Biomedical subjects

E R Dickson

Publications and source records attributed to E R Dickson.

At least 73 records · Page 4Linked to original sources

PubMed1995

Bone disease in primary biliary cirrhosis: does ursodeoxycholic acid make a difference?

Ursodeoxycholic acid (UDCA) has been proposed as beneficial therapy for patients with primary biliary cirrhosis (PBC). The effects of UDCA on metabolic bone disease, a major source of morbidity in patients with PBC, are essentially unknown. Preliminary information suggests that UDCA may improve biochemical indices of bone disease, although information about the effects of UDCA on bone density is lacking. In this study, we describe the effects of UDCA on lumbar spine bone mineral densities over a 3-year period during which patients were enrolled in a randomized, double-blind, therapeutic trial of UDCA for the treatment of PBC. Lumbar spine dual-photon densitometry was measured at entry and annually. Eighty-eight patients, 50 in the UDCA group and 38 in the placebo group, had serial measurements available for up to 3 years. There was no statistical difference between the two treatment groups at entry with respect to histological stage, total bilirubin, age, use of calcium supplement, vitamin D levels, or estrogen. After 3 years of treatment, there was no significant difference in the lumbar spine bone densitometry measurements between the UDCA-treated and placebo groups. We conclude that, after 3 years of treatment, UDCA is not associated with statistically significant differences in the rate of bone loss from the lumbar spine in patients when compared with placebo despite beneficial effects of treatment on the underlying liver disease. Further efforts to define effective treatments for the bone disease need to be pursued.

Adult↗

PubMed1995

Antimitochondrial antibody-negative primary biliary cirrhosis.

OBJECTIVES: We reviewed our experience with patients who had biochemical and histological features of primary biliary cirrhosis in the absence of antimitochondrial antibodies (AMA) to better understand this variant of the syndrome. METHODS: During the period between 1976 to 1992, 597 patients with clinical and histological features of primary biliary cirrhosis were seen at the Mayo Clinic. Thirty-five (5.8%) of these patients were negative for antimitochondrial antibody and had normal cholangiographic studies. The records of these patients were reviewed for this study. RESULTS: No difference was found between the two groups with respect to age, gender, or biochemical features. IgM and gamma-globulin levels were higher in the antimitochondrial antibody-positive than the antimitochondrial antibody-negative patients. What is more important, 96% of the AMA-negative patients who could be tested were positive for antinuclear antibody or anti-smooth-muscle antibodies. These tests were positive in only 56% of the antimitochondrial antibody-positive group (p < 0.05). The response of five of these patients to ursodeoxycholic acid appeared comparable to the response seen in antimitochondrial antibody-positive patients. CONCLUSIONS: Patients with histological features of primary biliary cirrhosis, whether antimitochondrial antibody positive or negative, are quite comparable with respect to clinical and biochemical features. Other autoantibodies, such as antinuclear or anti-smooth-muscle antibodies, are more common in the antimitochondrial antibody-negative group. These two conditions might be part of a spectrum that has been termed "autoimmune cholangitis" and that is characterized by chronic cholestasis, histological features of chronic nonsuppurative destructive cholangitis, and the presence of any of a variety of serum autoantibodies.

Antibodies, Antinuclear↗

PubMed1995

Preoperative predictors of resource utilization in liver transplantation.

Orthotopic liver transplantation (OLT) has been shown to be effective in prolonging life and improving its quality in patients with end-stage liver disease. However, it remains one of the most expensive surgical procedures performed today. In an era when economic efficiency and financial accountability are being emphasized, it is imperative to consider resource utilization in evaluating candidates for OLT. We prospectively followed 106 patients who underwent OLT at the Mayo Clinic for primary biliary cirrhosis and primary sclerosing cholangitis between 1990 and 1994. Hospital and professional charges for the initial hospitalization were obtained on all patients. Univariate and multivariate models were constructed using preoperative clinical variables that had been previously found to be important in predicting clinical outcomes. The preoperative variables considered were age, gender, diagnosis of liver disease, Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of albumin, bilirubin, and creatinine, and the presence/absence of ascites, edema, encephalopathy, renal failure (serum creatinine >2.0) and gastrointestinal bleeding. Of the 106 patients, 3 were excluded from the analysis because they received multiple transplants during the initial hospitalization. Of the hospital charges we analyzed, the surgical fee for transplantation and donor acquisition expense were fixed in advance and, therefore, excluded. The following preoperative variables were found to be significant in the univariate analysis: Mayo risk score, Child's score, nutritional status, Karnofsky score, INR, serum levels of bilirubin and creatinine, presence of renal failure, and gastrointestinal bleeding. In the multivariate analyses, Karnofsky score of 40 or less was associated with a 48% increase in total charges. Poor nutritional status and renal failure were associated with a 34% and 31% increase, respectively. We identified 3 preoperative variables as significant independent predictors of resource utilization in liver transplantation. In an effort to maximize the economic efficiency with which liver transplantation is performed, we believe these factors should be taken into consideration in determining both the timing of transplantation and the suitability of potential transplant recipients.

Adult↗

PubMed1994

Ursodeoxycholic acid in the treatment of primary biliary cirrhosis.

BACKGROUND/AIMS: A double-blind, placebo-controlled trial of ursodeoxycholic acid (UDCA) was conducted in 180 patients with primary biliary cirrhosis (PBC) to define the efficacy and safety of UDCA. Efficacy was assessed by time to treatment failure defined as death; liver transplantation; histological progression; development of varices, ascites, or encephalopathy; doubling of total serum bilirubin levels; progression of fatigue or pruritus; drug toxicity; or voluntary withdrawal. METHODS: Patients with well-defined PBC underwent complete history, physical examination, liver chemistries, ultrasonography, upper endoscopy, and liver biopsy at entry as well as at 2 years. Liver chemistries were determined every 3 months. RESULTS: In patients receiving UDCA, treatment failure was delayed compared with the placebo-treated group (P = 0.0003, log rank test). Seven patients receiving UDCA died or required transplantation compared with 12 in the placebo group (P = 0.18). No patients discontinued UDCA because of side effects of toxicity. CONCLUSIONS: UDCA was extraordinarily safe and well tolerated, and its use was associated with delayed progression of the disease as defined in this study. However, the lack of effects on symptoms, histology, and the need for liver transplantation or survival indicate that further evaluation is necessary to determine the ultimate role of UDCA in the treatment of PBC.

Adult↗

PubMed1994

Primary biliary cirrhosis: prediction of short-term survival based on repeated patient visits.

The progression of primary biliary cirrhosis was studied in 312 patients who were seen at the Mayo Clinic between January 1974 and May 1984. Follow-up was extended to April 30, 1988, by which time 140 of the patients had died and 29 had undergone orthotopic liver transplantation. These patients generated 1,945 patient visits that enabled us to study the change in the prognostic variables of primary biliary cirrhosis (age, bilirubin value, albumin value, prothrombin time and edema) from the time of referral. Also, using this database and the Cox proportional-hazards regression model, we developed an updated model for primary biliary cirrhosis that can be used to predict short-term survival at any time in the course of the disease. This model uses the values of the prognostic variables measured at the latest patient visit. Comparison of predicted survival from the update model and the natural history model of primary biliary cirrhosis showed that the updated model was superior to the original model for predicting short-term survival. This finding applied to both the Mayo Clinic patients and an independent set of 83 Dutch patients. The Mayo updated model is recommended for improving the accuracy of predictions of survival during the 2 yr after a patient visit.

Age Factors↗

PubMed1994

Effect of ursodeoxycholic acid on serum lipids of patients with primary biliary cirrhosis.

OBJECTIVE: To study the effects of ursodeoxycholic acid (UDCA) on lipid levels in patients with primary biliary cirrhosis (PBC). DESIGN: A randomized, placebo-controlled prospective trial of UDCA was conducted in 177 well-characterized patients with PBC. MATERIAL AND METHODS: The two treatment groups (placebo and UDCA) were matched at entry with respect to age, sex, histologic stage of PBC, biochemical values, and serum lipid levels. Serum cholesterol, high-density lipoprotein cholesterol, and triglyceride levels were measured at entry, 1 year, and 2 years. RESULTS: The decrease in total cholesterol level at 1 and 2 years in the UDCA-treated group was significant in comparison with that in the placebo group. Serum high-density lipoprotein cholesterol and triglyceride levels, however, were unchanged. No severe side effects from UDCA were noted. The changes in serum cholesterol levels at 2 years were directly and strongly correlated with changes in serum bilirubin concentrations (r = 0.70; P < 0.001) and inversely correlated with initial serum cholesterol levels (r = -0.86; P < 0.00001). CONCLUSION: The cholesterol-lowering effect of UDCA could be related to amelioration of the underlying liver disease or to a direct effect of the drug on the metabolism of cholesterol in patients with hypercholesterolemia.

Adult↗

PubMed1994

Systemic and renal effects of nifedipine in cyclosporine-associated hypertension.

Cyclosporine induces hypertension and wide-spread vasoconstriction after transplantation in addition to reducing kidney function. We studied hemodynamic, renal, and hormonal effects of monotherapy with nifedipine XL (n = 37) in liver transplant recipients within a year after transplant (median, 4.4 months). Systemic hemodynamics were determined with thoracic electrical bioimpedance. Blood pressure before therapy was 172 +/- 4/108 +/- 2 mm Hg. Sixty-four percent of recipients achieved blood pressures less than 140/90 mm Hg mediated by a fall in systemic vascular resistance index (2427 +/- 245 dyne.s.cm-5.m-2 in responders versus 2905 +/- 281 in nonresponders, P < .01). Despite the fall in systemic vascular resistance, glomerular filtration rates were not changed during nifedipine therapy, as measured by both creatinine and iothalamate clearances. Urinary prostacyclin (6-ketoprostaglandin F1 alpha) was suppressed below normal from 2468 +/- 323 ng/d before transplant to 1103 +/- 99 ng/d (P < .01) after transplant and did not change during nifedipine therapy. Urinary thromboxane B2 and plasma renin activity also fell after transplant and remained low during nifedipine. These data demonstrate that nifedipine can reverse systemic vasoconstriction associated with hypertension after transplantation. Systemic effects were not transmitted to the kidney sufficiently to improve glomerular filtration rate or reverse hormonal changes within the kidney. Hence, vascular and functional regulation of the kidney was dissociated from the systemic circulation during nifedipine administration after transplantation.

6-Ketoprostaglandin F1 alpha↗

PubMed1994

Enzyme inhibitory autoantibodies to pyruvate dehydrogenase complex in primary biliary cirrhosis: applications of a semiautomated assay.

Sera from patients with primary biliary cirrhosis inhibit the activity of the mitochondrial pyruvate dehydrogenase complex. We utilized this effect to develop a simple, miniaturized, semiautomated spectrophotometric assay as a diagnostic aid. The sera studied were from 71 patients with primary biliary cirrhosis and 62 other subjects. The assays included enzyme inhibition, immunofluorescence on HEp-2 cells, enzyme-linked immunosorbent assay using recombinant pyruvate dehydrogenase complex-E2 and immunoblotting on bovine heart mitochondria. With the 71 primary biliary cirrhosis sera, on which M2 antibody was detected by immunofluorescence in 64 (90%), antibodies against pyruvate dehydrogenase complex were detected in 53 (83%) by means of enzyme inhibition, in 57 (89%) by means of enzyme-linked immunosorbent assay and in 60 (94%) by means of immunoblotting. Of the 64 sera positive by immunofluorescence, 60 reacted with pyruvate dehydrogenase complex-E2 on immunoblotting, and the miniaturized enzyme inhibition assay was positive in 53 of these. The enzyme inhibition assay and enzyme-linked immunosorbent assay were calibrated to give a specificity of 100%. At this level, the sensitivities for detection of pyruvate dehydrogenase complex antibody were 83% and 87%, respectively. We found no significant changes in levels of reactivity with the enzyme inhibition assay or enzyme-linked immunosorbent assay according to disease stage. Treatment with cyclosporine was accompanied by a significant decrease in levels of antibody to pyruvate dehydrogenase complex-E2 that matched improved indexes of biochemical liver function.(ABSTRACT TRUNCATED AT 250 WORDS)

Autoantibodies↗

PubMed1994

The natural history of abdominal pain associated with primary biliary cirrhosis.

OBJECTIVES: The aim of the present study was to determine the prevalence and natural history of abdominal pain in patients with primary biliary cirrhosis. METHODS: We studied 178 patients with well-defined primary biliary cirrhosis enrolled in a prospective randomized trial of ursodeoxycholic acid. These patients underwent upper endoscopy and upper abdominal ultrasound prior to entry, at 2 yr, and as indicated. Fourteen patients had additional evaluations including abdominal CT (four), colon x-ray (five), colonoscopy (three), endoscopic retrograde cholangiopancreatography (two), and upper gastrointestinal x-ray (two). RESULTS: Patients with abdominal pain generally presented with right upper quadrant discomfort. Thirty-one patients (17%) had pain at study entry: 33% of these had pain persisting at 1 yr, and 20% of these had pain persisting at 2 yr. The resolution of pain was not clearly affected by ursodeoxycholic acid. Evaluation with ultrasound and upper endoscopy found four patients with asymptomatic cholelithiasis, one with esophageal erosions, four with gastric erosions, one with a gastric ulcer, and two with duodenal erosions. Additional tests were unrevealing in 14 patients. Patients with pain were similar to patients without pain with regard to age, histological stage, gender, and liver biochemistries. CONCLUSIONS: We conclude that chronic right upper quadrant pain is not uncommon in patients with primary biliary cirrhosis, that it usually resolves spontaneously, and that upper endoscopy is the most important diagnostic test to use to exclude treatable causes of pain.

Abdominal Pain↗

PubMed1994

Hepatic osteodystrophy in primary biliary cirrhosis: effects of medical treatment.

OBJECTIVES: Osteoporosis is a frequent extrahepatic complication of primary biliary cirrhosis. Although histologically similar to the osteoporosis commonly seen in postmenopausal females, the pathogenesis and management of bone disease in patients with primary biliary cirrhosis is poorly understood. The experience with a subgroup of patients with primary biliary cirrhosis treated with vitamin D, calcium, and estrogen supplementation was reviewed to determine the effects of medical treatment on hepatic osteodystrophy. METHODS: The records of 203 women with the diagnosis of primary biliary cirrhosis were reviewed retrospectively for lumbar spine bone mineral density, menopausal status, and supplementation with vitamin D, calcium, and estrogen. RESULTS: The 16 postmenopausal patients treated with estrogen replacement had a statistically significant increase in the lumbar spine bone mineral density at 1 yr (+0.014 +/- 0.049 vs. -0.03 +/- 0.046 g/cm2, p < 0.038), without a significant change in the serum bilirubin or alkaline phosphatase. In treated patients, vitamin D and calcium supplementation did not lead to significant improvement in lumbar spine bone mineral density. CONCLUSIONS: Calcium and vitamin D supplementation, even in the presence of vitamin D deficiency, do not improve lumbar spine bone mineral density in patients with primary biliary cirrhosis. Estrogen replacement in postmenopausal patients, however, does appear to improve lumbar spine bone mineral density without increasing clinical or biochemical cholestasis, a potential complication reported in animal studies. This study should serve as an impetus for a controlled trial of estrogen replacement in postmenopausal patients with primary biliary cirrhosis.

Adult↗

PubMed1993

Comparative metabolism and structure of BCKD-E2 in primary biliary cirrhosis.

The identification and cloning of the mitochondrial autoantigens in primary biliary cirrhosis (PBC) have provided new clues in disease pathogenesis. The two major autoantigens are the E2 subunits of pyruvate dehydrogenase and branched-chain ketoacid dehydrogenase (BCKD). Interestingly, one of these complexes, BCKD-E2, is already well known to clinical medicine based on its association with genetic mutations in maple syrup urine disease (MSUD). Patients with this disease have an inability to metabolize branched-chain amino acids. In the present study, we have taken advantage of the known sequence of BCKD-E2 from normal humans, and addressed the issue of whether there is an altered autoantigen sequence in hepatocytes of individuals with primary biliary cirrhosis. In particular, we examined both the leader sequence and the B-cell immunodominant epitope, the lipoic acid domain. In addition, because patients with PBC have autoantibodies to the BCKD-E2 complex, we have quantitated plasma levels of alpha-ketoacids potentially affected in maple syrup urine disease. These include pyruvic acid (PY), phenylpyruvic acid (PP), alpha-ketoisocaproic acid (KIC) alpha-ketoisovalerate (KIV) and alpha-keto-beta-methylvaleric acid (KMV). The levels of these alpha-ketoacids were compared in patients with primary sclerosing cholangitis and normal volunteers. The sequence of BCKD-E2 obtained from PBC hepatocytes showed homology with normal BCKD. Further studies of autoantigen structure and sequence are clearly indicated, including those involved in mitochondrial transport and localization. Finally, we noted a statistically significant increase in all plasma alpha-ketoacids except alpha-keto-beta-methylvaleric acid in PBC patients.(ABSTRACT TRUNCATED AT 250 WORDS)

3-Methyl-2-Oxobutanoate Dehydrogenase (Lipoamide)↗

PubMed1993

Immunohistochemical characterization of hepatic lymphocytes in primary biliary cirrhosis in comparison with primary sclerosing cholangitis and autoimmune chronic active hepatitis.

We analyzed the immunophenotypes of hepatic cellular infiltrates by quantitative immunohistochemical methods in biopsy specimens from 20 patients with primary biliary cirrhosis (PBC), 19 with primary sclerosing cholangitis, and 11 with autoimmune chronic active hepatitis. Specifically, we sought to identify activated T cells, interferon-gamma-producing cells, and natural killer cells. The portal cellular infiltrate in PBC contained a preponderance of CD4 cells in comparison with CD8 cells, with a CD4/CD8 ratio of 2.45:1. The cellular infiltrate in areas of piecemeal necrosis contained mostly CD8 cells. Infiltrating CD8 cells in PBC had the surface phenotype of cytotoxic (CD8-positive, CD11b-negative) cells. Approximately 4% of T cells expressed interleukin 2 receptors. Interferon-gamma-staining cells were rarely identified (in less than 2%). Cells that expressed the natural killer cell markers CD16, CD56, or CD57 were infrequent, constituting approximately 5% of the cellular infiltrate. The composition of the infiltrates was similar in patients with PBC and chronic active hepatitis. Natural killer cells were twice as common in patients with primary sclerosing cholangitis (P < 0.05) as in those with PBC. The inflammatory infiltrates in areas of piecemeal necrosis were similar in the three diseases and differed from those found within the portal area, in that CD8 cells were preponderant. In all three liver diseases, almost 90% of bile ducts expressed class II HLA antigens. These findings support the hypothesis that cytotoxic T cells of either the CD4 or CD8 immunophenotype but not natural killer cells may be involved in the pathogenesis of PBC and chronic active hepatitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

PubMed1993

Systemic and renal hemodynamic differences between FK506 and cyclosporine in liver transplant recipients.

Immunosuppression after transplantation is complicated by hypertension and nephrotoxicity, reflecting widespread vasoconstriction associated with CsA. FK506 is a novel alternative immunosuppressive agent, structurally unrelated to CsA. These studies compared systemic and renal vascular changes developing in the initial 4 weeks after liver transplantation in patients treated with FK506 (plus PRED) and CsA (plus PRED and AZA). We studied arterial pressure, cardiac index (pulsed doppler ultrasound), and systemic resistance index (SVRI) before and weekly after liver transplant in 32 patients treated with CsA (2 mg/kg initial dose plus PRED; median dose at week 4, 30 mg/day) and 14 patients treated with FK506 (0.15 mg/kg/day initial dose and PRED; mean week 4 dose, 12.5). Renal plasma flow and glomerular filtration rate (GFR) were measured by clearance of para-amino hippurate and 125-iothalamate. Renin activity, aldosterone, and urinary prostanoids were measured by RIA. Pretransplant pressures and hemodynamics reflected low SVRI and increased cardiac index typical of end-stage liver disease. After transplantation, SVRI and pressures rose in both groups, but after week 2, SVRI was lower in patients treated with FK506. This was associated with less prevalent clinical hypertension during the subsequent 4 months (4/14 FK506 (28%) vs. 25/32 (78%) CsA, P < 0.01). By contrast, renal blood flow and GFR fell in both treatment groups similarly, whereas renal vascular resistance rose. Urinary 6-keto-PG-F1-alpha was suppressed in all transplant recipients, but to a greater degree in FK506-treated patients. This value correlated directly to post-transplant GFR (r = 0.48, P < 0.001). These data indicate that FK506-based immunosuppression differs from CsA by inducing less systemic vasoconstriction and hypertension. Renal vasoconstrictive effects were at least as great as those seen with CsA, however, and indicate that nephrotoxicity will remain a common feature to both regimens.

6-Ketoprostaglandin F1 alpha↗

PubMed1993

Hepatopulmonary syndrome. Clinical observations and lack of therapeutic response to somatostatin analogue.

We retrospectively studied 22 patients with hepatopulmonary syndrome (HPS) evaluated at the Mayo Medical Center from 1984 to 1991. All patients had hepatic cirrhosis with clinical evidence of portal hypertension; 13 (59 percent) had severe hypoxemia while breathing room air in the supine position (PaO2 < 60 mm Hg), and 14 of 16 (88 percent) had orthodeoxia breathing room air. On the basis of angiographic observations, we defined type 1 and type 2 patterns of pulmonary vascular abnormalities in HPS. Response to 100 percent oxygen and therapeutic regimens may differ in the angiographic patterns. Substantial deterioration in PaO2 associated with clinically stable hepatic dysfunction was documented in five of seven patients studied with sequential arterial blood gas testing; four subsequently died within 48 months. Overall mortality was 41 percent, occurring a mean of 2.5 years after diagnosis. In 7 of the 22 patients, we prospectively studied the effect of somatostatin analogue given subcutaneously for 4 consecutive days. No significant improvement in PaO2 was documented while breathing room air or 100 percent oxygen (p < 0.05). We conclude that in selected patients with clinically stable hepatic dysfunction and deteriorating oxygenation, the prognosis is poor. Our data in combination with recent surgical reports suggest that liver transplantation may be the treatment of choice in patients with HPS and worsening oxygenation.

Adult↗

PubMed1993

Efficacy of hepatic transplantation in patients with primary sclerosing cholangitis.

Controlled trials to assess the therapeutic benefit of orthotopic hepatic transplantation (OHTx) for primary sclerosing cholangitis (PSC) cannot be justified in view of improvement of patient survival after this operation since 1981. However, the actual patient survival with OHTx can be compared with the Mayo model estimated survival probabilities without OHTx. This model, which encompasses physical, biochemical and histopathologic parameters of PSC, was constructed from a study of 392 conservatively treated PSC patients at five international centers in England and North America. We compared the actual survival of 216 adult patients with the diagnosis of advanced PSC who underwent hepatic replacement with the expected survival estimated by the Mayo PSC natural history model, "the simulated control technique." OHTx was performed at the University of Pittsburgh and Mayo Medical Center between 5 December 1981 and 26 December 1990. The mean (plus or minus standard deviation) post-OHTx follow-up period was 34 +/- 25 months (range of zero to 104 months). Before transplantation, biliary or portal hypertensive operation, or both, was performed upon 104 patients. At operation, the mean age of recipients was 42.1 +/- 11.3 years and the mean value of total serum bilirubin was 13.3 +/- 13.0 milligrams per deciliter. Extensive septal fibrosis and cirrhosis were histologically documented in 97 percent of the patients, with splenomegaly in 63 percent. Immunosuppressive therapy was based primarily on cyclosporin in 184 recipients and FK-506 in 32. Within six months, the Kaplan-Meier survival probability after OHTx (0.89) already was higher than predicted by the Mayo model (0.83). At five years, the Kaplan-Meier actual survival with OHTx was 0.73 compared with 0.28 expected Mayo model survival. The overall increased survival rate with transplantation was statistically significant (chi-square equals 126.6; p < 0.001). At all risk stratifications, OHTx significantly improved survival with a p value of 0.031 (low risk), 0.001 (moderate risk) and < 0.001 (high risk). Thus, OHTx is effective therapy for PSC. Disease gravity and unsuspected cholangiocarcinoma in the excised native liver adversely influenced short and long term survival rates after transplantation, respectively.

Actuarial Analysis↗

PubMed1992

Hypercholesterolemia and atherosclerosis in primary biliary cirrhosis: what is the risk?

Hypercholesterolemia is commonly associated with primary biliary cirrhosis. In the general population, elevated serum cholesterol is associated with an increased risk of atherosclerosis. The relative risk has been poorly defined in primary biliary cirrhosis patients with hyperlipidemia. In addition, the hyperlipidemic state seen with primary biliary cirrhosis has not been well studied. We prospectively observed 312 patients with primary biliary cirrhosis for a median of 7.4 yr. During this period, 128 patients died. The incidence of atherosclerotic death in patients with primary biliary cirrhosis was not statistically different when compared with an age-matched and sex-matched U.S. control population. A similar group of 50 consecutive PBC patients had detailed serum lipid profiles. Findings included progressive increases in total cholesterol and low-density lipoprotein cholesterol with an increasing histological stage or severity of disease. High-density lipoprotein cholesterol was elevated in all stages, with the highest levels in histological stage 2 and 3 disease. Triglycerides were normal or slightly elevated in all stages. Apoprotein A-I was elevated in all but histological stage 4 disease. Our study suggests the hyperlipidemia associated with primary biliary cirrhosis does not place these patients at risk for atherosclerotic death. In light of the limitations imposed by our relatively small sample size, however, additional patients should be studied. Furthermore, an examination of the pathophysiological mechanisms leading to hypercholesterolemia should be the topic of further study.

Adult↗

PubMed1992

Primary sclerosing cholangitis: refinement and validation of survival models.

The natural history of primary sclerosing cholangitis was studied in 426 patients from five medical centers. The median follow-up time was 3.0 years (range, 0.01-16.6 years); 100 patients had died by the time of last follow-up. Survival analysis (Cox proportional-hazards regression) was used to identify the variables most useful in predicting survival of patients with primary sclerosing cholangitis. Serum bilirubin concentration, histological stage on liver biopsy, age, and the presence of splenomegaly were independent predictors of a high risk of dying. A mathematical model to predict survival of patients with primary sclerosing cholangitis (based on referral values of those predictors) was statistically validated using two methods. Confidence intervals for predicting patient-specific survival probabilities are also presented. This model to predict survival could be used to stratify participants in therapeutic trials, counsel patients and their families, decide on candidacy for and timing of liver transplantation, and provide mathematical controls for evaluating the efficacy of therapies for primary sclerosing cholangitis, including transplantation.

Adult↗

PubMed1992

Renal hemodynamics, urinary eicosanoids, and endothelin after liver transplantation.

Patients with hepatic cirrhosis develop widespread abnormalities in kidney function and vasoactive hormones. These change rapidly after liver transplantation during immunosuppression with cyclosporine. The role of changing eicosanoid excretion and endothelin levels in regulating renal function after transplantation in humans remains uncertain. We studied 32 patients with regard to renal hemodynamics, glomerular filtration, urinary prostacyclin (6-keto-PG-F1-alpha), thromboxane (TBX2), and endothelin before and during the first four weeks after orthotopic liver transplantation. Arterial pressure rose from 106 +/- 2/61 +/- 2 to 146 +/- 4/81 +/- 2 mmHg, (P less than .001), while renal blood flow fell (686 +/- 38 to 453 +/- 24 ml/min/1.73 m2, P less than .05), as did GFR. Pretransplant excretion of 6-keto and TBX2 was above that of normal subjects and fell progressively after transplant, as did plasma renin activity and aldosterone. The 6-keto levels fell below normal after two weeks. The ratio of TBX2/6-keto remained elevated compared with normal subjects throughout the month after transplant (1.54 +/- 0.38 vs. 0.54 +/- 0.07, P less than .01). Endothelin levels rose during the first week (7.4 +/- 1.4 vs. 12.4 +/- 2.7 pg/ml, P less than .05), but fell back to baseline thereafter. These results indicate that high levels of urinary eicosanoids in patients with liver disease fall rapidly after liver transplantation during CsA immunosuppression. Unlike results in many experimental models, these data suggest that renal vasoconstriction in humans may be associated primarily with suppression in renal prostacyclin excretion rather than stimulation of thromboxane.

Adult↗