Reply to: “Direct-acting antiviral therapy in patients with hepatocellular cancer: The timing of treatment is everything” and “More extended indication of DAA therapy in patients with HCC, affordability, and further statistical considerations”

Abstract

We suggest that the application of multi-level analysis and missing-value analysis is a statistical necessity for this study. Firstly, in Beste et al. 1 , 426 patients with HCC were collected from 167 medical centers; therefore, small VA medical centers may have contributed few or no HCC patients. In Table 4 of the paper by Beste et al. 1 , there was no hospital or geographic information variable in the final regression model, which implies that large VA medical centers could over-represent patients or hospitals. This concern can be appropriately adjusted by a hierarchical modeling approach using multi-level analysis at patient, as well as at hospital levels. 9 Secondly, authors used an assumption of randomly missing data (11.6% of HCC patients) based on unclear multiple imputation methods. Randomness of missing data could be raised from not only the amount of missing data but also from a higher discontinuation rate in the missing group that might have resulted from these patients' intention to leave the VA health care system to receive additional or new therapy for any reason. To confirm the absence of missing not at random data, it is necessary to utilize multiple imputation methods by emerging approaches, multiple imputation using chained equations, and a visualization of Monte Carlo simulation results. 10 Conflict of interest The authors who have taken part in this study declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.

Direct acting antivirals treatment for hepatitis C virus infection does not increase the incidence of de novo hepatocellular carcinoma occurrence

“…In patients with HCC, without cirrhosis or with compensated cirrhosis, who have an indication for liver transplantation, the ideal timing for antiviral therapy (before or after liver transplantation) remains debated. 123,124 Lower SVR rates were reported in patients with HCC treated with regimens including sofosobuvir, sofosbuvir and ledipasvir, or ombitasvir and ritonavirboosted paritaprevir plus dasabuvir, with or without ribavirin, than in patients without HCC or in patients with HCC treated after liver transplantation (74% vs. 91% and 94%, respectively). 125 Post-liver transplantation treatment of HCV was reported to be cost-effective in patients with HCC.…”

Insufficient accuracy of computed tomography-based portal pressure assessment in hepatitis B virus-related cirrhosis: An analysis of data from CHESS-1601 trial

“…We thank Qi et al 1 for their interest in our study entitled ''Accurate computed tomography-based portal pressure assessment in patients with hepatocellular carcinoma". 2 This study proposes a non-invasive computed tomography (CT)-based model for predicting the level of hepatic venous pressure gradient (HVPG) in patients with cirrhosis, using the formula:…”

Direct-acting antiviral therapy in patients with hepatocellular cancer: The timing of treatment is everything

“…We read with interest the recent publication by Beste and colleagues, which focused on the negative impact of hepatocellular cancer (HCC) on SVR in a large cohort of patients treated with direct-acting antiviral agents (DAA) in the Veteran Affairs (VA) program. 1 The authors report that patients who had undergone liver transplantation for HCC (HCC/LT) had a rate of SVR similar to patients without HCC (no-HCC), with a lower rate of SVR seen in those patients with HCC who did not undergo LT (HCC).…”

“…In this study, patients with HCC were more likely to have advanced liver disease (85% vs. 28%), and decompensated cirrhosis (31% vs. 7%) compared to patients with no-HCC. 1 Moreover, advanced liver disease has been shown to negatively impact on the rate of SVR in patients treated with DAAs. 3 Lower SVR rates were seen in patients with genotype 1 HCV treated with a sofosbuvir based regimen, than patients treated with protease inhibitor based regimens.…”

“…We read with interest the study by Beste et al 1 identifying the remarkable achievement of a hepatitis C (HCV) viral cure with direct-acting antivirals (DAAs) in patients diagnosed with hepatocellular carcinoma (HCC), who did or did not receive liver transplantation (LT). The findings of Beste et al 1 are consistent with recent studies by Yang et al 2 showing that HCC was the leading cause of LT among waitlisted patients. The post-DAAs era (year 2011-2014) was associated with a decreased risk of graft loss or death, with the largest effect seen in HCV-infected recipients.…”