Combined prednisone and levothyroxine improve treatment of severe thrombocytopenia in hepatitis B with compensatory cirrhosis accompanied by subclinical and overt hypothyroidism
- 35 Downloads
The aim of the present study was to investigate the relationship between hypothyroidism and thrombocytopenia in hepatitis B-related compensatory liver cirrhosis and to determine whether treatment with levothyroxine and prednisone is superior in a multicenter, open-label, observational study in China. In total, 125 consecutive hepatitis B-related compensated liver cirrhosis patients with severe thrombocytopenia accompanied by hypothyroidism were included. The patients were divided into four groups according to treatment strategy: a control group (n=29), a prednisone group (n=25), a levothyroxine group (n=32) and a prednisone plus levothyroxine group (n=39). Severe thrombocytopenia was more prevalent in hepatitis B-associated compensatory liver cirrhosis patients with hypothyroidism than in euthyroid patients (29.6% vs. 14.7%, P<0.05). Combination treatment with prednisone and levothyroxine decreased the risk of bleeding and improved platelet recovery compared to control treatment and treatment with either prednisone or levothyroxine alone. The platelet count before therapy, serum thyroid stimulating hormone and combination treatment with prednisone and levothyroxine were associated with bleeding events. Therefore, the present study suggests that hypothyroidism is associated with severe thrombocytopenia in hepatitis B-associated compensatory liver cirrhosis. Treatment with prednisone plus levothyroxine may present a novel approach in these patients.
Keywordshepatitis B cirrhosis thrombocytopenia hypothyroidism treatment
Unable to display preview. Download preview PDF.
The authors thank their nurses’ team and technicians in executing this study. We also thank Yang Wang from State Key Laboratory of Translational Cardiovascular Medicine, Fuwai Hospital & Cardiovascular Institute for statistic analysis. This work was supported by National Natural Science Foundation of China (81470343, 81670116), National Natural Science Foundation for Young Scholars of China (81600132), Key Program of National Natural Science Foundation of China (81730004), Beijing Natural Science Foundation (7171013), Beijing Municipal Science and Technology Commission (Z171100001017084), the National Key Research and Development Program of China (2017YFA0105503) and the Foundation for Innovative Research Groups of the National Natural Science Foundation of China (81621001).
- Atalay, R., Ersoy, R., Demirezer, A.B., Akın, F.E., Polat, S.B., Cakir, B., and Ersoy, O. (2015). Day-night variations in thyroid stimulating hormone and its relation with clinical status and metabolic parameters in patients with cirrhosis of the liver. Endocrine 48, 942–948.CrossRefPubMedGoogle Scholar
- Baskin, H.J., Cobin, R.H., Duick, D.S., Gharib, H., Guttler, R.B., Kaplan, M.M., Segal, R.L., Garber, J.R., Hamilton Jr., C.R., Handelsman, Y., Hellman, R., Kukora, J.S., Levy, P., Palumbo, P.J., Petak, S.M., Rettinger, H.I., Rodbard, H.W., Service, F.J., Shankar, T.P., Stoffer, S.S., Tourtelot, J.B. (2002). American association of clinical endocrinologists medical guidelines for clinical practice for the evaluation and treatment of hyperthyroidism and hypothyroidism. Endocr Pract 8, 457–469.CrossRefPubMedGoogle Scholar
- Carulli, L., Ballestri, S., Lonardo, A., Lami, F., Violi, E., Losi, L., Bonilauri, L., Verrone, A.M., Odoardi, M.R., Scaglioni, F., Bertolotti, M., and Loria, P. (2013). Is nonalcoholic steatohepatitis associated with a highthough- normal thyroid stimulating hormone level and lower cholesterol levels? Intern Emerg Med 8, 297–305.CrossRefPubMedGoogle Scholar
- Committee, W.G.A.b.t.G.R. (2015). Guidelines for the Prevention, Care and Treatment of Persons with Chronic Hepatitis B Infection. (Geneva: World Health Organization).Google Scholar
- Garber, J.R., Cobin, R.H., Gharib, H., Hennessey, J.V., Klein, I., Mechanick, J.I., Pessah-Pollack, R., Singer, P.A., Woeber, K.A., Woeber, K.A. (2012). Clinical practice guidelines for hypothyroidism in adults: cosponsored by the american association of clinical endocrinologists and the american thyroid association. Thyroid 22, 1200–1235.CrossRefPubMedGoogle Scholar
- Hou, J.L. (2015). The guideline of prevention and treatment for chronic hepatitis B: a 2015 update (in Chinese). Chin J Hepatol 23, 888–905.Google Scholar
- Napolitano, M., Malato, A., Raffaele, F., Palazzolo, M., Lo Iacono, G., Pinna, R., Geraci, G., Modica, G., Saccullo, G., Siragusa, S., and Cajozzo, M. (2013). Ultrasonography-guided central venous catheterisation in haematological patients with severe thrombocytopenia. Blood Transfus 11, 506–509.PubMedPubMedCentralGoogle Scholar
- Rodeghiero, F., Stasi, R., Gernsheimer, T., Michel, M., Provan, D., Arnold, D.M., Bussel, J.B., Cines, D.B., Chong, B.H., Cooper, N., Godeau, B., Lechner, K., Mazzucconi, M.G., McMillan, R., Sanz, M.A., Imbach, P., Blanchette, V., Kühne, T., Ruggeri, M., George, J.N. (2009). Standardization of terminology, definitions and outcome criteria in immune thrombocytopenic purpura of adults and children: report from an international working group. Blood 113, 2386–2393.CrossRefPubMedGoogle Scholar
- Rugge, B., Balshem, H., Sehgal, R., Relevo, R., Gorman, P., and Helfand, M. (2011). AHRQ Comparative Effectiveness Reviews. In Screening and Treatment of Subclinical Hypothyroidism or Hyperthyroidism (Rockville (MD), Agency for Healthcare Research and Quality (US)).Google Scholar
- Sarin, S.K., Kumar, M., Lau, G.K., Abbas, Z., Chan, H.L.Y., Chen, C.J., Chen, D.S., Chen, H.L., Chen, P.J., Chien, R.N., Dokmeci, A.K., Gane, E., Hou, J.L., Jafri, W., Jia, J., Kim, J.H., Lai, C.L., Lee, H.C., Lim, S. G., Liu, C.J., Locarnini, S., Al Mahtab, M., Mohamed, R., Omata, M., Park, J., Piratvisuth, T., Sharma, B.C., Sollano, J., Wang, F.S., Wei, L., Yuen, M.F., Zheng, S.S., Kao, J.H. (2016). Asian-Pacific clinical practice guidelines on the management of hepatitis B: a 2015 update. Hepatol Int 10, 1–98.CrossRefPubMedGoogle Scholar
- Tahir, H., Sheraz, F., Sagi, J., and Daruwalla, V. (2016). Immune thrombocytopenia (ITP) secondary to subclinical hashimoto’s thyroiditis: role of levothyroxine in improving the clinical outcome of ITP. J Investig Med High Impact Case Rep 4, 2324709616647085.Google Scholar
- Teixeira, P.F.S., Reuters, V.S., Ferreira, M.M., Almeida, C.P., Reis, F.A.A., Melo, B.A., Buescu, A., Costa, A.J.L., and Vaisman, M. (2008). Treatment of subclinical hypothyroidism reduces atherogenic lipid levels in a placebo-controlled double-blind clinical trial. Horm Metab Res 40, 50–55.CrossRefPubMedGoogle Scholar
- Wong, G.L.H., Chan, H.L.Y., Mak, C.W.H., Lee, S.K.Y., Ip, Z.M.Y., Lam, A.T.H., Iu, H.W.H., Leung, J.M.S., Lai, J.W.Y., Lo, A.O.S., Chan, H.Y., Wong, V.W.S. (2013). Entecavir treatment reduces hepatic events and deaths in chronic hepatitis B patients With liver cirrhosis. Hepatology 58, 1537–1547.CrossRefPubMedGoogle Scholar
- Zhang, X.H., Feng, R., Xu, L.P., Jiang, Q., Jiang, H., Fu, H.X., Liu, H., Niu, T., Wang, X., Hu, J.D., Jiang, M., Wang, Z., Wang, J.W., Ma, H., Xie, Y. D., Zhu, X.L., Wang, H., Wei, L., Huang, X.J. (2015). Immunosuppressive treatment combined with nucleoside analog is superior to nucleoside analog only in the treatment of severe thrombocytopenia in patients with cirrhosis associated with hepatitis B in China: a multicenter, observational study. Platelets 26, 672–679.CrossRefPubMedGoogle Scholar
- Zhang, X.H., He, Y., Feng, R., Xu, L.P., Jiang, Q., Jiang, H., Lu, J., Fu, H. X., Liu, H., Wang, J.W., Wang, Q.M., Feng, F.E., Zhu, X.L., Xu, L.L., Xie, Y.D., Ma, H., Wang, H., Liu, K.Y., Huang, X.J. (2016). Helicobacter pylori infection influences the severity of thrombocytopenia and its treatment response in chronic hepatitis B patients with compensatory cirrhosis: a multicenter, observational study. Platelets 27, 223–229.CrossRefPubMedGoogle Scholar