Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus
ABSTRACT Chronic hepatitis B virus (HBV) infection is associated with potential complications of liver cirrhosis and hepatocellular carcinoma. To date, there are no effective and noninvasive clinical markers that can predict the risk of liver fibrosis early and accurately in chronic hepatitis B (CHB...
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| Format: | Article |
| Language: | English |
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Wiley
2025-06-01
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| Series: | Kaohsiung Journal of Medical Sciences |
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| Online Access: | https://doi.org/10.1002/kjm2.70015 |
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| author | Yi‐Shan Tsai Po‐Cheng Liang Yi‐Hung Lin Tyng‐Yuan Jang Yu‐Ju Wei Po‐Han Chen Jia‐Ning Hsu Meng‐Hsuan Hsieh Ming‐Yen Hsieh Chih‐Wen Wang Zu‐Yau Lin Ming‐Lun Yeh Chung‐Feng Huang Jee‐Fu Huang Ming‐Lung Yu Wan‐Long Chuang Chia‐Yen Dai |
| author_facet | Yi‐Shan Tsai Po‐Cheng Liang Yi‐Hung Lin Tyng‐Yuan Jang Yu‐Ju Wei Po‐Han Chen Jia‐Ning Hsu Meng‐Hsuan Hsieh Ming‐Yen Hsieh Chih‐Wen Wang Zu‐Yau Lin Ming‐Lun Yeh Chung‐Feng Huang Jee‐Fu Huang Ming‐Lung Yu Wan‐Long Chuang Chia‐Yen Dai |
| author_sort | Yi‐Shan Tsai |
| collection | DOAJ |
| description | ABSTRACT Chronic hepatitis B virus (HBV) infection is associated with potential complications of liver cirrhosis and hepatocellular carcinoma. To date, there are no effective and noninvasive clinical markers that can predict the risk of liver fibrosis early and accurately in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogs (NAs). This study aimed to investigate the association of circulating let‐7b/c/g levels with the severity of hepatic fibrosis with a FIB‐4 index of 1.5–2.9 in CHB patients. We conducted a retrospective longitudinal study in patients with CHB after 6 months of NAs therapy to investigate whether serum let‐7b/c/g levels can be monitored as an early biomarker for liver fibrogenesis based on multivariate logistic regression analyses. We also used the hepatic stellate cell line LX‐2 treated with transforming growth factor‐β (TGF‐β) to evaluate the suppression effect of let‐7b/c/g on hepatic fibrogenesis. The study showed that circulating let‐7b/c/g could predict 12 months of antiviral treatment for HBV‐related significant fibrosis (FIB‐4 index ≥ 2.9) at baseline and was significantly negatively correlated with the FIB‐4 score. Moreover, let‐7b/c/g could directly target the TGF‐βR1–3′ untranslated region (3′ UTR) and inhibit TGF‐β induced p‐SMAD2 phosphorylation to reduce α‐smooth muscle actin levels, a fibrogenesis marker in LX‐2 cells. These results confirm that let‐7b/c/g could be a biomarker for monitoring HBV‐induced fibrogenesis. |
| format | Article |
| id | doaj-art-622b921d56c44a3ebaa36b6acf3cbb2c |
| institution | Matheson Library |
| issn | 1607-551X 2410-8650 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj-art-622b921d56c44a3ebaa36b6acf3cbb2c2025-06-26T12:15:34ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502025-06-01416n/an/a10.1002/kjm2.70015Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B VirusYi‐Shan Tsai0Po‐Cheng Liang1Yi‐Hung Lin2Tyng‐Yuan Jang3Yu‐Ju Wei4Po‐Han Chen5Jia‐Ning Hsu6Meng‐Hsuan Hsieh7Ming‐Yen Hsieh8Chih‐Wen Wang9Zu‐Yau Lin10Ming‐Lun Yeh11Chung‐Feng Huang12Jee‐Fu Huang13Ming‐Lung Yu14Wan‐Long Chuang15Chia‐Yen Dai16Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHealth Management Center & Department of Occupational Medicine Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanHepatobiliary Division, Department of Internal Medicine and Hepatitis Center Kaohsiung Medical University Hospital, Kaohsiung Medical University Kaohsiung TaiwanABSTRACT Chronic hepatitis B virus (HBV) infection is associated with potential complications of liver cirrhosis and hepatocellular carcinoma. To date, there are no effective and noninvasive clinical markers that can predict the risk of liver fibrosis early and accurately in chronic hepatitis B (CHB) patients treated with nucleos(t)ide analogs (NAs). This study aimed to investigate the association of circulating let‐7b/c/g levels with the severity of hepatic fibrosis with a FIB‐4 index of 1.5–2.9 in CHB patients. We conducted a retrospective longitudinal study in patients with CHB after 6 months of NAs therapy to investigate whether serum let‐7b/c/g levels can be monitored as an early biomarker for liver fibrogenesis based on multivariate logistic regression analyses. We also used the hepatic stellate cell line LX‐2 treated with transforming growth factor‐β (TGF‐β) to evaluate the suppression effect of let‐7b/c/g on hepatic fibrogenesis. The study showed that circulating let‐7b/c/g could predict 12 months of antiviral treatment for HBV‐related significant fibrosis (FIB‐4 index ≥ 2.9) at baseline and was significantly negatively correlated with the FIB‐4 score. Moreover, let‐7b/c/g could directly target the TGF‐βR1–3′ untranslated region (3′ UTR) and inhibit TGF‐β induced p‐SMAD2 phosphorylation to reduce α‐smooth muscle actin levels, a fibrogenesis marker in LX‐2 cells. These results confirm that let‐7b/c/g could be a biomarker for monitoring HBV‐induced fibrogenesis.https://doi.org/10.1002/kjm2.70015hepatic stellate cellsliver fibrosismicroRNAsnucleos(t)ide analogsTGF‐β |
| spellingShingle | Yi‐Shan Tsai Po‐Cheng Liang Yi‐Hung Lin Tyng‐Yuan Jang Yu‐Ju Wei Po‐Han Chen Jia‐Ning Hsu Meng‐Hsuan Hsieh Ming‐Yen Hsieh Chih‐Wen Wang Zu‐Yau Lin Ming‐Lun Yeh Chung‐Feng Huang Jee‐Fu Huang Ming‐Lung Yu Wan‐Long Chuang Chia‐Yen Dai Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus Kaohsiung Journal of Medical Sciences hepatic stellate cells liver fibrosis microRNAs nucleos(t)ide analogs TGF‐β |
| title | Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus |
| title_full | Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus |
| title_fullStr | Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus |
| title_full_unstemmed | Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus |
| title_short | Circulating let‐7 Predicts Hepatic Fibrogenesis of 12‐Month Post‐Nucleos(t)ide Analog Treatment in Patients With Hepatitis B Virus |
| title_sort | circulating let 7 predicts hepatic fibrogenesis of 12 month post nucleos t ide analog treatment in patients with hepatitis b virus |
| topic | hepatic stellate cells liver fibrosis microRNAs nucleos(t)ide analogs TGF‐β |
| url | https://doi.org/10.1002/kjm2.70015 |
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