Factors Linked to Variceal Aggravation in Cirrhotic HCV Patients After DAA Therapy

Uncovering Risks of Varix Aggravation Post-DAA Therapy in Cirrhotic HCV Patients

Recent observations indicate that some cirrhotic patients may experience worsening gastroesophageal varices after undergoing direct-acting antiviral (DAA) therapy.

Risk Stratification and Outcomes of Gastroesophageal Varices in HCV Cirrhosis Undergoing DAA Therapy

This study prospectively enrolled 478 patients with hepatitis C virus (HCV)-related cirrhosis who initiated direct-acting antiviral (DAA) therapy between February 2019 and December 2021 across 33 Japanese institutions.

Decompensated cirrhosis was defined as Child-Pugh class B or C at the initiation of DAA therapy, or Child-Pugh class A with a prior history of decompensation.

Gastroesophageal varices were classified as F1 (small-caliber), F2 (moderately enlarged), and F3 (markedly enlarged) according to Japanese criteria (Tajiri T, et al. 2010; 22:1–9).

Patients were categorized into two variceal risk groups: low-risk varices, defined as no varices or F1 varices without red color signs, and high-risk varices, defined as F2 or greater varices, those with red color signs, or a history of variceal rupture.

Variceal aggravation was defined as requiring prophylactic treatment or the rupture of gastroesophageal varices.

The study assessed cumulative incidence rates and factors associated with variceal aggravation following DAA therapy.

Sustained virologic response (SVR) was defined as undetectable serum HCV-RNA at 12 or 24 weeks after the conclusion of therapy.

Variceal Aggravation Risk Factors and Outcomes in HCV Cirrhosis Post-DAA Therapy

The median patient age was 70 years, with 43% presenting with decompensated cirrhosis and 16% having high-risk varices (13% in compensated vs. 33% in decompensated, p < 0.001).

SVR rates were 94.9% for patients with compensated cirrhosis and 91.3% for those with decompensated cirrhosis (p = 0.120).

Over a median follow-up of 35.7 months, 25 patients required prophylactic treatment for varices, and 4 experienced variceal rupture.

The cumulative 3-year variceal aggravation rate was 6.2% (3.5% in compensated cirrhosis vs. 9.9% in decompensated cirrhosis, p = 0.001).

In multivariate Cox proportional hazards analysis, factors significantly associated with variceal aggravation included high-risk varices (p < 0.001), elevated baseline gamma-glutamyl transpeptidase (GGT) levels (p = 0.001), and virologic failure (p = 0.018). The variceal aggravation rates were as follows:

22.8% in patients with high-risk varices vs. 3.9% in those with low-risk varices,

11.3% in patients with baseline GGT ≥75 U/L vs. 4.5% in those with GGT <75 U/L, and

46.7% in patients with virologic failure vs. 5.9% in those achieving SVR.

Key Insight

Over a three-year period, the cumulative aggravation rate of varices was significantly higher in patients with decompensated cirrhosis (9.9%) compared to those with compensated cirrhosis (3.5%).

In hepatitis C virus (HCV) cirrhotic patients treated with direct-acting antivirals (DAAs), key risk factors for variceal aggravation included baseline variceal status, elevated baseline gamma-glutamyl transpeptidase (GGT) levels, and virologic response.

By - Eeshan Aggarwal

Reference: Hepatology. Volume 80, Issue S1. Abstract Supplement for The Liver Meeting by the American Association for the Study of Liver Diseases (AASLD), November 15-19, 2024, San Diego, CA.