1.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
2.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
3.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
4.Effect of mild hypercapnia during the recovery period on the emergence time from total intravenous anesthesia: a randomized controlled trial
Lan LIU ; Xiangde CHEN ; Qingjuan CHEN ; Xiuyi LU ; Lili FANG ; Jinxuan REN ; Yue MING ; Dawei SUN ; Pei CHEN ; Weidong WU ; Lina YU
Korean Journal of Anesthesiology 2025;78(3):215-223
Background:
Intraoperative hypercapnia reduces the time to emergence from volatile anesthetics, but few clinical studies have explored the effect of hypercapnia on the emergence time from intravenous (IV) anesthesia. We investigated the effect of inducing mild hypercapnia during the recovery period on the emergence time after total IV anesthesia (TIVA).
Methods:
Adult patients undergoing transurethral lithotripsy under TIVA were randomly allocated to normocapnia group (end-tidal carbon dioxide [ETCO2] 35–40 mmHg) or mild hypercapnia group (ETCO2 50-55 mmHg) during the recovery period. The primary outcome was the extubation time. The spontaneous breathing-onset time, voluntary eye-opening time, and hemodynamic data were collected. Changes in the cerebral blood flow velocity in the middle cerebral artery were assessed using transcranial Doppler ultrasound.
Results:
In total, 164 patients completed the study. The extubation time was significantly shorter in the mild hypercapnia (13.9 ± 5.9 min, P = 0.024) than in the normocapnia group (16.3 ± 7.6 min). A similar reduction was observed in spontaneous breathing-onset time (P = 0.021) and voluntary eye-opening time (P = 0.008). Multiple linear regression analysis revealed that the adjusted ETCO2 level was a negative predictor of extubation time. Middle cerebral artery blood flow velocity was significantly increased after ETCO2 adjustment for mild hypercapnia, which rapidly returned to baseline, without any adverse reactions, within 20 min after extubation.
Conclusions
Mild hypercapnia during the recovery period significantly reduces the extubation time after TIVA. Increased ETCO2 levels can potentially enhance rapid recovery from IV anesthesia.
5.Comparative study of total knee arthroplasty assisted by robot and remote sensing navigation system
Hai TANG ; Hong-Mei ZHANG ; Peng-Cheng SHAN ; Pei-Yan HU ; Lin JING ; Qi YAN ; Yuan-Yuan LI ; Xin-Yue WANG ; Si-Ye LIU ; Ming-Jiang HE
China Journal of Orthopaedics and Traumatology 2024;37(9):862-869
Objective To compare clinical efficacy of robot-assisted(RA)and remote sensing navigation alignment(RSNA)system-assisted total knee arthroplasty(TKA).Methods From March 2023 to June 2023,60 patients who underwent the first unilateral TKA due to severe knee osteoarthritis(KOA)were admitted and divided into RSNA group and RA group according to different treatment methods,with 30 patients in each group.There were 5 males and 25 females in RSNA group,aged from 56 to 81 years old with an average of(66.33±7.16)years old;body mass index(BM1)ranged from 19.87 to 38.54 kg·m-2 with an average of(28.40±6.18)kg·m-2;the courses of disease ranged from 5 to 36 months with an average of(18.20±8.98)months;RSNA system was used to assist the positioning of osteotomy.There were 7 males and 23 females in RA group,aged from 55 to 82 years old with an average of(67.83±8.61)years old;BMI ranged from 19.67 to 37.25 kg·m-2 with an aver-age of(28.01±4.89)kg·m-2;the courses of disease ranged from 3 to 33 months with an average of(17.93±9.20)months;RA was performed.Operation time,incision length,latent blood loss at 2 weeks after operation and incidence of lower extremity thrombosis were compared between two groups.Hip-knee ankle angle(HKAA),HKAA deviation,lateral distal femoral angle(LDFA),medial proximal tibial angle(MPTA)and posterior tibial slope(PTS)were compared between two groups;Western Ontario McMaster Universities Osteoarthritis Index(WOMAC)and Knee Society score(KSS)were used to evaluate functional recovery before operation,3 and 6 months after operation.Results The operation was performed successfully in both groups,and there were no serious complications such as vascular and nerve injury during operation.The wound healed well at stage Ⅰafter operation,and the follow-up time was 6 months.The operation time,latent blood loss at 2 weeks after operation and inci-sion length in RSNA group were(94.35±5.75)min,(130.54±17.53)mland(14.73±2.14)cm,respectively;while(102.57±6.88)min,(146.33±19.47)ml and(16.78±2.32)cm in RA group,respectively.RSNA group was better than RA group(P<0.05).No deep vein thrombosis occurred in both groups at 2 weeks after operation,5 patients occurred intermuscular vein throm-bosisin in RSNA group and 8 patients in RA group,the difference was not statistically significant(P>0.05).In RSNA group,HKAA,LDFA and MPTA were(173.00±5.54)°,(86.96±3.45)°,(82.79±3.35)° before operation,and(178.34±1.85)°,(89.92±0.42)°,(89.84±0.73)° at 1 week after operation,respectively.In RA group,HKAA,LDFA and MPTA were(173.31±6.48)°,(87.15±3.40)° and(82.99±3.05)° before operation,and(178.52±1.79)°,(90.03±0.39)° and(90.15±0.47)° at 1 week after operation,respectively.HKAA,LDFA and MPTA were significantly improved in both groups at 1 week after oper-ation(P<0.05).There were no significant difference in HKAA,LDFA,MPTA and PTS between two groups before operation and 1 week after operation(P>0.05).There was no significant difference in deviation distribution of HKAA at 1 week after op-eration(x2=2.61 1,P=0.456).There were no significant difference in WOMAC and KSS between two groups before operation,3 and 6 months after operation(P>0.05),and postoperative WOMAC and KSS at 3 and 6 months between two groups were im-proved compared with those before operation(P<0.05).Conclusion Both RA and RSNA system assisted TKA could obtain ac-curate osteotomy,RA has higher surgical accuracy,RSNA system assisted operation has less trauma,and operation is simpler.
6.Application of remote sensing navigation system in total knee arthroplasty
Yuan-Yuan LI ; Ming-Jiang HE ; Peng-Cheng SHAN ; Pei-Yan HU ; Lin JING ; Qi YAN ; Hai TANG ; Xin-Yue WANG ; Si-Ye LIU ; Hong-Mei ZHANG
China Journal of Orthopaedics and Traumatology 2024;37(9):878-885
Objective To explore clinical accuracy of remote sensing navigation alignment(RSNA)system in total knee arthroplasty(TKA)and its influence on postoperative clinical efficacy.Methods From May 2021 to May 2022,60 knee os-teoarthritis(KOA)patients with Kellgren-Lawrence(K-L)grade Ⅲ to Ⅳ treated by unilateral primary TKA were selected and divided into RSNA group and traditional operation group according to treatment methods,and 30 patients in each group.There were 6 males and 24 females in RSNA group,aged from 55 to 86 years old with an average of(68.06±8.23)years old;body mass index(BMI)ranged from 22.15 to 34.58 kg·m-2 with an average of(28.20±3.01)kg·m-2;the courses of disease ranged from 2 to 60 months with an average of(18.80±14.80)months;13 patients with grade Ⅲ and 17 patients with grade Ⅳaccording to K-L grading.In traditional operation group,there were 8 males and 22 females,aged from 57 to 85 years old with an average of(67.26±6.32)years old;BMI ranged from 23.94 to 34.55 kg·m-2 with an average of(27.49±2.32)kg·m-2;the courses of disease ranged from 3 to 60 months with an average of(21.30±16.44)months;14 patients with grade Ⅲ and 16 pa-tients with grade Ⅳ according to K-L grading.Western Ontario and McMaster Universities(WOMAC)osteoarthritis index and Knee Society score(KSS)were used to evaluate functional recovery of patients.Hip-knee-ankle angle(HKAA),distal femoral valgus angle(FVA)and distal fermoral flexion angle(DFFA)were measured before operation.HKAA and HKAA deviation angle were measured at 1 week after operation,and defective rate of lower limb force line,femur prosthesis valgus angle(FP-VA)and femoral prosthesis flexion angle(FPFA),respectively,were calculated.Results There were no serious complications such as vascular and nerve injury during operation,and wound healed at stage Ⅰ.Both groups were followed up for 6 months.There were no significant difference in WOMAC index,KSS,HKAA,FVA and DFFA between two groups before operation(P>0.05).The force line defect rate,HKAA,HKAA deviation angle,FPVA deviation angle and FPFA of RSNA group were 6.7%,(178.74±1.56)°,(1.25±1.56)°,(1.84±0.16)° and(4.85±2.46)°,respectively;while in traditional operation group were 20%,(176.73±3.46)°,(3.27±3.46)°,(2.44±0.26)°,(6.60±1.86)°;the difference between two groups were statistically sig-nificant(P<0.05).There were no significant difference in WOMAC index and KSS between two groups at 3 and 6 months after operation(P>0.05).Conclusion RSNA system could reduce defective rate of lower limb force line,FPVA deviation angle and FPFA after TKA,which is more accurate and easy to operate than traditional intramedullary localization surgery while ensuring postoperative efficacy.
7.Analysis of Genes Related to Platelet Activation in Essential Thrombocythemia Based on Transcriptomics
Yan SUN ; Er-Peng YANG ; Yu-Meng LI ; Ji-Cong NIU ; Pei ZHAO ; Wei-Yi LIU ; Zhuo CHEN ; Ming-Jing WANG ; Teng FAN ; Xiao-Mei HU
Journal of Experimental Hematology 2024;32(6):1814-1821
Objective:To analyze the genes related to platelet activation in essential thrombocythemia (ET)based on transcriptome sequencing technology (RNA-seq ),and to explore the potential targets related to ET thrombosis. Methods:Blood samples from ET patients and healthy individuals were collected for RNA-seq,and differentially expressed lncRNAs,miRNAs,and mRNAs were selected to construct a lncRNA-miRNA-mRNA regulatory network. Differential mRNAs in the regulatory network were enriched and analyzed using Gene Ontology (GO ) and Kyoto Encyclopedia of Genes and Genomes (KEGG).The real-time PCR method was applied to validate differential mRNAs on crucial signaling pathways.Results:A total of 32 lncRNAs (3 up-regulated,29 down-regulated),16 miRNAs (8 up-regulated,8 down-regulated),and 35 mRNAs (27 up-regulated,8 down-regulated)were identified as differentially expressed.Among them,5 lncRNAs,12 miRNAs,and 19 mRNAs constituted the regulatory network.KEGG enrichment analysis showed that the differential mRNAs were related to the platelet activation signaling pathway,and there were 6 differential mRNAs related to platelet activation,namely F2R,ITGA2B,ITGB1,ITGB3,PTGS1,and GP1 BB,which were all up-regulated in their expression.RT-PCR results showed that the expression of five mRNAs including F2R,ITGA2B,ITGB1,ITGB3,and GP1BB were upregulated in ET patients compared with healthy subjects,and consistent with RNA-seq results,while PTGS1 expression was not significantly different.Conclusion:Differential mRNAs in ET patients are related to the platelet activation pathway,and F2R,ITGA2B,ITGB1,ITGB3,and GP1BB mRNAs may serve as novel targets associated with platelet activation in ET.
8.Clinical features of hereditary leiomyomatosis and renal cell carcinoma syndrome-associated renal cell carcinoma: a multi-center real-world retrospective study
Yunze XU ; Wen KONG ; Ming CAO ; Guangxi SUN ; Jinge ZHAO ; Songyang LIU ; Zhiling ZHANG ; Liru HE ; Xiaoqun YANG ; Haizhou ZHANG ; Lieyu XU ; Yanfei YU ; Hang WANG ; Honggang QI ; Tianyuan XU ; Bo YANG ; Yichu YUAN ; Dongning CHEN ; Dengqiang LIN ; Fangjian ZHOU ; Qiang WEI ; Wei XUE ; Xin MA ; Pei DONG ; Hao ZENG ; Jin ZHANG
Chinese Journal of Urology 2024;45(3):161-167
Objective:To investigate the clinical features and therapeutic efficacy of patients with hereditary leiomyomatosis and renal cell carcinoma(RCC) syndrome-associated RCC (HLRCC-RCC) in China.Methods:The clinical data of 119 HLRCC-RCC patients with fumarate hydratase (FH) germline mutation confirmed by genetic diagnosis from 15 medical centers nationwide from January 2008 to December 2021 were retrospectively analyzed. Among them, 73 were male and 46 were female. The median age was 38(13, 74) years. The median tumor diameter was 6.5 (1.0, 20.5) cm. There were 38 cases (31.9%) in stage Ⅰ-Ⅱand 81 cases (68.1%) in stage Ⅲ-Ⅳ. In this group, only 11 of 119 HLRCC-RCC patients presented with skin smooth muscle tumors, and 44 of 46 female HLRCC-RCC patients had a history of uterine fibroids. The pathological characteristics, treatment methods, prognosis and survival of the patients were summarized.Results:A total of 86 patients underwent surgical treatment, including 70 cases of radical nephrectomy, 5 cases of partial nephrectomy, and 11 cases of reductive nephrectomy. The other 33 patients with newly diagnosed metastasis underwent renal puncture biopsy. The results of genetic testing showed that 94 patients had FH gene point mutation, 18 had FH gene insertion/deletion mutation, 4 had FH gene splicing mutation, 2 had FH gene large fragment deletion and 1 had FH gene copy number mutation. Immunohistochemical staining showed strong 2-succinocysteine (2-SC) positive and FH negative in 113 patients. A total of 102 patients received systematic treatment, including 44 newly diagnosed patients with metastasis and 58 patients with postoperative metastasis. Among them, 33 patients were treated with tyrosine kinase inhibitor (TKI) combined with immune checkpoint inhibitor (ICI), 8 patients were treated with bevacizumab combined with erlotinib, and 61 patients were treated with TKI monotherapy. Survival analysis showed that the median progression-free survival (PFS) of TKI combined with ICI was 18 (5, 38) months, and the median overall survival (OS) was not reached. The median PFS and OS were 12 (5, 14) months and 30 (10, 32) months in the bevacizumab combined with erlotinib treatment group, respectively. The median PFS and OS were 10 (3, 64) months and 44 (10, 74) months in the TKI monotherapy group, respectively. PFS ( P=0.009) and OS ( P=0.006) in TKI combined with ICI group were better than those in bevacizumab combined with erlotinib group. The median PFS ( P=0.003) and median OS ( P=0.028) in TKI combined with ICI group were better than those in TKI monotherapy group. Conclusions:HLRCC-RCC is rare but has a high degree of malignancy, poor prognosis and familial genetic characteristics. Immunohistochemical staining with strong positive 2-SC and negative FH can provide an important basis for clinical diagnosis. Genetic detection of FH gene germ line mutation can confirm the diagnosis. The preliminary study results confirmed that TKI combined with ICI had a good clinical effect, but it needs to be confirmed by the results of a large sample multi-center randomized controlled clinical study.
9.Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program
Ming-Ying LU ; Chung-Feng HUANG ; Chao-Hung HUNG ; Chi‐Ming TAI ; Lein-Ray MO ; Hsing-Tao KUO ; Kuo-Chih TSENG ; Ching-Chu LO ; Ming-Jong BAIR ; Szu-Jen WANG ; Jee-Fu HUANG ; Ming-Lun YEH ; Chun-Ting CHEN ; Ming-Chang TSAI ; Chien-Wei HUANG ; Pei-Lun LEE ; Tzeng-Hue YANG ; Yi-Hsiang HUANG ; Lee-Won CHONG ; Chien-Lin CHEN ; Chi-Chieh YANG ; Sheng‐Shun YANG ; Pin-Nan CHENG ; Tsai-Yuan HSIEH ; Jui-Ting HU ; Wen-Chih WU ; Chien-Yu CHENG ; Guei-Ying CHEN ; Guo-Xiong ZHOU ; Wei-Lun TSAI ; Chien-Neng KAO ; Chih-Lang LIN ; Chia-Chi WANG ; Ta-Ya LIN ; Chih‐Lin LIN ; Wei-Wen SU ; Tzong-Hsi LEE ; Te-Sheng CHANG ; Chun-Jen LIU ; Chia-Yen DAI ; Jia-Horng KAO ; Han-Chieh LIN ; Wan-Long CHUANG ; Cheng-Yuan PENG ; Chun-Wei- TSAI ; Chi-Yi CHEN ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(1):64-79
Background/Aims:
Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1–3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy.
Methods:
We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment.
Results:
The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset.
Conclusions
Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
10.Metformin and statins reduce hepatocellular carcinoma risk in chronic hepatitis C patients with failed antiviral therapy
Pei-Chien TSAI ; Chung-Feng HUANG ; Ming-Lun YEH ; Meng-Hsuan HSIEH ; Hsing-Tao KUO ; Chao-Hung HUNG ; Kuo-Chih TSENG ; Hsueh-Chou LAI ; Cheng-Yuan PENG ; Jing-Houng WANG ; Jyh-Jou CHEN ; Pei-Lun LEE ; Rong-Nan CHIEN ; Chi-Chieh YANG ; Gin-Ho LO ; Jia-Horng KAO ; Chun-Jen LIU ; Chen-Hua LIU ; Sheng-Lei YAN ; Chun-Yen LIN ; Wei-Wen SU ; Cheng-Hsin CHU ; Chih-Jen CHEN ; Shui-Yi TUNG ; Chi‐Ming TAI ; Chih-Wen LIN ; Ching-Chu LO ; Pin-Nan CHENG ; Yen-Cheng CHIU ; Chia-Chi WANG ; Jin-Shiung CHENG ; Wei-Lun TSAI ; Han-Chieh LIN ; Yi-Hsiang HUANG ; Chi-Yi CHEN ; Jee-Fu HUANG ; Chia-Yen DAI ; Wan-Long CHUNG ; Ming-Jong BAIR ; Ming-Lung YU ;
Clinical and Molecular Hepatology 2024;30(3):468-486
Background/Aims:
Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients.
Methods:
We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan’s cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray’s cumulative incidence and Cox subdistribution hazards models to analyze HCC development.
Results:
Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients.
Conclusions
Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

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