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Introduction: In this multicenter clinical study, we aimed to investigate the efficacy and safety of the transhepatic arterial administration of granulocyte-colony stimulating factor (G–CSF)–mobilized autologous peripheral blood (PB)-CD34+ cells compared with standard therapy in patients with decompensated cirrhosis type C. Methods: Patients were randomly assigned (2:1) to the CD34+ cell transplant (CD34+ cell) or standard-of-care (SOC) group and followed up for 52 weeks. The primary endpoints were the non-progression rate of Child-Pugh (CP) scores at 24 weeks post-enrollment and the safety of the protocol treatment. Results: Fourteen patients (CD34+ cell group: 10; SOC group: 4) were enrolled. CP scores at 24 weeks had a non-progression rate of 90% in the CD34+ cell group and 100% in the SOC group, with no significant difference between groups. Importantly, 4 out of 10 patients in the CD34+ cell group exhibited an improvement from decompensated to compensated cirrhosis, whereas all patients in the SOC group remained in decompensated cirrhosis. With regard to secondary endpoints, a trend toward increased serum albumin levels in the CD34+ cell group was noted. Serious adverse events (SAEs) occurred in three patients in the CD34+ cell group and in one patient in the SOC group. No causal relationship was observed between all SAEs and G-CSF, leukapheresis, or cell transplantation in the CD34+ cell group. No patients died and no hepatocellular carcinoma occurred within the study period. Conclusions: PB-CD34+ cell infusion therapy may have the potential to circumvent the decompensated stage of cirrhosis, thus avoiding the need for liver transplantation.

Backgrounds and Aims: Cirrhosis and hepatocellular carcinoma (HCC) are potentially fatal complications of chronic hepatitis C virus (HCV) infection. We investigated how compensated cirrhosis and a history of curatively treated HCC influenced patient mortality after HCV eradication, that is, sustained virologic response (SVR). Methods: We studied 5458 patients with confirmed SVR who were prospectively followed up for more than 1 year after SVR achieved with direct-acting antivirals. Mortality and the incidence of HCC development after SVR were analyzed based on the presence or absence of compensated cirrhosis or a history of curatively treated HCC before the start of therapy. Results: Mortality and the incidence of post-SVR HCC were significantly higher in patients with compensated cirrhosis and those with a history of curatively treated HCC than in those without these complications. Multivariate analysis showed that a history of HCC was associated with high mortality after SVR. In patients with no history of HCC, cirrhosis was associated with high mortality. Although both liver-related and nonliver-related mortality rates were significantly higher in patients with a history of HCC or cirrhosis, nonliver-related mortality did not differ based on HCC history, and liver-related and nonliver-related mortality were comparable regardless of cirrhosis after propensity score matching with age, gender, alcohol intake, and comorbidities. Conclusion: Mortality after SVR was significantly higher in patients with compensated cirrhosis or a history of HCC. While a history of HCC significantly increased mortality after SVR, even following curative treatment, the impact of pre-SVR compensated cirrhosis on post-SVR mortality was modest.

Introduction and aim. We assessed the characteristics of virological response to a combination treatment of ombitasvir, paritaprevir, and ritonavir in hepatitis C virus genotype 1-infected elderly Japanese patients.Material and Methods. This multicenter prospective study was conducted at six locations in Japan. Seventy patients with chronic hepatitis C virus genotype 1b infection were orally administered ombitasvir/paritaprevir/ritonavir once daily for 12 weeks. The primary endpoint was the proportion of elderly patients with sustained virological response (SVR) 12 weeks after the completion of treatment. Adverse events were also recorded to evaluate drug safety and tolerability during the trial period. SVR in elderly patients (age > 65; 94% [47 / 50]) was lower than that in younger patients (100% [20 / 20]).Results. No significant differences in SVR 12 weeks after the completion of treatment were observed between the age groups (P = 0.153). Adverse events were observed in 16 patients (23.3%). Multivariate analysis confirmed that the change or discontinuation of concomitant drugs owing to drug interactions was independent of risk factors for adverse events associated with this drug combination (P = 0.015; odds ratio, 15.9; 95% confidence interval, 1.79 - 148). Ombitasvir/paritaprevir/ritonavir combination treatment was highly effective in elderly patients.Conclusion. Tolerability should be monitored in older patients for whom concomitant medications are discontinued or changed because of drug interactions.