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Biomedical subjects

Paul Angulo

Publications and source records attributed to Paul Angulo.

At least 19 recordsLinked to original sources
PubMed2006

Clinical predictors for hepatocellular carcinoma in patients with primary biliary cirrhosis.

BACKGROUND & AIMS: Although hepatocellular carcinoma (HCC) occurs with increased frequency in patients with primary biliary cirrhosis (PBC), the exact frequency is relatively low. Optimal selection of PBC patients for HCC screening needs to be determined for effective screening. In this study, we aimed to explore clinical predictors of HCC in PBC patients. METHODS: We performed a case-control study using 17 PBC patients with HCC identified from 1976 to 2002 at the Mayo Clinic. Control PBC patients who had no evidence of HCC were selected for each case by matching the first year of their visit to the Mayo Clinic. All medical information was collected within 2 years from when the cases were diagnosed with HCC. Logistic regression models were used for the analyses. RESULTS: Age, sex, history of blood transfusion, current smoking, histologic stage at PBC diagnosis, any signs of portal hypertension, Mayo score, hemoglobin level, platelet count, aspartate aminotransferase level, and albumin level were associated with the presence of HCC (P < .05 for each). In multivariable analysis, older age (OR, 1.7; 95% confidence interval [CI], 1.1-2.5 for 5 years), male sex (OR, 9.7; 95% CI, 1.4-68.3), history of blood transfusion (OR, 5.0; 95% CI, 1.0-24.3), and any signs of portal hypertension (OR, 22.9; 95% CI, 3.4-155.3) were associated significantly with increased odds of HCC and yielded an excellent diagnostic performance (area under the receiver operating characteristics curve rate, 0.91). CONCLUSIONS: Older age, male sex, history of blood transfusion, and any signs of portal hypertension or cirrhosis indicate higher likelihood of HCC and should be considered for HCC screening. Further studies in larger patient cohorts are required to verify the diagnostic model.

Adult↗
PubMed2006

Abnormal hepatic biochemistries in patients with inflammatory bowel disease.

OBJECTIVES: The relationship between abnormal hepatic biochemistries and inflammatory bowel disease (IBD) is unclear. We determined the prevalence of abnormal hepatic biochemistries and chronic liver disease in a cohort of IBD patients, and we compared patients with normal and abnormal liver biochemistries. METHODS: Patients with IBD evaluated at our institution between January 1, 2000 and December 31, 2000 were identified. Data on gender, age, IBD subtype, extent and activity, medications, liver disease history, liver biochemistries, and vital status were collected. The chi(2) test, Student's t-test, and Cox proportional regression were used. RESULTS: We identified 544 patients with available hepatic biochemistries. Abnormal hepatic biochemistries were found in 159 (29%). Defined chronic liver disease was present in 5.8% of patients (primary sclerosing cholangitis in 4.6%). The prevalence of abnormal hepatic biochemistries was 27% for those with active IBD and 36% for those in remission (P= 0.06). Patients with abnormal hepatic biochemistries were less frequently on 5-aminosalicylates (35%vs 51%, P < 0.001), and a smaller proportion was alive at last follow-up (90.4%vs 98.5%, P < 0.0001). The age-adjusted risk of death was 4.8 times higher in patients with abnormal hepatic biochemistries, after excluding patients with any diagnosis of liver disease. CONCLUSIONS: Abnormal hepatic biochemistries were present in nearly one-third of our patients, and surprisingly, they were not associated with IBD activity. Abnormal hepatic biochemistries and chronic liver disease appeared to have a negative impact on vital status. Persistently abnormal hepatic biochemistries should be evaluated, and not attributed to IBD activity.

Adolescent↗
PubMed2006

Utility of a new model to diagnose an alcohol basis for steatohepatitis.

BACKGROUND & AIMS: Distinguishing an alcohol basis from a nonalcoholic basis for the clinical and histologic spectrum of steatohepatitic liver disease is difficult because of unreliability of alcohol consumption history. Unfortunately, various biomarkers have had limited utility in distinguishing alcoholic liver disease (ALD) from nonalcoholic fatty liver disease (NAFLD). Thus, the aim of our study was to create and validate a model to diagnose ALD in patients with steatohepatitis. METHODS: A cross-sectional cohort study was performed at the Mayo Clinic, Rochester, Minnesota, to create a model using multivariable logistic regression analysis. This model was validated in 3 independent data sets comprising patients of varying severity of steatohepatitis spanning over 10 years. RESULTS: Logistic regression identified mean corpuscular volume, aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, body mass index, and gender as the most important variables that separated patients with ALD from NAFLD. These variables were used to generate the ALD/NAFLD Index (ANI), with ANI of greater than zero incrementally favoring ALD and ANI of less than zero incrementally favoring a diagnosis of NAFLD, thus making ALD unlikely. ANI had a c-statistic of 0.989 in the derivation sample, and 0.974, 0.989, 0.767 in the 3 validation samples. ANI performance characteristics were significantly better than several conventional and recently proposed biomarkers used to differentiate ALD from NAFLD, including the histopathologic marker protein tyrosine phosphatase 1b, AST/ALT ratio, gamma-glutamyl transferase, and carbohydrate-deficient transferrin. CONCLUSIONS: ANI, derived from easily available objective variables, accurately differentiates ALD from NAFLD in hospitalized, ambulatory, and pretransplantation patients and compares favorably with other traditional and proposed biomarkers.

Adult↗
PubMed2006

NAFLD in children: a prospective clinical-pathological study and effect of lifestyle advice.

Nonalcoholic fatty liver disease (NAFLD), a common cause of chronic liver disease in adults, is incompletely characterized in children. We conducted a prospective study to better characterize the clinical presentation of NAFLD in children and to determine the effect of lifestyle advice in the management of pediatric NAFLD. From June 2001 to April 2003, 84 children (age 3-18.8 yr) who had elevated aminotransferases and the diagnosis of NAFLD confirmed via liver biopsy underwent a 2-hour oral glucose tolerance test and a 12-month program of lifestyle advice consisting of diet and physical exercise. Thirty-four (40.5%) patients were obese (body mass index [BMI] >97th percentile), and 43 (51.2%) were overweight (BMI 85th-97th percentile). Ten (12%) had abnormal glucose tolerance; 10 (12%) had elevated triglycerides, cholesterol, or both; and all had normal blood pressure. Most children (67/84, 80%) were insulin-resistant, including the 7 children with normal BMI (<85th percentile). Increased liver fibrosis was present in 49 (58.1%) patients and was independently associated with obesity (OR 2.7, 95% CI 1.2-6.2) and age (1-year increase; OR 1.2, 95% CI 1.04-1.5). A 12-month program with diet and physical exercise resulted in a significant decrease in BMI, and levels of fasting glucose, insulin, lipids, and liver enzymes, as well as liver echogenicity on ultrasonography. In conclusion, children with NAFLD are almost always insulin-resistant regardless of BMI. Obesity and older age are independently associated with increased liver fibrosis. A simple lifestyle advice program significantly improves insulin resistance, and the liver disease in pediatric NAFLD.

Adolescent↗
PubMed2006

Nonalcoholic fatty liver disease and liver transplantation.

Nonalcoholic fatty liver disease affects a substantial proportion of the general population worldwide. This high prevalence of nonalcoholic fatty liver disease has important consequences in the donor selection process for liver transplantation, and in the posttransplant period given the high recurrence rate of disease. This paper reviews the prevalence of nonalcoholic fatty liver disease, its progressive potential, and the implications of this liver condition in both the pre- and post-liver transplantation setting.

Disease Progression↗
PubMed2006

The effect of the metabolic syndrome, hepatic steatosis and steatohepatitis on liver fibrosis in hereditary hemochromatosis.

OBJECTIVES: The variability in phenotypic expression of hereditary hemochromatosis (HH) is not fully understood. We sought to examine whether the metabolic syndrome, hepatic steatosis or steatohepatitis influenced hepatic fibrosis among patients with HH and iron overload. METHODS: We identified 86 patients with C282Y/C282Y or C282Y/H63D HH and iron overload (hepatic iron concentration (HIC) >2,200 microg/g for males, >1,600 microg/g for females). Features of the metabolic syndrome were assessed at the time of liver biopsy. Biopsies were scored by a blinded pathologist. Significant fibrosis was defined as peri-portal fibrosis or greater. RESULTS: The mean (+/-SD) age of the study population was 53+/-12 years and 68 (79%) were male. The median (range) values of ferritin and HIC were 1,125 (253-9,530) microg/l and 9963 (1926-50 887) microg/g, respectively. The metabolic syndrome was present in 23 (27%), hepatic steatosis in 43 (50%), steatohepatitis in 18 (21%) and significant fibrosis in 38 (44%). Overall, neither the metabolic syndrome nor any of its components were associated with significant fibrosis or a higher mean fibrosis stage. Hepatic steatosis but not steatohepatitis was associated with a lower fibrosis stage. C282Y/H63D compound heterozygous individuals who had glucose intolerance had more severe fibrosis compared with those without glucose intolerance (1.0+/-1.0 vs. 0.1+/-0.3, P=0.01). CONCLUSIONS: Overall, the metabolic syndrome and fatty liver were not associated with hepatic fibrosis among individuals with HH and iron overload. However, glucose intolerance may be important risk factor for the development of hepatic fibrosis in subjects with the C282Y/H63D HFE genotype.

Adult↗
PubMed2006

Values and limitations of serum aminotransferases in clinical trials of nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Choosing endpoints in nonalcoholic steatohepatitis (NASH) trials is challenging because of the lack of validated surrogates and the trade-off between accuracy and invasiveness. In this study, we assessed diagnostic accuracy of serum aminotransferase changes in predicting histological changes in NASH trials. METHODS: We conducted a longitudinal cohort study by using 102 participants in ursodeoxycholic acid-NASH trial who had both baseline and 2-year liver biopsy and multiple measurements of serum aminotransferases. We calculated rates of alanine aminotransferase (ALT) [or aspartate aminotransferase (AST)] change as slopes of linear regression over 2 years (IU/l/month) and changes in each histological feature as differences in Brunt's scores of two biopsies in each individual. RESULTS: Rate of aminotransferase change correlated with changes in inflammation and fibrosis, but not steatosis and only with change in inflammation in multivariable analysis. In each histological feature, changes were inversely correlated with baseline histological grade. In predicting improvement of inflammation, areas under the receiver-operating characteristic curve of aminotransferase information alone were 0.72 for ALT and 0.73 for AST and were improved to 0.88 and 0.89, respectively, when baseline histology were taking account of. CONCLUSIONS: Serum aminotransferase changes could be useful as surrogates in screening therapies for NASH in clinical trials with appropriate consideration of baseline aminotransferase and histology.

Adult↗
PubMed2005

Effect of changes on body weight and lifestyle in nonalcoholic fatty liver disease.

BACKGROUND/AIMS: The effects of lifestyle modifications in nonalcoholic fatty liver disease (NAFLD) are incompletely defined. We aimed at determining the association of changes in body weight and lifestyle with changes in serum ALT levels. METHODS: We analyzed annual health checkup data from 1546 employees. Of 469 subjects with elevated ALT, we selected 348 male subjects by excluding those who had other causes of liver disease. They were followed for one year to assess the association of change in lifestyle with change in serum ALT. The 136 subjects who had ALT normalization were followed for two years to assess the association between lifestyle management and persistently normal ALT. RESULTS: In adjusted analysis, weight loss and regular exercise were significantly associated with improvement in serum ALT and increased the odds of ALT normalization, while starting smoking was significantly associated with deterioration in serum ALT. Subjects achieving > or = 5% weight reduction showed improvement in serum ALT. Reduction in alcohol consumption was not associated with changes in serum ALT. Maintaining reduced weight (<5% gain) was significantly associated with persistently normal ALT. CONCLUSIONS: Reducing weight by at least 5% with subsequent weight control and exercising regularly may be beneficial in treating NAFLD.

Adult↗
PubMed2005

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is emerging as the most common chronic liver condition in the Western world. It is associated with insulin resistance and frequently occurs with features of the metabolic syndrome. Disease presentation ranges from asymptomatic elevated liver enzyme levels to cirrhosis with complications of liver failure and hepatocellular carcinoma. Current treatment recommendations are limited to weight loss and exercise, although several promising medications are on the horizon. In this article we discuss the etiology, pathogenesis and diagnosis of nonalcoholic fatty liver disease as well as approaches to its management.

Biopsy↗
PubMed2005

Chronological development of elevated aminotransferases in a nonalcoholic population.

The incidence and risk factors of nonalcoholic fatty liver disease (NAFLD) have never been prospectively determined. To determine the frequency and risk factors of NAFLD and chronological ordering between NAFLD, weight gain, and features of insulin resistance, a historical cohort study was conducted in a Japanese workplace. A cohort free of previous liver injury, alcohol consumption of more than 140 g/wk, and hepatitis B or C infection (529 of 1537 subjects), and a subcohort of 287 subjects free of insulin resistance-related features were identified. Elevated aminotransferases in nonalcoholics were used as a surrogate for NAFLD. High aminotransferases together with weight gain of more than 2 kg and insulin resistance-related features in the subcohort were sought for up to 5 years. The incidence of high aminotransferases was 31 per 1000 person-years (71 events). A significant interaction occurred between age and sex in the development of high aminotransferases. In subjects younger than age 40 years, male sex (hazard ratio [HR]: 4.6), elevated body mass index (HR: 2.1), hypertension (HR: 2.6), and low high-density lipoprotein cholesterol (HR: 2.8) increased the risk of high aminotransferases, whereas age (HR: 0.6 for each 5 years) decreased the risk. In subjects older than age 40 years, glucose intolerance (HR: 5.3) was the only significant risk factor. In the subcohort, weight gain preceded high aminotransferases and other insulin resistance-related features, which appeared sequentially in order of low high-density lipoprotein cholesterol, hypertriglyceridemia/hypertransaminasemia/hypertension, and glucose intolerance. In conclusion, this cohort study clearly showed chronological ordering and an association between development of elevated aminotransferases and risk factors of NAFLD.

Adult↗
PubMed2005

Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial.

Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a double-blinded, randomized, placebo-controlled trial. Patients with a PBC and BMD t score of less than -1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement (P = .005) in spine BMD was observed in the alendronate group (0.09 +/- 0.03 g/cm2 SD from baseline) compared with the placebo group (-0.003 +/- 0.02 g/cm2 SD from baseline). A larger improvement (P = .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups. In conclusion, in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety.

Aged↗
PubMed2005

The value of serum CA 19-9 in predicting cholangiocarcinomas in patients with primary sclerosing cholangitis.

CA 19-9 has been used with questionable accuracy to aid diagnosis of cholangiocarcinoma complicating primary sclerosing cholangitis. We aimed to characterize the test properties of CA 19-9 and of a change in CA 19-9 over time in predicting cholangiocarcinoma. Charts of 208 patients were reviewed. Fourteen patients had cholangiocarcinoma. Median CA 19-9 was higher with cholangiocarcinoma (15 vs. 290 U/ml, p < 0.0001). A cutoff of 129 U/ml provided: sensitivity 78.6%, specificity 98.5%, adjusted positive predictive value 56.6% and negative predictive value 99.4%. The median change over time was 664 U/ml in cholangiocarcinoma compared to 6.7 U/ml in primary sclerosing cholangitis alone (p < 0.0001). A cutoff of 63.2 U/ml for change in CA 19-9 provided: sensitivity 90%, specificity 98% and positive predictive value 42%. Only 2 patients with cholangiocarcinoma were the candidates for curative therapy. In conclusion, the positive predictive value of an elevated CA 19-9 was 56.6%; only advanced cases were detected by this method.

Bile Duct Neoplasms↗
PubMed2005

The histological course of nonalcoholic fatty liver disease: a longitudinal study of 103 patients with sequential liver biopsies.

BACKGROUND/AIMS: The histological course of nonalcoholic fatty liver disease (NAFLD) remains undescribed. Therefore, we examined the liver histology of NAFLD patients who had undergone sequential liver biopsies. METHODS: Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. RESULTS: Mean interval between biopsies was 3.2+/-3.0 years (range 0.7-21.3). Fibrosis stage apparently progressed in 37%, remained stable in 34% and regressed in 29%. Severity of steatosis, inflammation, hepatocyte ballooning and Mallory's hyaline improved significantly. Aminotransferases decreased significantly between biopsies, paralleling improvement in steatosis and inflammatory features but not fibrosis stage. The rate of fibrosis change ranged from -2.05 to 1.7 stages/year. By multivariate analysis, diabetes (P = 0.007) and low initial fibrosis stage (P < 0.001) were associated with higher rate of fibrosis progression, as was higher body mass index (P = 0.008) when cirrhotics were excluded. CONCLUSIONS: Fibrosis in NAFLD progresses slowly over time with considerable variability in the rate of changes among patients. Changes of aminotransferases do not parallel changes in fibrosis stage. Diabetic patients with elevated BMI and low fibrosis stage are at risk for higher rates of fibrosis progression.

Adult↗
PubMed2005

Hepatic stellate cells and fibrosis progression in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Many patients with nonalcoholic fatty liver disease (NAFLD) have a benign clinical course, but a subgroup of patients progress to advanced fibrosis and cirrhosis. However, there are no available clinical tools to predict fibrosis progression in this population. Activated hepatic stellate cells (HSCs) are the source of collagen deposition in the liver. We aimed at determining whether an HSC activation score predicts fibrosis progression in NAFLD patients. METHODS: The cohort consisted of 39 untreated patients with NAFLD with paired liver biopsies performed 5-59 months apart (mean, 22 months). Patients were divided into 2 groups on the basis of whether fibrosis progression was noted on their second liver biopsy. Liver tissue was immunostained for alpha-smooth muscle actin, and the HSC score was determined independently by 2 pathologists in the NAFLD population and in control subjects without liver disease. RESULTS: The HSC activation score was significantly increased in patients with fibrosis progression versus patients in whom no fibrosis progression was observed (4.8 +/- 0.5 vs 1.8 +/- 0.6, respectively; P < .001). The HSC score was accurate in predicting fibrosis progression, with a positive predictive value of 90%, specificity of 94%, and an area under the receiver operating characteristic curve of 0.82. However, the negative predictive value and sensitivity were 56% and 41%, respectively. The inter-pathologist agreement for the HSC score was excellent (kappa coefficient, 0.95). CONCLUSIONS: These findings suggest that the HSC activation score is a suitable clinical tool to determine the risk of fibrosis progression in patients with NAFLD.

Adult↗
PubMed2005

The natural history of nonalcoholic fatty liver disease: a population-based cohort study.

BACKGROUND & AIMS: The natural history of nonalcoholic fatty liver disease (NAFLD) in the community remains unknown. We sought to determine survival and liver-related morbidity among community-based NAFLD patients. METHODS: Four hundred twenty patients diagnosed with NAFLD in Olmsted County, Minnesota, between 1980 and 2000 were identified using the resources of the Rochester Epidemiology Project. Medical records were reviewed to confirm diagnosis and determine outcomes up to 2003. Overall survival was compared with the general Minnesota population of the same age and sex. RESULTS: Mean (SD) age at diagnosis was 49 (15) years; 231 (49%) were male. Mean follow-up was 7.6 (4.0) years (range, 0.1-23.5) culminating in 3192 person-years follow-up. Overall, 53 of 420 (12.6%) patients died. Survival was lower than the expected survival for the general population (standardized mortality ratio, 1.34; 95% CI, 1.003-1.76; P = .03). Higher mortality was associated with age (hazard ratio per decade, 2.2; 95% CI, 1.7-2.7), impaired fasting glucose (hazard ratio, 2.6; 95% CI, 1.3-5.2), and cirrhosis (hazard ratio, 3.1, 95% CI, 1.2-7.8). Liver disease was the third leading cause of death (as compared with the thirteenth leading cause of death in the general Minnesota population), occurring in 7 (1.7%) subjects. Twenty-one (5%) patients were diagnosed with cirrhosis, and 13 (3.1%) developed liver-related complications, including 1 requiring transplantation and 2 developing hepatocellular carcinoma. CONCLUSIONS: Mortality among community-diagnosed NAFLD patients is higher than the general population and is associated with older age, impaired fasting glucose, and cirrhosis. Liver-related death is a leading cause of mortality, although the absolute risk is low.

Adult↗
PubMed2005

Raloxifene improves bone mass in osteopenic women with primary biliary cirrhosis: results of a pilot study.

BACKGROUND/AIMS: Bone disease is common in patients with primary biliary cirrhosis (PBC). Our aim was to evaluate safety and efficacy of raloxifene in this population. METHODS: Nine postmenopausal women with PBC were enrolled and seven completed the study. Subjects received raloxifene 60 mg daily for 1 year. Each patient on raloxifene was age-matched to three controls. Liver biochemistries were monitored periodically; bone mineral density (BMD) of the lumbar spine (LS) and femoral neck (FN) was measured at baseline and at 1 year. RESULTS: No significant adverse effects were reported. Liver biochemistries remained unchanged. Baseline LS-BMD was similar in the treatment group and controls [median 0.720 g/cm(2) (range 0.620-0.867) vs. 0.740 g/cm(2) (0.570-1.040), P=0.5]. CONCLUSION: Compared with baseline, LS-BMD improved significantly with 1 year of therapy [0.72 g/cm(2) (0.62-0.87) vs. 0.74 g/cm(2) (0.63-0.97), P=0.02]. FN-BMD remained stable [0.53 g/cm(2) (0.50-0.60) vs. 0.54 g/cm(2) (0.49-0.63), P=0.6]. Improvement in LS BMD was seen in patients on raloxifene but not in matched controls [0.02 g/cm(2) (0.01-0.10) vs. 0.00 g/cm(2) (-0.120-0.040), P=0.06)]. In conclusion, raloxifene appears safe and of benefit in preventing bone loss in patients with PBC. Larger studies with longer follow-up are warranted.

Administration, Oral↗