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. Data on 103 patients w...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. Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. 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. 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.展开更多
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- ...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.展开更多
Background&Aims: Despite evidence for therapeutic efficacy with ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC), only 30-50%of patients achieve complete biochemical remission within 1 year of therap...Background&Aims: Despite evidence for therapeutic efficacy with ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC), only 30-50%of patients achieve complete biochemical remission within 1 year of therapy. Mycophenolate mofetil (MMF) is an immunosuppressive medication that inhibits T and B lymphocyte proliferation. The aim of this investigation was to determine the safety and estimated efficacy of MMF in patients with PBC. Methods: Twenty-five patients with incomplete responses to UDCA (defined as persistent elevation of serum alkaline phosphatase ≥2 times the upper limit of normal) received MMF 1 g daily to a maximum of 3 g daily with UDCA (13-15 mg/kg per day) for 1 year. Liver biochemistries were determined at 3-month intervals with Mayo Risk Score calculated at baseline and end of therapy. Results: Nineteen (76%) patients completed 1 year of therapy. Despite improvements in serum alkaline phosphatase (920 ±308 vs. 709 ±242 IU/L, P = 0.001) and AST (65 ±31 vs. 51 ±19 IU/L, P = 0.007) levels, these findings were clinically insignificant. Exploratory analysis revealed a strong correlation between advanced PBC defined by higher Mayo Risk Score and reduction in serum alkaline phosphatase levels (r = -0.74, P = 0.006). Six patients (24%) did not complete therapy; adverse drug events were responsible for study withdrawal in 3 individuals. Adverse reactions that resolved spontaneously or by dose reduction occurred in 13 patients. Conclusions: MMF is not associated with important clinical benefits in PBC based on the results of this pilot investigation.展开更多
Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease ...Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD) remains undefined. We aimed at determining the relation between leptin and liver fibrosis in human NAFLD. Human plasma leptin and several indicators of insulin resistance were measured in 88 NAFLD patients and matched controls. Leptin levels were significantly greater in patients with more advanced fibrosis (P=0.005). By multivariate analysis, the significant association between leptin and fibrosis was abolished (adjusted P=0.3) when controlling for confounders including age, gender, BMI, diabetes and insulin resistance. Only age (adjusted P=0.006) and insulin sensitivity (adjusted P=0.04) correlated significantly with fibrosis stage. A second liver biopsy was performed in 39 out of the 88 patients at 27.9±16 months. Leptin levels were not significantly different between patients who had fibrosis progression (n=10) and those who did not (n=29). In human NAFLD, no relationship between leptin levels and fibrosis stage was demonstrated. The correlation of leptin and fibrosis severity seems to be an indicator of the factors that determine leptin production.展开更多
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, weigh...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 1,537 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 1,000 personyears (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 die subcohort, weight gain preceded high aminotransferases and other insulin resistancerelated 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.展开更多
文摘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. Data on 103 patients who underwent serial liver biopsies in the absence of effective treatment were reviewed, and biopsies scored in a blind fashion. 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. 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.
文摘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.
文摘Background&Aims: Despite evidence for therapeutic efficacy with ursodeoxycholic acid (UDCA) in primary biliary cirrhosis (PBC), only 30-50%of patients achieve complete biochemical remission within 1 year of therapy. Mycophenolate mofetil (MMF) is an immunosuppressive medication that inhibits T and B lymphocyte proliferation. The aim of this investigation was to determine the safety and estimated efficacy of MMF in patients with PBC. Methods: Twenty-five patients with incomplete responses to UDCA (defined as persistent elevation of serum alkaline phosphatase ≥2 times the upper limit of normal) received MMF 1 g daily to a maximum of 3 g daily with UDCA (13-15 mg/kg per day) for 1 year. Liver biochemistries were determined at 3-month intervals with Mayo Risk Score calculated at baseline and end of therapy. Results: Nineteen (76%) patients completed 1 year of therapy. Despite improvements in serum alkaline phosphatase (920 ±308 vs. 709 ±242 IU/L, P = 0.001) and AST (65 ±31 vs. 51 ±19 IU/L, P = 0.007) levels, these findings were clinically insignificant. Exploratory analysis revealed a strong correlation between advanced PBC defined by higher Mayo Risk Score and reduction in serum alkaline phosphatase levels (r = -0.74, P = 0.006). Six patients (24%) did not complete therapy; adverse drug events were responsible for study withdrawal in 3 individuals. Adverse reactions that resolved spontaneously or by dose reduction occurred in 13 patients. Conclusions: MMF is not associated with important clinical benefits in PBC based on the results of this pilot investigation.
文摘Data from animal models of fibrosis and fatty liver suggest that leptin may mediate the profibrogenic responses in the liver, but the association of leptin and liver fibrosis in human nonalcoholic fatty liver disease (NAFLD) remains undefined. We aimed at determining the relation between leptin and liver fibrosis in human NAFLD. Human plasma leptin and several indicators of insulin resistance were measured in 88 NAFLD patients and matched controls. Leptin levels were significantly greater in patients with more advanced fibrosis (P=0.005). By multivariate analysis, the significant association between leptin and fibrosis was abolished (adjusted P=0.3) when controlling for confounders including age, gender, BMI, diabetes and insulin resistance. Only age (adjusted P=0.006) and insulin sensitivity (adjusted P=0.04) correlated significantly with fibrosis stage. A second liver biopsy was performed in 39 out of the 88 patients at 27.9±16 months. Leptin levels were not significantly different between patients who had fibrosis progression (n=10) and those who did not (n=29). In human NAFLD, no relationship between leptin levels and fibrosis stage was demonstrated. The correlation of leptin and fibrosis severity seems to be an indicator of the factors that determine leptin production.
文摘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 1,537 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 1,000 personyears (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 die subcohort, weight gain preceded high aminotransferases and other insulin resistancerelated 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.
