4fcf659781c2fdc960e09e774b859a29 pmc_34209831.pdf 476851f12d6a058d4438c181d058a96e5a66678b pmc_34209831.pdf 663a3966200079ac7678ec67377c205a3706d04643405dd96b76ab77545d543c pmc_34209831.pdf Title: TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population Subject: Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18–75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 12 years; 61% female). Subjects with TSH 2.5 IU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH 2.5 (IU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of 8.0 kPa and 9.2 kPa, respectively, in subjects with TSH 2.5 IU/mL compared with TSH < 2.5 IU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values 10 IU/mL. Keywords: thyroid stimulating hormone; thyroid function; metabolic syndrome; obesity; liver fibrosis; transient elastography; non-alcoholic fatty liver disease Author: Alba Martínez-Escudé, Guillem Pera, Anna Costa-Garrido, Lluís Rodríguez, Ingrid Arteaga, Carmen Expósito-Martínez, Pere Torán-Monserrat and Llorenç Caballería Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jul 1 03:13:13 2021 CEST ModDate: Thu Jul 1 03:17:06 2021 CEST Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 15 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1048480 bytes Optimized: no PDF version: 1.7 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- CYVJLM+VnURWPalladioL Type 1 Custom yes yes no 10 0 CAMXTK+EURM10 Type 1 Builtin yes yes no 15 0 KPHXXE+URWPalladioL-Ital Type 1 Custom yes yes no 19 0 TMRBNI+URWPalladioL-Bold Type 1 Custom yes yes no 24 0 DPOEJQ+URWPalladioL-Roma Type 1 Custom yes yes no 28 0 SSJMKU+CMSY10 Type 1 Builtin yes yes no 32 0 JYPLJJ+VnURWPalladioL-Bold Type 1 Custom yes yes no 36 0 XPUSBJ+TimesNewRomanPS-BoldItalicMT Type 1C WinAnsi yes yes no 44 0 BSDWLC+TimesNewRomanPSMT Type 1C WinAnsi yes yes no 47 0 MCBCCI+SourceSansRoman-Regular Type 1C Custom yes yes no 69 0 MCBCCM+SourceSansRoman.613wght Type 1C Custom yes yes no 73 0 MCBCCO+SourceSansRoman-Bold Type 1C Custom yes yes no 77 0 QLBIEB+URWPalladioL-BoldItal Type 1 Custom yes yes no 95 0 DCHECN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 116 0 DCHECO+PalatinoLinotype CID TrueType Identity-H yes yes yes 119 0 DCHECP+PalatinoLinotype TrueType WinAnsi yes yes no 125 0 DCHEEA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 128 0 DCHECN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 145 0 DCHECO+PalatinoLinotype CID TrueType Identity-H yes yes yes 148 0 DCHECP+PalatinoLinotype TrueType WinAnsi yes yes no 154 0 DCHEEA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 157 0 DCHECN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 176 0 DCHECO+PalatinoLinotype CID TrueType Identity-H yes yes yes 179 0 DCHECP+PalatinoLinotype TrueType WinAnsi yes yes no 185 0 DCHEEA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 188 0 DCHECN+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 206 0 DCHECO+PalatinoLinotype CID TrueType Identity-H yes yes yes 209 0 DCHECP+PalatinoLinotype TrueType WinAnsi yes yes no 215 0 DCHEEA+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 218 0 DCHFMJ+PalatinoLinotype,BoldItalic TrueType WinAnsi yes yes no 221 0 CRUZTT+VnURWPalladioL-Italic Type 1 Custom yes yes no 239 0 Jhove (Rel. 1.22.1, 2019-04-17) Date: 2021-09-11 03:03:46 CEST RepresentationInformation: pmc_34209831.pdf ReportingModule: PDF-hul, Rel. 1.12.1 (2019-04-17) LastModified: 2021-07-12 03:36:36 CEST Size: 1048480 Format: PDF Version: 1.7 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 435 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@13c27452 Item: Title: Methods Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@262b2c86 Children: Item: Title: Study Design and Population Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@371a67ec Item: Title: Clinical and Laboratory Parameters Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@5ed828d Item: Title: Evaluation of MetS Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@50d0686 Item: Title: Evaluation of NAFLD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@7a3d45bd Item: Title: Evaluation of Liver Fibrosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1e7c7811 Item: Title: Statistical Analysis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77ec78b9 Item: Title: Results Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@1a3869f4 Children: Item: Title: Basal Characteristics Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@a38d7a3 Item: Title: Relationship between TSH and NAFLD Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@77f99a05 Item: Title: Relationship between TSH and Hypertransaminasemia Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@63440df3 Item: Title: Association between TSH and Liver Fibrosis Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@3aeaafa6 Item: Title: Discussion Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@76a3e297 Item: Title: Conclusions Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@4d3167f4 Item: Title: References Destination: edu.harvard.hul.ois.jhove.module.pdf.PdfSimpleObject@ed9d034 Info: Title: TSH Levels as an Independent Risk Factor for NAFLD and Liver Fibrosis in the General Population Author: Alba Martínez-Escudé, Guillem Pera, Anna Costa-Garrido, Lluís Rodríguez, Ingrid Arteaga, Carmen Expósito-Martínez, Pere Torán-Monserrat and Llorenç Caballería Subject: Thyroid hormones may be a risk factor for the development of non-alcoholic fatty liver disease (NAFLD) and its progression to liver fibrosis. The aim of this study is to investigate the relationship between thyroid stimulating hormone (TSH) levels, NAFLD, and liver fibrosis in the general population. A descriptive cross-sectional study was performed in subjects aged 18 75 years randomly selected from primary care centers between 2012 and 2016. Each subject underwent clinical evaluation, physical examination, blood tests and transient elastography. Descriptive and multivariate logistic regression analyses were used to identify factors associated with NAFLD and fibrosis. We included 2452 subjects (54 12 years; 61% female). Subjects with TSH 2.5 IU/mL were significantly associated with obesity, atherogenic dyslipidemia, metabolic syndrome (MetS), hypertransaminasemia and altered cholesterol and triglycerides. The prevalence of NAFLD and liver fibrosis was significantly higher in subjects with TSH 2.5 (IU/mL). We found a 1.5 times increased risk of NAFLD, 1.8 and 2.3 times increased risk of liver fibrosis for cut-off points of 8.0 kPa and 9.2 kPa, respectively, in subjects with TSH 2.5 IU/mL compared with TSH < 2.5 IU/mL (control group), independent of the presence of MetS. These findings remained significant when stratifying TSH, with values 10 IU/mL. Keywords: thyroid stimulating hormone; thyroid function; metabolic syndrome; obesity; liver fibrosis; transient elastography; non-alcoholic fatty liver disease Creator: LaTeX with hyperref Producer: pdfTeX-1.40.21 CreationDate: Thu Jul 01 03:13:13 CEST 2021 ModDate: Thu Jul 01 03:17:06 CEST 2021 ID: 0x495d59a80fe59114b0115b210ef32645, 0x495d59a80fe59114b0115b210ef32645 Filters: FilterPipeline: FlateDecode Fonts: Type1: Font: BaseFont: SSJMKU+CMSY10 FontSubset: true FirstChar: 0 LastChar: 21 FontDescriptor: FontName: SSJMKU+CMSY10 Flags: Symbolic FontBBox: -29, -960, 1116, 775 FontFile: true Font: BaseFont: KPHXXE+URWPalladioL-Ital FontSubset: true FirstChar: 42 LastChar: 121 FontDescriptor: FontName: KPHXXE+URWPalladioL-Ital Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: JYPLJJ+VnURWPalladioL-Bold FontSubset: true FirstChar: 161 LastChar: 226 FontDescriptor: FontName: JYPLJJ+VnURWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: TMRBNI+URWPalladioL-Bold FontSubset: true FirstChar: 3 LastChar: 231 FontDescriptor: FontName: TMRBNI+URWPalladioL-Bold Flags: Symbolic FontBBox: -152, -301, 1000, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CYVJLM+VnURWPalladioL FontSubset: true FirstChar: 129 LastChar: 226 FontDescriptor: FontName: CYVJLM+VnURWPalladioL Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: DPOEJQ+URWPalladioL-Roma FontSubset: true FirstChar: 2 LastChar: 243 FontDescriptor: FontName: DPOEJQ+URWPalladioL-Roma Flags: Symbolic FontBBox: -166, -283, 1021, 943 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CAMXTK+EURM10 FontSubset: true FirstChar: 12 LastChar: 22 FontDescriptor: FontName: CAMXTK+EURM10 Flags: Symbolic FontBBox: -32, -243, 1060, 720 FontFile: true Font: BaseFont: QLBIEB+URWPalladioL-BoldItal FontSubset: true FirstChar: 110 LastChar: 112 FontDescriptor: FontName: QLBIEB+URWPalladioL-BoldItal Flags: Symbolic FontBBox: -170, -300, 1073, 935 FontFile: true EncodingDictionary: Differences: true Font: BaseFont: CRUZTT+VnURWPalladioL-Italic FontSubset: true FirstChar: 189 LastChar: 189 FontDescriptor: FontName: CRUZTT+VnURWPalladioL-Italic Flags: Symbolic FontBBox: -170, -305, 1010, 941 FontFile: true EncodingDictionary: Differences: true Pages: Page: Sequence: 1 Annotations: Annotation: Subtype: Link Rect: 35, 759, 176, 795 Annotation: Subtype: Link Rect: 515, 759, 560, 795 Annotation: Subtype: Link Rect: 156, 659, 167, 673 Annotation: Subtype: Link Rect: 244, 659, 255, 673 Annotation: Subtype: Link Rect: 288, 647, 299, 661 Annotation: Subtype: Link Rect: 416, 647, 427, 661 Annotation: Subtype: Link Rect: 99, 346, 154, 355 Annotation: Subtype: Link Rect: 35, 334, 102, 343 Annotation: Subtype: Link Rect: 35, 162, 97, 184 Annotation: Subtype: Link Rect: 153, 89, 154, 98 Annotation: Subtype: Link Rect: 35, 77, 147, 86 Annotation: Subtype: Link Rect: 380, 155, 387, 164 ActionDest: 236 Annotation: Subtype: Link Rect: 435, 117, 442, 126 ActionDest: 236 Annotation: Subtype: Link Rect: 375, 79, 382, 88 ActionDest: 236 Annotation: Subtype: Link Rect: 131, 17, 268, 28 Annotation: Subtype: Link Rect: 422, 17, 558, 28 Annotation: Subtype: Link Rect: 35, 446, 87, 465 Page: Sequence: 2 Annotations: Annotation: Subtype: Link Rect: 303, 712, 310, 721 ActionDest: 236 Annotation: Subtype: Link Rect: 247, 686, 254, 695 ActionDest: 236 Annotation: Subtype: Link Rect: 254, 686, 261, 695 ActionDest: 236 Annotation: Subtype: Link Rect: 209, 636, 216, 645 ActionDest: 236 Annotation: Subtype: Link Rect: 410, 586, 417, 595 ActionDest: 236 Annotation: Subtype: Link Rect: 431, 573, 438, 582 ActionDest: 236 Annotation: Subtype: Link Rect: 202, 548, 214, 557 ActionDest: 236 Annotation: Subtype: Link Rect: 447, 548, 459, 557 ActionDest: 236 Annotation: Subtype: Link Rect: 544, 548, 556, 557 ActionDest: 236 Annotation: Subtype: Link Rect: 366, 511, 378, 520 ActionDest: 236 Annotation: Subtype: Link Rect: 378, 511, 390, 520 ActionDest: 236 Annotation: Subtype: Link Rect: 530, 384, 542, 393 ActionDest: 236 Page: Sequence: 3 Annotations: Annotation: Subtype: Link Rect: 197, 685, 208, 694 ActionDest: 236 Annotation: Subtype: Link Rect: 209, 685, 221, 694 ActionDest: 236 Annotation: Subtype: Link Rect: 202, 621, 214, 631 ActionDest: 236 Annotation: Subtype: Link Rect: 207, 483, 219, 492 ActionDest: 236 Annotation: Subtype: Link Rect: 531, 395, 543, 404 ActionDest: 236 Annotation: Subtype: Link Rect: 544, 395, 556, 404 ActionDest: 236 Page: Sequence: 4 Annotations: Annotation: Subtype: Link Rect: 489, 565, 496, 577 ActionDest: 99 Page: Sequence: 5 Annotations: Annotation: Subtype: Link Rect: 215, 463, 222, 475 ActionDest: 99 Annotation: Subtype: Link Rect: 549, 221, 556, 232 ActionDest: 102 Page: Sequence: 6 Annotations: Annotation: Subtype: Link Rect: 352, 448, 359, 460 ActionDest: 102 Page: Sequence: 7 Annotations: Annotation: Subtype: Link Rect: 420, 707, 427, 719 ActionDest: 163 Annotation: Subtype: Link Rect: 549, 190, 556, 202 ActionDest: 99 Annotation: Subtype: Link Rect: 295, 153, 303, 165 ActionDest: 102 Annotation: Subtype: Link Rect: 383, 90, 390, 102 ActionDest: 166 Page: Sequence: 8 Annotations: Annotation: Subtype: Link Rect: 432, 458, 439, 470 ActionDest: 166 Annotation: Subtype: Link Rect: 338, 96, 345, 108 ActionDest: 192 Annotation: Subtype: Link Rect: 338, 84, 345, 96 ActionDest: 192 Annotation: Subtype: Link Rect: 452, 84, 459, 96 ActionDest: 192 Page: Sequence: 9 Annotations: Annotation: Subtype: Link Rect: 312, 349, 319, 361 ActionDest: 226 Page: Sequence: 10 Annotations: Annotation: Subtype: Link Rect: 316, 390, 328, 399 ActionDest: 236 Annotation: Subtype: Link Rect: 544, 390, 556, 399 ActionDest: 236 Annotation: Subtype: Link Rect: 275, 378, 287, 387 ActionDest: 236 Annotation: Subtype: Link Rect: 393, 365, 404, 374 ActionDest: 236 Annotation: Subtype: Link Rect: 307, 340, 319, 349 ActionDest: 243 Annotation: Subtype: Link Rect: 390, 302, 401, 311 ActionDest: 236 Annotation: Subtype: Link Rect: 205, 290, 217, 299 ActionDest: 243 Annotation: Subtype: Link Rect: 444, 265, 456, 274 ActionDest: 243 Annotation: Subtype: Link Rect: 437, 252, 449, 261 ActionDest: 243 Annotation: Subtype: Link Rect: 544, 252, 556, 261 ActionDest: 243 Annotation: Subtype: Link Rect: 205, 240, 217, 249 ActionDest: 243 Annotation: Subtype: Link Rect: 273, 240, 285, 249 ActionDest: 243 Annotation: Subtype: Link Rect: 369, 227, 381, 236 ActionDest: 243 Annotation: Subtype: Link Rect: 412, 214, 424, 224 ActionDest: 243 Annotation: Subtype: Link Rect: 229, 202, 241, 211 ActionDest: 243 Annotation: Subtype: Link Rect: 386, 152, 398, 161 ActionDest: 243 Annotation: Subtype: Link Rect: 529, 127, 541, 136 ActionDest: 243 Annotation: Subtype: Link Rect: 341, 89, 353, 98 ActionDest: 243 Page: Sequence: 11 Annotations: Annotation: Subtype: Link Rect: 446, 722, 458, 731 ActionDest: 243 Annotation: Subtype: Link Rect: 253, 685, 265, 694 ActionDest: 243 Annotation: Subtype: Link Rect: 491, 672, 503, 681 ActionDest: 243 Annotation: Subtype: Link Rect: 454, 647, 466, 656 ActionDest: 243 Annotation: Subtype: Link Rect: 383, 522, 395, 530 ActionDest: 243 Annotation: Subtype: Link Rect: 543, 496, 555, 505 ActionDest: 243 Annotation: Subtype: Link Rect: 361, 471, 373, 480 ActionDest: 243 Annotation: Subtype: Link Rect: 412, 459, 424, 468 ActionDest: 243 Annotation: Subtype: Link Rect: 544, 446, 556, 455 ActionDest: 243 Annotation: Subtype: Link Rect: 543, 408, 555, 417 ActionDest: 243 Annotation: Subtype: Link Rect: 544, 358, 556, 367 ActionDest: 243 Annotation: Subtype: Link Rect: 430, 320, 442, 330 ActionDest: 236 Annotation: Subtype: Link Rect: 304, 308, 316, 317 ActionDest: 243 Annotation: Subtype: Link Rect: 407, 220, 419, 229 ActionDest: 246 Annotation: Subtype: Link Rect: 500, 195, 512, 204 ActionDest: 243 Annotation: Subtype: Link Rect: 512, 195, 524, 204 ActionDest: 246 Annotation: Subtype: Link Rect: 203, 182, 215, 192 ActionDest: 246 Annotation: Subtype: Link Rect: 293, 182, 305, 192 ActionDest: 246 Annotation: Subtype: Link Rect: 336, 132, 348, 141 ActionDest: 246 Annotation: Subtype: Link Rect: 463, 120, 475, 129 ActionDest: 246 Annotation: Subtype: Link Rect: 441, 95, 453, 104 ActionDest: 246 Annotation: Subtype: Link Rect: 439, 69, 451, 79 ActionDest: 246 Page: Sequence: 12 Annotations: Annotation: Subtype: Link Rect: 328, 672, 340, 681 ActionDest: 246 Annotation: Subtype: Link Rect: 544, 659, 556, 669 ActionDest: 246 Annotation: Subtype: Link Rect: 371, 634, 383, 643 ActionDest: 246 Annotation: Subtype: Link Rect: 237, 622, 249, 631 ActionDest: 246 Annotation: Subtype: Link Rect: 290, 559, 297, 568 ActionDest: 236 Page: Sequence: 13 Annotations: Annotation: Subtype: Link Rect: 474, 718, 511, 729 Annotation: Subtype: Link Rect: 518, 718, 554, 729 Annotation: Subtype: Link Rect: 511, 706, 549, 717 Annotation: Subtype: Link Rect: 259, 672, 296, 683 Annotation: Subtype: Link Rect: 214, 637, 251, 648 Annotation: Subtype: Link Rect: 263, 603, 300, 614 Annotation: Subtype: Link Rect: 307, 603, 343, 614 Annotation: Subtype: Link Rect: 59, 581, 97, 591 Annotation: Subtype: Link Rect: 103, 581, 139, 591 Annotation: Subtype: Link Rect: 444, 557, 481, 568 Annotation: Subtype: Link Rect: 59, 523, 97, 533 Annotation: Subtype: Link Rect: 265, 499, 303, 510 Annotation: Subtype: Link Rect: 291, 476, 329, 487 Annotation: Subtype: Link Rect: 335, 476, 371, 487 Annotation: Subtype: Link Rect: 199, 442, 236, 453 Annotation: Subtype: Link Rect: 303, 419, 340, 430 Annotation: Subtype: Link Rect: 424, 373, 462, 384 Annotation: Subtype: Link Rect: 287, 338, 325, 349 Annotation: Subtype: Link Rect: 178, 305, 216, 315 Annotation: Subtype: Link Rect: 403, 269, 441, 280 Annotation: Subtype: Link Rect: 145, 224, 182, 234 Annotation: Subtype: Link Rect: 454, 200, 492, 211 Annotation: Subtype: Link Rect: 255, 177, 293, 188 Annotation: Subtype: Link Rect: 122, 143, 160, 154 Annotation: Subtype: Link Rect: 166, 143, 202, 154 Annotation: Subtype: Link Rect: 234, 108, 272, 119 Annotation: Subtype: Link Rect: 278, 108, 314, 119 Annotation: Subtype: Link Rect: 465, 97, 560, 108 Annotation: Subtype: Link Rect: 56, 85, 174, 96 Page: Sequence: 14 Annotations: Annotation: Subtype: Link Rect: 153, 709, 190, 720 Annotation: Subtype: Link Rect: 196, 709, 232, 720 Annotation: Subtype: Link Rect: 323, 686, 360, 697 Annotation: Subtype: Link Rect: 427, 663, 464, 674 Annotation: Subtype: Link Rect: 59, 630, 97, 640 Annotation: Subtype: Link Rect: 376, 594, 413, 605 Annotation: Subtype: Link Rect: 140, 572, 177, 582 Annotation: Subtype: Link Rect: 59, 538, 97, 548 Annotation: Subtype: Link Rect: 294, 514, 332, 525 Annotation: Subtype: Link Rect: 350, 491, 387, 502 Annotation: Subtype: Link Rect: 222, 456, 259, 467 Annotation: Subtype: Link Rect: 265, 456, 301, 467 Annotation: Subtype: Link Rect: 104, 423, 141, 433 Annotation: Subtype: Link Rect: 148, 423, 184, 433 Annotation: Subtype: Link Rect: 189, 387, 227, 398 Annotation: Subtype: Link Rect: 272, 365, 310, 375 Annotation: Subtype: Link Rect: 258, 341, 295, 352 Annotation: Subtype: Link Rect: 59, 308, 97, 318 Annotation: Subtype: Link Rect: 103, 308, 139, 318 Annotation: Subtype: Link Rect: 378, 284, 416, 295 Annotation: Subtype: Link Rect: 441, 261, 479, 272 Annotation: Subtype: Link Rect: 446, 238, 483, 249 Annotation: Subtype: Link Rect: 145, 204, 182, 214 Annotation: Subtype: Link Rect: 188, 204, 224, 214 Annotation: Subtype: Link Rect: 204, 181, 242, 191 Annotation: Subtype: Link Rect: 363, 157, 400, 168 Annotation: Subtype: Link Rect: 154, 135, 191, 145 Annotation: Subtype: Link Rect: 229, 100, 266, 111 Annotation: Subtype: Link Rect: 104, 66, 141, 76 Annotation: Subtype: Link Rect: 148, 66, 184, 76 Page: Sequence: 15 Annotations: Annotation: Subtype: Link Rect: 309, 722, 346, 732 Annotation: Subtype: Link Rect: 59, 687, 97, 697 Annotation: Subtype: Link Rect: 59, 653, 97, 663 Annotation: Subtype: Link Rect: 252, 618, 290, 628 Annotation: Subtype: Link Rect: 392, 594, 430, 605 Annotation: Subtype: Link Rect: 59, 561, 97, 571 Annotation: Subtype: Link Rect: 95, 526, 133, 536 Annotation: Subtype: Link Rect: 139, 526, 175, 536 Annotation: Subtype: Link Rect: 218, 492, 255, 502 Annotation: Subtype: Link Rect: 261, 492, 297, 502 Annotation: Subtype: Link Rect: 454, 468, 492, 479 Annotation: Subtype: Link Rect: 359, 433, 396, 444 Checksum: d870b40e Type: CRC32 Checksum: 4fcf659781c2fdc960e09e774b859a29 Type: MD5 Checksum: 476851f12d6a058d4438c181d058a96e5a66678b Type: SHA-1