Management of betablocked patients after sustained virological response in hepatitis C cirrhosis

Abstract

BACKGROUND Current guidelines do not address the post–sustained virological response management of patients with baseline hepatitis C virus (HCV) cirrhosis and oesophageal varices taking betablockers as primary or secondary prophylaxis of variceal bleeding. We hypothesized that in some of these patients portal hypertension drops below the bleeding threshold after sustained virological response, making definitive discontinuation of the betablockers a safe option. AIM To assess the evolution of portal hypertension, associated factors, non-invasive assessment, and risk of stopping betablockers in this population. METHODS Inclusion criteria were age > 18 years, HCV cirrhosis (diagnosed by liver biopsy or transient elastography > 14 kPa), sustained virological response after direct-acting antivirals, and baseline oesophageal varices under stable, long-term treatment with betablockers as primary or secondary bleeding prophylaxis. Main exclusion criteria were prehepatic portal hypertension, isolated gastric varices, and concomitant liver disease. Blood tests, transient elastography, and upper gastrointestinal endoscopy were performed. Hepatic venous pressure gradient (HVPG) was measured five days after stopping betablockers. Betablockers could be stopped permanently if gradient was < 12 mmHg, at the discretion of the attending physician. RESULTS Sample comprised 33 patients under treatment with propranolol or carvedilol: median age 64 years, men 54.5%, median Model for End-Stage Liver Disease (MELD) score 9, Child-Pugh score A 77%, median platelets 77.000 × 10 3 /µL, median albumin 3.9 g/dL, median baseline transient elastography 24.8 kPa, 88% of patients received primary prophylaxis. Median time from end of antivirals to gradient was 67 wk. Venous pressure gradient was < 12 mmHg in 13 patients (39.4%). In univariate analysis the only associated factor was a MELD score decrease from baseline. On endoscopy, variceal size regressed in 19/27 patients (70%), although gradient was ≥ 12 mmHg in 12/19 patients. The elastography area under receiver operating characteristic for HVPG ≥ 12 mmHg was 0.62. Betablockers were stopped permanently in 10/13 patients with gradient < 12 mmHg, with no bleeding episodes after a median follow-up of 68 wk. CONCLUSION Portal hypertension dropped below the bleeding threshold in 39% of patients more than one year after antiviral treatment. Endoscopy and transient elastography are inaccurate for reliable detection of this change. Stopping betablockers permanently seems uneventful in patients with a gradient < 12 mmHg.

Should we continue surveillance for hepatocellular carcinoma and gastroesophageal varices in patients with cirrhosis and cured HCV infection?

“…As follow-up of patients cured with DAAs extends, more data concerning their effect on the development of GEV is emerging (Supplementary table 2) [90][91][92][93][94][95][96]. In a large French cohort including 246 patients with Child-Pugh A cirrhosis due to chronic viral hepatitis (70% HCV), the cumulative rates of de novo large GEV at 1, 3 and 5 years after SVR were 2%, 4% and 4%, respectively [92].…”

“…Achieving SVR has been related to a reduced risk of variceal bleeding in patients with advanced liver disease [35,99]. Indeed, although GEV progression is often reported, variceal bleeding after DAA-based HCV eradication appears to be rare within the first years, especially in patients without GEV prior to antiviral therapy (Table 2) [47,86,87,90,96,[99][100][101]. The average bleeding rate from four prospective studies (including a total of 1323 patients with HCV-related cirrhosis) was 1% after a follow-up of approximately 3 years following SVR [47,86,87,101].…”

Kinetics of emergence of liver complications in hepatitis C virus infected patients and advanced fibrosis, with and without HIV-coinfection, after sustained virological response

“…In individuals lost to follow-up, the vital status was determined by contacting the patient or a next of kin and information on liver events was obtained from patients' electronic clinical records at each centre. In line with other studies, patients with liver stiffness value at least 14.0 kPa before DAA therapy were considered as cirrhotic [23][24][25][26]. SVR was defined as undetectable HCV RNA 12 weeks after the end of HCV therapy.…”

Beta-blockers and Statins: Role in Portal Hypertension and Beyond

“…New non-invasive methods, especially hepatic elastography and, more recently, splenic elastography for monitoring the hemodynamic response of these patients may facilitate the performance of long-term studies with a larger patient population. Splenic elastography has a higher correlation with portal hypertension than hepatic elastography [7,[17][18][19] . It is believed that the measurement of splenic stiffness is directly related to portal hypertension and is highly accurate as a non-invasive method for the diagnosis of esophageal varices, especially in those at high risk of bleeding is more precise to hemodynamic changes in the course of liver disease.…”