Transarterial chemoembolization (TACE) is a standard treatment for intermediate-stage hepatocellular carcinoma (HCC). In this review, we summarize recent updates on the use of TACE for HCC. TACE can be performed using two techniques; conventional TACE (cTACE) and drug-eluting beads using TACE (DEB-TACE). The anti-tumor effect of the two has been reported to be similar; however, DEB-TACE carries a higher risk of hepatic artery and biliary injuries and a relatively lower risk of post-procedural pain than cTACE. TACE can be used for early stage HCC if other curative treatments are not feasible or as a neoadjuvant treatment before liver transplantation. TACE can also be considered for selected patients with limited portal vein thrombosis and preserved liver function. When deciding to repeat TACE, the ART (Assessment for Retreatment with TACE) score and ABCR (AFP, BCLC, Child-Pugh, and Response) score can guide the decision process, and TACE refractoriness needs to be considered. Studies on the combination therapy of TACE with other treatment modalities, such as local ablation, radiation therapy, or systemic therapy, have been actively conducted and are still ongoing. Recently, new prognostic models, including analysis of the neutrophil-lymphocyte ratio, radiomics, and deep learning, have been developed to help predict survival after TACE.

Alpha-fetoprotein (AFP), Lens culinaris-agglutinin-reactive fraction of AFP (AFP-L3), and protein induced by vitamin K absence or antagonist-II (PIVKA-II) are widely used as tumor markers for the diagnosis of hepatocellular carcinoma (HCC). This study compared the diagnostic values of AFP, AFP-L3, and PIVKA-II individually and in combination to find the best biomarker or biomarker panel. Seventy-nine patients with newly diagnosed HCC and 77 non-HCC control patients with liver cirrhosis were enrolled. AFP, AFP-L3, and PIVKA-II were measured in the same serum samples using microchip capillary electrophoresis and a liquid-phase binding assay on an automatic analyzer. Receiver-operating characteristic curve analyses were also applied to all combinations of the markers. When the 3 biomarkers were analyzed individually, AFP showed the largest area under the receiver-operating characteristic curve (AUC) (0.751). For combinations of the biomarkers, the AUC was highest (0.765) for “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL.” The combination of “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL and AFP-L3 > 10%” had worse sensitivity and lower AUC (P = 0.001). The highest AUC of a single biomarker was highest for AFP and of a combination was “PIVKA-II > 40 mAU/mL and AFP > 10 ng/mL,” with this also being the case when the cut-off value of AFP and AFP-L3 was changed. Alpha-fetoprotein showed the best diagnostic performance as a single biomarker for HCC. The diagnostic value of AFP was improved by combining it with PIVKA-II, but adding AFP-L3 did not contribute to the ability to distinguish between HCC and non-HCC liver cirrhosis. These findings were not altered when the cut-off value of AFP and AFP-L3 was changed.

We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.

Hepatitis C virus (HCV) alters mitochondrial dynamics associated with persistent viral infection and suppression of innate immunity. Mitochondrial dysfunction is also a pathologic feature of direct‐acting antiviral (DAA) treatment. Despite the high efficacy of DAAs, their use in treating patients with chronic hepatitis C in interferon‐sparing regimens occasionally produces undesirable side effects such as fatigue, migraine, and other conditions, which may be linked to mitochondrial dysfunction. Here, we show that clinically prescribed DAAs, including sofosbuvir, affect mitochondrial dynamics. To counter these adverse effects, we examined HCV‐induced and DAA‐induced aberrant mitochondrial dynamics modulated by ginsenoside, which is known to support healthy mitochondrial physiology and the innate immune system. We screened several ginsenoside compounds showing antiviral activity using a robust HCV cell culture system. We investigated the role of ginsenosides in antiviral efficacy, alteration of mitochondrial transmembrane potential, abnormal mitochondrial fission, its upstream signaling, and mitophagic process caused by HCV infection or DAA treatment. Only one of the compounds, ginsenoside Rg3 (G‐Rg3), exhibited notable and promising anti‐HCV potential. Treatment of HCV‐infected cells with G‐Rg3 increased HCV core protein–mediated reduction in the expression level of cytosolic p21, required for increasing cyclin‐dependent kinase 1 activity, which catalyzes Ser616 phosphorylation of dynamin‐related protein 1. The HCV‐induced mitophagy, which follows mitochondrial fission, was also rescued by G‐Rg3 treatment. Conclusion: G‐Rg3 inhibits HCV propagation. Its antiviral mechanism involves restoring the HCV‐induced dynamin‐related protein 1–mediated aberrant mitochondrial fission process, thereby resulting in suppression of persistent HCV infection. (Hepatology 2017;66:758–771)

Hepatitis B virus (HBV) reactivation associated with various therapeutic interventions is an important cause of morbidity and mortality in patients with current or resolved HBV infection. Because no curative treatment for HBV infection is yet available, there are many individuals at risk for HBV reactivation in the general population. Populations at risk for HBV reactivation include patients who are currently infected with HBV or who have been exposed to HBV in the past. HBV reactivation and its potential consequences is a concern when these populations are exposed to anti-cancer chemotherapy, immunosuppressive or immunomodulatory therapies for the management of various malignancies, rheumatologic diseases, inflammatory bowel disease, or solid-organ or hematologic stem cell transplantation. Accordingly, it has become important to understand the basics of HBV reactivation and the mechanisms by which certain therapies are more susceptible to HBV reactivation. This review aims to raise the awareness of HBV reactivation and to understand the mechanisms and the risks of HBV reactivation in various clinical settings.

Recent studies have demonstrated the utility of the FibroScan^® device in diagnosing liver steatosis, but its usefulness has not been thoroughly appraised. We investigated the usefulness of the controlled attenuation parameter (CAP) in detecting and quantifying liver steatosis. A prospective analysis was applied to 79 chronic liver disease patients who underwent a liver biopsy, a FibroScan investigation, ultrasonography, and hepatic steatosis index (HSI). The presence and degree of steatosis as measured by the FibroScan device, ultrasonography and HSI were compared with the results for the liver biopsy tissue. There was substantial concordance between the liver biopsy results and the CAP as evaluated by the kappa (κ) index test for detecting liver steatosis (κ_CAP = 0.77, P<0.001; κ_{ultrasonography} = 0.60, P<0.001; κ_HSI = 0.47, P<0.001). The areas under the receiver operating characteristic curve (AUROCs) of the CAP, ultrasonography, and HSI were 0.899 [95% confidence interval (CI) = 0.826–0.972)], 0.859 (95% CI = 0.779–0.939), and 0.766 (95% CI = 0.655–0.877), respectively. The optimal CAP cutoff value for differentiating between normal and hepatic steatosis was 247 dB/m, which produced sensitivity and specificity values of 91.9% and 85.7%, respectively, as well as a positive predictive value of 85.0% and a negative predictive value of 92.3%. The CAP produces results that are highly concordant with those of a liver biopsy in detecting steatosis. Therefore, the CAP is a noninvasive and reliable tool for evaluating liver steatosis, even in the early stages.