乾癬介紹
乾癬是一常見的免疫調節發炎性疾病，特徵是皮膚有帶皮屑的紅色斑塊，並且常合併其他疾病如關節炎和心血管疾病。乾癬的成因和多種基因與環境因子有關，本研究團隊和加州大學戴維斯分校合作，致力於研究飲食對乾癬的影響。
肥胖、飲食和乾癬
肥胖和乾癬的相關性已廣為人知，肥胖會惡化乾癬，肥胖的病人減重之後則會改善乾癬。然而，飲食中的脂肪和糖(例如蔗糖)，都會引發肥胖，一般人常接觸到的是西方飲食(Western diet，WD)，這種飲食不只是攝取過多脂肪，也會從含糖飲料等來源攝取過多的糖。另一方面，探討肥胖和疾病關係的動物實驗，常常使用脂肪含量高但含糖量正常的配方(以下簡稱高脂飲食，high-fat diet，HFD)來誘導肥胖，本研究主要是想比較西方飲食和高脂飲食，在同樣會誘導肥胖的前提下，對乾癬性發炎的影響是否有所不同。
西方飲食、高脂飲食和乾癬
實驗設計上，將小鼠分成四組，分別餵食WD、control diet(CD，即WD的對照組配方)、HFD、low-fat diet(LFD，即HFD的對照組配方)，在餵食小鼠三個月後，在耳朵塗抹imiquimod cream連續五天以誘導乾癬性皮膚炎，期間測量小鼠兩耳的厚度作為發炎水腫程度的指標。塗抹imiquimod cream滿五天後，取耳朵觀察組織變化，並作RT-qPCR和組織染色檢視乾癬相關的發炎因子變化。
餵食小鼠滿三個月後，HFD組的小鼠體重顯著高於其他三個組別，換句話說，食用HFD配方的小鼠肥胖程度較食用WD配方的小鼠嚴重，然而，經過imiquimod cream塗抹五天去誘導乾癬性發炎，WD組和HFD組相比，WD組小鼠在第四天後耳朵水腫程度較嚴重，組織學的檢視也發現，WD組小鼠發炎細胞如嗜中性球浸潤程度較嚴重，且Munro microabscess的密度也較高，用RT-qPCR檢視發炎因子的表現，也發現WD組的IL-17A、Ly6g、IL-6等表現顯著較HFD組高。
結論: 西方飲食誘導乾癬，食物中的高糖組成可能是一大關鍵。
綜合所述，在這個實驗所用的配方，雖然HFD較WD更會誘導肥胖，但是在小鼠imiquimod誘導乾癬性發炎的模式中，反而是WD組的乾癬性發炎較嚴重，依據此發現，對於乾癬病人的衛教可能不只要注意體重的控制，也要避免攝取過多糖類。將來需要更多的轉譯醫學研究和人類資料庫研究來驗證此實驗結果。
圖說: 西方飲食(高脂高糖飲食)，相較於高脂低糖飲食和常規飲食，會引發較多的IL-17細胞激素表現，此細胞激素對乾癬性發炎扮演重要角色。當遇到誘發因子，例如imiquimod藥膏，接受西方飲食的小鼠會有顯著的發炎性細胞激素表現增加，也會有較多的嗜中性球聚集，如果和接受高脂低糖飲食或常規飲食的小鼠比較，接受西方飲食的小鼠會有較嚴重的乾癬樣皮膚炎，顯示西方飲食中的高糖成分對乾癬性發炎扮演重要角色。
Introduction of psoriasis
Psoriasis is a common, immunologically mediated, inflammatory disease characterized by scaly erythematous plaques on the skin and have comorbidities such as arthritis and cardiovascular disease. Pathogenesis of psoriasis involves polygenic predisposition and multiple environmental factors. Our team has collaborated with University of California Davis to investigate the effects of diets on psoriasis.
Obesity, diets, and psoriasis
The relationship between obesity and psoriasis is well known. Obesity exacerbates psoriasis while body weight reduction ameliorates psoriasis. However, both fat and sugars (ex. sucrose) induces obesity, and general people more often eats the Western diet (WD, high-fat and high-sugar content), which not only contains excessive fat but has excessive sugars from sugary drinks. On the other hand, the high-fat diet (HFD, high-fat and normal sugar content) is also used in animal experiments to investigate the relationship between obesity and disease. In this research, we aim at investigating if there is difference in psoriasiform inflammation between WD and HFD, both induce obesity.
WD, HFD, and psoriasis
For study design, mice were classified into four groups based on the diets: WD, control diet (CD, a control recipe of WD), HFD, low-fat diet (LFT, a control recipe of HFD). After feeding them for 3 months, we applied imiquimod cream on ears of mice for 5 consecutive days to induce psoriasiform dermatitis, and measure ear thickness as an indicator of inflammation during the course. After applying imiquimod cream for 5 days, mice were sacrificed and their ears were harvested to examine histological change, RT-qPCR and immunohistochemistry specific to psoriasis-related inflammatory mediators.
After feeding for 3 months, mice fed with HFD had significantly more body weight than other groups. This is, mice fed with HFD had more severe obese than mice fed with WD. After applying imiquimod cream for 5 consecutive days to induce psoriasiform dermatitis, however, mice fed with WD had more severe ear swelling after day 4. Histological analysis also demonstrated that mice fed with WD had more neutrophils and higher density of Munromicroabscess as well as higher expression levels of IL-17A, Ly6g, IL-6 than mice fed with HFD.
Conclusion: WD induces psoriasis, and the high-sugar content may play a crucial role.
Taken together, while HFD induced more obesity than WD in these recipes, it was WD group that had more severe psoriasiform inflammation in terms of the murine imiquimod model. According to this finding, health education for patients with psoriasis should not only focus on body weight control but avoid excessive sugar intake. Further translational medicine investigation and human database research are need to verify these experimental results.
人格特質與糖尿病有關，強化飲食及運動自我照顧行為有解
高雄醫學大學護理學院王瑞霞教授，2019年指導碩士班研究生，進行200位第二型糖尿病人與人格特質的研究時，發現糖尿病人中，性格為外向的、友善的、謹慎性的病人，他們的糖尿病自我照顧行為比較好；也發現神經性人格異常的病人，糖尿病自我照顧行為比較差；另發現開放性人格與糖尿病自我照顧行為沒有明顯的相關。研究者同時發現，糖尿病自我照顧行為中，以飲食控制及運動行為與人格特質有比較強的關係，而飲食及運動自我照顧行為，正是國內糖尿病病人自我照顧行為執行最差的兩項。
高醫大的研究結果提供臨床專業人員重要的線索，可以依照病人的人格特質不同，提供不同的衛生教育策略。糖尿病病人為避免合併症發生，須進行飲食控制、藥物、 血糖監測、高低血糖處理及足部照護等自我照顧行為，但也因這些行為會干擾病人日常生活而影響其持續性，專業人員也試圖找出影響行為的重要因素，以做為擬定策略的參考。因此，此糖尿病人與其人格特質的前瞻研究，為台灣的糖尿病照護增加新的照護知識，預期可以幫助更多糖尿病病人提升自我照護能力。
高醫大護理學院王瑞霞教授從事第一型糖尿病青少年及第二型糖尿病已近12年，共發表30多篇糖尿病相關論文，並刊登於國際優良期刊。她的研究著重於探討心理社會因子對糖尿病的影響，也發展量表以做為臨床評估病人心理社會問題參考，她強調除了藥物治療外，不應忽略糖尿病個案在心理社會層面的照護，也因她在糖尿病的全方位研究及表現，王瑞霞教授獲得2017 年傑出護理人員專業貢獻獎，並多次獲得學校優秀論文獎及研究成果績優等獎項。
王瑞霞強調，該研究提供專業人員在衛教病人自我照顧行為時，可先了解糖尿病人的人格特質，擬定適合人格特質的照護計畫，如針對具外向性人格特質者，可利用其積極主動個性，提供最新資訊鼓勵其持續執行自我照顧行為；謹慎性人格特質者則，可以較有組織的方式提供相關訊息；友善性人格特質者則可以較開放溝通的方式與病人討論自我照顧行為的執行；神經性人格特質者則應鼓勵其正向看待其罹病，避免因負向情緒反而放棄自我照顧行為的執行。
2017年王瑞霞教授獲傑出護理人員獎
慢性B型與C型肝炎雙重感染病患接受口服抗病毒藥物成功治療C型肝炎後，可能引發B型肝炎嚴重發作及死亡
慢性B型與C型肝炎雙重感染常會加重C型肝炎之嚴重度並加速病程惡化。新型C型肝炎口服抗病毒藥物(DAA)上市後，可以有效清除95%以上之C型肝炎病毒，然而其對合併之B型肝炎感染之長期預後仍不得而知。高醫肝炎團隊針對台灣慢性B型與C型肝炎雙重感染病患接受C型肝炎口服抗病毒藥物治療後對B型肝炎相關預後及機轉進行研究，研究顯示有高達38%慢性B型與C型肝炎雙重感染病患接受DAA治療後，發生B型肝炎病毒發作，其中五分之一出現臨床肝炎發作，當中又有三分之一導致死亡。然而，也有10%病患在接受DAA治療後B型肝炎表面抗原消失，代表病患由B型肝炎帶原者轉變成非帶原者。我們進一步發現， 使用B型肝炎表面抗原濃度(HBsAg)，以10 IU/ml分水嶺，可以成功預測病人未來會發生B型肝炎病毒發作(>10 IU/ml, (hazard ratio [HR] 2.88; 95% CI 1.057–7.844)或者是B型肝炎表面抗原消失(。這些發現顯示，治療前B型肝炎表面抗原濃度可以作為預測這類病患接受DAA治療是否能產生B型肝炎表面抗原消失及發生B型肝炎病毒發作的標記，近一步幫助指引臨床醫師治療此類病患前是否給予預防性B型肝炎抗病毒藥。我們的研究報告中另一重要發現是這些接受DAA治療後發生B型肝炎發作導致死亡的病患都是肝硬化同時沒有接受預防性抗B型肝炎藥物之病患，因此未來應考慮對肝硬化病患同時給予預防性B型肝炎抗病毒藥以減少風險。
除此之外，本研究也進行一系列細胞激素與微核醣核酸檢測來探討兩種病毒間免疫反應。 我們發現，治療前血清miR-122及miR-125b濃度較低、或治療過程當中血清IP-10濃度沒有降低的病人，B型肝炎表面抗原消失的機會明顯較高；相對的，B型肝炎病毒發作的病人，其治療過程當中血清miR-122及miR-125b濃度有持續降低的現象。
本研究結果可作為臨床醫師在診療此類病患之參考，幫助指引臨床醫師治療此類病患前是否給予預防性B型肝炎抗病毒藥以避免治療過程中可能發生的B型肝炎嚴重發作及死亡。同時減少無或微風險病患可能接受預防性B型肝炎抗病毒藥物之副作用風險與醫療花費。
本校主要研究者之簡介:
葉明倫副教授和余明隆講座教授為高雄醫學大學醫學院肝炎研究中心成員，也是高雄醫學大學附屬機構肝膽胰內科的主治醫師，致力於肝臟疾病之病因、致病機轉、治療及預防的研究及服務。
研究聯繫Email:
fish6069@gmail.com; fishya@ms14.hinet.net
期刊出處:
Yeh ML, Huang CF, Huang CI, Holmes JA, Hsieh MH, Tsai YS, Liang PC, Tsai PC, Hsieh MY, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Chung RT, Yu ML*. Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection. J Hepatol. 2020 Jul;73(1):62-71.
研究全文下載:
Taiwanese patients with HBV and HCV co-infection are likely to experience HBV functional cure, but also HBV reactivation following direct-acting antiviral treatment for HCV
This study shows the outcomes after the direct acting antiviral (DAA) treatment in patients with chronic hepatitis B (HBV)/ hepatitis C (HCV) dual-infection, that including 10% of hepatitis B surface antigen (HBsAg) loss and 38% of HBV reactivation. Our findings published in the Journal of Hepatology provide new insights into understanding the viral interaction between HBV and HCV.
The research group led by Chair Professor Ming-Lung Yu from Hepatitis Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan, in collaboration with Professor Raymond T Chung from Massachusetts General Hospital, Boston; Department of Medicine, Harvard Medical School, reported a new insight into the viral interaction between HBV and HCV following DAA treatment and found it might be a blessing (HBsAg loss) in disguise (HBV reactivation) for patients. They also suggested the high risked cirrhotic patients to undergo HBV prophylaxis simultaneously.
The new all-oral DAA regimens for HCV have greatly improved treatment efficacy with sustained virological response rates of > 95% for HCV monoinfected patients. Unfortunately, HBV reactivation and HBV-related clinical reactivation during or after DAA therapy were not infrequent, and might lead to mortality in HBV/HCV-coinfected patients, especially among those with cirrhosis.
This study enrolled 79 HBV/HCV-coinfected patients receiving DAA therapy to investigate their HBV-related outcomes. One exciting finding was that during one year post-DAA follow up, 8 (10.1%) patients experienced HBsAg loss (an ideal outcome of “HBV functional cure”) with a 12-month cumulative probability of 10.3%. Another new finding was the specific decline of HBsAg level during therapy, and rebound after stopping DAA.
Alternatively, up to 30 (38%) patients were found developing a HBV reactivation (means a rebound of HBV replication). Of them, 6 (20%) patients even experienced a HBV related clinical reactivation (means a clinical hepatitis) and 3 patients further developed hepatic failure with 2 died despite the immediate anti-HBV therapy. All these 2 patients had liver cirrhosis and were without an HBV prophylaxis before DAA. Thus prophylactic anti-HBV therapy is mandatory for cirrhotic patients, irrespective of baseline HBV DNA levels.
Pre-treatment HBsAg titer can be a surrogated marker to guide decision making. This study further found that using the pre-treatment HBsAg titer of less than 10 IU/mL could predict the higher chance of HBsAg loss and lower risk of HBV reactivation.
Researchers from Kaohsiung Medical University and Harvard Medical School also demonstrates a complex interaction among the host and the two viruses in determining HBV outcomes following the results from cytokines and micro RNAs experiments.
Getting together, this study provides a new insight into the management of HBV/HCV-coinfected patients being treated with DAA.
Main researcher Intro.
Associate Professor Ming-Lun Yeh and Chair Professor Ming-Lung Yu are members of Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital and Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. They dedicate in the research and service of Liver diseases, including etiologies, epidemiology, pathogenesis, therapeutic modalities and prevention of hepatitis B, hepatitis C, steatohepatitis and liver cancers.
Author Email
fish6069@gmail.com; fishya@ms14.hinet.net
Paper cited from:
Yeh ML, Huang CF, Huang CI, Holmes JA, Hsieh MH, Tsai YS, Liang PC, Tsai PC, Hsieh MY, Lin ZY, Chen SC, Huang JF, Dai CY, Chuang WL, Chung RT, Yu ML*. Hepatitis B-related outcomes following direct-acting antiviral therapy in Taiwanese patients with chronic HBV/HCV co-infection. J Hepatol. 2020 Jul;73(1):62-71.
Research Paper available online on website
勿貪圖便宜，購買來源不明之黑心食品、藥品與商品，俾確保身體健康。
◎正確用藥觀念保健康，生病看醫生用藥找藥師，請提醒家中長輩勿購買來路不明藥品，以免花錢又傷身。
◎食品安全很重要，民眾應善盡監督者角色，與政府合作揪出不肖廠商，徹底打擊黑心商品，以維護民眾健康。
2021 © 高雄醫學大學 Kaohsiung Medical University
建議使用 Chrome / Safari / Firefox 瀏覽
