Long-Term Risk of Hepatic and Extrahepatic-Related Events After Direct Antiviral Therapy for Chronic Hepatitis C: A Prospective Long-Term Study Cohort

Abstract

Novel direct antiviral-acting (DAA) molecules significantly improved efficacy and ameliorated outcomes of patients with chronic hepatitis C (CHC). The extensive use of DAA from 2015, due to large access to therapy, maximized rates of viral eradication with a safety profile in the majority of cases.

Aims: We evaluated risk factors and the incidence of related clinical events and hepatocellular carcinoma (HCC) in cases with sustained virologic response (SVR) after DAA. We also aimed to apply a score assessment to identify the individual patient with unfavorable outcomes during an average follow-up (FU) of five years.

Methods: In total, 470 cases consecutively recruited with CHC have been compared by non-invasive tests (NIT), as APRI, FORNS, FIB-4, LSPS, and transient elastography (TE) liver stiffness measurement (LSM), to identify cutoff related to major event onset.

Results: Grouping of cases without or with related events development of both types hepatic (HE) (i.e., HCC or further cirrhosis decompensation or/with hospitalized septic state) or extrahepatic (EHE) (i.e., other tumors, bleeding, or thrombotic episodes and other organs pathologic conditions not liver related)allowed us to select the parameters to propose a novel risk stratification system (RISS) for the identification of the remnant individual patient's risk for HCC occurrence, orthotopic liver transplant (OLT) need, or death during long-term follow-up (FU).

Conclusions: Patients with cirrhosis and portal hypertension (PH) maintained a higher LSM mean value (>25 kPa), showed the lowest reduction of NIT scores, and developed events in 80/108 (74%) cases (67 and 13 of HE and EHE type), even after long-term successful DAA therapy. Furthermore, cases with RISS score ≥ 8 demonstrated a significant incidence of HCC (37/46, 80.4%) and a reduction in survival rate to 65.4% at 5-year FU.

Keywords: chronic hepatitis C; direct-acting antivirals; hepatic and extrahepatic events; hepatitis C virus infection; hepatocellular carcinoma.

Figure 1

Flowchart of patients recruited, grouping by CLDS at basal time and at last FU and by cases without or with incidence of events during a 5-year FU.

Figure 2

Survival probability according to basal time CLDS at 5-year FU estimation.

Figure 3

Survival probability according to cases without or with PH at 5-year FU estimation.

Figure 4

Probability of all events (HE and EHE type) according to categories of RISS.

Figure 5

Probability of HCC occurrence according to risk categories of RISS.

Figure 6

Probability of requiring OLT or dead according to risk categories of RISS.