurochemical/neurotransmitter homeostasis, cerebral blood flow, metabolism, and fluid homeostasis that can be observed in patients with cirrhosis who have no clinical evidence of hepatic encephalopathy; the prevalence is as high as 84% in patients with hepatic cirrhosis. Physician does generally not perceive cirrhosis complications, and neuropsychological tests and another especial measurement like evoked potentials and image studies like positron emission tomography can only make diagnosis. Diagnosis of minimal hepatic encephalopathy may have prognostic and therapeutic implications in cirrhotic patients. The present review pretends to explore the clinic, therapeutic, diagnosis and prognostic aspects of this complication.

[Clinical characteristics associated to resectability in patients with tumors of the ampulla of Vater in a third-level hospital in Mexico: an 18-year experience]. / Caracteristicas clínicas asociadas a resecabilidad en pacientes con tumores del ámpula de Vater en un hospital de tercer nivel en Mexico: experiencia de 18 años.

BACKGROUND: Ampulla of Vater's tumors (AVT) are rare and account for 0.2% of neoplasia in necropsies. The stage, comorbidities and surgical experience are crucial for prognosis. The aim of this work is to report the clinical characteristics, treatment and complication of a group of patients with AVT. MATERIAL AND METHODS: Patients with AVT were included in a retrospective manner. Descriptive statistics was used and data were shown as means and SD. RESULTS: One hundred and six patients were included with a mean age of 58.5 +/- 14 years and 58% were women. Jaundice was the most common clinical data and it was present in 90% of cases. Two-thirds of patients underwent a Whipple surgical procedure. Complications of surgery were present in 35% of cases and abdominal sepsis and pancreatic fistulae were the most common (32% and 29%, respectively). Adenocarcinoma was the most common histological type and 39% of cases were in stage IV at diagnosis. Age higher or equal to 65 years was associated with less surgical possibilities. Melena at presentation was associated with a higher probability of surgical resection. CONCLUSION: The probability of surgical resection is lower in patients older than 65 years and higher in those with melena at the diagnosis.

High diversity of vacA and cagA Helicobacter pylori genotypes in patients with and without gastric cancer.

BACKGROUND: Helicobacter pylori is associated with chronic gastritis, peptic ulcers, and gastric cancer. The aim of this study was to assess the topographical distribution of H. pylori in the stomach as well as the vacA and cagA genotypes in patients with and without gastric cancer. METHODOLOGY/PRINCIPAL FINDINGS: Three gastric biopsies, from predetermined regions, were evaluated in 16 patients with gastric cancer and 14 patients with dyspeptic symptoms. From cancer patients, additional biopsy specimens were obtained from tumor centers and margins; among these samples, the presence of H. pylori vacA and cagA genotypes was evaluated. Positive H. pylori was 38% and 26% in biopsies obtained from the gastric cancer and non-cancer groups, respectively (p = 0.008), and 36% in tumor sites. In cancer patients, we found a preferential distribution of H. pylori in the fundus and corpus, whereas, in the non-cancer group, the distribution was uniform (p = 0.003). A majority of the biopsies were simultaneously cagA gene-positive and -negative. The fundus and corpus demonstrated a higher positivity rate for the cagA gene in the non-cancer group (p = 0.036). A mixture of cagA gene sizes was also significantly more frequent in this group (p = 0.003). Ninety-two percent of all the subjects showed more than one vacA gene genotype; s1b and m1 vacA genotypes were predominantly found in the gastric cancer group. The highest vacA-genotype signal-sequence diversity was found in the corpus and 5 cm from tumor margins. CONCLUSION/SIGNIFICANCE: High H. pylori colonization diversity, along with the cagA gene, was found predominantly in the fundus and corpus of patients with gastric cancer. The genotype diversity observed across systematic whole-organ and tumor sampling was remarkable. We find that there is insufficient evidence to support the association of one isolate with a specific disease, due to the multistrain nature of H. pylori infection shown in this work.

Salmonella sp group A: a rare cause of bacterascites. A case report.

Bacterascites (BA) is a minimally studied and defined entity. Its prognosis and clinical course are not well defined, and currently there are no management guidelines. We present a rare cause of BA in which Salmonella sp group A was isolated in a 44 year old man with cirrhosis who had diarrhea and fever three days earlier. Treatment with intravenous ceftriaxone was effective.

Intestinal flora, probiotics, and cirrhosis.

Intestinal microflora constitutes a symbiotic ecosystem in permanent equilibrium, composed mainly of anaerobic bacteria. However, such equilibrium may be altered by daily conditions as drug use or pathologies interfering with intestinal physiology, generating an unfavorable environment for the organism. Besides, there are factors which may cause alterations in the intestinal wall, creating the conditions for translocation or permeation of substances or bacteria. In cirrhotic patients, there are many conditions that combine to alter the amount and populations of intestinal bacteria, as well as the functional capacity of the intestinal wall to prevent the permeation of substances and bacteria. Nowadays, numerous complications associated with cirrhosis have been identified, where such mechanisms could play an important role. There is evidence that some probiotic microorganisms could restore the microbiologic and immunologic equilibrium in the intestinal wall in cirrhotic patients and help in the treatment of complications due to cirrhosis. This article has the objective to review the interactions between intestinal flora, gut permeability, and the actual role of probiotics in the field of cirrhotic patients.

[Coagulation disorders in cirrhosis]. / Trastornos de coagulación en el cirrótico.

The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.

Trastornos de coagulación en el cirrótico / Coagulation disorders in cirrhosis

The liver plays a central role in the clotting process. In this organ are sintetizated the major part of the coagulation factors. Historically, was considered that alteration in liver function causes important bleeding disorders. However, actual evidence is not in agreement with this asseveration. Decreased synthesis of clotting and inhibitor factors, decrease clearance of activated factors, quantitative and qualitative platelet defects, hyperfibrinolysis and intravascular coagulation are some of the defects observed in liver diseases. Thrombotic events, even if rare in cirrhotic patients, occur manly in the portal and mesenteric veins. The aim of the present work is to review the present evidence in coagulation disorders and liver disease.

El hígado participa de manera importante en el proceso de la coagulación. En él se sintetizan la mayor parte de los factores pro- y anticoagulantes. De manera histórica se ha considerado que las alteraciones en la función de este órgano provoca trastornos predisponentes para eventos de sangrado. La evidencia actual pone en tela de juicio esta aseveración. En los casos de hepatopatía se hacen evidentes alteraciones en el número y funcionamiento de las plaquetas, disminución de la síntesis de factores de la coagulación, disfibrinogenemia, alteraciones en la fibrinólisis, deficiencia de vitamina K y cambios similares a los ocurridos en la coagulación intravascular diseminada (CID). El presente trabajo está dirigido a revisar los conocimientos actuales respecto a las alteraciones de la coagulación presentes en los pacientes con hepatopatías.

The molecular basis of susceptibility to infection in liver cirrhosis.

There is much clinical evidence of a relationship between infectious disease and chronic liver disease. The consequences of this adverse association have been described and advances in the treatment and prophylaxis of infectious disease have had an important effect on the management of patients with chronic liver disease. The association between infectious disease and chronic liver disease involves altered cytokine production, cellular immunity, and vascular response. However, there is little information on the mechanisms underlying these phenomena. In this report, we review the mechanistic basis of this common association.