Development and progression of portal hypertensive gastropathy in patients with chronic hepatitis C

Abstract

Objectives: The objective of this study was to determine the incidence and risk factors associated with new-onset and worsening portal hypertensive gastropathy (PHG) in patients with chronic hepatitis C (CHC).

Methods: A total of 831 CHC patients with bridging fibrosis or cirrhosis at the time of entry were prospectively monitored for clinical and histological liver disease progression while receiving either low-dose peginterferon α2a or no antiviral therapy in the HALT-C (Hepatitis C Antiviral Long-term Treatment against Cirrhosis) trial. Upper endoscopy with grading of PHG was performed at baseline and at year 4 of the study. The presence and severity of PHG were determined using the NIEC (New Italian Endoscopy Conference) criteria, and worsening PHG was defined as a score increase of ≥1 point.

Results: During a median follow-up of 3.85 years, 50% of 514 subjects without PHG developed new-onset PHG, whereas 26% of 317 patients with baseline PHG had worsening PHG. Independent predictors of new-onset PHG included higher alkaline phosphatase and being diabetic, whereas predictors of worsening PHG were Caucasian race, lower albumin, as well as higher serum aspartate transaminase/alanine transaminase ratio and homeostatic model assessment levels. New-onset and worsening PHG were significantly associated with clinical and histological progression. They were also associated with new-onset and worsening gastroesophageal varices.

Conclusions: New-onset and worsening PHG develop at a rate of 12.9% per year and 6.7% per year, respectively, in non-responder CHC patients with advanced fibrosis. If confirmed in other studies, endoscopic surveillance for PHG may need to be tailored to individual patient risk factors.

Trial registration: ClinicalTrials.gov NCT00006164.

Figures

Figure 1

Description of the HALT-C Trial cohort. Among the 637 subjects without baseline portal hypertensive gastropathy (PHG), 258 continued to not have PHG during follow-up while 256 developed new onset PHG. Among the 374 subjects with baseline PHG, 235 had stable or improved PHG scores while 82 subjects had worsening PHG.

Figure 2

New or worsening PHG and clinical outcomes. During follow-up, the 256 subjects who developed new onset PHG were also significantly more likely to develop a clinical outcome compared to the 258 without PHG (p

Figure 3

New or worsening PHG and histological progression. The 156 non-cirrhotic patients who developed new onset PHG were significantly more likely to experience histological fibrosis progression compared to the 181 patients without de novo PHG (p=0.030). In addition, there was a trend for the 21 non-cirrhotic patients with worsening PHG during follow-up to have histological progression compared to the 118 patients with stable or improved PHG (p=0.18). BL PHG = baseline portal hypertensive gastropathy

Figure 4

Relationship between PHG evolution and de novo varices. The 178 patients who developed new onset PHG were also more likely to develop de novo varices compared to the 236 patients without PHG during follow-up (p < 0.0001). The 38 patients who had worsening PHG were also more likely to develop de novo varices compared to the 141 patients with stable PHG but this trend was not significant (p=0.38). BL PHG= baseline portal hypertensive gastropathy

Figure 5

Relationship of PHG evolution and variceal progression. The 70 patients with new onset PHG were also more likely to have variceal progression compared to the 20 patients without new onset PHG (p=0.023). Similarly, the 41 patients with worsening PHG were significantly more likely to have variceal progression compared to the 77 subjects with stable/ improved PHG (p