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Paul Angulo

Publications and source records attributed to Paul Angulo.

At least 55 records · Page 3Linked to original sources
PubMed2003

When is liver biopsy needed in the diagnosis of primary biliary cirrhosis?

BACKGROUND & AIMS: Liver biopsy has been largely replaced by less invasive measurements applied to mathematical models in defining the prognosis of patients with primary biliary cirrhosis (PBC). The need for liver biopsy in the diagnosis of patients with positive antimitochondrial antibodies (AMAs) in the setting of biochemical cholestasis remains uncertain. This study was undertaken to determine which variables indicate the need for liver biopsy in patients with positive AMA and suspected PBC. METHODS: A total of 3198 patients that were tested for AMA in 1999 and 2000 were identified. Of these, 198 (6.2%) were AMA positive. Forty-two patients were excluded because of unavailable laboratory data or liver biopsy specimens. Data on the remaining 156 patients were analyzed to determine which variables among patients with positive AMA with and without a histopathologic diagnosis of PBC indicate the need for liver biopsy. RESULTS: In 131 of 156 (84.6%) patients, a diagnosis of PBC was established by liver biopsy. The histological diagnosis of PBC was associated with a cholestatic biochemical profile (alkaline phosphatase [AP] >1.5 times the upper limits of normal [ULN] and aspartate aminotransferase [AST] <5 times ULN) in 112 of 131 (85.5%) patients. The combination of AP >1.5 times the ULN and AST <5 times the ULN yielded a 98.2% positive predictive value of PBC diagnosis on liver biopsy in AMA-positive subjects. These results were corroborated by cross-validation in an independent set of patients. CONCLUSIONS: In patients with positive AMA, a cholestatic biochemical profile (AP >1.5 times the ULN), and absence of markedly elevated AST (<5 times the ULN), liver biopsy is rarely required to establish the diagnosis of PBC. Liver biopsy would be beneficial to establish the diagnosis of PBC in only a minority of AMA-positive patients with AP <1.5 times the ULN or AST >5 times the ULN.

Alkaline Phosphatase↗
PubMed2003

Primary sclerosing cholangitis in children: a long-term follow-up study.

Primary sclerosing cholangitis (PSC) is increasingly diagnosed in children and adolescents, but its long-term prognosis remains uncertain. The aim of this longitudinal, cohort study was to determine the long-term outcome of children with PSC. Fifty-two children with cholangiography-proven PSC (34 boys and 18 girls; mean age 13.8 +/- 4.2 years; range, 1.5-19.6 years) who were seen at our institution over a 20-year period were followed-up for up to 16.7 years. Two thirds presented with symptoms and/or signs of PSC and 81% had concomitant inflammatory bowel disease (IBD). Twenty-five percent had total alkaline phosphatase activity within the normal range for the age group, but all of them had elevated gamma-glutamyl transpeptidase levels. Autoimmune hepatitis overlapping with PSC was present in 35% of children. A positive but transient clinical and/or biochemical response occurred under therapy with ursodeoxycholic acid, alone or in combination with immunosuppressive medications. During follow-up, 11 children underwent liver transplantation for end-stage PSC and 1 child died. The median (50%) survival free of liver transplantation was 12.7 years. Compared with an age- and gender-matched U.S. population, survival was significantly shorter in children with PSC (P <.001). In a Cox regression model, lower platelet count, splenomegaly, and older age were associated with shorter survival. Presence of autoimmune hepatitis overlapping with PSC (P =.2) or medical therapy (P =.2) did not affect survival. In conclusion, PSC significantly decreases survival in this child population. Although pharmacologic therapy may improve symptoms and liver test results initially, it does not seem to impact the long-term outcome.

Adolescent↗
PubMed2003

Treatment with ursodeoxycholic acid is associated with weight gain in patients with primary biliary cirrhosis.

BACKGROUND: Ursodeoxycholic acid (UDCA) is the established treatment of primary biliary cirrhosis (PBC) and is a safe and well-tolerated medication. Nevertheless, patients often anecdotally complain of weight gain while on this drug. GOALS: We compared weight changes in patients treated with UDCA and those on placebo to characterize this potential side effect. STUDY: One-hundred eighty patients with PBC who were enrolled into a randomized, controlled trial received either UDCA (13-15 mg/kg/d) or an identical placebo. Changes from baseline weight were calculated at 12, 24, 36, and 48 months. Other markers of disease activity, including liver biochemistries, serum lipids, histologic stage, and Mayo Risk Score were evaluated in both groups. RESULTS: The proportion of patients who gained weight during the first 12 months of therapy was significantly greater in the UDCA than placebo group (67/86 [78%] versus 43/73 [57%] respectively, P = 0.005). Patients in the UDCA group gained an average of 3.6 +/- 6.5% kg (2.2 +/- 5.1 kg) which was significantly greater than the average of 0.6 +/- 6.9% kg (0.6 +/- 4.9 kg) gained in the placebo group (P = 0.04). The biggest change in weight occurred in the first 12 months of treatment (P < 0.001); after this, weight was maintained for the 4-year duration of treatment. There was no significant correlation between initial body mass index (BMI) and weight change or changes in disease activity and weight. CONCLUSION: UDCA treatment in patients with PBC is associated with a significant weight gain that occurs in the first 12 months of treatment, persists for the duration of treatment, and occurs independent of baseline BMI. Discussions with PBC patients beginning UDCA treatment should include the beneficial effects this medication has on disease outcome, but should also mention weight gain as a possible side effect.

Body Mass Index↗
PubMed2003

Recurrent idiopathic hepatitis: a new entity?

Our goals were to describe a new clinical entity, which we termed recurrent idiopathic hepatitis. We provide a case report of this entity and conclude that this is perhaps a new entity somewhat analogous to recurrent idiopathic cholestasis.

Acute Disease↗
PubMed2003

Association of primary biliary cirrhosis and rheumatoid arthritis.

Primary biliary cirrhosis (PBC) and rheumatoid arthritis (RA) are chronic medical conditions in which, although the etiology is uncertain, autoimmune features predominate. These two conditions are, in fact, multisystemic diseases, with a multitude of manifestations that are not limited to their target end organ. It has been well established that patients with PBC may have musculoskeletal complaints and patients with RA may have evidence of hepatic dysfunction. Both of these conditions are fairly rare, with RA being found in approximately 1% of the population and PBC being found in approximately 20/100,000 women and 2/100,000 men.The likelihood of these uncommon conditions occurring in the same patient is very rare and unusual. We have identified a unique group of 25 patients who have met disease-defining criteria for both RA and PBC. Awareness of this combination should prompt rheumatologists to assess for PBC with antimitochondrial antibody testing in patients with abnormal liver tests and also to raise awareness that abnormal liver tests in RA patients are not always due to drugs.

Journal Article↗
PubMed2003

Safety and efficacy of estrogen therapy in preventing bone loss in primary biliary cirrhosis.

OBJECTIVE: Estrogen therapy has been found to be useful in the treatment of postmenopausal osteoporosis. However, concern about its potential for worsening cholestasis has limited its use in postmenopausal women with primary biliary cirrhosis. The aim of the present study was to determine the safety as well as the efficacy of estrogen replacement therapy with respect to bone mass in postmenopausal women with primary biliary cirrhosis. METHODS: Bone mineral density of the lumbar spine (measured using dual energy x-ray absorptiometry) of 46 unselected postmenopausal women with primary biliary cirrhosis receiving estrogen replacement therapy was compared with 46 age-matched women with primary biliary cirrhosis not receiving estrogen replacement therapy, and with the expected normal bone mineral density adjusted for age and ethnic group. RESULTS: The mean duration of follow-up was 4.8 +/- 0.4 yr. Treatment with estrogens resulted in a significantly lower rate of bone loss (0.002 g/cm(2)/yr +/- 0.028 vs 0.009 g/cm(2)/yr +/- 0.020, p = 0.05). Worsening cholestasis attributable to estrogen replacement therapy did not occur in any patient. One patient (2%) discontinued therapy because of side effects. CONCLUSIONS: Estrogen replacement therapy in postmenopausal patients with primary biliary cirrhosis is safe and may be effective in decreasing the rate of bone loss.

Adult↗
PubMed2003

Is there a role for liver biopsy in primary sclerosing cholangitis?

OBJECTIVE: Liver biopsies are performed in patients with primary sclerosing cholangitis (PSC) to stage disease and to rule out coexisting liver disease. The purpose of this study was to examine how often routine liver biopsies provide important information in patients with PSC. METHODS: We reviewed the charts of 138 patients with a cholangiographic diagnosis of PSC to determine whether information from liver biopsy had an impact on clinical management. RESULTS: A total of 30 patients did not have a liver biopsy, whereas 29 patients had a biopsy before cholangiography. In 79 patients the liver biopsy was performed after the diagnosis of PSC was established by cholangiography (median time from cholangiography to liver biopsy, 21 days). In 78 of 79 patients (98.7%) the liver biopsy revealed no atypical findings and did not affect clinical management. In one patient the liver biopsy revealed findings of an overlap syndrome with autoimmune hepatitis, and the patient was treated with corticosteroids and azathioprine. This patient had biochemical features consistent with autoimmune hepatitis. One patient developed a bile leak after liver biopsy, requiring hospitalization (complication rate 0.9%). CONCLUSIONS: Liver biopsies rarely contribute new information that affects the management of patients with PSC. Given the risks of the procedure, liver biopsies for patients with a diagnosis of PSC established by cholangiography may not routinely be necessary.

Adolescent↗
PubMed2003

Current best treatment for non-alcoholic fatty liver disease.

Treatment of patients with non-alcoholic fatty liver disease (NAFLD) has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipidaemia. NAFLD associated with obesity may be resolved by weight reduction, although the benefits of weight loss have been inconsistent. Improving insulin sensitivity with lifestyle modifications or medications usually improves glucose and lipid levels in patients with diabetes and hyperlipidaemia. Improving insulin sensitivity is expected to improve the liver disease but in many diabetic/hyperlipidaemic patients with NAFLD, the appropriate control of glucose and lipid levels is not always accompanied by improvement of the liver condition. Results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, alphatocopherol, metformin and thiazolidinedione derivatives suggest that these medications may be of potential benefit. This article reviews the treatment modalities currently available for patients with NAFLD, including emerging data from clinical trials evaluating promising medications as well as possibilities for the future.

Antioxidants↗
PubMed2002

Use of ursodeoxycholic acid in patients with liver disease.

Ursodeoxycholic acid (UDCA), the 7beta-epimer of chenodeoxycholic acid, has multiple hepatoprotective activities. UDCA modifies the bile acid pool, decreasing levels of endogenous, hydrophobic bile acids while increasing the proportion of nontoxic hydrophilic bile acids. UDCA has a choleretic effect, increasing hepatocellular bile acid excretion, as well as cytoprotective, antiapoptotic, and immunomodulatory properties. UDCA has been shown to delay development of gastroesophageal varices and progression to cirrhosis as well as to improve long-term survival in patients with primary biliary cirrhosis. Significant improvement of abnormal liver tests may be achieved during UDCA therapy in patients with primary sclerosing cholangitis, intrahepatic cholestasis of pregnancy, cystic fibrosis-associated liver disease, nonalcoholic fatty liver disease, graft-versus-host disease of the liver, total parenteral nutrition-induced cholestasis, and in some pediatric cholestatic liver diseases. However, unlike the effects of UDCA in primary biliary cirrhosis, the long-term effects of UDCA in disease progression and survival in these other conditions remain to be established.

Cholagogues and Choleretics↗
PubMed2002

Pirfenidone in the treatment of primary sclerosing cholangitis.

Our aim was to evaluate the safety and assess the efficacy of pirfenidone, an antifibrotic drug, in patients with primary sclerosing cholangitis (PSC). Twenty-four patients with PSC were enrolled in this pilot study. Oral pirfenidone, 2400 mg daily, was given for one year. Liver biochemistries were determined at three-month intervals. The Mayo risk score was calculated, and liver biopsy and endoscopic cholangiography were performed at entry and at one year of treatment. No significant changes in liver biochemistries were noted at the end of the treatment period or at any of the three-month intervals. The Mayo risk score did not change significantly, and no significant changes were noted in the degree of inflammation, fibrosis, histologic stage of disease, or cholangiographic findings at the end of the treatment period. Adverse events occurred in 20/24 (83%) patients, but disappeared shortly after pirfenidone was discontinued. Pirfenidone did not benefit patients with PSC, and it was frequently associated with adverse events. The results of this pilot study discourage further trials of pirfenidone in patients with PSC.

Administration, Oral↗
PubMed2002

Non-alcoholic fatty liver disease.

Non-alcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects a high proportion of the world's population. Insulin resistance and oxidative stress play a critical role in the pathogenesis of NAFLD. Clinical, biochemical and imaging studies are of value in the diagnostic evaluation of patients with NAFLD, but liver biopsy remains the most sensitive and specific means of providing important diagnostic and prognostic information. Simple steatosis has the best prognosis within the spectrum of NAFLD, but NAFLD has the potential to progress to steatohepatitis, fibrosis and even cirrhosis. No effective medical therapy is currently available for all patients with NAFLD. In patients with diabetes mellitus and hyperlipidemia, appropriate metabolic control is always recommended, but rarely effective in resolving the liver disease. Weight reduction, when achieved and sustained, may improve the liver disease, although the results with weight loss have been inconsistent. Pharmacological therapy aimed at the underlying liver disease holds promise. Several medications with different mechanisms of action and potential benefit are currently being evaluated in clinical trials. Liver transplantation is a life-extending therapeutic alternative for patients with end-stage NAFLD, but NAFLD may recur after liver transplantation.

Biopsy↗
PubMed2002

Tumor necrosis factor-alpha and transforming growth factor-beta reflect severity of liver damage in primary biliary cirrhosis.

BACKGROUND AND AIMS: The pathogenesis of primary biliary cirrhosis (PBC) is unknown. The role of cytokines such as tumor necrosis factor-alpha (TNF-alpha) and transforming growth factor-beta (TGF-beta), and the effect of ursodeoxycholic acid (UDCA) in modifying the cytokine environment in patients with PBC has remained largely unstudied. Our aims were to determine: (i) the relationship between serum levels of TNF-alpha and TGF-beta and the severity of PBC; and (ii) the effects of UDCA therapy on TNF-alpha and TGF-beta levels in patients with PBC. METHODS: We studied 90 patients who had been treated with UDCA (53 patients) or placebo (37 patients) for 2 years as part of a randomized, double-blind, controlled trial. Patients were divided into histological stage I/II or stage III/IV disease. Serum TNF-alpha and TGF-beta levels were quantified by enzyme-linked immunoabsorbent assay. RESULTS: Baseline levels of TNF-alpha were significantly greater in patients with stage III/IV compared to stage I/II disease. After 2 years of treatment with UDCA, patients showed a significantly greater decrease in TNF-alpha levels and progression risk score compared to placebo-treated patients. TNF-alpha and TGF-beta levels were significantly reduced compared to baseline levels in the UDCA-treated group after 2 years, while there was no significant change in the levels of placebo-treated patients. CONCLUSIONS: Serum TNF-alpha and TGF-beta levels may reflect severity of disease in patients with PBC. The beneficial effects of UDCA therapy may be explained by lowering serum levels of these two cytokines.

Adult↗
PubMed2002

Treatment of non-alcoholic steatohepatitis.

Treatment of patients with non-alcoholic steatohepatitis (NASH) has typically been focused on the management of associated conditions such as obesity, diabetes mellitus and hyperlipidaemia. NASH associated with obesity may resolve with weight reduction, although the benefits of weight loss have been inconsistent. Appropriate control of glucose and lipid levels is always recommended, but is not always effective in reversing the liver condition. Results of pilot studies evaluating ursodeoxycholic acid, gemfibrozil, betaine, N-acetylcysteine, alpha-tocopherol, metformin and thiazolidinedione derivatives suggest that these medications may be of potential benefit for patients with NASH. These medications, however, need first to be tested in well-controlled trials with clinically relevant end-points and extended follow-up. A better understanding of the pathogenesis and natural history of NASH will help to identify the subset of patients at risk of progressing to advanced liver disease and, hence, those patients who should derive the most benefit from medical therapy.

Diabetes Mellitus, Type 2↗
PubMed2002

Small-duct primary sclerosing cholangitis: a long-term follow-up study.

Some patients with inflammatory bowel disease (IBD) have chronic cholestasis and hepatic histology compatible with primary sclerosing cholangitis (PSC) but normal findings on cholangiography. These patients with small-duct PSC have remained largely unstudied. Our aim was to determine the prevalence and long-term outcomes of patients with small-duct PSC. Eighteen patients with small-duct PSC (7 female and 11 male patients; mean age, 39.9 +/- 15.3 years [range, 13-68 years]) seen over a 4-year period were matched blindly by age and sex to 36 patients with classic PSC and followed up for 32.5 years. Small-duct PSC represented 5.8% of patients (18 of 309) with sclerosing cholangitis. Subsequent endoscopic retrograde cholangiography (ERC) performed in 5 patients with small-duct PSC showed progression to typical PSC in 3 patients at 4, 5.5, and 21 years of follow-up. None of the patients with small-duct PSC but 4 of the patients with classic PSC developed hepatobiliary malignancy. There were 3 deaths (17%) or liver transplantations in patients with small-duct PSC (2 after progressing to classic PSC) and 15 (42%) in the classic PSC group. Survival free of liver transplantation was significantly greater in the small-duct than in the classic PSC group (P =.04). Compared with the general U.S. population, survival in patients with small-duct PSC was similar (P =.4) but significantly lower in patients with classic PSC (P <.001). In conclusion, small-duct PSC may represent an earlier stage of PSC associated with a significantly better long-term prognosis. Some patients, however, progress to classic PSC and/or end-stage liver disease with the consequent necessity of liver transplantation.

Adolescent↗
PubMed2002

Oral tolerance and pyruvate dehydrogenase in patients with primary biliary cirrhosis.

Primary biliary cirrhosis (PBC) is a chronic cholestatic liver disease characterized by the immunological destruction of intralobular bile ducts and serum anti-mitochondrial antibodies (AMA). Based upon previous work of oral tolerance and autoimmunity, we hypothesized that feeding the mitochondrial autoantigens of PBC would alter the clinical course and the level of antimitochondrial antibodies. The bovine pyruvate dehydrogenase complex (PDC) was purified and 5 mg fed in gelatin capsules to 6 patients with early stage PBC for 6 months. Antimitochondrial antibodies and liver biochemistries were measured at every 3 months for 12 months. The clinical trial was completed for all patients except for 1 who showed deterioration of pre-existing skin rash during treatment, which disappeared within 2 weeks after treatment was discontinued. However, after 1 year, neither the titers of AMAs nor liver biochemistries were significantly changed by this treatment. This is the first trial to test the efficacy of oral tolerance induction in PBC. However, the data, which limited in scope, did not demonstrate efficacy and further highlights the difficulties in showing continuing evidence of tolerance induction in autoimmunity.

Administration, Oral↗
PubMed2002

Overlap of autoimmune hepatitis and primary biliary cirrhosis: an evaluation of a modified scoring system.

OBJECTIVE: The coexistence of autoimmune hepatitis (AIH) with primary biliary cirrhosis (PBC) as an overlap syndrome has been previously described. The ability to detect AIH overlap with a revised version of the International Autoimmune Hepatitis Group (IAHG) scoring system, however, remains unknown. Our specific aim was to evaluate the revised IAHG scoring system and its ability to identify AIH overlap in PBC. METHODS: One hundred forty-one PBC patients with first-time visits to the Mayo Clinic from January 1, 1990 to December 31, 1992 were evaluated. The calculation of individual revised IAHG scores was performed and compared to original IAHG scores. RESULTS: Among 137 PBC patients with available liver histologies, use of the original IAHG scoring system detected "definite" and "probable" AIH overlap among 2.2% and 62% of cases, respectively. Application of the revised IAHG scoring system, however, revealed no individuals (0%) with definite AIH overlap (>15 points). Twenty-six subjects (19%) fulfilled IAHG criteria for probable AIH overlap (10-15 points). The presence of antinuclear antibody and/or smooth muscle antibody positivity (p = 0.05), other autoimmune disorders (p < 0.01), and total histological score (p < 0.001) were significantly greater in the PBC plus probable AIH group than in subjects with PBC alone. CONCLUSION: A reduction in the prevalence of definite 2.2% vs 0%) and probable (62% vs. 19%) AIH overlap among PBC subjects was observed with use of the revised IAHG coring system relative to the original criteria. Applicability of the revised IAHG scoring system, however, remains questionable, as nearly 20% of PBC patients will be classified with probable AIH overlap.

Autoimmune Diseases↗