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- 저자 : ( George Boon Bee Goh ) (검색결과 3 건)
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Comparisons between non-alcoholic steatohepatitis and alcohol-related hepatocellular carcinoma
Rahul Kumar,Boon-Bee George Goh,Jia-Wen Kam,Pik-Eu Chang,Chee-Kiat Tan 대한간학회 2020 Clinical and Molecular Hepatology(대한간학회지) Vol.26 No.2
Background/Aims: Non-alcoholic liver disease and alcoholic liver disease begin as simple steatosis that may progress to steatohepatitis and ensuing liver-related complications such as cirrhosis and hepatocellular carcinoma (HCC). We explored differences in characteristics between non-alcoholic steatohepatitis (NASH) and alcoholic steatohepatitisrelated (ASH) HCC. Methods: NASH and ASH patients were identified from our department’s prospective HCC database. A total of 54 and 45 patients met predefined inclusion and exclusion criteria for the NASH-HCC and ASH-HCC groups, respectively. Clinical, biochemical and tumor characteristics were studied. Results: NASH-HCC patients were older compared to ASH-HCC patients (72±9 vs. 66±9 years, P<0.001) and less male predominant (65% vs. 98%, P<0.001). Prevalence of diabetes mellitus (78% vs. 36%, P<0.001) and hypertension (80% vs. 58%, P<0.001) were significantly higher in the NASH-HCC group. Liver function tests and Child-Pugh scores were similar. There were no differences in alpha-fetoprotein level, lesions found at diagnosis (unifocal/multifocal) or prevalence of portal vein invasion. In both groups, almost half of the patients were in TNM stage 4 at the time of diagnosis and more than 50% of patients were not suitable for any therapy. Median survival in the NASH-HCC and ASH-HCC groups were 13 and 7 months respectively (P=0.113). Conclusions: Despite significant differences in demography of the NASH-HCC and ASH-HCC groups, liver and tumor characteristics were comparable. Most patients were diagnosed late and were not amenable to curative or locoregional therapies. Better characterization of patients with NASH and ASH at risk of HCC is necessary to optimize screening, surveillance, and management strategies.
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( Jin-woo Lee ),( George Boon Bee Goh ),( Quentin M. Anstee ),( Mi-chael Trauner ),( Eric J. Lawitz ),( Natalie Bzowej ),( Raj Vuppalan-chi ),( Ziad Younes ),( Dora Ding ),( Georgia Li ),( Kathryn Ker 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Aims: Surrogate endpoints that predict complications are necessary for approval of new therapies for NASH. We assessed associations between histologic and noninvasive fibrosis markers with disease progression in NASH. Methods: Patients with advanced fibrosis (Ishak stages 3-6) due to NASH (NAS ≥3) were enrolled in Phase 3, placebo-controlled trials of selonsertib. Treatment groups were combined for this analysis. Liver fibrosis at baseline[BL] and W48 were staged according to the Ishak classification. Hepatic collagen and a-SMA expression were quantified by morphometry. Noninvasive tests of fibrosis such as LS by TE, ELF and NAFLD Fibrosis Score (NFS) were calculated. Cox regression determined associations between these parameters with disease progression (i.e. progression to cirrhosis in patients with bridging fibrosis and adjudicated clinical events [e.g. decompensation, transplantation, death] in those with cirrhosis), and discrimination was assessed using c-statistics. Results: 1679 subjects with bridging fibrosis(n=802) or cirrhosis( n=877) were randomized (median age 59 yrs, 60% female, 74% diabetes). During a median follow-up(FU) of 14.3 mos, 16% of subjects (117/748 with W48 biopsies) with bridging fibrosis progressed to cirrhosis. Risk of histological progression was greater with higher BL Ishak stage, hepatic collagen, a-SMA expression, ELF, NFS, and LS, as well as greater increases in these markers over time(Table). BL ELF(c-statistic, 0.68) and LS(0.70) more accurately discriminated progression to cirrhosis than BL Ishak stage(0.58) and hepatic collagen(0.56; all P<0.05). During a median FU of 14.3 mos, 26(3%) cirrhotic subjects had clinical events. BL factors associated with clinical events included higher Ishak stage, hepatic collagen, a-SMA, ELF, NFS, and LS(Table). After adjustment for BL, increases in hepatic collagen, a-SMA, NFS, and LS were associated with an increased risk of events. Prediction of future clinical events was greatest for BL ELF (c-statistic, 0.84 vs. 0.66 for Ishak stage and 0.62 for hepatic collagen; both P<0.05). Conclusions: Clinical disease progression in patients with advanced fibrosis due to NASH is associated with greater fibrosis burden at baseline and larger increases over time, measured histologically or with noninvasive markers. These data support the utility of noninvasive fibrosis markers as endpoints in NASH clinical trials.
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( Won Young Tak ),( Vincent Wai-sun Wong ),( George Boon Bee Goh ),( Pin-nan Cheng ),( Eric J. Lawitz ),( Zobair M. Younossi ),( Raj Vuppalanchi ),( Natalie H. Bzowej ),( Ziad Younes ),( Naim Alkhouri 대한간학회 2020 춘·추계 학술대회 (KASL) Vol.2020 No.1
Background: Routinely available noninvasive tests of fibrosis (NITs) can be used to identify patients with advanced fibrosis due to NASH, but their performance may vary by race. Our aim was to evaluate the effect of patient race on the diagnostic performance of NITs using data from the global phase 3 STELLAR studies of selonsertib. Methods: The STELLAR studies (NCT03053050 and NCT03053063) enrolled patients with bridging fibrosis (F3) or compensated cirrhosis (F4) due to NASH (NAFLD Activity Score [NAS] ≥3). Baseline liver biopsies were centrally read using the NASH Clinical Research Network classification and NITs, including the NAFLD fibrosis score (NFS), Fibrosis-4 (FIB-4) index, Enhanced Liver Fibrosis (ELF) test, and liver stiffness by transient elastography (LS by TE) were measured. The performance of these tests to discriminate advanced (F3-F4) fibrosis by self-reported patient race was evaluated using areas under the receiver operating characteristics curves (AUROCs) with 5-fold cross-validation repeated 100x. Results for White and Asian patients are presented; data for other races (5% of patients screened) are excluded. Results: Among 3202 patients screened for the STELLAR studies with evaluable liver histology, 24% were Asian and 71% were White. The median age was 58 years in both groups; 47% of Asians and 57% of Whites were female (p<0.0001). The prevalence of F3-F4 fibrosis was 67% in Asians and 72% in Whites (p=0.01). AUROCs for each of the NITS for the discrimination of advanced fibrosis were similar between Asian and White patients (Table). In general, literature-based thresholds for the NITs had similar sensitivity and specificity among the specific racial subgroups. Conclusion: In these large, global phase 3 trials, the diagnostic performance of routinely available NITs for the discrimination of advanced fibrosis due to NASH was acceptable and similar between Asian and White patients.
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