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      • KCI등재

        Combination Therapy for Chronic Hepatitis B: Current Updates and Perspectives

        ( Tung-hung Su ),( Chun-jen Liu ) 대한간학회 2017 Gut and Liver Vol.11 No.5

        Nucleos(t)ide analogues (NUCs) and interferon have been used for several decades to treat chronic hepatitis B; how-ever, the therapeutic response remains unsatisfactory. Although NUC therapy exhibits potent on-treatment viral sup-pression, frequent off-therapy virological relapses suggest an indefinite treatment course. Interferon modulates the innate and adaptive antiviral immune responses and thus increases the chance of viral eradication. Interferon therapy has the advantage of a finite duration, absence of drug resis-tance, and durable posttreatment responses. Therefore, the combination of NUCs and interferon can theoretically facili-tate a synergistic therapeutic effect. This paper summarizes the current strategies of various combination therapies into three categories: the simultaneous “dual” strategy, sequen-tial combination “add-on” strategy, and “switch” strategy. Generally, dual therapy exhibits greater on-treatment and off-therapy viral suppression and lower drug resistance compared with NUC monotherapy. Compared with inter-feron monotherapy, dual therapy has greater on-treatment viral suppression but shows no difference in off-therapy sustained virological responses. Specific add-on or switch strategies provide promising on-treatment efficacy in select patients. Pretreatment or on-treatment quantitative hepatitis B surface antigen and e antigen are predictive for the treat-ment efficacy of combination therapy. The optimal schedule of combination regimens and individualized therapy remain to be comprehensively evaluated. (Gut Liver 2017;11:590- 603)

      • KCI등재

        Clinical practice guidelines and real-life practice in hepatocellular carcinoma: A Taiwan perspective

        Tung-Hung Su,Chih-Horng Wu,Tsung-Hao Liu,Cheng-Maw Ho,Chun-Jen Liu 대한간학회 2023 Clinical and Molecular Hepatology(대한간학회지) Vol.29 No.2

        Hepatocellular carcinoma (HCC) is the fourth most common cancer and the second leading cause of cancer-related death in Taiwan. The Taiwan Liver Cancer Association and the Gastroenterological Society of Taiwan developed and updated the guidelines for HCC management in 2020. In clinical practice, we follow these guidelines and the reimbursement policy of the government. In Taiwan, abdominal ultrasonography, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) tests are performed for HCC surveillance every 6 months or every 3 months for high-risk patients. Dynamic computed tomography, magnetic resonance imaging, and contrast-enhanced ultrasound have been recommended for HCC surveillance in extremely high-risk patients or those with poor ultrasonographic visualization results. HCC is usually diagnosed through dynamic imaging, and pathological diagnosis is recommended. Staging of HCC is based on a modified version of the Barcelona Clinic Liver Cancer (BCLC) system, and the HCC management guidelines in Taiwan actively promote curative treatments including surgery and locoregional therapy for BCLC stage B or C patients. Transarterial chemoembolization (TACE), drug-eluting bead TACE, transarterial radioembolization, and hepatic artery infusion chemotherapy may be administered for patients with BCLC stage B or C HCC. Sorafenib and lenvatinib are reimbursed as systemic therapies, and regorafenib and ramucirumab may be reimbursed in cases of sorafenib failure. First-line atezolizumab with bevacizumab is not yet reimbursed but may be administered in clinical practice. Systemic therapy and external beam radiation therapy may be used in specific patients. Early switching to systemic therapy in TACE-refractory patients is a recent paradigm shift in HCC management.

      • KCI등재

        Chrysophanol-induced Necrotic-like Cell Death through an Impaired Mitochondrial ATP Synthesis in Hep3B Human Liver Cancer Cells

        Chien-Hang Ni,Jing-Gung Chung,Po-Yuan Chen,Hsu-Feng Lu,Jai-Sing Yang,Hui-Ying Huang,Shin-Hwar Wu,Siu-Wan Ip,Chin-Tung Wu,Su-Yin Chiang,Jaung-Geng Lin,W. Gibson Wood 대한약학회 2012 Archives of Pharmacal Research Vol.35 No.5

        Liver cancer is the most common form of cancer in Taiwan and it usually responds to chemotherapy. However, patients often have side effects to the chemotherapeutic drugs. Thus new agents are urgently required to treat liver cancer. Chrysophanol, one of the anthraquinone derivatives, was reported to inhibit some human cancer cell growth which may be due to the induction of apoptosis similar to other anthraquinone derivatives though such actions have not been reported. In the present study, we reported that chrysophanol inhibits cell growth in Hep3B liver cancer cells based on the following observations: 1) induc cell morphological changes; 2) decreased percentage of viable cells; 3) induced S phase arrest of cell cycle progression; 4) induced DNA damage as measured by comet assay and DAPI staining. Chrysophanolinduced cell death however, seems to be related to necrotic processes rather than typical apoptosis. Chrysophanol induced reactive oxygen species and Ca2+ production and decreased mitochondrial membrane potential (ΔΨm) and ATP levels in Hep3B cells. No effects were observed on known protein regulators of apoptosis such as Bax and Bcl-2. Chrysophanolinduced cell death took place independently of caspase-8 and -9. Based on our findings, we propose that chrysophanol reduces cellular ATP levels causing a drop in energy resulting in necrotic-like cell death.

      • SCIESCOPUSKCI등재

        Clinical and Histologic Features of Patients with Biopsy-Proven Metabolic Dysfunction-Associated Fatty Liver Disease

        ( Shang-chin Huang ),( Hau-jyun Su ),( Jia-horng Kao ),( Tai-chung Tseng ),( Hung-chih Yang ),( Tung-hung Su ),( Pei-jer Chen ),( Chun-jen Liu ) 대한간학회 2021 Gut and Liver Vol.15 No.3

        Background/Aims: Fatty liver disease is defined as a cluster of diseases with heterogeneous etiologies, and its definition continues to evolve. The novel conceptional criteria for metabolic dysfunction-associated fatty liver disease (MAFLD) were proposed in 2020 to avoid the exclusion of a certain subpopulation, but their evaluations have been limited. We aimed to examine and compare the clinical as well as histologic features of MAFLD versus nonalcoholic fatty liver disease (NAFLD) in patients with biopsy-proven hepatic steatosis. Methods: From January 2009 to December 2019, 175 patients with histology-proven hepatic steatosis and 10 with cryptogenic cirrhosis who were treated at National Taiwan University Hospital, Taipei, Taiwan, were enrolled. Patients were classified into different groups according to the diagnostic criteria of MAFLD and NAFLD. The clinical and histologic features were then analyzed and compared. Results: In total, 76 patients (41.1%) were diagnosed with both MAFLD and NAFLD, 81 patients (43.8%) were diagnosed with MAFLD alone, nine patients (4.9%) were diagnosed with NAFLD alone, and 19 patients (10.3%) were diagnosed with neither. Those with MAFLD alone exhibited a higher degree of disease severity regarding histology and laboratory data than those with NAFLD alone. Advanced fibrosis was associated with the presences of hepatitis B virus infection and metabolic diseases. Conclusions: The novel diagnostic criteria for MAFLD include an additional 38.9% of patients with hepatic steatosis and can better help identify those with a high degree of disease severity for early intervention than can the previous NAFLD criteria. (Gut Liver 2021;15:451-458)

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