Systemic inflammatory response and serum lipopolysaccharide levels predict multiple organ failure and death in alcoholic hepatitis.

UNLABELLED: Alcoholic hepatitis (AH) frequently progresses to multiple organ failure (MOF) and death. However, the driving factors are largely unknown. At admission, patients with AH often show criteria of systemic inflammatory response syndrome (SIRS) even in the absence of an infection. We hypothesize that the presence of SIRS may predispose to MOF and death. To test this hypothesis, we studied a cohort including 162 patients with biopsy-proven AH. The presence of SIRS and infections was assessed in all patients, and multivariate analyses identified variables independently associated with MOF and 90-day mortality. At admission, 32 (19.8%) patients were diagnosed with a bacterial infection, while 75 (46.3%) fulfilled SIRS criteria; 58 patients (35.8%) developed MOF during hospitalization. Short-term mortality was significantly higher among patients who developed MOF (62.1% versus 3.8%, P < 0.001). The presence of SIRS was a major predictor of MOF (odds ratio = 2.69, P = 0.025) and strongly correlated with mortality. Importantly, the course of patients with SIRS with and without infection was similar in terms of MOF development and short-term mortality. Finally, we sought to identify serum markers that differentiate SIRS with and without infection. We studied serum levels of high-sensitivity C-reactive protein, procalcitonin, and lipopolysaccharide at admission. All of them predicted mortality. Procalcitonin, but not high-sensitivity C-reactive protein, serum levels identified those patients with SIRS and infection. Lipopolysaccharide serum levels predicted MOF and the response to prednisolone. CONCLUSION: In the presence or absence of infections, SIRS is a major determinant of MOF and mortality in AH, and the mechanisms involved in the development of SIRS should be investigated; procalcitonin serum levels can help to identify patients with infection, and lipopolysaccharide levels may help to predict mortality and the response to steroids.

Hernia umbilical eviscerada en pacientes cirróticos: reporte de un caso / Eviscerated umbilical hernia in cirrhotic patients: case report

La evisceración espontánea de las hernias umbilicales en pacientes con cirrosis hepática y ascitis es una complicación rara y potencialmente fatal que ocurre en menos de un 2% de los pacientes con esta patología. Se presenta un caso de un paciente masculino de 58 años de edad conocido con el diagnóstico de cirrosis hepática por alcohol, Child B, con síndrome de hipertensión portal, que consultó por dolor abdominal tipo cólico difuso y salida espontánea de líquido ascítico de color amarillo, no fétido, a través de hernia umbilical, de gran tamaño, con erosiones en su superficie. El citoquímico del líquido ascítico fue compatible con peritonitis bacteriana secundaria. Se manejó conjuntamente con cirugía, de forma conservadora con antibioticoterapia parenteral. Al cuarto día se apreció salida del epiplón a través del saco herniario. Se realizó herniorrafia umbilical sin complicaciones, evolucionando satisfactoriamente. Desde el primer caso reportado en 1901, son pocos los casos registrados en la literatura. Los factores precipitantes descritos son traumatismos y aumento de presión intra-abdominal. El manejo de la hernia umbilical en el paciente cirrótico es controversial, cuando se desarrollan complicaciones como la evisceración, la conducta quirúrgica es urgente

Spontaneous evisceration of umbilical hernias in patients with cirrhosis and ascites is a rare and potentially fatal complication that occurs in less than 2% of patients. We report a case of a 58-year old male patient with Child B alcoholic liver cirrhosis,with portal hypertension, who presented with diffuse crampy abdominal pain and spontaneous leaking of yellow not foul ascitic fluid through a large umbilical hernia with superficial tiny erosions. Cytochemical ascitic fluid analysis was consistent with secondary bacterial peritonitis. Patient was managed conservatively with parenteral antibiotics in conjunction with surgery. On fourth day, the omentum was seen through the hernia sac and surgical repair was performed without complications and the patient did well in the postoperative period. Since the first case reported in 1901, there had been few cases reported in the literature. Trauma and increased intra-abdominal pressure are among the precipitants reported. Management of umbilical hernia in cirrhotic patients is controversial, however when they develop complications, surgical treatment become urgent

Human and experimental evidence supporting a role for osteopontin in alcoholic hepatitis.

UNLABELLED: We identified, in the transcriptome analysis of patients with alcoholic hepatitis (AH), osteopontin (OPN) as one of the most up-regulated genes. Here, we used a translational approach to investigate its pathogenic role. OPN hepatic gene expression was quantified in patients with AH and other liver diseases. OPN protein expression and processing were assessed by immmunohistochemistry, western blotting and enzyme-linked immunosorbent assay. OPN gene polymorphisms were evaluated in patients with alcoholic liver disease. The role of OPN was evaluated in OPN(-/-) mice with alcohol-induced liver injury. OPN biological actions were studied in human hepatic stellate cells (HSCs) and in precision-cut liver slices. Hepatic expression and serum levels of OPN were markedly increased in AH, compared to normal livers and other types of chronic liver diseases, and correlated with short-term survival. Serum levels of OPN also correlated with hepatic expression and disease severity. OPN was mainly expressed in areas with inflammation and fibrosis. Two proteases that process OPN (thrombin and matrix metalloproteinase 7) and cleaved OPN were increased in livers with AH. Patients with AH had a tendency of a lower frequency of the CC genotype of the +1239C single-nucleotide polymorphism of the OPN gene, compared to patients with alcohol abuse without liver disease. Importantly, OPN(-/-) mice were protected against alcohol-induced liver injury and showed decreased expression of inflammatory cytokines. Finally, OPN was induced by lipopolysaccharide and stimulated inflammatory actions in HSCs. CONCLUSION: Human and experimental data suggest a role for OPN in the pathogenesis of AH. Further studies should evaluate OPN as a potential therapeutic target.

Aspectos clínicos y epidemiológicos de pacientes con carcinoma hepatocelular en dos centros de referencia de Venezuela / Clinical and epidemiological aspects of patients with hepatocellular carcinoma in two reference centers Venezuela

El carcinoma hepatocelular (CHC) es la neoplasia primaria del hígado más frecuente, constituyendo un problema mundial de salud pública por su alta prevalencia y tasa de mortalidad. Evaluar las características clínicas y epidemiológicas de los pacientes con carcinoma hepatocelular. Estudio de casos consecutivos con revisión retrospectiva de los registros médicos de pacientes con diagnóstico de CHC que acudieron a la consulta de hepatología de dos centros caraqueños entre 1997 y 2011. Se evaluaron características clínicas, epidemiológicas y de estadiaje según Barcelona Clinic Liver Cancer, BCLC. Se incluyó 116 pacientes con diagnóstico de CHC. La edad media fue 61,34 ± 12,02 años, 75% eran hombres y 89,7% de los pacientes tenían cirrosis hepática subyacente, siendo confirmada histológicamente en 33,7%. El 70,7% de los pacientes tenían alguna complicación asociada a hipertensión portal. El virus de la hepatitis C (VHC) constituyó la principal etiología de enfermedad hepática (31%), alcohol (21,6%), virus de la hepatitis B, VHB (14,7%) y enfermedad hepática grasa no alcohólica (14,7%). El hepatocarcinoma fue diagnosticado más frecuentemente en pacientes con cirrosis por HBV 15,56%. El 56% de los casos tenían niveles de alfafetoproteína mayores de 300 ng/ml. El lóbulo derecho fue la localización más frecuente (64,7%) y 79,3% de las lesiones mostraron patrón vascular típico en los estudios radiológicos. El estadio tumoral según los criterios de Barcelona Clinic Liver Cancer (BCLC) fueron estadio C (37,9%) D (25,9%), B (24,1%), A (7,8%) y 0 (2,6%). La infección por HCV es la etiología más frecuente de cirrosis hepática en pacientes con CHC, pero la infección por VHB tiene mayor impacto en términos relativos. El diagnóstico se hace en forma tardía (estadios intermedios o avanzados), siendo necesario intensificar medidas de pesquisa en estos pacientes

The hepatocellular carcinoma (HCC) is the main primary liver neoplasia and is a public health problem in the world due to high prevalence and mortality. Evaluate clinical and epidemiological characteristics in patients with Hepatocellular carcinoma. A retrospective analysis of a prospectively maintained database of 116 patients with diagnosis of HCC in two centers of Caracas between 1997 and 2011 was conducted. We evaluated epidemiological, clinical, biochemical and tumor aspects according to Barcelona Clínic Liver Cancer in patients with HCC. Mean age was 61.34 ± 12.02 years, 75% were male and 89.7% of patients had liver cirrhosis. Portal hypertension complications (ascites, hepatic encephalopathy, esophageal varices) were present in 70.7% of patients. Hepatitis C virus (HCV) was the main etiology of hepatic disease (31%) followed by alcohol (21.6%), hepatitis B virus (14.7%) and non alcoholic steatohepatitis (14.7%). HCC was more frequent in patients with cirrhosis associated to HBV infection. The 56% of patients had alpha-fetoprotein levels higher than 300 ng/ml. The 64.7% of tumors were localized in the right lobe of liver and 79.3% of tumor lesions demonstrated typical pattern in radiologic studies. The most patients had advanced disease according to Barcelona Clinic Liver Cancer (BCLC) staging classification (Stage C, 37.9%; stage D, 25.9%; stage B, 24.1%; stage A, 7.8% and stage 0, 2.6%). HCV infection was main cause of cirrhosis in patients with HCC, but HBV infection had higher impact in these patients. Our study showed that the diagnosis of these patients undergo late and is very important intensify screening measures in patients with liver cirrhosis

Neumonía por Mycoplasma pneumoniae complicada con pancreatitis y hepatitis aguda: a propósito de un caso / Mycoplasma pneumoniae pneumonia complicated with acute pancreatitis and hepatitis: a case study

La infección por Mycoplasma pneumoniae (M pneumoniae) puede producir manifestaciones pulmonares y extrapulmonares a nivel cardiológico, dermatológico, neurológico, hematológico, musculoesquelético y gastrointestinal (vómitos, diarrea, hiporexia, dolor abdominal, hepatomegalia, hepatitis aguda, colecistitis alitiásica, y pancreatitis aguda). Presentamos un caso de infección aguda por M pneumoniae que se manifestó con neumonía, pancreatitis aguda y hepatitis colestásica. Paciente masculino de 15 años, con clínica de neumonía y dolor abdominal con elevación de pruebas hepáticas, amilasa y lipasa, y cambios sugestivos de pancreatitis aguda por ultrasonido abdominal y tomografía de abdomen y pelvis con doble contraste. El paciente evolucionó satisfactoriamente con el tratamiento indicado. Es importante considerar la posibilidad de infección por M. pneumoniae en pacientes con cuadros infecciosos respiratorios y manifestaciones digestivas sobre todo elevación de amilasa y enzimas hepáticas. Se describe el primer caso en nuestro país de pancreatitis y hepatitis asociada con infección por M. pneumoniae y el segundo en la literatura internacional

Mycoplasma pneumoniae (M pneumoniae) infection can cause pulmonary and extrapulmonary manifestations such as: cardiac, dermatological, neurological, hematological, musculoskeletal and gastrointestinal (vomiting, diarrhea, decreased appetite, abdominal pain, hepatomegaly, acute hepatitis, acalculous cholecystitis and acute pancreatitis). We report the case of a 15 years old male with pneumonia, abdominal pain, elevated liver tests with hyperamylasemia, elevated lipase, and changes suggestive of acute pancreatitis on abdominal ultrasound and double contrast CT scan of the abdomen and pelvis. The patient did well with the indicated treatment. It’s important to consider M pneumoniae infection in patients with respiratory disease and digestive manifestations including elevated liver tests and hyperamylasemia. To our knowledge this is the first case reported in our country of M pneumonia associated with pancreatitis and hepatitis and the second one in the literature

Transcriptome analysis identifies TNF superfamily receptors as potential therapeutic targets in alcoholic hepatitis.

OBJECTIVE: Alcoholic hepatitis (AH) is a severe clinical condition that needs novel therapies. The identification of targets for therapy is hampered by the lack of animal models of advanced AH. The authors performed a translational study through a transcriptome analysis in patients with AH to identify new molecular targets. DESIGN: Hepatic gene expression profiling was assessed by DNA microarray in patients with AH (n=15) and normal livers (n=7). Functional analysis was assessed by gene set enrichment analysis. Quantitative PCR was performed in patients with AH (n=40), hepatitis C (n=18), non-alcoholic steatohepatitis (n=20) and in mouse models of acute and chronic liver injury. Protein expression was assessed by immunohistochemistry and western blotting. RESULTS: Gene expression analysis showed 207 genes >5-fold differentially expressed in patients with AH and revealed seven pathways differentially regulated including 'cytokine-cytokine receptor interaction'. Several tumour necrosis factor (TNF) superfamily receptors, but not ligands, were overexpressed in AH. Importantly, Fn14 was the only TNF superfamily receptor exclusively upregulated in AH compared with other liver diseases and correlated with both 90-day mortality and severity of portal hypertension. Fn14 protein expression was detected in areas of fibrogenesis and in a population of hepatocytes. Fn14 expression was increased in experimental models of liver injury and was detected in progenitor cells. CONCLUSION: Translational research revealed that TNF superfamily receptors are overexpressed in AH. Fn14, the receptor for TNF-like weak inducer of apoptosis, is selectively upregulated in patients with AH. TNF superfamily receptors could represent a potential target for therapy.

Acute kidney injury is an early predictor of mortality for patients with alcoholic hepatitis.

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is a severe condition with high mortality. To improve therapeutic strategies, it is important to identify factors that affect survival times. The age, bilirubin, international normalized ratio, and creatinine scoring system (also known as the ABIC scoring system) was developed previously to determine the prognosis of patients with AH. We studied effects of acute kidney injury (AKI) on survival of patients with AH. METHODS: We retrospectively analyzed data from 103 patients with biopsy-proven AH. AKI was defined as an abrupt reduction (within 48 h) in kidney function that resulted in an absolute increase of at least 0.3 mg/dL (or a 50% increase) in serum levels of creatinine from baseline (the AKI network [AKIN] criteria). RESULTS: Twenty-nine patients (28%) developed AKI during hospitalization, with a median time to diagnosis of 3 days. Overall 90-day mortality was 23%, which was significantly higher among patients with AKI than those without (65% vs 7%; P < .0001). The age, bilirubin, international normalized ratio, and creatinine score (P < .0001) and development of AKI (P < .0001) were the most accurate independent predictors of 90-day mortality. The presence of systemic inflammatory response syndrome (P < .0001), serum bilirubin (P = .01), and international normalized ratio at admission (P = .03) were the most accurate predictors of AKI. Importantly, the AKIN criteria were more accurate than traditional criteria for renal failure (serum creatinine >1.5 mg/dL) in predicting 90-day mortality (area under the receiver operating characteristic, 0.83 vs 0.70, respectively; P = .02). CONCLUSIONS: Development of AKI reduces survival of patients with AH, in the short term. The AKIN criteria are useful and more accurate than traditional criteria in predicting mortality. Strategies to prevent AKI therefore should be considered in the management of patients with AH.

The amount of alcohol consumption negatively impacts short-term mortality in Mexican patients with alcoholic hepatitis.

OBJECTIVES: Mexicans have an increased rate of alcohol abuse and alcoholic liver disease. Factors influencing the severity of alcoholic hepatitis (AH) in Mexicans are unknown. The aims of the present study were to identify the prognostic factors of short-term mortality in Mexican patients with AH and to validate the existing prognostic models. METHODS: One hundred seventy-five consecutive patients with AH were recruited from four hospital centers in Mexico. Demographic, clinical, and biochemical parameters were obtained at admission. Univariate and multivariate logistic regression analyses were used for the identification of prognostic factors. The accuracy of different models was evaluated by their area under the receiver operating characteristic (AUROC) curve and comparative risk analysis was performed using the Kaplan-Meier method. RESULTS: Age, serum creatinine, serum bilirubin, leukocyte count, and alcohol consumption >120 g/day were independently associated with short-term mortality. The impact of alcohol consumption was significant among patients with severe AH (48 vs. 72% risk of death, P=0.03). The AUROC (95% confidence interval) curves for the different scores were Maddrey's discriminant function 0.79 (0.72-0.86); model for end-stage liver disease (MELD) 0.83 (0.75-0.89); Glasgow AH score 0.77 (0.70-0.84); and age-bilirubin-international normalized ratio-creatinine (ABIC) score 0.82 (0.75-0.88). The ABIC score allowed an accurate stratification into three different risk subgroups with 13%, 50%, and 81% mortality rate at 90 days (P<0.001). CONCLUSIONS: The amount of alcohol consumption has a negative impact on short-term mortality among Mexicans with AH. The ABIC score is useful and comparable with MELD score for the prognostic stratification of these patients.

Quiste mesentérico como causa de abdomen agudo, presentación de un caso / Mesenteric cyst as a cause of acute abdomen, a case report

Los quistes mesentéricos son una causa poco frecuente de masa abdominal de origen benigno en niños, el diagnóstico suele ser incidental, pueden presentarse como abdomen agudo, con complicaciones como: infección, obstrucción, torsión o ruptura, no existiendo signos específicos de presentación. Se presenta este caso por la rareza del mismo, el caso de una niña de 8 años que ingresa con dolor abdominal y signos de irritación peritoneal siendo sometida a laparotomía; diagnosticándose en el intraoperatorio quiste de epiplón torcido.

Mesenteric cysts are a rare cause of abdominal mass in children benign origin, the diagnosis is often incidental, may present as acute abdomen, with complications such as infection, obstruction, torsion or rupture, with no specific signs of submission. We present this case because of the rarity of it, the case of an 8 year old girl who was admitted with abdominal pain and signs of peritoneal irritation undergoing laparotomy, intraoperative cyst diagnosed in the twisted omentum.

Acidic sphingomyelinase controls hepatic stellate cell activation and in vivo liver fibrogenesis.

The mechanisms linking hepatocellular death, hepatic stellate cell (HSC) activation, and liver fibrosis are largely unknown. Here, we investigate whether acidic sphingomyelinase (ASMase), a known regulator of death receptor and stress-induced hepatocyte apoptosis, plays a role in liver fibrogenesis. We show that selective stimulation of ASMase (up to sixfold), but not neutral sphingomyelinase, occurs during the transdifferentiation/activation of primary mouse HSCs into myofibroblast-like cells, coinciding with cathepsin B (CtsB) and D (CtsD) processing. ASMase inhibition or genetic down-regulation by small interfering RNA blunted CtsB/D processing, preventing the activation and proliferation of mouse and human HSCs (LX2 cells). In accordance, HSCs from heterozygous ASMase mice exhibited decreased CtsB/D processing, as well as lower levels of alpha-smooth muscle actin expression and proliferation. Moreover, pharmacological CtsB inhibition reproduced the antagonism of ASMase in preventing the fibrogenic properties of HSCs, without affecting ASMase activity. Interestingly, liver fibrosis induced by bile duct ligation or carbon tetrachloride administration was reduced in heterozygous ASMase mice compared with that in wild-type animals, regardless of their sensitivity to liver injury in either model. To provide further evidence for the ASMase-CtsB pathway in hepatic fibrosis, liver samples from patients with nonalcoholic steatohepatitis were studied. CtsB and ASMase mRNA levels increased eight- and threefold, respectively, in patients compared with healthy controls. These findings illustrate a novel role of ASMase in HSC biology and liver fibrogenesis by regulating its downstream effectors CtsB/D.

Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats.

UNLABELLED: The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n = 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. Finally, smoking regulated ERK and AKT phosphorylation. The deleterious effects of CS were not observed after a short exposure (5 days). CONCLUSION: CS causes oxidative stress and worsens the severity of NAFLD in obese rats. Further studies should assess whether this finding also occurs in patients with obesity and NAFLD.

Ghrelin attenuates hepatocellular injury and liver fibrogenesis in rodents and influences fibrosis progression in humans.

UNLABELLED: There are no effective antifibrotic therapies for patients with liver diseases. We performed an experimental and translational study to investigate whether ghrelin, an orexigenic hormone with pleiotropic properties, modulates liver fibrogenesis. Recombinant ghrelin was administered to rats with chronic (bile duct ligation) and acute (carbon tetrachloride) liver injury. Hepatic gene expression was analyzed by way of microarray analysis and quantitative polymerase chain reaction. The hepatic response to chronic injury was also evaluated in wild-type and ghrelin-deficient mice. Primary human hepatic stellate cells were used to study the effects of ghrelin in vitro. Ghrelin hepatic gene expression and serum levels were assessed in patients with chronic liver diseases. Ghrelin gene polymorphisms were analyzed in patients with chronic hepatitis C. Recombinant ghrelin treatment reduced the fibrogenic response, decreased liver injury and myofibroblast accumulation, and attenuated the altered gene expression profile in bile duct-ligated rats. Moreover, ghrelin reduced the fibrogenic properties of hepatic stellate cells. Ghrelin also protected rats from acute liver injury and reduced the extent of oxidative stress and inflammation. Ghrelin-deficient mice developed exacerbated hepatic fibrosis and liver damage after chronic injury. In patients with chronic liver diseases, ghrelin serum levels decreased in those with advanced fibrosis, and ghrelin gene hepatic expression correlated with expression of fibrogenic genes. In patients with chronic hepatitis C, polymorphisms of the ghrelin gene (-994CT and -604GA) influenced the progression of liver fibrosis. CONCLUSION: Ghrelin exerts antifibrotic effects in the liver and may represent a novel antifibrotic therapy.

Síndrome de Peutz-Jeghers y Obstrucción Intestinal Baja, Reporte de un Caso / Peutz-Jeghers Syndrome and Low Intestinal Obstruction, Report of a Case

El presentamos el caso clínico de un niño de 12 años, que acude al Servicio de Pediatría del Hospital Manuel Ascencio Villarroel, transferido del Centro Pediátrico Albina Rodríguez de Patiño con los posibles diagnósticos de estreñimiento pertinaz, desnutrición de III grado secundario, Síndrome de Peutz-Jeghers probable, anemia microcítica e hipocrómica severa y soplo sistólico en estudio. Si bien el Síndrome de Peutz-Jeghers se presenta en contadas ocasiones en nuestro medio, el diagnóstico diferencial y sus complicaciones deben ser mejor estudiadas para así poder ser tratada de forma más oportuna. Consideramos importante este reporte porque en nuestro medio es una rara causa de abdomen agudo.

The present case report of a child 12 year old boy, who was admitted to the pediatric department of the Hospital Manuel AscencioVillarroel, transferred to the Pediatric Center Albina Rodriguez Patiño with possible diagnoses of persistent constipation, grade III secondary malnutrition, Peutz-Jeghers probable syndrome, severe hypochromic microcytic anemia and systolic murmur in the study.While the Peutz-Jeghers syndrome rarely occurs in our environment, the differential diagnosis and its complications should be better studied so we can be treated in a more timely manner. We consider it important our report because this disease is a rare cause of acute abdomen in our environment.

Síndrome de peuzz - jeghers, a propósito de un caso / Syndrome of Peutz - Jeghers a case especially designed

Se presenta un caso clínico de un niño de 12 años de edad de sexo masculino, Referido al Hospital del Niñ@ Manuel A. Villarroel por un cuadro de obstrucción intestinal baja de 10 días de evolución asociado a manchas melanóticas en piel y mucosas; posterior a múltiples estudios de gabinete y laboratorio, se evidencia masa sólida que ocupa mesogastrio, de 88 mms, que desplaza asas de yeyuno hacia craneal, se le realiza una laparotomía exploratoria, hallándose dos segmentos de intususcepción de intestino delgado y en cada una de ellas, dos masas tumorales en lumen conformando las cabezas de invaginación, se logra la desinvaginación de ambos segmentos resencando dichas masas. El reporte histo-patológico indica Pólipos con núcleos hamartomatosos llegándose al diagnóstico final de Síndrome de Peutz Jeghers.

We present a case report of a 12 years oíd boy refered to HNMAV with 10 days of lower gastroinstestinal obstruction and mococutaneous melanotic spots, after laboratory and immaging studies was found to have an 88 mm solid rnass in mesogastrium wich displace the jejunum superiorly, exploratory laparotomy was made, the surgical findings were: two tumoral masses at the lumen of the small bowel configuring two heads of invagination, both invagiantions were resolved and both masses were removed. The pathology reports as hamartomatous polyps confirming diagnosis of Peutz - Jeghers Syndrome.

[Treatment of liver fibrosis]. / Tratamiento de la fibrosis hepática.

Liver fibrosis is the progressive deposition of extracellular matrix in the liver parenchyma that precedes the development of cirrhosis. In the last few years, knowledge of the cellular and molecular bases of liver fibrosis has increased considerably. Environmental and genetic factors have been described that influence the progression of liver fibrosis, while non-invasive methods have been developed that allow the grade of fibrosis to be estimated without the need for liver biopsy. Currently, the only clearly effective treatment to attenuate or reverse liver fibrosis is elimination of the causative agent. When this is not feasible, fibrogenic factors (such as insulin resistance, obesity, alcohol intake, cannabis consumption, etc.) should be identified and treated. However, several agents are able to reduce liver fibrosis in experimental models of chronic liver damage. Few controlled clinical trials have been performed that evaluate the efficacy and safety of these agents and consequently the level of evidence supporting their use as anti-fibrogenic therapy is still low. The efficacy of the anti- fibrogenic drugs, renin-angiotensin system inhibitors, is currently being evaluated.

Effects of losartan on hepatic expression of nonphagocytic NADPH oxidase and fibrogenic genes in patients with chronic hepatitis C.

Angiotensin II promotes liver fibrogenesis by stimulating nonphagocytic NADPH oxidase (NOX)-induced oxidative stress. Angiotensin II type 1 (AT1) receptor blockers attenuate experimental liver fibrosis, yet their effects in human liver fibrosis are unknown. We investigated the effects of losartan on hepatic expression of fibrogenic, inflammatory, and NOX genes in patients with chronic hepatitis C (CHC). Fourteen patients with CHC and liver fibrosis received oral losartan (50 mg/day) for 18 mo. Liver biopsies were performed at baseline and after treatment. The degree of inflammation and fibrosis was evaluated by histological analysis (METAVIR). Collagen content was measured by morphometric quantification of Sirius red staining. Overall collagen content and fibrosis stage remained stable in the whole series, yet the fibrosis stage decreased in seven patients. Inflammatory activity improved in seven patients. The effect of losartan on hepatic expression of 31 profibrogenic and inflammatory genes and components of the NOX complex was assessed by quantitative PCR. Losartan treatment was associated with a significant decrease in the expression of several profibrogenic and NOX genes including procollagen alpha1(I) and alpha1(IV), urokinase-type plasminogen activator, metalloproteinase type 2, NOX activator 1 (NOXA-1) and organizer 1 (NOXO-1), and Rac-1. Losartan was well tolerated in all patients and was effective in attenuating the activity of the systemic renin-angiotensin system. No effects on serum liver tests or viral load were observed. We conclude that prolonged administration of losartan, an oral AT1 receptor blocker, is associated with downregulation of NOX components and fibrogenic genes in patients with CHC. Controlled studies are warranted to assess the effect of AT1 receptor blockers in chronic liver injury.

Hepatic expression of CXC chemokines predicts portal hypertension and survival in patients with alcoholic hepatitis.

BACKGROUND & AIMS: Alcoholic hepatitis (AH) is characterized by hepatocellular damage, inflammation, and fibrosis. We performed a prospective study to associate hepatic expression of the CXC subfamily of chemokines with histology findings and prognosis of patients with AH. METHODS: Liver biopsy samples from 105 patients with AH and 5 normal liver samples (controls) were evaluated for steatosis, inflammation, fibrosis, and cholestasis. Computer-based morphometric analysis assessed the numbers of infiltrating CD3+ T cells and CD15+ cells (neutrophils); terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling staining was used to quantify apoptosis. Expression of CXC and CC chemokines and selected signaling components were assessed by quantitative reverse-transcription polymerase chain reaction; protein levels of interleukin (IL)-8 and Gro-alpha also were determined by immunohistochemistry. Serum levels of IL-8 and Gro-alpha were measured by enzyme-linked immunosorbent assay. The Cox regression model identified variables associated with mortality. RESULTS: Most patients (75%) had severe AH; their 90-day mortality rate was 21.9%. In AH liver samples, expression of the CXC subfamily members IL-8, Gro-alpha, CXCL5, CXCL6, CXCL10, and platelet factor 4 was up-regulated and compared with controls. The CC chemokine CCL2, but not CCL5, also was up-regulated. Higher expression levels of IL-8, CXCL5, Gro-gamma, and CXCL6 were associated with worse prognosis. Expression of CXC components correlated with neutrophil infiltration and the severity of portal hypertension. In the multivariate analysis, IL-8 protein levels were an independent predictor of 90-day mortality. IL-8 and Gro-alpha serum levels did not correlate with prognosis. CONCLUSIONS: Hepatic expression of CXC components correlates with prognosis of patients with AH. Reagents that target CXC chemokines might be developed as therapeutics.

Tratamiento de la fibrosis hepática / Treatment of liver fibrosis

La fibrosis hepática (FH) es el depósito progresivo de matriz extracelular en el parénquima hepático que precede al desarrollo de cirrosis. El conocimiento de las bases celulares y moleculares de la FH ha aumentado considerablemente en las dos últimas décadas. Se han descrito factores ambientales y genéticos que influyen en su progresión, así como métodos no invasivos que permiten estimar el grado de fibrosis sin necesidad de realizar una biopsia hepática. En la actualidad, el único tratamiento claramente efectivo para atenuar o revertir la FH es la eliminación del agente causal. En los casos en los que esto no es posible, se recomienda identificar y tratar factores profibrogénicos (como la resistencia a la insulina, la obesidad, el consumo de alcohol, el consumo de cannabis, etc.). Se han descrito diversos agentes capaces de reducir la FH en modelos experimentales de daño hepático crónico. No obstante, apenas existen estudios clínicos controlados que evaluen la eficacia y la seguridad de estos agentes, por lo que no existe suficiente evidencia científica para indicarlos como tratamiento antifibrogénicos. La eficacia de los inhibidores del sistema renina-angiotensina como fármacos antifibrogénicos se está evaluando en la actualidad(AU)

Liver fibrosis is the progressive deposition of extracellular matrix in the liver parenchyma that precedes the development of cirrhosis. In the last few years, knowledge of the cellular and molecular bases of liver fibrosis has increased considerably. Environmental and genetic factors have been described that influence the progression of liver fibrosis, while non-invasive methods have been developed that allow the grade of fibrosis to be estimated without the need for liver biopsy. Currently, the only clearly effective treatment to attenuate or reverse liver fibrosis is elimination of the causative agent. When this is not feasible, fibrogenic factors (such as insulin resistance, obesity, alcohol intake, cannabis consumption, etc.) should be identified and treated. However, several agents are able to reduce liver fibrosis in experimental models of chronic liver damage. Few controlled clinical trials have been performed that evaluate the efficacy and safety of these agents and consequently the level of evidence supporting their use as anti-fibrogenic therapy is still low. The efficacy of the anti- fibrogenic drugs, renin-angiotensin system inhibitors, is currently being evaluated(AU)

Atorvastatin attenuates angiotensin II-induced inflammatory actions in the liver.

Statins exert beneficial effects in chronically damaged tissues. Angiotensin II (ANG II) participates in liver fibrogenesis by inducing oxidative stress, inflammation, and transforming growth factor-beta1 (TGF-beta1) expression. We investigate whether atorvastatin modulates ANG II-induced pathogenic effects in the liver. Male Wistar rats were infused with saline or ANG II (100 ng kg(-1) min(-1)) for 4 wk through a subcutaneous osmotic pump. Rats received either vehicle or atorvastatin (5 mg kg(-1) day(-1)) by gavage. ANG II infusion resulted in infiltration of inflammatory cells (CD43 immunostaining), oxidative stress (4-hydroxynonenal), hepatic stellate cells (HSC) activation (smooth muscle alpha-actin), increased intercellular adhesion molecule (ICAM-1), and interleukin-6 hepatic gene expression (quantitative PCR). These effects were markedly blunted in rats receiving atorvastatin. The beneficial effects of atorvastatin were confirmed in an additional model of acute liver injury (carbon tetrachloride administration). We next explored whether the beneficial effects of atorvastatin on ANG II-induced actions are also reproduced at the cellular level. We studied HSC, a cell type with inflammatory and fibrogenic properties. ANG II (10(-8)M) stimulated cell proliferation, proinflammatory actions (NF-kappaB activation, ICAM-1 expression, interleukin-8 secretion) as well as expression of procollagen-alpha(1(I)) and TGF-beta1. All of these effects were reduced in the presence of atorvastatin (10(-7)M). These results indicate that atorvastatin attenuates the pathogenic events induced by ANG II in the liver both in vivo and in vitro. Therefore, statins could have beneficial effects in conditions characterized by hepatic inflammation.

A new scoring system for prognostic stratification of patients with alcoholic hepatitis.

OBJECTIVES: Prognostic stratification of patients with alcoholic hepatitis (AH) may improve the clinical management and facilitate clinical trials. We aimed at developing a scoring system capable of providing prognostic stratification of patients with AH. METHODS: Patients with biopsy-proven AH were prospectively included between 2000 and 2006. The biochemical, clinical, portal hemodynamic and histological parameters were evaluated. A Cox regression model was used for univariate and multivariate analyses. A predictive score was built using variables obtained at admission identified in the multivariate analysis. The resulting score was validated in an independent prospective cohort. RESULTS: In total, 103 patients with biopsy-proven AH were included in the study cohort. Age, serum bilirubin, serum creatinine, and international normalized ratio (INR) independently predicted 90-day mortality. We generated the Age, serum Bilirubin, INR, and serum Creatinine (ABIC) score: (age x 0.1) + (serum bilirubin x 0.08) + (serum creatinine x 0.3) + (INR x 0.8). The area under the curve (AUC) was 0.82. Using the Kaplan-Meier analysis with the cutoff values of 6.71 and 9.0, we identified patients with low, intermediate, and high risk of death at 90 days (100%, 70%, and 25% of survival rate, respectively). Using the same cutoff values, the ABIC score also stratified patients according to their risk of death at 1 yr. These results were validated by a confirmatory cohort (N = 80). CONCLUSIONS: The ABIC score is a new tool that allows the stratification of risk of death in patients with AH at 90 days and 1 yr. This score can help improve the management of these patients and also help to perform clinical trials.