Short-term hepatocyte function and portal hypertension outcomes of sofosbuvir/velpatasvir for decompensated hepatitis C-related cirrhosis

Abstract

Background: It is unclear whether hepatocyte function and/or portal hypertension improves if a sustained virologic response (SVR) is achieved with direct-acting antivirals in patients with decompensated hepatitis C-related cirrhosis.

Methods: We examined the safety and efficacy of a 12-week course of sofosbuvir/velpatasvir (SOF/VEL) in 20 patients with decompensated hepatitis C-related cirrhosis. We also investigated changes in the hepatocyte receptor index (LHL15) and blood clearance index (HH15) by Tc-99 m-galactosyl human serum albumin scintigraphy, liver stiffness measurement (LSM) by transient elastography, and hepatic venous pressure gradient (HVPG) in patients who achieved an SVR at 24 weeks after treatment (SVR24).

Results: One patient discontinued treatment because of rectal variceal hemorrhage, and 19 patients completed treatment. SVR24 was achieved in 17 patients (89%). Median LHL15 increased from 0.72 pre-treatment to 0.82 after SVR24 (p = 0.012), and median HH15 decreased from 0.82 pre-treatment to 0.76 after SVR24 (p = 0.010). The percentage of patients with LSM ≥ 20 kPa was 90% before treatment and remained at 90% after SVR24. However, the percentage with severe portal hypertension (defined as HVPG ≥ 12 mmHg) decreased from 92% pre-treatment to 58% after SVR24 (p = 0.046). Patients with a decreased HVPG from pre-treatment to after SVR24 had a smaller pre-treatment spleen volume than those with an increased HVPG (median, 252 vs. 537 mL, p = 0.028).

Conclusion: Achieving SVR24 with SOF/VEL treatment in patients with decompensated hepatitis C-related cirrhosis can be expected to improve hepatocyte function and portal hypertension on short-term follow-up.

Keywords: Hepatitis C; Liver cirrhosis; Portal hypertension; Sofosbuvir; Velpatasvir.

Fig. 1

Study flowchart. HCV hepatitis C virus, CT computed tomography, Tc-99 m-GSA technetium-99 m-galactosyl human serum albumin, TE transient elastography, HVPG hepatic venous pressure gradient, SOF sofosbuvir, VEL velpatasvir, SVR24 sustained virologic response at 24 weeks after treatment

Fig. 2

Changes in Tc-99 m-galactosyl human serum albumin scintigraphy data before sofosbuvir/velpatasvir treatment and after sustained virologic response at 24 weeks post-treatment (SVR24). Hepatocyte receptor index (LHL15) increased from 0.72 (0.61–0.77) to 0.82 (0.71–0.86) (p = 0.012) (a), and blood clearance index (HH15) decreased from 0.82 (0.77–0.84) to 0.76 (0.62–0.80) (p = 0.010) (b), after SVR24 compared with before treatment

Fig. 3

Tc-99 m-galactosyl human serum albumin scintigraphic images obtained from a 65-year-old man with genotype 2b infection before sofosbuvir/velpatasvir treatment and after sustained virologic response at 24 weeks post-treatment (SVR24). Before treatment, the planar image shows weak accumulation of radiotracer in the liver and enhanced pooling in the heart; hepatocyte receptor index (LHL15) and blood clearance index (HH15) were 0.70 and 0.78, respectively (a). After SVR24, liver accumulation of radiotracer increased and cardiac pooling decreased; LHL15 and HH15 improved to 0.85 and 0.63, respectively (b). The patient’s hepatic functional reserve improved from Child–Pugh-Turcotte grade B to grade A after SVR24

Fig. 4

Changes in percentages of patients with severe portal hypertension, defined as hepatic venous pressure gradient (HVPG) ≥ 12 mmHg, before sofosbuvir/velpatasvir treatment and after sustained virologic response at 24 weeks post-treatment (SVR24). The percentage was 92% (11/12) before treatment and significantly decreased to 58% (7/12) after SVR24 (p = 0.046)