Search PubMed⌕ Search

Biomedical subjects

K D Lindor

Publications and source records attributed to K D Lindor.

At least 55 records · Page 3Linked to original sources
PubMed2000

A pilot study of pentoxifylline for the treatment of primary sclerosing cholangitis.

OBJECTIVE: There is no effective therapy for patients with primary sclerosing cholangitis (PSC). Rats with experimental small bowel bacterial overgrowth develop hepatobiliary injury similar to PSC. The hepatobiliary injury results from peptidoglycan-polysaccharide-mediated activation of Kupffer cells, release of cytokines such as tumor necrosis factor (TNF-alpha), and is prevented by pentoxifylline. Our aims were to assess the safety and effects of pentoxifylline on symptoms and biochemical liver tests in patients with PSC. METHODS: A total of 20 patients with clinical, cholangiographic, and histological features of PSC of varying severity were treated with pentoxifylline sustained release (SR) tablets (400 mg q.i.d.) for < or = 1 yr. Serum alkaline phosphatase, aspartate aminotransferase, and bilirubin were monitored every 3 months for 1 year; serum TNF-alpha and TNF receptor subtypes I and II were assessed at baseline and 1 year. RESULTS: Of 20 patients, 16 tolerated pentoxifylline and completed the study. Two patients were withdrawn because of severe nausea, and two patients were noncompliant with medication and withdrew. Pentoxifylline did not significantly alter symptoms of fatigue or pruritus, serum liver tests, serum TNF-alpha or TNF receptor levels. CONCLUSIONS: In the current regimen, pentoxifylline alone does not significantly improve symptoms or liver tests in patients with PSC.

Administration, Oral↗
PubMed2000

An assessment of the role of liver biopsies in asymptomatic patients with chronic liver test abnormalities.

OBJECTIVE: The role of liver biopsy in the management of patients with nonspecific chronic liver enzyme abnormalities is not well established. The aim of this study is to determine whether liver histology changes the clinical impression formed before liver biopsy and the preliminary management plan. METHODS: Consenting asymptomatic adult patients with persistent (> or = 6 months) liver test abnormalities were enrolled. Patients with a strong suspicion for a specific liver disease were excluded. A presumptive diagnosis and a preliminary management plan were documented before a liver biopsy. After the liver biopsy, the patients were reassessed to determine the effect of the biopsy on the diagnosis and management plan. RESULTS: A total of 36 patients were enrolled: 15 men and 21 women, with a median age of 51 yr. The prebiopsy diagnoses were nonalcoholic steatohepatitis (24), autoimmune hepatitis (3), primary biliary cirrhosis (2), primary sclerosing cholangitis (2), and miscellaneous (5 patients). The liver biopsy changed the diagnosis in 14% of cases. Lifestyle recommendations were not significantly altered by the biopsy. The liver biopsy affected the frequency of liver test monitoring in 13 patients (36%). Treatment recommendations were affected in 12 cases, 10 of whom were offered investigational therapy. CONCLUSIONS: Although a liver biopsy may help to definitively establish the final diagnosis in patients, the results alter the presumptive prebiopsy diagnosis infrequently, and no proven therapy exists for the vast majority of these patients. Therefore, the risks and benefits of a liver biopsy should be carefully weighed, especially in settings in which investigational therapies are unavailable.

Biopsy↗
PubMed2000

Medical management of chronic cholestatic liver diseases.

The purpose of the present review is to discuss the diagnosis and management of cholestatic liver diseases. Differential diagnoses to consider are described, including causes of extrahepatic biliary obstruction such as gallstones, strictures, extrabiliary malignancies and pancreatitis. In addition, diseases that cause intrahepatic cholestasis such as primary biliary cirrhosis, primary sclerosing cholangitis, hepatocellular diseases and a variety of miscellaneous causes including drugs that may cause cholestasis are discussed. Primary biliary cirrhosis and primary sclerosing cholangitis are reviewed in detail, and management options are identified. The prognosis of patients with these diseases is discussed, and the Mayo Mathematical Models in Cholestatic Liver Disease for both primary biliary cirrhosis and primary sclerosing cholangitis are provided. Finally, management options for the complications of cholestasis are provided.

Cholestasis↗
PubMed2000

A revised natural history model for primary sclerosing cholangitis.

OBJECTIVE: To describe a natural history model for primary sclerosing cholangitis (PSC) that is based on routine clinical findings and test results and eliminates the need for liver biopsy. PATIENTS AND METHODS: Using the Cox proportional hazards analysis, we created a survival model based on 405 patients with PSC from 5 clinical centers. Independent validation of the model was undertaken by applying it to 124 patients who were not included in the model creation. RESULTS: Based on the multivariate analysis of 405 patients, a risk score was defined by the following formula: R = 0.03 (age [y]) + 0.54 loge (bilirubin [mg/dL]) + 0.54 loge (aspartate aminotransferase [U/L]) + 1.24 (variceal bleeding [0/1]) - 0.84 (albumin [g/dL]). The risk score was used to obtain survival estimates up to 4 years of follow-up. Application of this model to an independent group of 124 patients showed good correlation between estimated and actual survival. CONCLUSIONS: A new model to estimate patient survival in PSC includes more reproducible variables (age, bilirubin, albumin, aspartate aminotransferase, and history of variceal bleeding), has accuracy comparable to previous models, and obviates the need for a liver biopsy.

Adult↗
PubMed1999

Cost-effectiveness of ursodeoxycholic acid therapy in primary biliary cirrhosis.

Ursodeoxycholic acid (UDCA) is a safe and effective treatment for patients with primary biliary cirrhosis (PBC), but the cost of this drug has raised concerns regarding cost-effectiveness. The aim of our study was to determine the cost-effectiveness of UDCA in PBC. We compared the costs and outcomes of managing PBC patients with and without UDCA. From two previously published trials, the effectiveness of UDCA was determined by comparing the annual reduction in the development of ascites, varices, variceal bleeding, encephalopathy, liver transplantation, and death between the treatment groups. Average annual costs for each of these events were estimated based on literature and institutional data. Approximately twice as many major events occurred in the placebo group compared with the UDCA group. The relative risk (RR) of liver transplantation (1.95; 95% CI: 1.14-3.68) and development of esophageal varices (3. 11; 95% CI: 1.57-10.65) were significantly higher in the placebo group compared with the UDCA group. There were no significant increases in the RR of ascites, variceal bleeding, encephalopathy, or death between the two groups. Based on the estimated annual cost of managing these events and the annual costs of UDCA ($2,500), there was an annual cost savings per patient of $1,372. Compared with the placebo group, patients receiving UDCA had a lower incidence of major complications and lower medical care costs.

Canada↗
PubMed1999

Clinical significance of serum bilirubin levels under ursodeoxycholic acid therapy in patients with primary biliary cirrhosis.

We determined whether the normalization of serum bilirubin level (SBL) induced by ursodeoxycholic acid (UDCA) therapy was associated with an improved clinical outcome in patients with primary biliary cirrhosis (PBC). We estimated the prognostic values of SBL measured after 6 months of UDCA treatment for survival free of orthotopic liver transplantation (OLT). We used a database of 548 patients with PBC followed in three trials of UDCA. Among UDCA-treated patients, we compared survival free of OLT in patients with normalized SBL (</=17 micromol/L) with those who had persistently elevated SBL. Difference in survival was tested between UDCA-treated patients whose SBL normalized with treatment and placebo patients who had normal baseline SBL. We evaluated, in each treatment group, the prognostic value of 6-month SBL. Survival was estimated using the Kaplan-Meier method and compared by the Cox model. Survival free of OLT was significantly longer in patients who had normalized SBL (P <. 0001; relative risk [RR]: 3.7, UDCA group). Survival free of OLT was not significantly different between UDCA patients with normalized SBL and placebo patients with a normal baseline SBL (P =.69). For several cutoffs of 6-month SBL, RRs of OLT or death were similar in UDCA-treated and placebo patients: the RR of OLT or death associated with a 6-month SBL more than 30 micromol/L was 6.0 for UDCA and 5.7 for placebo groups. In conclusion, normalization of SBL during therapy is associated with improved clinical outcome. SBL under UDCA therapy is a prognostic factor in PBC. SBL under UDCA therapy should be interpreted as in untreated patients.

Bilirubin↗
PubMed1999

Long-term ursodeoxycholic acid delays histological progression in primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a progressive cholestatic liver disease frequently leading to development of cirrhosis and its complications. Ursodeoxycholic acid (UDCA) is a beneficial medical therapy for patients with PBC. Improvement in some histological features, but not in histological stage, has been reported after 2 years of UDCA therapy. Thus, longer follow-up may be necessary to determine whether UDCA has a favorable effect on histological stage of disease and progression to cirrhosis. Our aim was to determine the long-term effects of UDCA therapy on histological stage and progression to cirrhosis in patients with PBC. Sixteen unselected patients with noncirrhotic PBC who had been on long-term UDCA therapy (13-15 mg/kg/d) for 6.6 +/- 0.4 years (range, 5-9 years) were identified and their histological finding during treatment compared with that of 51 noncirrhotic patients with PBC who had received ineffective therapy (D-penicillamine [DPCA] or placebo) for 5.6 +/- 0.07 years (range, 5-8 years). Histological stage was determined using the Ludwig classification. The rate of progression to cirrhosis (stage 4) was significantly less in the UDCA group than in the control group (13% vs. 49%; P =.009). Although the overall rate of progression of histological stage was less in the UDCA group than in the control group (50% vs. 71%), this difference was not significant (P =.1). A marked improvement in liver biochemistries and Mayo risk score was noted in all patients during UDCA therapy; however, this improvement was not significantly different between patients who progressed and those who did not. In conclusion, long-term UDCA therapy appeared to delay the development of cirrhosis in PBC.

Adult↗
PubMed1999

Incidence of cancer in primary biliary cirrhosis: the Mayo experience.

Patients with primary biliary cirrhosis (PBC) may be at increased risk for malignancies. Several studies have addressed the risk of specific malignancies; however, there is little information about overall incidences of malignancies in these patients. We hypothesize that these patients may be at an increased risk for cancer. We performed a retrospective chart review evaluating patients with the diagnosis of PBC and malignancies. We reviewed records of patients with PBC presenting to the Mayo Clinic between 1976 and 1985. The diagnosis of PBC was made using evidence of cholestasis, positive antimitochondrial antibody titers and liver biopsy findings consistent with PBC. The incidence of malignancies were then compared with published data by the Surveillance, Epidemiology and End Results (SEER) program of the National Cancer Institute. Of the 1,692 patients with PBC in the Mayo Clinic data base, 114 patients were identified with primary cancer. The number of malignancies was higher than would be anticipated by chance alone; with 93 observed versus 62.4 expected events (P <.001). Hepatobiliary malignancies had a relative risk of 46 (P <.0001) for women and 55 (P <.0001) in men. There was a dramatic increased risk for development of hepatobiliary malignancies. PBC patients might benefit from more aggressive surveillance for hepatobiliary malignancies during their lifetime.

Adolescent↗
PubMed1999

The relative role of the Child-Pugh classification and the Mayo natural history model in the assessment of survival in patients with primary sclerosing cholangitis.

The Child-Pugh classification is a simple, convenient prognostic measure in patients with liver cirrhosis. We investigated the relative role of the Child-Pugh classification and the Mayo model in the assessment of survival in patients with primary sclerosing cholangitis (PSC). Of the 173 patients described in the original Mayo PSC natural history model, 147 patients had sufficient information in the medical record to allow computation of the Child-Pugh score. We used our most recent modification of the Mayo model to compute the risk score, based on patient's age, serum levels of bilirubin, albumin, and aspartate aminotransferase and history of variceal bleeding. Using the risk score (R), patients were divided into the low- (R < 0), intermediate- (0 </= R < 2), and high-risk (R >/= 2) groups. Kaplan-Meier estimates and proportional hazards analysis were used to evaluate the two prognostic models. Although there was a statistically significant correlation between the Child-Pugh and Mayo risk scores, two-thirds of the patients had a Child-Pugh score of 5 or 6 and a relatively wide range of risk scores (-1.1-4.3). The probability of survival for 7 years in patients in the low-, intermediate-, and high-risk groups was 92%, 74%, and 40% for Child-Pugh class A (n = 96) and 100%, 62%, and 28% for Child-Pugh class B patients (n = 44), respectively. There were only a small number (n = 7) of Child-Pugh class C patients. In our age-adjusted multivariate analysis, each unit increase in the Mayo risk score was associated with a 2.5-fold increase in the risk of death (95% confidence interval: 1.8-3.4, P <.01), whereas Child-Pugh classification had no significant impact on survival (Child-Pugh B vs. A: risk ratio = 1.1 [95% confidence interval: 0.6-2.0]; Child-Pugh C versus A: risk ratio = 0.6 [95% confidence interval: 0. 2-1.8]). In contrast to the Child-Pugh classification, which was developed for advanced liver cirrhosis, the Mayo model provides valid survival information, particularly in patients early in the course of PSC.

Adult↗
PubMed1999

Ursodeoxycholic acid inhibits eosinophil degranulation in patients with primary biliary cirrhosis.

Eosinophilia is a distinctive feature of primary biliary cirrhosis (PBC), especially in its early stages. Intriguingly, treatment with ursodeoxycholic acid (UDCA) ameliorates eosinophilia as well as liver tests in patients with PBC. It remains unknown, however, whether eosinophils in PBC patients are functionally activated and whether UDCA inhibits eosinophil activation. In the present study, we systematically examined eosinophil dynamics in the blood and liver in patients with stage I to II PBC before and after UDCA treatment. We determined serum concentrations of eosinophil granule proteins (major basic protein [MBP] and eosinophil-derived neurotoxin [EDN]) by radioimmunoassay and quantitated eosinophil degranulation using computer-assisted morphometry after MBP immunohistochemistry. Before UDCA treatment, patients with PBC (n = 25) showed significantly higher circulating eosinophil counts (P <. 05) and serum concentrations of MBP (P <.0005) and EDN (P <.02) compared with patients with chronic viral hepatitis (n = 22), autoimmune hepatitis (n = 10), and obstructive jaundice (n = 12). Four-week UDCA treatment significantly reduced blood eosinophil counts (P <.0001) and serum MBP (P <.0001) and EDN (P <.0001) levels in PBC patients. MBP immunohistochemistry and computer-assisted quantitative morphometry showed infiltration and degranulation of eosinophils in the portal tract in patients with PBC and significant reductions in the number of sites and the area occupied by extracellular MBP deposits after UDCA treatment for 2 years (P <.02) but not in placebo-treated patients. Our results suggest that eosinophils in patients with PBC are not only increased in number, but also release granule proteins, and that UDCA treatment inhibits this eosinophil activation/degranulation.

Blood Proteins↗
PubMed1999

Ursodeoxycholic acid as adjunctive therapy for problematic type 1 autoimmune hepatitis: a randomized placebo-controlled treatment trial.

To evaluate the efficacy of ursodeoxycholic acid as adjunctive therapy in type 1 autoimmune hepatitis, 37 patients who had experienced treatment failure, repeated relapse, or incomplete response were randomized to ursodeoxycholic acid (13-15 mg/kg daily) or placebo for 6 months in addition to their usual corticosteroid schedule. Serum aspartate transaminase (70% vs. 31%, P =.04) and alkaline phosphatase (47% vs. 7%, P =.02) levels improved more commonly in the 21 patients randomized to ursodeoxycholic acid. Mean serum levels, however, were similar before and after the treatment period. The frequency of dose reduction or corticosteroid withdrawal was comparable in both groups (29% versus 31%, P >.9), and clinical improvement (48% vs. 44%, P >.9) or its absence (52% vs. 56%, P >.9) occurred as commonly in patients receiving ursodeoxycholic acid or placebo. The modified histological activity score (3.5 +/- 0.8 vs. 3. 5 +/- 0.9) and the modified fibrosis score (2.4 +/- 0.4 vs. 2.4 +/- 0.4) were similar before and after treatment with ursodeoxycholic acid and no different than after placebo therapy. We conclude that ursodeoxycholic acid can improve certain laboratory tests in problematic patients with type 1 autoimmune hepatitis when administered adjunctively for 6 months. Short-term therapy, however, does not facilitate reduction in the dose of corticosteroids or its withdrawal, affect clinical outcome, or reduce histological activity.

Adult↗
PubMed1999

Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) may present with increased hepatic fibrosis progressing to end-stage liver disease. No factors that determine increasing fibrosis and histologically advanced disease have been recognized, thus, liver biopsy is recommended in all patients for diagnosis and prognosis. Our aim was to identify independent predictors of severe hepatic fibrosis in patients with NASH. One hundred and forty-four patients were studied. All patients underwent liver biopsy. Clinical and biochemical variables were examined with univariate and multivariate analysis. Thirty-seven (26%) patients had no abnormal fibrosis, 53 (37%) had mild fibrosis, 15 (10%) had moderate fibrosis, 14 (10%) had bridging fibrosis, and 25 (17%) had cirrhosis. In multivariate analysis, older age (P =. 001), obesity (P =.002), diabetes mellitus (P =.009), and aspartate transaminase/alanine transaminase (AST/ALT) ratio greater than 1 (P =.03) were significant predictors of severe liver fibrosis (bridging/cirrhosis). Body mass index (P =.003) was the only independent predictor of the degree of fat infiltration. Increased transferrin saturation correlated positively with the severity of fibrosis (P =.02) in univariate analysis, and there was a trend for more female patients among those with more advanced fibrosis (P =. 09). However, iron studies or gender were not significant when controlled for age, obesity, diabetes, and AST/ALT ratio. In conclusion, older age, obesity, and presence of diabetes mellitus help identify those NASH patients who might have severe liver fibrosis. This is the subgroup of patients with NASH who would be expected to derive the most benefit from having a liver biopsy and considering investigational therapies.

Adolescent↗
PubMed1999

Effect of pretransplantation ursodeoxycholic acid therapy on the outcome of liver transplantation in patients with primary biliary cirrhosis.

As ursodeoxycholic acid (UDCA) delays the need for transplantation, this could result in patients with more comorbid disease, therefore more likely to have a worse outcome posttransplantation. The aim of this study is to compare posttransplantation outcome in patients who received UDCA versus placebo who subsequently required a liver transplant. Data on all trial patients referred for transplantation were retrospectively collected from three randomized controlled trials of UDCA in patients with primary biliary cirrhosis (PBC). An intent-to-treat analysis was conducted with patients assigned to their original treatment allocation. UDCA and placebo groups were compared at trial entry, transplant referral, just before transplantation, and 1 month and 1 year posttransplantation. From 1987 to 1996, 37 UDCA-treated and 53 placebo patients were referred for transplantation; their age, sex, and serum bilirubin levels were similar at study entry. Immediately before transplantation, these two groups were again similar with respect to age, bilirubin level, Mayo risk score, and serum creatinine level. Posttransplantation survival rates at 1 month were 93.9% in the UDCA group and 88.4% in the placebo group, and 1 year survival rates were 90.3% and 78.4%, respectively (not significant). Posttransplantation, the two groups had similar rates of infection (53.9% v 58%); however, rejection occurred significantly less often in the UDCA group; 42.9% versus 68. 8% in the placebo group (P =.04). The posttransplantation outcome of UDCA-treated patients with PBC is no different from those who were administered placebo. There is no evidence to suggest the beneficial effect of UDCA in delaying the need for transplantation is associated with a worse outcome once liver transplantation becomes necessary.

Age Factors↗
PubMed1999

Unsedated small-caliber esophagogastroduodenoscopy (EGD) versus conventional EGD: a comparative study.

BACKGROUND & AIMS: Significant portions of the cost and complications of esophagogastroduodenoscopy (EGD) are related to sedation. This study aimed to assess the feasibility, acceptability, and accuracy of unsedated small-caliber transoral EGD (sc-EGD). METHODS: A 4-phase study was performed in healthy volunteers and patients. Phases 1 and 2 involved assessment of the technical feasibility of sedated sc-EGD and the tolerability of unsedated sc-EGD, respectively, in volunteers. Subsequently, the technical feasibility, tolerability, and diagnostic accuracy of sedated and unsedated sc-EGD were determined by having each patient undergo sc-EGD (Pentax EG-1840) with (phase 3) and without (phase 4) sedation, followed by sedated conventional EGD (c-EGD) (Olympus GIF-100 or GIF-Q140) by a staff endoscopist blinded to the findings of the sc-EGD. The t test for paired samples was used for statistical analysis. A P value of <0.05 was considered significant. RESULTS: Sedated and unsedated sc-EGD were technically feasible and tolerable in all volunteers. In patients, compared with sedated c-EGD, sedated and unsedated sc-EGD were 96% and 97% accurate, respectively. The overall acceptability of unsedated sc-EGD was only slightly worse than that of sedated c-EGD (median, 2 vs. 1 on a scale of 1-10). After unsedated sc-EGD, 98% of patients expressed willingness to undergo the procedure again. No complications were observed during any phase of the study. CONCLUSIONS: Unsedated sc-EGD is technically feasible, tolerable, and accurate. It can potentially decrease the costs and complications of sedated conventional EGD.

Adult↗
PubMed1999

A randomized prospective study comparing rigid to balloon dilators for benign esophageal strictures and rings.

BACKGROUND: The optimum choice of dilator (rigid vs. balloon) for benign esophageal strictures has not been well studied. The aim of this study was to compare the immediate relief of dysphagia and the incidence of repeat dilatation within the first year with the use of either a rigid (Savary) dilator or balloon dilator for benign lower esophageal strictures. METHODS: Patients with dysphagia found to have benign esophageal strictures during endoscopy were randomized to undergo dilation with a rigid (Savary) or a balloon dilator (Microvasive or Bard). The 1-year incidence of repeat dilatation was estimated by the Kaplan-Meier method. RESULTS: A total of 251 subjects were stratified at entry according to the type of stricture (peptic vs. Schatzki ring) and severity of stricture (mild vs. moderate/severe) and then randomized to either a Savary (n = 88), Microvasive (n = 81), or Bard (n = 82) dilator. There were no significant differences between the rigid dilator or the two balloons with regard to immediate relief of dysphagia or the need for repeat dilatation at one year. Patients with moderate/severe strictures required repeat dilatation at one year twice as often as those with mild strictures. There were no significant complications reported in these patients. CONCLUSIONS: Both rigid and balloon dilators are equally effective and safe in the treatment of benign lower esophageal strictures caused by acid reflux and Schatzki rings.

Aged↗