Successful antiviral treatment of chronic hepatitis C leads to a rapid decline of liver stiffness without an early effect on spleen stiffness
Authors: Wim Verlinden, Sven Francque, Peter Michielsen, Thomas Vanwolleghem
Journal: Hepatology (2016)

Recently, Sack et al. reported the development of a variceal hemorrhage in a patient with cirrhosis 3.5 years after pegylated interferon (IFN)/ribavirin-induced hepatitis C virus (HCV) eradication.1 This case highlights a persistent risk of portal hypertensive complications in cirrhosis despite attaining sustained viral response (SVR). The authors suggested that similar cases are to be expected with the increased treatment and SVR rates of patients with cirrhosis with IFN-free regimens. We hereby present a case of a 49-year-old patient of Asian descent diagnosed with HCV cirrhosis and esophageal varices, without ascites or encephalopathy. Laboratory results showed trombocytopenia, but a preserved liver function, illustrated by a Model for End-Stage Liver Disease score of 7. Real-time shear wave elastography (SWE) before treatment showed liver stiffness (LS) of 17.5 kPa. Treatment consisted of 12 weeks simeprevir, sofosbuvir, and ribavirin, but the patient presented at week 11 with melena and anemia. Endoscopy showed large esophageal varices that were treated successfully by band ligation. SWE at that time showed LS of 15.3 kPa and spleen stiffness (SS) of 43 kPa. Continued antiviral treatment led to an end-of-treatment (EoT) and sustained viral response at week 12 (SVR12), at which LS had decreased further to 12.0 kPa, but SS had remained unchanged (43.8 kPa). This case demonstrates a persistent risk of variceal hemorrhage near the end of successful antiviral treatment at a stage where LS had already decreased. We currently evaluate the immediate effect of direct-acting antiviral treatment on tissue stiffness in patients with advanced fibrosis. Fifty-eight patients have reached EoT, of which 39 reached SVR12. Paired baseline (BL)-EoT and EoT-SVR12 SS results were obtained for 10 and 16 patients, respectively. Overall, LS significantly decreased from BL (12.9 kPa) to EoT (10.9 kPa) and decreased further from EoT to SVR12 (10.1 kPa). SS did not decrease significantly from BL (26.7 kPa) to EoT (25.3 kPa), nor from EoT (25.0 kPa) to SVR12 (25.1 kPa) (Fig. 1). To our knowledge, this is the first study that investigates the effect of SVR on SS. Our preliminary results show that HCV eradication is associated with a rapid decline in LS, without any effect on SS. This decrease in LS was paralleled by a significant decline in transaminase values, which suggests that the decrease in LS can be attributed to a reduction in inflammation. Previous studies have shown a very good diagnostic accuracy of SS to predict the presence of portal hypertension and varices,2 with one study showing an immediate decrease in SS, but not in LS, after transjugular intrahepatic portosystemic shunt placement.3 We presume that the rapid effect of treatment on LS does not translate into an immediate effect on portal hypertension represented by an unchanged SS, and thus does not diminish the risk of variceal hemorrhage in the short term. Wim Verlinden, M.D.1,2 Sven Francque, M.D., Ph.D.1,2 Peter Michielsen, M.D., Ph.D.1 Thomas Vanwolleghem, M.D., Ph.D.1,2 1Department of Gastroenterology and HepatologyAntwerp University Hospital 2Laboratory of Experimental Medicine and Pediatrics University of Antwerp Antwerp, Belgium