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Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C.

ABSTRACT: BACKGROUND & AIMS:We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis. METHODS:All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameters were analyzed as predictors of de novo variceal formation and variceal progression. RESULTS:De novo varices developed in 157 of the 598 (26.2%) patients. Most of the new varices were small (76.4%) and only 1% of patients developed variceal hemorrhage. The likelihood of developing varices was associated with subject race (Hispanic > Caucasian > African American; P = .0005), lower baseline levels of albumin (P = .051), and higher levels of hyaluronic acid (P < .001) with an area under the receiver operating characteristic curve = .70. Among 210 patients with existing gastroesophageal varices, 74 (35.2%) had variceal progression or bleeding during follow-up. Patients with higher baseline ratios of serum aspartate/alanine aminotransferase (P = .028) and lower platelet counts (P = .0002) were at greatest risk of variceal progression (area under the receiver operating characteristic = .72). Prolonged, low-dose peginterferon-alpha2a therapy and beta-blockers did not influence the risk of developing new or enlarging varices. CONCLUSION:Development of varices in patients with chronic hepatitis C is associated with patient race/ethnicity and laboratory markers of disease severity. Prolonged low-dose peginterferon-alpha2a therapy and beta-blockers do not reduce the risk of variceal development or progression.

SUBMITTER: Fontana RJ

PROVIDER: S-EPMC2883673 | biostudies-literature | 2010 Jun

REPOSITORIES: biostudies-literature

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Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C.

Fontana Robert J RJ Sanyal Arun J AJ Ghany Marc G MG Lee William M WM Reid Andrea E AE Naishadham Deepa D Everson Gregory T GT Kahn Jeffrey A JA Di Bisceglie Adrian M AM Szabo Gyongyi G Morgan Timothy R TR Everhart James E JE

Gastroenterology 20100306 7

<h4>Background & aims</h4>We aimed to identify the incidence and predictors of de novo gastroesophageal variceal formation and progression in a large cohort of patients with chronic hepatitis C and advanced fibrosis.<h4>Methods</h4>All participants in the Hepatitis C Antiviral Long-Term Treatment against Cirrhosis Trial were offered an endoscopy before treatment and again after 4 years. Patients with varices at baseline also had an endoscopy at 2 years. Baseline laboratory and clinical parameter ...[more]

PMID: 20211180

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Project description:Noninvasive tests cannot differentiate between adjacent stages of fibrosis, which limits assessment of disease progression and regression during therapy. We investigated whether levels of cytokines and extracellular matrix proteins in serum and biopsy samples can be used to determine actual stage of liver fibrosis in patients with chronic hepatitis C (CHC) and in prognosis.We collected data from 383 treatment-naive patients with CHC from the Duke Hepatology Clinical Research Database and Biorepository, from 2006 through 2009, for use in the training set. Serum samples were obtained from 100 individuals without CHC (controls). We selected 37 serum biomarkers for customized array analysis by using the SearchLight multiplex sandwich enzyme-linked immunosorbent assay. Data from 434 treatment-naive patients with CHC, which were obtained from the Trent HCV cohort, were used in the validation analysis. Multivariable modeling, marker selection, and validation included randomForest and Obuchowski measures, with independent comparison with FibroSURE.Four serum markers (levels of hyaluronic acid, vascular cell adhesion molecule 1, alpha-2 macroglobulin, and retinol-binding protein 4) and age associated with fibrosis stage (F0-1, F2-3, or F4); these had Obuchowski measures of 0.85-0.89, with misclassification rates of 38% and 29% in training and validation sets, compared with 50% for the FibroSURE test. In the training set, area under the curve values for the multiplex markers were similar to those from the FibroSURE test: stages F0 vs F1 (0.51 vs 0.53), F1 vs F2 (0.60 vs 0.59), F2 vs F3 (0.69 vs 0.72), and F3 vs F4 (0.51 vs 0.52). Area under the curve values were similar in the validation cohort. In longitudinal analyses of 133 paired biopsies, 9 markers (level of alanine aminotransferase, ?-glutamyltransferase, hyaluronic acid, intracellular adhesion molecule 1, interleukin 4, CXCL10, CXCL9, and vascular cell adhesion molecule 1) were associated with change in the histologic activity index (P values ranging from .000 to .049), and 4 (granulocyte-macrophage colony-stimulating factor, interleukin 12, interleukin 2, and matrix metalloproteinase 13) were associated with a change in fibrosis stage (P values ranging from .001 to .042).We identified serum biomarkers that can be measured by multiplex enzyme-linked immunosorbent assay to determine levels of fibrosis in patients with CHC, although misclassification is frequent and results are comparable with those from the FibroSURE test. Changes in protein levels in biopsy samples were associated with progression of fibrosis in patients.

Project description:BACKGROUND: Although chronic liver disease is associated with gastroesophageal reflux disease (GERD), the impact of chronic hepatitis B virus (HBV) infection on this association remains unclear. We thus aimed to evaluate the relationship between chronic HBV infection and GERD. METHODS: In this prospective population-based study, 1,001 adult subjects who underwent an upper gastrointestinal endoscopic examination in a health check-up and completed a gastroesophageal reflux questionnaire were consecutively enrolled. Endoscopic findings were classified according to the Los Angeles classification. Hepatitis B surface antigen was used as a marker of HBV infection. Univariate and multivariate approaches were used to evaluate the effects of chronic HBV infection on GERD. RESULTS: Chronic HBV infection was associated with heartburn sensation [odds ratio (OR) 1.27, 95% confidence interval 1.01-1.61, P = 0.037], and erosive esophagitis (adjusted OR 1.75, 1.03-2.97, P = 0.037). Although male gender is a risk factor of erosive esophagitis, further analyses stratified by gender and aspartate aminotransferase to platelet ratio index (APRI) showed that chronic HBV infection was associated with erosive esophagitis in female subjects (adjusted OR 2.70, 1.14-6.39, P = 0.024) and those with APRI of more than 0.3 (adjusted OR 3.94, 1.73-8.96, P = 0.001). Moreover, higher serum aspartate aminotransferase (AST) and triglyceride (TG) levels were risk factors of erosive esophagitis in patients with chronic HBV infection. CONCLUSIONS: Our findings indicate a close association between chronic HBV infection and GERD, especially in female subjects and those with higher APRI levels. Moreover, HBV carriers with higher AST or TG levels have higher incidence of erosive esophagitis. The interactions between chronic HBV infection and GERD need further studies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12072-010-9184-4) contains supplementary material, which is available to authorized users.

Project description:BACKGROUND:A recent retrospective study confirmed that hepatic stiffness and splenic stiffness measured with magnetic resonance elastography (MRE) are strongly associated with the presence of esophageal varices. In addition, strong correlations have been reported between splenic stiffness values measured with MRE and hepatic venous pressure gradients in animal models. However, most studies have been conducted on adult populations, and previous pediatric MRE studies have only demonstrated the feasibility of MRE in pediatric populations, while the actual clinical application of spleen MRE has been limited. AIM:To assess the utility of splenic stiffness measurements by MRE to predict gastroesophageal varices in children. METHODS:We retrospectively reviewed abdominal MRE images taken on a 3T system in pediatric patients. Patients who had undergone Kasai operations for biliary atresia were selected for the Kasai group, and patients with normal livers and spleens were selected for the control group. Two-dimensional spin-echo echo-planar MRE acquisition centered on the liver, with a pneumatic driver at 60 Hz and a low amplitude, was performed to obtain hepatic and splenic stiffness values. Laboratory results for aspartate aminotransferase to platelet ratio index (APRI) were evaluated within six months of MRE, and the normalized spleen size ratio was determined with the upper normal size limit. All Kasai group patients underwent gastroesophageal endoscopy during routine follow-up. The Mann-Whitney U test, Kendall's tau b correlation and diagnostic performance analysis using the area under the curve (AUC) were performed for statistical analysis. RESULTS:The median spleen MRE value was 5.5 kPa in the control group (n = 9, age 9-18 years, range 4.7-6.4 kPa) and 8.6 kPa in the Kasai group (n = 22, age 4-18 years, range 5.0-17.8 kPa). In the Kasai group, the APRI, spleen size ratio and spleen MRE values were higher in patients with portal hypertension (n = 11) than in patients without (n = 11) (all P < 0.001) and in patients with gastroesophageal varices (n = 6) than in patients without (n = 16) (all P < 0.05), even though their liver MRE values were not different. The APRI (? = 0.477, P = 0.007), spleen size ratio (? = 0.401, P = 0.024) and spleen MRE values (? = 0.426, P = 0.016) also correlated with varices grades. The AUC in predicting gastroesophageal varices was 0.844 at a cut-off of 0.65 (100% sensitivity and 75% specificity) for the APRI, and 0.844 at a cut-off of 9.9 kPa (83.3% sensitivity and 81.3% specificity) for spleen MRE values. CONCLUSION:At a cut-off of 9.9 kPa, spleen MRE values predicted gastroesophageal varices as well as the APRI and spleen size ratio in biliary atresia patients after the Kasai operation. However, liver MRE values were not useful for this purpose.

Dataset Information

Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C.

Publications

Factors that determine the development and progression of gastroesophageal varices in patients with chronic hepatitis C.

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