Viral elimination is essential for improving surgical outcomes of hepatitis C virus‐related hepatocellular carcinoma: Multicenter retrospective analysis

Abstract

Aim The impact of sustained virologic response (SVR) on surgical outcomes for patients with hepatitis C virus (HCV)‐related hepatocellular carcinoma (HCC) remains controversial. This study aimed to evaluate the influence of SVR on long‐term surgical outcomes after hepatectomy. Methods This multicenter study included 504 patients who underwent curative resection for HCV‐related HCC. Patients with a history of HCC treatment, HBV infection, poor liver function, and tumor with major vascular invasion were excluded. Long‐term surgical outcomes (overall survival [OS] and recurrence‐free survival [RFS]) among patients who achieved SVR before hepatectomy (Pre‐SVR group: 58 patients), after hepatectomy (Post‐SVR group: 54 patients), and without SVR (Non‐SVR group: 186 patients) were compared after adjusting for 13 confounding factors. Using the surgically resected specimens, comparison of the pathological changes in liver fibrosis between the first and second hepatectomy were analyzed. Results Patients with SVR were younger, had better liver function, and less liver fibrosis compared to patients without SVR. Propensity score‐matched OS and RFS were significantly better in Pre‐SVR group than Non‐SVR group ( P = .029 and P = .009, respectively). Inverse probability‐weighted OS and RFS were also significantly better in the Post‐SVR group ( P = .001 and P = .021, respectively) than in the Non‐SVR group. Histopathological evaluation revealed that only the patients with SVR had regression of liver fibrosis ( P < .05). Conclusion Achievement of SVR before or after hepatectomy is essential for improving long‐term surgical outcomes in patients with HCV‐related HCC.

Effects of Achieving SVR on Clinical Characteristics and Surgical Outcomes in Patients Who Developed Early-Stage HCV-Related Hepatocellular Carcinoma and Received Curative Resection: Preoperative versus Postoperative SVR

“…In our study, lower levels of liver enzymes, a higher proportion of ALBI grade I, higher platelet counts, and a numerically lower incidence of liver cirrhosis in patients achieving SVR before HCC diagnosis indicated that HCV clearance improved hepatitis, leading to a lower degree of liver fibrosis and incidence of cirrhosis as well as a better liver function. These findings were consistent with the results of prior studies [24][25][26][27]. Notably, as many as 75.6% of patients who developed HCC after achieving SVR did not have cirrhosis.…”

“…At the same time, patients with persistent viremia had worse surgical outcomes. One multicenter study including 504 Japanese patients who had HCV-related HCC and underwent curative resection exhibited significantly better survival outcomes in patients achieving SVR either before or after hepatectomy than those without SVR [27]. Another study from Japan showed that achieving SVR before HCC development allowed a superior clinical outcome after curative ablation in HCV-related HCC patients [36].…”

The Recent Development of the Surgical Treatment for Hepatocellular Carcinoma

“…Today HCV can be eliminated in almost all cases, and it is necessary to clarify that at least antiviral treatment has not worsened the surgical outcomes of HCC. Therefore, in a multicenter study, we investigated the impact of SVR before and after hepatectomy on the long-term surgical outcomes of HCV-related HCC after statistically minimizing bias arising from patients' background characteristics [77]. Two hundred ninety-six patients underwent radical hepatectomy for primary HCV related HCC, of which 58 achieved SVR before hepatectomy (Pre-SVR group), 54 achieved SVR after hepatectomy, and 186 without achieving SVR (Non-SVR group).…”

Phase I study of a novel therapeutic vaccine as perioperative treatment for patients with surgically resectable hepatocellular carcinoma: The YCP02 trial

“…Liver resection is one of the most favorable treatments for HCC, but the recurrence rate after surgery is 70%, which is extremely high 2,3 . Various adjuvant therapies, including viral elimination, hepatic infusion chemotherapy, systemic chemotherapy, and immunotherapy, have been used to prevent recurrence 4–7 . However, no adjuvant therapy in phase III trials has shown a significant survival benefit for patients with resectable HCC, and the development of effective adjuvant therapies is warranted.…”

“…2,3 Various adjuvant therapies, including viral elimination, hepatic infusion chemotherapy, systemic chemotherapy, and immunotherapy, have been used to prevent recurrence. [4][5][6][7] However, no adjuvant therapy in phase III trials has shown a significant survival benefit for patients with resectable HCC, and the development of effective adjuvant therapies is warranted. By contrast, the effectiveness of the combination therapy of atezolizumab, an immune checkpoint inhibitor (ICI), and bevacizumab, an angiogenesis inhibitor, for the treatment of unresectable HCC was reported in 2020, and this drug combination is now the standard treatment for unresectable HCC with preserved liver function.…”