Rodrigo Zapata

Selenium, zinc and copper plasma levels in intrahepatic cholestasis of pregnancy, in normal pregnancies and in healthy individuals, in Chile

BACKGROUND/AIMS Low blood Se levels have been previously shown in normal pregnancies (third trimester) and significantly lower levels in patients with intrahepatic cholestasis of pregnancy (ICP), in Finland and in Chile, suggesting that a low or marginal dietary availability of Se may contribute to the pathogenesis of this disease. The aim of this study was to investigate whether a temporal change in plasma concentration of Se, and seasonal fluctuations in plasma concentrations of Se, Zn and Cu, could coincide with changes in the prevalence of ICP. METHODS A cross-sectional cohort study was done including 21 ICP patients, 98 women in the third trimester of a normal pregnancy, 29 non-pregnant women, and also 13 individuals (seven non-pregnant women and six men) who had been studied 9 years before. Plasma Se, Zn and Cu were measured by atomic spectroscopy. Plasma Se levels in the present study were compared to the results obtained 5 to 7 years before, employing identical methodology in similar population samples. RESULTS Plasma Se concentrations in non-pregnant women were higher than in the previous study: 1.43+/-0.34 micromol/l vs 0.85+/-0.13; p<0.001. In comparison to non-pregnant women, normal pregnancies near term had lower plasma levels of Se: 1.08+/-0.25 micromol/l; p<0.01, and Zn: 17.90+/-3.61 micromol/l vs 19.71+/-3.21; p<0.05, but higher plasma levels of Cu: 34.35+/-7.12 micromol/l vs 20.62+/-3.34; p<0.01. In normal pregnancies, plasma Se concentration was significantly higher in summer (1.34+/-0.19 micromol/l) than in the other seasons, while Zn and Cu diminished. Similar to previous studies, ICP patients had significantly lower Se plasma levels than normal pregnancies: 0.94+/-0.12 micromol/l, p<0.05, and Cu levels were significantly higher: 50.80+/-7.02 micromol/l, p<0.01. Cu plasma levels correlated with the biochemical severity of the disease. Zn did not change in ICP. CONCLUSIONS The present study shows that the decrease in the prevalence of ICP in Chile during the last decade coincides with an increase in plasma Se levels. Its lower incidence during summer coincides with a higher plasma Se concentration in summer than in other seasons, as observed in normal pregnancies.

Ursodeoxycholic acid in the treatment of intrahepatic cholestasis of pregnancy. A 12-year experience.

Abstract: Objective: To assess the efficacy of ursodeoxycholic acid (UDCA) in patients with intrahepatic cholestasis of pregnancy (ICP) and in the outcome of pregnancy.

Is a leaky gut involved in the pathogenesis of intrahepatic cholestasis of pregnancy

Increased gastrointestinal permeability has been demonstrated in several liver diseases. It may facilitate the absorption of gut‐derived endotoxin‐stimulating Kupffer cells to release proinflammatory cytokines or other potentially hepatotoxic compounds. We examined gastrointestinal permeability, plasma levels of anti‐lipopolysacharides (anti‐LPS), and four proinflammatory cytokines in 20 patients with intrahepatic cholestasis of pregnancy (ICP) compared with 22 normal pregnant and 29 non‐pregnant women. Urinary excretion of sucrose and the urinary lactulose/mannitol (L/M) ratio after a standard oral load were used to assess gastrointestinal permeability. Anti‐LPS (IgA, IgM, and IgG) were measured in peripheral blood by Human EndoCAb test kit; TNF‐α, IL‐1β, IL‐6, and IL‐10 by Quantikine HS human immunoassays. Sucrose urinary excretion was similar in the three groups, indicating normal gastric permeability. The urinary L/M ratio was significantly higher in ICP than in the other groups [median (interquartile range): 0.018% (0.011‐0.023) in ICP, 0.012% (0.009‐0.016) in normal pregnancies, and 0.009% (0.008‐0.012) in non‐pregnant women, P < .01]. No significant differences were found in anti‐LPS or cytokines plasma levels except slightly higher levels of IL‐6 in ICP patients than in non‐pregnant women (P < .05). Four of five women with abnormal urinary L/M ratio during ICP continued to show abnormalities in tests up to 2 years after delivery. In conclusion, an increased intestinal permeability was detected in ICP patients during and after pregnancy. A “leaky gut” may participate in the pathogenesis of ICP by enhancing the absorption of bacterial endotoxin and the enterohepatic circulation of cholestatic metabolites of sex hormones and bile salts. (HEPATOLOGY 2006;43:715–722.)

Gallbladder motility and lithogenesis in obese patients during diet-induced weight loss

Obesity and weight loss are important risk factors for gallstone development. The mechanisms involved are unknown. We prospectively studied changes in gallbladder (GB) emptying and bile composition during weight loss. We studied 12 alithiasic obese subjects who entered a six-month diet program (800–1200 kcal/day, 26 g fat/day). As controls we evaluated 12 healthy nulliparous nonobese young women. GB volumes were studied by ultrasonography (fasting volume, GBFV; residual volume after a liquid meal, GBRV) at entry and after 4 and 20 weeks of dieting. Bile acid pool size, biliary lipid composition, presence of cholesterol crystals, and nucleation time were also studied. Of 12 obese subjects studied (mean BMI 35.1 kg/m2), 10 remained in the program for six months, but only six completed the entire study protocol, obtaining a significant weight loss (BMI: 31.2 kg/m2, P < 0.001). GBFV was greater in obese subjects than in nonobese controls (27.5 ± 10.7 vs 11.7 ± 6 ml; P < 0.05). GBRV and GB emptying curves were similar in both groups and did not change during weight loss. The obese subject who developed gallstones (1/10) was the only one who had cholesterol crystals in bile and a sluggish initial GB emptying. In conclusion: (1) obese subjects had a greater GBFV than controls; however, the GB emptying was adequate. (2) During weight loss we did not observe significant changes in GB kinetics or the bile parameters studied. (3) We observed a relatively low frequency of gallstone formation, which can be explained by a high fat content of the diet (26 g/day) and by the adequate GB emptying of our group of patients. (4) An abnormal GB contractility and cholesterol crystals in bile could be considered premonitory to gallstone formation.

Management of nonalcoholic fatty liver disease: An evidence-based clinical practice review

AIM To build a consensus among Chilean specialists on the appropriate management of patients with nonalcoholic fatty liver disease (NAFLD) in clinical practice. METHODS NAFLD has now reached epidemic proportions worldwide. The optimal treatment for NAFLD has not been established due to a lack of evidence-based recommendations. An expert panel of members of the Chilean Gastroenterological Society and the Chilean Hepatology Association conducted a structured analysis of the current literature on NAFLD therapy. The quality of the evidence and the level of recommendations supporting each statement were assessed according to the recommendations of the United States Preventive Services Task Force. A modified three-round Delphi technique was used to reach a consensus among the experts. RESULTS A group of thirteen experts was established. The survey included 17 open-ended questions that were distributed among the experts, who assessed the articles associated with each question. The levels of agreement achieved by the panel were 93.8% in the first round and 100% in the second and third rounds. The final recommendations support the indication of lifestyle changes, including diet and exercise, for all patients with NAFLD. Proven pharmacological therapies include only vitamin E and pioglitazone, which can be used in nondiabetic patients with biopsy-proven nonalcoholic steatohepatitis (the progressive form of NAFLD), although the long-term safety and efficacy of these therapies have not yet been established. CONCLUSION Current NAFLD management is rapidly evolving, and new pathophysiology-based therapies are expected to be introduced in the near future. All NAFLD patients should be evaluated using a three-focused approach that considers the risks of liver disease, diabetes and cardiovascular events.

Liver transplantation for hepatocellular carcinoma: evaluation of the alpha-fetoprotein model in a multicenter cohort from Latin America.

The French alpha‐fetoprotein (AFP) model has recently shown superior results compared to Milan criteria (MC) for prediction of hepatocellular carcinoma (HCC) recurrence after liver transplantation (LT) in European populations. The aim of this study was to explore the predictive capacity of the AFP model for HCC recurrence in a Latin‐American cohort.

Severe novel H1N1 influenza A infection in the immediate postoperative period of a liver transplant patient.

In 2009, the World Health Organization recognized the novel H1N1 influenza A virus as a pandemic infection. Since April 2009, thousands of cases of novel H1N1 influenza A infection have been reported worldwide, and they have resulted in thousands of deaths. South American countries were affected by this infection during their winter season, and Chile presented one of the highest incidence rates. We have recently managed a liver transplant patient who presented with a severe novel H1N1 influenza A infection in the early postoperative period and required prolonged mechanical ventilation. The early suspicion of this infection during the current pandemic influenza in Chile made possible a timely treatment with oseltamivir. We decided to report this case because no other cases of liver transplant patients affected by H1N1 influenza A have been reported so far. We intend to alert clinicians about this potentially devastating viral infection in view of the current pandemic scenario, and here we review some of the recommendations for its prevention, diagnosis, therapy, and possible complications. Liver Transpl, 2010.

A changing etiologic scenario in liver transplantation for hepatocellular carcinoma in a multicenter cohort study from Latin America

BACKGROUND AND AIM Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of hepatocellular carcinoma (HCC) and liver transplantation (LT). Our study focused on changing trends of liver related HCC etiologies during the last years in Latin America. METHODS From a cohort of 2761 consecutive adult LT patients between 2005 and 2012 in 17 different centers, 435 with HCC were included. Different periods including years 2005-2006, 2007-2008, 2009-2010 and 2011-2012 were considered. Etiology of liver disease was confirmed in the explant. RESULTS Participating LT centers per country included 2 from Brazil (n=191), 5 transplant programs from Argentina (n=98), 2 from Colombia (n=65), 4 from Chile (n=49), 2 from Mexico (n=12), and 1 from Peru (n=11) and Uruguay (n=9). Chronic hepatitis C infection was the leading cause of HCC in the overall cohort (37%), followed by HBV (25%) and alcoholic liver disease (17%). NAFLD and cryptogenic cirrhosis accounted for 6% and 7%, respectively. While HCV decreased from 48% in 2005-06 to 26% in 2011-12, NAFLD increased from 1.8% to 12.8% during the same period, accounting for the third cause of HCC. This represented a 6-fold increase in NAFLD-HCC, whereas HCV had a 2-fold decrease. Patients with NAFLD were older, had lower pre-LT serum AFP values and similar 5-year survival and recurrence rates than non-NAFLD. CONCLUSION There might be a global changing figure regarding etiologies of HCC in Latin America. This epidemiological change on the incidence of HCC in the world, although it has been reported, should still be confirmed in prospective studies.

Evaluación comparativa entre MELD y Child-Pugh como escalas pronosticas de sobrevida en pacientes con Cirrosis Hepática en Chile

Background: Currently, most liver units use the Child-Pugh (CP) or the Model for End-Stage Liver Disease (MELD) scores to establish survival prognosis among patients with liver cirrhosis. Which classification is superior, is not well defined. Aim: To compare CP and MELD classification scores to predict survival among adult patients with liver cirrhosis in Chile. Material and methods: Follow-up of 137 consecutive adult patients with liver cirrhosis aged 59 ± 12 years (55% women). The diagnosis was reached by clinical, laboratory and image studies at three different centers of Santiago. Patients were staged with CP and MELD classification scores at baseline and followed over a period of 12 months. The predictive capacity of the scores for survival was analyzed using a multivariate statistical analysis (Kaplan-Meier curves). Results: The most common etiology was alcohol (37.9%). The actuarial survival rate was 79.6% at 12 months of follow-up. When comparing groups with areas under curve of receiver operating characteristic curves (AUROC), there was no statistically significant difference in survival between less severe and advanced disease, assessed with both survival scales. The AUROC for MELD and CP were 0.80 and 0.81, respectively. Conclusions: This clinical study did not find a statistically significant difference between the two classifications for the prediction of 12 months survival in patients with cirrhosis.