Guía Práctica ESPEN: nutrición clínica en las enfermedades del hígado / ESPEN Practical Guideline: clinical nutrition in liver disease

Introducción: la Guía Práctica se basa en la actual guía científica de la ESPEN sobre nutrición clínica en las enfermedades hepáticas. Métodos: se ha reducido y transformado en diagramas de flujo para facilitar su uso en la práctica clínica. La guía está dedicada a todos los profesionales, incluidos médicos, dietistas, Nutriciónistas y enfermeras, que trabajan con pacientes con enfermedad hepática crónica. Resultados: la guía presenta un total de 103 pronunciamientos y recomendaciones con breves comentarios para el manejo Nutricional y metabólico de pacientes con (i) insuficiencia hepática aguda grave, (ii) esteatohepatitis alcohólica, (iii) enfermedad hepática grasa no alcohólica, (iv) cirrosis hepática, y (v) cirugía o trasplante de hígado. Conclusión: las recomendaciones relacionadas con enfermedades están precedidas por recomendaciones generales sobre el diagnóstico del estado Nutricional en los pacientes hepáticos y sobre las complicaciones hepáticas asociadas a la nutrición médica (AU)

Background: the Practical Guideline is based on the current scientific ESPEN guide on Clinical Nutrition in Liver Disease Methods: it has been shortened and transformed into flow charts for easier use in clinical practice. The guideline is dedicated to all professionals including physicians, dieticians, nutritionists and nurses working with patients with chronic liver disease. Results: a total of 103 statements and recommendations are presented with short commentaries for the nutritional and metabolic management of patients with (i) acute liver failure, (ii) alcoholic steatohepatitis, (iii) non-alcoholic fatty liver disease, (iv) liver cirrhosis, and (v) liver surgery/transplantation. Disease-related recommendations are preceded by general recommendations on the diagnosis of nutritional status in liver patients and on liver complications associated with medical nutrition. Conclusion: this Practical Guideline gives guidance to health care providers involved in the management of liver disease on how to offer optimal nutritional care (AU)

Safety and efficacy of bariatric surgery in patients with advanced fibrosis.

BACKGROUND: Bariatric surgery is performed safely in non-alcoholic fatty liver disease (NAFLD) patients with minimal fibrosis (stage 1-2). However, the safety and potential benefits of bariatric surgery for NAFLD with advanced fibrosis (stage 3-4) remain unclear. This study was designed to compare the safety and efficacy of bariatric surgery in patients with biopsy proven advanced fibrosis to those with minimal fibrosis. METHODS: All patients who underwent bariatric surgery between 2005 and 2014 and had evidence of NAFLD with fibrosis score 3-4 (advanced fibrosis) based on the staging system defined by Kleiner et al. on intraoperative liver biopsy were included and compared with patients who had fibrosis score 1-2 (minimal fibrosis). The groups were compared for length of hospital stay after bariatric surgery and incidence of postoperative complications over a follow-up period of 1 year. An improvement in hepatic function tests before and 1 year after surgery was used as a parameter to evaluate for NAFLD improvement. RESULTS: Ninety-nine patients with F3-4 (group 1) and 198 patients with F1-2 (group 2) were included. Mean age (51.9 vs 50.1 years) and body mass index (46.4 vs 46.5 kg m-2) were similar in the two groups. Median serum aspartate aminotransferase (43 vs 30 U l-1; normal 10-40 U l-1) and alanine aminotransferase (40.5 vs 34 U l-1; normal 10-50 U l-1) were significantly higher in group 1 and improved 1 year after surgery. Median length of hospital stay after surgery was higher in group 1 than that in group 2 (4 days vs 3 days; P-value=0.002). The proportion of patients developing postoperative complications over 1 year was similar in both groups (36.4% vs 32.8%; P-value=0.54). CONCLUSIONS: Advanced fibrosis does not increase the risk of developing postoperative complications in medically optimized patients undergoing bariatric surgery. Improvement in serum transaminase levels suggests a reduction in hepatic necroinflammatory activity following bariatric surgery.

The effect of hyperammonemia on myostatin and myogenic regulatory factor gene expression in broiler embryos.

Myogenesis is facilitated by four myogenic regulatory factors and is significantly inhibited by myostatin. The objective of the current study was to examine embryonic gene regulation of myostatin/myogenic regulatory factors, and subsequent manipulations of protein synthesis, in broiler embryos under induced hyperammonemia. Broiler eggs were injected with ammonium acetate solution four times over 48 h beginning on either embryonic day (ED) 15 or 17. Serum ammonia concentration was significantly higher (P<0.05) in ammonium acetate injected embryos for both ED17 and ED19 collected samples when compared with sham-injected controls. Expression of mRNA, extracted from pectoralis major of experimental and control embryos, was measured using real-time quantitative PCR for myostatin, myogenic regulatory factors myogenic factor 5, myogenic determination factor 1, myogenin, myogenic regulatory factor 4 and paired box 7. A significantly lower (P<0.01) myostatin expression was accompanied by a higher serum ammonia concentration in both ED17 and ED19 collected samples. Myogenic factor 5 expression was higher (P<0.05) in ED17 collected samples administered ammonium acetate. In both ED17 and ED19 collected samples, myogenic regulatory factor 4 was lower (P⩽0.05) in ammonium acetate injected embryos. No significant difference was seen in myogenic determination factor 1, myogenin or paired box 7 expression between treatment groups for either age of sample collection. In addition, there was no significant difference in BrdU staining of histological samples taken from treated and control embryos. Myostatin protein levels were evaluated by Western blot analysis, and also showed lower myostatin expression (P<0.05). Overall, it appears possible to inhibit myostatin expression through hyperammonemia, which is expected to have a positive effect on embryonic myogenesis and postnatal muscle growth.

Evaluation of endoscopy-based diagnostic methods for the detection of Helicobacter pylori.

BACKGROUND: Helicobacter pylori is an etiological factor in duodenal ulcer. Few studies have objectively assessed the accuracy of diagnostic methods for the detection of H. pylori. METHODS: The sensitivity and specificity of histology, touch smear, rapid urease test (RUT) and brush cytology of endoscopic antral biopsy from patients with duodenal ulcer were compared. Forty-nine patients were evaluated before, and 34 after, eradication therapy. Each time, sampling was done for all 4 tests. The infection status for each sample was established by a positive concordance of results of three of four tests. RESULTS: The highest degree of agreement was between RUT and cytology (kappa = 0.69). Brush cytology (100%) followed by RUT (94.5%) were the most sensitive tests. Histology had the highest specificity (89.3%). A combination of RUT or brush cytology with histology had the maximum chance of detecting H. pylori. As single tests, brush cytology and touch smear had high diagnostic accuracies with a Youdin J value of 1.79 and 1.78, respectively. CONCLUSION: The best method for diagnosis of H. pylori is a combination of the rapid urease test or brush cytology with histology. Brush cytology or touch smear are diagnostic tests of choice if a single test is desired.

Magnitude of hepatitis C virus infection in India: prevalence in healthy blood donors, acute and chronic liver diseases.

An enzyme immunoassay (EIA) was developed in-house for the detection of anti-hepatitis C virus (HCV) antibody against the prevailing genotypes in India. The specific reactivity of the test was compared with commercial second and third-generation EIAs and reverse transcription nested polymerase chain reaction (RT-nested PCR). Fifteen thousand nine hundred twenty-two healthy blood donors at the All India Institute of Medical Sciences (AIIMS), New Delhi, India, were screened for anti-HCV antibody. Two hundred ninety-five (1.85%) of these donors were positive. The screening was also used to determine how many patients with acute hepatitis and chronic liver diseases were positive for anti-HCV antibody. Five hundred sixty-four chronic liver disease patients were screened for anti-HCV antibody and 78 (13.83%) were found positive. Two hundred forty-seven sporadic acute viral hepatitis patients were screened for viral infection markers. Hepatitis B and E viruses (HBV and HEV) were the major etiologic agents. HCV was associated with 9% of the acute cases. Anti-HCV core IgM with HCV RNA detection were found to be helpful for the diagnosis of acute HCV infection.

Prognostic markers in amebic liver abscess: a prospective study.

OBJECTIVES: Amebic liver abscess (ALA) is being increasingly recognized with the progressive spread of AIDS. The prognosis of ALA needs to be determined to decide whether aggressive intervention therapy should be used. A prospective study was conducted to determine the factors that predicted mortality in patients with ALA. METHODS: The study population consisted of 135 consecutive patients with ALA who were treated with 80 mg/kg/day of metronidazole for 10 days if they survived. Needle aspiration or open surgical drainage was performed in patients who deteriorated despite drug therapy or had an abscess that clinically appeared to be at risk of impending rupture. Survivors and nonsurvivors were compared by univariate and multivariate analysis to identify predictors of outcome. These predictors were then prospectively evaluated in a subsequent cohort of patients with ALA. RESULTS: Twenty-four patients died during the acute phase. Significant differences between survivors and nonsurvivors were observed. A stepwise logistic regression suggested that a bilirubin level >3.5 mg/dl, encephalopathy, volume of abscess cavity, hypoalbuminemia (serum albumin level <2.0 g/dl), and the number of abscesses were independent risk factors for mortality. The duration of symptoms and type of treatment did not influence mortality. The regression equation derived was then applied prospectively to 64 subsequent patients with ALA, and the validity of the prediction rule was confirmed. The qualities of simplicity, availability, low cost of derivation, and good discriminating power suggest that this index would be useful in assessing prognosis in patients with ALA.

Fulminant hepatitis in a tropical population: clinical course, cause, and early predictors of outcome.

The profiles of patients with fulminant hepatic failure (FHF) from developing countries have not been reported earlier. The current study was conducted prospectively, at a single tertiary care center in India, to document the demographic and clinical characteristics, natural course, and causative profile of patients with FHF as well as to define simple prognostic markers in these patients. Four hundred twenty-three consecutive patients with FHF admitted from January 1987 to June 1993 were included in the study. Each patient's serum was tested for various hepatotropic viruses. Univariate Cox's regression for 28 variables, multivariate Cox's proportional hazard regression, stepwise logistic regression, and Kaplan-Meier survival analysis were done to identify independent predictors of outcome at admission. All patients presented with encephalopathy within 4 weeks of onset of symptoms. Hepatotropic viruses were the likely cause in most of these patients. Hepatitis A (HAV), hepatitis B (HBV), hepatitis D (HDV) viruses, and antitubercular drugs could be implicated as the cause of FHF in 1.7% (n= 7), 28% (n= 117), 3.8% (n= 16), and 4.5% (n= 19) patients, respectively. In the remaining 62% (n= 264) of patients the serological evidence of HAV, HBV, or HDV infection was lacking, and none of them had ingested hepatotoxins. FHF was presumed to be caused by non-A, non-B virus(es) infection. Sera of 50 patients from the latter group were tested for hepatitis E virus (HEV) RNA and HCV RNA. In 31 (62%), HEV could be implicated as the causative agent, and isolated HCV RNA could be detected in 7 (19%). Two hundred eighty eight (66%) patients died. Approximately 75% of those who died did so within 72 hours of hospitalisation. One quarter of the female patients with FHF were pregnant. Mortality among pregnant females, nonpregnant females, and male patients with FHF was similar (P > .1). Univariate analysis showed that age, size of the liver assessed by percussion, grade of coma, presence of clinical features of cerebral edema, presence of infection, serum bilirubin, and prothrombin time prolongation over controls at admission were related to survival (P < .01). The rapidity of onset of encephalopathy and cause of FHF did not influence the outcome. Cox's proportional hazard regression showed age > or = 40 years, presence of cerebral edema, serum bilirubin > or = 15 mg/dL, and prothrombin time prolongation of 25 seconds or more over controls were independent predictors of outcome. Ninety-three percent of the patients with three or more of the above prognostic markers died. The sensitivity, specificity, positive predictive value, and the negative predictive value of the presence of three or more of these prognostic factors for mortality was 93%, 80%, 86%, and 89.5%, respectively, with a diagnostic accuracy of 87.3%. We conclude that most of our patients with FHF might have been caused by hepatotropic viral infection, and non-A, non-B virus(es) seems to be the dominant hepatotropic viral infection among these patients. They presented with encephalopathy within 4 weeks of the onset of symptoms. Pregnancy, cause, and rapidity of onset of encephalopathy did not influence survival. The prognostic model developed in the current study is simple and can be performed at admission.

Gastroduodenal manifestations in patients with skeletal fluorosis.

A prospective case-controlled study was performed to evaluate the gastrointestinal symptoms and mucosal abnormalities occurring in patients with osteofluorosis. Ten patients with documented osteofluorosis and ten age- and sex-matched healthy volunteers were included in the study. Clinical evaluation, real-time ultrasound, and upper gastrointestinal endoscopy and biopsy from the gastric antrum and duodenum were performed in all subjects. The biopsies were subjected to a rapid urease test and light and electron microscopic examinations. Ionic fluoride levels were estimated in the drinking water, serum, and urine using an ION 85 ion analyzer. All patients with osteofluorosis had gastrointestinal symptoms, the most common being abdominal pain. Endoscopic abnormalities were found in seven patients with osteofluorosis. In all 7 of these patients, chronic atrophic gastritis was seen on histology. Electron microscopic abnormalities were observed in all 10 patients with osteofluorosis. These included loss of microvilli, cracked-clay appearance, and the presence of surface abrasions on the mucosal cells. None of the control subjects had any clinical symptoms or mucosal abnormalities. It was concluded that gastrointestinal symptoms as well as mucosal abnormalities are common in patients with osteofluorosis.

Sonographic signs in portal hypertension: a multivariate analysis.

A prospective case controlled study was conducted to evaluate the value of real time ultrasound in establishing the diagnosis and the etiology of portal hypertension. Patients attending the outpatient department of a tertiary care centre were included. There were 324 consecutive patients with portal hypertension due to cirrhosis (n = 229), non cirrhotic portal fibrosis (NCPF: n = 64) and extrahepatic portal venous obstruction (EHPVO: n = 31). During this period, 146 patients with dyspepsia, 35 with splenomegaly and 32 with ascites due to varied causes served as negative and positive controls. Real time ultrasonography using a 3.5 MHz linear array scanner was performed in a fasting state in all subjects. Portal and splenic vein diameter greater than 10 mm, splenomegaly, hepatic and splenic hilar collaterals were suggestive of portal hypertension. Non visualization of the portal vein which was replaced by a cavernoma had a diagnostic accuracy of 98% in EHPVO. Splenic infarcts and absence of ascites were features of non cirrhotic portal hypertension (NCPF and EHPVO). Sonography had an overall diagnostic accuracy of 80%. A stepwise logistic regression with multivariate analysis using discriminate function showed that collaterals at the hepatic and splenic hilum, hepatomegaly, ascites and splenic infarcts were independent markers to differentiate cirrhotic from noncirrhotic causes of portal hypertension. The discriminate equation generated had a mismatch of 9.8%. Correlations between the sonographic signs demonstrated that the variceal grade correlated positively with the presence of splenic hilar collaterals and the liver size inversely correlated with presence of ascites. It was concluded that real time ultrasonography is an accurate method to establish the presence and etiology of portal hypertension.

Long-Term Management of Esophageal Varices by Endoscopic Sclerotherapy (EST): A Review of 12 Years' Experience.

A total of 566 patients with variceal bleeding caused by cirrhosis of the liver, noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHO) were treated by repeated endoscopic injection sclerotherapy. This decreased rebleeding was evidenced by a reduction in mean bleeding risk factor and transfusion requirement. Both the factors were significantly (P < 0.001) decreased in all three groups of patients. Rebleeding occurred before eradication in 27.7% of patients with cirrhosis, 24.3% of those with NCPF, and 11% of those with EHO. Significantly more patients with cirrhosis and NCPF bled in comparison to EHO. Irrespective of the etiology, fewer patients of Child's A class bled than those of Child's B and C classes (P < 0.001). The median bleeding-free period was longer in patients with EHO than in those with cirrhosis (P < 0.05). This period was also significantly longer in Child's A class than in Child's B and the latter had a longer median bleeding-free period than Child's C class (P < 0.01). Variceal eradication was achieved in 80% of patients with cirrhosis, 87% of patients with NCPF, and 90% of patients with EHO. The success of variceal eradication was higher in EHO patients in contrast with patients with cirrhosis of the liver. Similarly, eradication was better in Child's A class patients than in Child's B and C class patients. Recurrence of varices and complications were not influenced by the Child's status or etiology of portal hypertension. The probability of survival at 10 years was higher in patients with EHO (88%) and NCPF (80%) than in patients with cirrhosis (50%). Similarly, patients with Child's A (88%) status survived longer than those with Child's B (42%) status, and patients with Child's B status had a longer survival than Child's C status patients (0%). Thus, endoscopic variceal sclerotherapy appears to be a useful procedure for the long-term management of patients after an esophageal variceal bleeding irrespective of the etiology of portal hypertension.

Gastrointestinal leiomyomas in a developing country.

Twenty one consecutive patients with leiomyoma of the gastrointestinal tract were studied. Recurrent gastrointestinal bleeding was found in 18 (85.7%) and recurrent intestinal obstruction in 3 (14.3%) patients. The commonest site of the lesion was the stomach followed by ileum, jejunum and duodenum. Barium meal examination and gastrointestinal endoscopy were suggestive of the diagnosis in 8 and angiography in 2 patients. The remaining patients were diagnosed peroperatively. All patients underwent excision and remained asymptomatic on follow up except two patients who had a recurrence of the tumor as leiomyosarcoma.

Long term follow-up of amebic liver abscess: clinical and ultrasound patterns of resolution.

A prospective study was undertaken to evaluate the clinical and sonographic patterns of resolution in amebic liver abscess (ALA). There were 146 patients of ALA attending the gastroenterology clinic of a tertiary care centre of whom 25 died. Of the remaining 121 patients, 107 were followed up for 20.9 +/- 11.4 months. 14 (11.3%) patients were lost to follow up before complete disappearance of the cavity. Complete disappearance of the cavity was seen in 84 (78.5%) and a reduction in volume to 50% at entry in 23 (21.5%). Abdominal pain, fever and hepatomegaly were the predominant forms of clinical presentation. On ultrasound, there were 121 cavities in 107 patients. The most frequent type of lesion was solitary, (96%) round cavity (80.4%) in the right lobe of liver (85%). Clinical and hematological parameters of resolution occurred rapidly (3.2 +/- 2.9 months). Sonographic resolution took much longer (9.6 +/- 6.8% months) in the 84 patients. The remaining 23 patients are on follow up. Three pattern of resolution were observed: Type I--where complete disappearance of the cavity occurred within 3 months (29.8%), Type II--where a gradual reduction and disappearance of the cavity occurred (64.3%) and Type III--where a rapid reduction till 25% of original cavity size remained and then a delayed resolution occurred (5.9%). There were no relapses in the patients on follow up. Factors that influenced healing time included the size of the abscess cavity at admission, hypoalbuminemia and anemia. The type of clinical presentation, nature of therapy, number or location of abscesses and time for clinical resolution did not influence the resolution time. None of the variables studied influenced the pattern of resolution. We conclude that rapid clinical resolution is common in patients with ALA. Sonographic resolution may be delayed and does not warrant additional or prolonged therapy.

Prospective study of plasma fibronectin in fulminant hepatitis: association with infection and mortality.

BACKGROUND/AIMS: Plasma fibronectin is an opsonic glycoprotein, normally synthesized by the liver, which decreases subsequent to severe liver damage and low levels of which may contribute to reticuloendothelial system dysfunction by compromising opsonic activity. This may result in an increased frequency of infection and death. The present study was conducted to evaluate the association of plasma fibronectin activity with infection and mortality in patients with fulminant hepatic failure. METHODS: Plasma fibronectin was estimated serially in 69 consecutive patients with fulminant hepatic failure, nine patients with uncomplicated acute viral hepatitis and 32 normal volunteers. RESULTS: Plasma fibronectin levels in patients with fulminant hepatic failure (85.6 +/- 75.8 micrograms/ml) were significantly lower than in patients with uncomplicated acute viral hepatitis (295.5 +/- 88.5 micrograms/ml) and healthy volunteers (362.6 +/- 69.2 micrograms/ml). Forty-nine (72%) patients with fulminant hepatic failure died. The initial values of fibronectin in fulminant hepatic failure did not correlate with mortality. Patients with fulminant hepatic failure who survived showed a progressive rise in the fibronectin levels compared to the absence of an increase in fibronectin levels in the non-survivors. The mortality in patients with fulminant hepatic failure with infection (24/27) was significantly higher (p < 0.05) compared to those without infection (25/42). Initial fibronectin levels in patients with infection (70.3 +/- 54.2 micrograms/ml) were significantly lower (p < 0.05) than in those without infection (92.3 +/- 64.4 micrograms/ml). We conclude that plasma fibronectin levels in patients with fulminant hepatic failure are decreased compared to healthy subjects and the absence of an increase in levels indicates a poor prognosis. Low levels of fibronectin are associated with an increased incidence of infection, which increases the mortality in these patients.

Colonoscopy for unexplained lower gastrointestinal bleeding in a tropical country.

Two hundred and forty consecutive patients with recurrent lower gastrointestinal bleeding were studied by colonoscopic examination. These included 187 adults and 53 children. The procedure was successful either in identifying the lesion or in excluding it up to the cecum in 216 (90% patients). The source of bleeding was identified in 138 (74%) adults and 43 (81%) Children. Predominant lesions in adults were nonspecific colitis and ulcers (58%), polyps (19%), cancer (10%), rectal varices (4%) and tuberculosis (3%). Juvenile polyps (77%) and nonspecific colitis and ulcers (23%) were the cause of bleeding in children. Both in adults and children, 92% of these lesions involved the left colon. Rectum and sigmoid colon were mainly involved. Diffuse lesions were seen when nonspecific colitis and ulcers were the source of bleeding. Thus colonoscopic examination was useful in localizing the cause of rectal bleeding and the predominant lesions were different from those reported in the Western hemisphere.