Hepatocellular Carcinoma after Achievement of Sustained Viral Response with Daclatasvir and Asunaprevir in Patients with Chronic Hepatitis C Virus Infection.

Interferon-based antiviral therapies against hepatitis C virus (HCV) infection have been shown to reduce the incidence of hepatocellular carcinoma (HCC) in patients with sustained viral response (SVR). Recently, direct-acting antivirals (DAAs) have been proven to be much more effective in achieving SVR than interferon-based therapies. However, whether DAAs can efficiently prevent the occurrence of HCC after SVR remains controversial. To clarify this issue, we analyzed the clinical features of patients in whom HCC developed after achievement of SVR with DAAs for chronic HCV infection. Among patients who achieved SVR with daclatasvir and asunaprevir (n = 100), HCC developed in 17 patients (HCC group; n = 17) and did not develop in 83 patients (non-HCC group; n = 83) during a mean observation period of 15 months. A multivariate Cox proportional hazards analysis identified past history of HCC and male sex as significant risk factors for the emergence of HCC after DAAs. Sixteen cases with HCC after DAAs were in the very early or early stage (16/17, 94.1%), and one case was in the advanced stage (1/17, 5.9%) with portal venous tumor thrombus. Radiofrequency ablation and/or transarterial chemoembolization were performed in most cases as curative therapy (16/17, 94.1%). Key Messages: SVR by DAAs did not completely prevent the occurrence of HCC. However, even if HCC did develop after SVR, curative anticancer therapy was applicable in most cases.

Ida H ，Hagiwara S ，Kono M ，Minami T ，Chishina H ，Arizumi T ，Takita M ，Yada N ，Minami Y ，Ueshima K ，Nishida N ，Kudo M ... -  《-》

Hypovascular tumors developed into hepatocellular carcinoma at a high rate despite the elimination of hepatitis C virus by direct-acting antivirals.

Tabu K ，Mawatari S ，Oda K ，Kumagai K ，Inada Y ，Uto H ，Saisyoji A ，Hiramine Y ，Hashiguchi M ，Tamai T ，Hori T ，Fujisaki K ，Imanaka D ，Kure T ，Taniyama O ，Toyodome A ，Ijuin S ，Sakae H ，Sakurai K ，Moriuchi A ，Kanmura S ，Ido A ... -  《-》

Sustained virologic response to direct-acting antiviral therapy in patients with chronic hepatitis C and hepatocellular carcinoma: A systematic review and meta-analysis.

The effect of hepatocellular carcinoma (HCC) on the response to interferon-free direct-acting antiviral (DAA) therapy in patients with chronic hepatitis C (CHC) infection remains unclear. Using a systematic review and meta-analysis approach, we aimed to investigate the effect of DAA therapy on sustained virologic response (SVR) among patients with CHC and either active, inactive or no HCC. PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from 1/1/2013 to 9/24/2018. The pooled SVR rates were computed using DerSimonian-Laird random-effects models. We included 49 studies from 15 countries, comprised of 3,341 patients with HCC and 35,701 without HCC. Overall, the pooled SVR was lower in patients with HCC than in those without HCC (89.6%, 95% CI 86.8-92.1%, I2 = 79.1% vs. 93.3%, 95% CI 91.9-94.7%, I2 = 95.0%, p = 0.0012), translating to a 4.8% (95% CI 0.2-7.4%) SVR reduction by meta-regression analysis. The largest SVR reduction (18.8%) occurred in patients with active/residual HCC vs. inactive/ablated HCC (SVR 73.1% vs. 92.6%, p = 0.002). Meanwhile, patients with HCC who received a prior liver transplant had higher SVR rates than those who did not (p <0.001). Regarding specific DAA regimens, patients with HCC treated with ledipasvir/sofosbuvir had lower SVR rates than patients without HCC (92.6%, n = 884 vs. 97.8%, n = 13,141, p = 0.026), but heterogeneity was high (I2 = 84.7%, p <0.001). The SVR rate was similar in patients with/without HCC who were treated with ombitasvir/paritaprevir/ritonavir ± dasabuvir (n = 101) (97.2% vs. 94.8%, p = 0.79), or daclatasvir/asunaprevir (91.7% vs. 89.8%, p = 0.66). Overall, SVR rates were lower in patients with HCC, especially with active HCC, compared to those without HCC, though heterogeneity was high. Continued efforts are needed to aggressively screen, diagnose, and treat HCC to ensure higher CHC cure rates. There are now medications (direct-acting antivirals or "DAAs") that can "cure" hepatitis C virus, but patients with hepatitis C and liver cancer may be less likely to achieve cure than those without liver cancer. However, patients with liver cancer are also more likely to have advanced liver disease and risk factors that can decrease cure rates, so better controlled studies are needed to confirm these findings.

Ji F ，Yeo YH ，Wei MT ，Ogawa E ，Enomoto M ，Lee DH ，Iio E ，Lubel J ，Wang W ，Wei B ，Ide T ，Preda CM ，Conti F ，Minami T ，Bielen R ，Sezaki H ，Barone M ，Kolly P ，Chu PS ，Virlogeux V ，Eurich D ，Henry L ，Bass MB ，Kanai T ，Dang S ，Li Z ，Dufour JF ，Zoulim F ，Andreone P ，Cheung RC ，Tanaka Y ，Furusyo N ，Toyoda H ，Tamori A ，Nguyen MH ... -  《-》

Hepatitis C virus relapse after successful treatment with direct-acting antivirals, followed by sarcomatous changes in hepatocellular carcinoma: a case report.

Kurokawa K ，Ohki T ，Kato J ，Fukumura Y ，Imai M ，Shibata C ，Arai J ，Kondo M ，Takagi K ，Kojima K ，Seki M ，Mori M ，Toda N ，Tagawa K ... -  《-》

Hepatocellular carcinoma decreases the chance of successful hepatitis C virus therapy with direct-acting antivirals.

The approval of all-oral direct-acting antiviral (DAA) regimens for the treatment of hepatitis C virus (HCV) has led to the expansion of therapy to include patients with cirrhosis who have hepatocellular carcinoma (HCC). Data on the use of DAAs in HCV+ patients with HCC is limited. The aim of this study was to assess the efficacy of all-oral-DAA regimens in HCV+ cirrhotic patients who have or had HCC compared to those without HCC. A retrospective cohort study was conducted on all cirrhotic patients who were treated for HCV with DAAs at our institution between January 2014 and November 2015. A total of 421 HCV+ patients with cirrhosis were identified, of whom 33% had active or a history of HCC. Failure to achieve sustained virologic response (SVR) occurred in 21% of patients with HCC compared to 12% of patients without HCC (p=0.009). Of the 29 patients with HCC who did not achieve SVR, 27 (93%) occurred when an active tumor was present. DAA therapy in the presence of an inactive tumor or after removal of tumor (resection/transplant) resulted in excellent SVR rates, similar to those without HCC (p<0.0001). In multivariable analysis, the primary predictor of DAA treatment failure was the presence of active HCC at the time of HCV treatment initiation (adjusted odds ratio=8.5, 95% confidence interval=3.90-18.49). The presence of active HCC tumor at the initiation of HCV therapy is significantly associated with all-oral DAA treatment failure. HCV treatment after curative therapies for HCC resulted in excellent SVR. The new medications for hepatitis C have excellent cure rates. However, our study shows that in patients with both liver cancer and hepatitis C, they do not achieve these cure rates. Patients with liver cancer are almost 8 times more likely to fail hepatitis C treatment than patients without liver cancer.

Prenner SB ，VanWagner LB ，Flamm SL ，Salem R ，Lewandowski RJ ，Kulik L ... -  《-》