The fourth version of Clinical Practice Guidelines for Hepatocellular Carcinoma was revised by the Japan Society of Hepatology, according to the methodology of evidence‐based medicine and partly to the Grading of Recommendations Assessment, Development, and Evaluation system, which was published in October 2017 in Japanese. New or revised recommendations were described, herein, with a special reference to the surveillance, diagnostic, and treatment algorithms.
SUMMARY. Genotype 2 hepatitis C virus (HCV) accounts for up to 30% of chronic HCV infections in Japan. The standard of care for patients with genotype 2 HCV -peginterferon and ribavirin for 24 weeks -is poorly tolerated, especially among older patients and those with advanced liver disease. We conducted a phase 3, open-label study to assess the efficacy and safety of an all-oral combination of the NS5B polymerase inhibitor sofosbuvir and ribavirin in patients with chronic genotype 2 HCV infection in Japan. We enrolled 90 treatment-na€ ıve and 63 previously treated patients at 20 sites in Japan. All patients received sofosbuvir 400 mg plus ribavirin (weight-based dosing) for 12 weeks. The primary endpoint was sustained virologic response at 12 weeks after therapy (SVR12). Of the 153 patients enrolled and treated, 60% had HCV genotype 2a, 11% had cirrhosis, and 22% were over the aged 65 or older. Overall, 148 patients (97%) achieved SVR12. Of the 90 treatment-na€ ıve patients, 88 (98%) achieved SVR12, and of the 63 previously treated patients, 60 (95%) achieved SVR12. The rate of SVR12 was 94% in patients with cirrhosis and in those aged 65 and older. No patients discontinued study treatment due to adverse events. The most common adverse events were nasopharyngitis, anaemia and headache. Twelve weeks of sofosbuvir and ribavirin resulted in high rates of SVR12 in treatment-na€ ıve and previously treated patients with chronic genotype 2 HCV infection. The treatment was safe and well tolerated by patients, including the elderly and those with cirrhosis.
Hepatocellular carcinoma (HCC) is one of the most common and aggressive malignancies in the world. Recent advances in diagnostic modalities, such as imaging techniques and measurement of serum tumor markers, have improved the rate of early detection of HCC, and therapeutic approaches to HCC have also progressed. However, the long-term survival of HCC patients has been poor because of the high incidence of recurrence within the liver after initial treatment. 1,2 Pathological and genetic studies have identified two types of recurrence of HCC: multicentric development of new tumors 3-5 and intrahepatic metastasis of the original HCC.Intrahepatic metastasis of HCC is frequently observed with the advance of the disease and it is thought to develop through tumor cell dispersal via the portal vein. 6 A clinicopathological study showed that intrahepatic metastatic tumors develop more frequently in cases of HCC with a replacing or infiltrative growth component than in cases without such a component. 7 Proliferating cell nuclear antigen expression by HCCs seems to be related to tumor invasiveness and the prognosis, 8,9 and the nuclear DNA content of the tumor cells correlates with the postoperative recurrence of HCC. 10 Several chromosomal alterations appear to be responsible for the development of human HCC, 11,12 especially loss of heterozygosity of chromosome 16, which is detected at a higher rate in HCCs with intrahepatic metastasis and portal vein tumor thrombi. 13 Furthermore, E-cadherin expression seems to be involved in secondary tumor formation by HCC cells in the liver. 14 However, the molecular and cellular mechanisms underlying intrahepatic metastasis of HCC are not fully understood.Cancer metastasis is a multistep process that involves cell detachment from the primary tumor, entry into the vascular or lymphatic system, dispersal through the circulation, and extravasation and proliferation in the target organ. Metastatic cancer cells are equipped with properties that help them complete each step of this process. 15 In case of intrahepatic metastasis of human HCC, the dispersed cancer cells proliferate in the same environment as the primary lesion. Therefore, the initial step, including detachment of the cancer cells from the primary lesion, may offer the best chance to regulate metastatic ability.In this study, to clarify the molecular and cellular mechanisms underlying intrahepatic metastasis of human HCC, we have developed a model of intrahepatic metastasis using orthotopic implantation of human HCC cell lines in SCID Abbreviations: HCC, hepatocellular carcinoma; GTPase, guanosine triphosphatase; p160ROCK, Rho-associated coiled-coil forming protein kinase; LPA, lysophosphatidic acid.From the
In a GWAS, we identified the association between the SNP rs17047200, within the intron of TLL1, and development of HCC in patients who achieved an SVR to treatment for chronic HCV infection. We found levels of Tll1/TLL1 mRNA to be increased in rodent models of liver injury and liver tissues of patients with fibrosis, compared with controls. We propose that this SNP might affect splicing of TLL1 mRNA, yielding short variants with high catalytic activity that accelerates hepatic fibrogenesis and carcinogenesis. Further studies are needed to determine how rs17047200 affects TLL1 mRNA levels, splicing, and translation, as well as the prevalence of this variant among other patients with HCC. Tests for the TLL1 SNP might be used to identify patients at risk for HCC after an SVR to treatment of HCV infection.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.