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.

Trial registration: ClinicalTrials.gov NCT00006164.

Copyright 2010 AGA Institute. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Description of the HALT-C Trial cohort. Amongst the 744 patients without baseline varices, 441 continued to have no detectable varices during follow-up while 157 developed new gastroesophageal varices. Amongst the 272 patients with baseline gastroesophageal varices, 136 patients had stable or improved varices while 74 subjects had worsening varices.

Figure 2

Logistic regression model to predict the likelihood of developing new varices in HALT-C Trial patients. The predicted probability of developing new varices over 4 years according to baseline hyaluronic acid level and subject ethnicity using an imputed serum albumin level of 3.9 g/dl in the model. (log HA 126 ng/ml).

Figure 3

Gastroesophageal varices in peginterferon treated and untreated patients. 3A). Amongst the 598 patients without baseline varices, 302 were randomized to receive peginterferon and 296 to receive no further treatment. By year 4, the proportion of patients with new varices in the treated and untreated groups was similar (27% vs 26%, p= 0.81). In addition, the distribution of the types of varices that were detected was similar (p=0.06) 3B). Amongst the 210 patients with baseline gastroesophageal varices, 99 received peginterferon and 111 received no further antiviral treatment. By year 4, the proportion of patients with worsening, stable, and improved varices was similar (p=0.35).

Figure 3

Gastroesophageal varices in peginterferon treated and untreated patients. 3A). Amongst the 598 patients without baseline varices, 302 were randomized to receive peginterferon and 296 to receive no further treatment. By year 4, the proportion of patients with new varices in the treated and untreated groups was similar (27% vs 26%, p= 0.81). In addition, the distribution of the types of varices that were detected was similar (p=0.06) 3B). Amongst the 210 patients with baseline gastroesophageal varices, 99 received peginterferon and 111 received no further antiviral treatment. By year 4, the proportion of patients with worsening, stable, and improved varices was similar (p=0.35).