Hepatitis C Eradication With Direct-acting Anti-virals Reduces the Risk of Variceal Bleeding

Andrew M. Moon; Pamela K. Green; Don C. Rockey; Kristin Berry; George N. Ioannou

Disclosures

Aliment Pharmacol Ther. 2020;51(3):364-373. 

In This Article

Results

Characteristics of Study Population

Patients with (n = 29,998) and without SVR (n = 3,584) were of similar age (61.1 vs 60.6 years), sex (96.6% vs 98.1% male), and race/ethnicity (52.4% vs 52.7% white/non-Hispanic) (Table 1). Patients without SVR were more likely to have cirrhosis (41.1% vs 26.4%), nonbleeding varices (11.6% vs 5.0%), and bleeding varices (2.9% vs 1.4%).

There were 9,399 patients with cirrhosis, including 7,927 (84.3%) who achieved SVR and 1,472 (15.7%) who did not achieve SVR (Table 2). Baseline demographic characteristics and MELD scores were similar among cirrhotic patients who did and did not achieve SVR. Patients without SVR had a higher proportion of complications of cirrhosis, including varices without bleeding (27.5% vs 18.2%), varices with bleeding (7.1% vs 5.1%), encephalopathy (28.2% vs 18.3%) and hepatocellular carcinoma (13.5% vs 6.1%).

Association Between SVR and Variceal Bleeding

All Patients. During a mean follow-up time of 3.1 years, 549 patients developed variceal bleeding (incidence 0.53 per 100 patient-years) (Table 3). Among patients with SVR (n = 29,998), 434 developed variceal bleeding (incidence 0.46 per 100 patient-years) compared to 115 of 3,584 patients without SVR (1.26 per 100 patient-years) and this difference was statistically significantly different after adjustment for baseline characteristics (adjusted hazards ratio [AHR] 0.66, 95% CI 0.52–0.83). SVR was also associated with a reduced risk of variceal bleeding in many clinically relevant subgroups that we evaluated, such as patients with cirrhosis (AHR 0.73, 95% CI 0.57–0.93), without cirrhosis (AHR 0.33, 95% CI 0.17–0.65), MELD < 9 (AHR 0.41, 95% CI 0.28–0.61), alcohol use disorder (AHR 0.65, 95% CI 0.48–0.88) and no alcohol use disorder (AHR 0.67, 95% CI 0.45–0.99).

Patients With Cirrhosis. Among 9,399 patients with cirrhosis, 480 (5.1%) developed variceal bleeding during 3.1 years of mean follow-up (incidence 1.66 per 100 patient years). The incidence of variceal bleeding was lower among those with SVR (1.55 per 100 patient-years) compared to those without SVR (2.96 per 100 patient-years) and this difference remained statistically significantly after multivariable adjustment in Cox proportional hazards models (AHR 0.73, 95% CI 0.57–0.93) (Table 3 and Figure 2).

Figure 2.

Cumulative incidence curves among patients with SVR vs no SVR by presence of cirrhosis, varices and variceal bleeding. The cumulative incidence of variceal haemorrhage among patients with and without sustained virologic response (SVR) after direct-acting anti-viral (DAA) treatment for hepatitis C virus (HCV) in (A) patients with cirrhosis, (B) patients without prior cirrhosis, (C) patients with prior variceal bleed and (D) patients with prior varices

Patients With a Prior History of Varices or Variceal Bleeding. The absolute incidence of variceal bleeding after anti-viral treatment was much greater in patients who had a prior history of variceal bleeding (13.38 per 100 patient-years) or varices without bleeding (3.71 per 100 patient-years) than in patients who had no prior history of varices (0.20 per 100 patient-years). Patients with SVR had a lower incidence of variceal bleeding than patients without SVR among those without prior varices (0.17 vs 0.56 per 100 patient-years), with prior nonbleeding varices (3.48 vs 4.87 per 100 patient-years) and with prior bleeding varices (12.86 vs 16.38 per 100 patient-years) (Table 3 and Figure 2). In the Cox proportional hazards models, the difference in variceal bleeding rate by SVR was statistically significant among patients without prior varices (AHR 0.52, 95% CI 0.35–0.76) but not among those with nonbleeding varices (AHR 0.77, 95% CI 0.52–1.15) or bleeding varices (AHR 0.60, 95% CI 0.33–1.09).

Characteristics Associated With Variceal Bleeding. In the multivariable Cox proportional hazards model among patients with cirrhosis (Table 4), characteristics associated with the risk of variceal bleeding included prior varices without bleeding (AHR 3.09, 95% CI 2.39–4.00), prior varices with bleeding (AHR 9.39, 95% CI 7.08–12.46), nonselective beta blocker use (AHR 1.37, 95% CI 1.08–1.72), ascites (AHR 1.71, 95% CI 1.02–2.87), spontaneous bacterial peritonitis (SBP) (AHR 2.15, 95% CI 1.31–3.52), PLT > 100–150 (AHR 4.42, 95% CI 1.08–18.07) and PLT ≤ 100 (AHR 6.68, 95% CI 1.64–27.17) vs PLT > 250, and haemoglobin ≤ 13.6 vs > 15.6 (AHR 2.12, 95% CI 1.43–3.15). Increasing MELD scores were associated with an increased risk of variceal bleed, although this did not meet statistical significance for MELD 16–19 (AHR 1.31, 95% CI 0.69–2.51) or MELD > 19 (AHR 2.00, 95% CI 0.90–4.43) potentially due to fewer patients with advanced cirrhosis receiving DAAs. Variables associated with a decreased risk of variceal bleeding included SVR (AHR 0.68, 95% CI 0.53–0.86) and black/non-Hispanic race/ethnicity (AHR 0.74, 95% CI 0.56–0.99).

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