Diagnosis and management of hemochromatosis: 2011 Practice Guideline by the American Association for the Study of Liver Diseases

Name: Work Video:
Duration: 3 min 30 s
Bruce R. Bacon; Paul C. Adams; Kris V. Kowdley; Lawrie W. Powell; Anthony S. Tavill
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697, 737, 743, 752, 762, 811, 861, 887, 920, 943, 948, 969, 975, 993, 1021, 1035, 1063, 1106, 1111, 1118, 1132, 1169, 1207, 1219, 1236, 1258, 1262, 1272, 1289, 1292, 1302, 1312, 1321, 1383, 1385, 1403, 1405, 1408, 1423, 1436, 1440, 1445, 1472, 1481, 1509, 1579, 1590, 1612, 1623, 1647, 1652, 1658, 1670, 1676, 1694, 1698, 1715, 1723, 1766, 1798, 1817, 1830, 1858, 1872, 1956, 1959, 2006, 2047, 2083, 2092, 2104, 2124, 2139, 2201, 2246, 2257, 2261, 2273, 2285, 2296, 2302, 2328, 2357, 2366, 2379, 2389, 2397, 2401, 2413, 2424, 2429, 2434, 2473, 2483, 2494, 2507, 2537, 2559, 2567, 2578, 2590, 2631, 2639, 2651, 2657, 2685, 2707, 2720, 2743, 2755, 2761, 2764, 2848, 2868, 2887, 2927, 2976, 2993, 3025, 3066, 3078, 3127, 3136, 3142, 3160, 3172, 3175, 3185, 3189, 3209, 3250, 3283, 3287, 3297, 3316, 3363, 3378, 3390, 3393, 3396, 3427, 3431, 3448, 3476, 3504, 3533, 3555, 3561, 3591, 3605, 3675, 3685, 3726, 3753, 3760, 3768, 3797, 3808, 3812, 3832, 3835, 3851, 3868, 3879, 3885, 3896, 3916, 3921, 3938, 3946, 3984, 3989, 3997, 4009, 4019, 4037, 4047, 4063, 4071, 4082, 4087, 4091, 4098, 4104, 4113, 4118, 4141, 4157, 4183, 4191, 4205, 4229, 4232, 4256, 4292, 4340, 4348, 4356, 4379, 4394, 4407, 4410, 4424], 'Liver': [7, 85, 3870], 'Diseases;': [8], 'ALD,': [9, 3703, 4305], 'alcoholic': [10], 'liver': [11, 57, 780, 905, 1145, 1248, 1920, 2403, 2599, 2640, 2776, 3086, 3089, 3099, 3686, 3695, 3855, 3922, 3964, 4032, 4055, 4077, 4240, 4263, 4280, 4286, 4293, 4300, 4311, 4349], 'disease;': [12], 'ALT,': [13], 'alanine': [14], 'aminotransferase;': [15, 18], 'AST,': [16], 'aspartate': [17, 439, 3414], 'BMP6,': [19], 'bone': [20, 1211, 1628], 'morphogenetic': [21, 1629], 'protein-6;': [22], 'C282Y,': [23], 'Cys282Tyr': [24], 'mutation;': [25, 36, 65], 'GRADE,': [26], 'Grading': [27, 202], 'Recommendation': [29, 204], 'Assessment,': [30, 205], 'Development,': [31, 206], 'and': [32, 88, 114, 136, 150, 155, 169, 207, 274, 382, 395, 450, 515, 550, 620, 629, 683, 724, 785, 821, 852, 1011, 1032, 1055, 1144, 1152, 1282, 1324, 1328, 1339, 1369, 1394, 1415, 1489, 1504, 1520, 1522, 1531, 1549, 1566, 1577, 1665, 1687, 1708, 1776, 1788, 1800, 1819, 1860, 1878, 1934, 1953, 1962, 1975, 1991, 2050, 2161, 2199, 2252, 2291, 2335, 2369, 2377, 2519, 2541, 2571, 2575, 2580, 2704, 2717, 2750, 2801, 2822, 2857, 2891, 2952, 3011, 3042, 3095, 3104, 3221, 3238, 3247, 3257, 3285, 3312, 3338, 3366, 3417, 3450, 3540, 3543, 3579, 3608, 3641, 3757, 3810, 3828, 3844, 3910, 3940, 4116, 4152, 4260, 4322, 4337, 4387, 4427], 'Evaluation;': [33], 'H63D,': [34], 'His63Asp': [35], 'HAMP,': [37], 'hepcidin;': [38], 'HCC,': [39], 'hepatocellular': [40, 378, 1977], 'carcinoma;': [41], 'HH,': [42, 817, 889, 957, 1041, 1931, 2497, 2744], 'hereditary': [43], 'hemochromatosis;': [44], 'HIC,': [45], 'hepatic': [46, 50, 961, 1932, 1945, 1999, 2672, 2721, 4049, 4127, 4234, 4341, 4396], 'iron': [47, 51, 367, 472, 498, 506, 575, 596, 618, 622, 654, 671, 681, 698, 744, 759, 764, 773, 783, 789, 795, 812, 822, 844, 908, 934, 950, 982, 1006, 1036, 1048, 1074, 1080, 1088, 1107, 1126, 1134, 1142, 1158, 1171, 1174, 1183, 1208, 1216, 1242, 1259, 1304, 1341, 1387, 1413, 1417, 1424, 1446, 1457, 1523, 1540, 1547, 1551, 1562, 1572, 1580, 1608, 1689, 1824, 1881, 1894, 1925, 1946, 2109, 2168, 2174, 2219, 2287, 2303, 2543, 2618, 2659, 2673, 2686, 2697, 2765, 2779, 2849, 2870, 2890, 3034, 3080, 3119, 3162, 3213, 3302, 3326, 3345, 3491, 3592, 3633, 3658, 3666, 3728, 3738, 3801, 4128, 4269, 4342, 4397], 'concentration;': [48], 'HII,': [49], 'index;': [52], 'HJV,': [53, 1793], 'hemojuvelin;': [54], 'OLT,': [55], 'orthotopic': [56], 'transplantation;': [58], 'PCT,': [59, 3699], 'porphyria': [60, 2414], 'cutanea': [61, 2415], 'tarda;': [62], 'S65C,': [63], 'Ser65Cys': [64], 'TfR2,': [66], 'transferrin': [67, 70, 512, 831, 1358, 1780, 1834, 1839, 2905], 'receptor-2;': [68], 'TS,': [69, 3056, 3319, 3341], 'saturation.': [71], 'This': [72, 633, 1361, 2115, 2531], 'guideline': [73, 141], 'has': [74, 195, 720, 727, 1226, 2449, 2573, 2916, 3007, 3051, 3059, 3518, 3857], 'been': [75, 502, 855, 1227, 1376, 2229, 2450, 3519, 3925, 4399], 'approved': [76], 'by': [77, 200, 245, 263, 842, 936, 1072, 1189, 1209, 1331, 1525, 1538, 1561, 1760, 1884, 2019, 2037, 2226, 2231, 2481, 2487, 2502, 2562, 2662, 2681, 2845], 'Diseases': [86], '(AASLD)': [87], 'represents': [89], 'position': [91, 412, 447, 463], 'association.': [94], 'These': [95, 466, 517, 929, 3784, 4170, 4295], 'recommendations': [96, 219, 242, 266, 302], 'provide': [97, 2795, 2816], 'a': [98, 111, 349, 397, 479, 546, 685, 709, 885, 898, 1064, 1109, 1190, 1220, 1234, 1355, 1401, 1450, 1603, 1627, 1638, 1662, 1796, 1804, 2031, 2293, 2548, 2556, 2740, 2949, 2964, 2974, 2989, 3008, 3022, 3060, 3154, 3183, 3200, 3205, 3216, 3225, 3231, 3295, 3306, 3332, 3339, 3349, 3361, 3376, 3418, 3436, 3446, 3459, 3501, 3514, 3550, 3606, 3680, 3764, 3790, 3862, 3944, 3963, 3974, 3987, 4001, 4054, 4069, 4085, 4126, 4162, 4346], 'data-supported': [99], 'approach': [100, 2841], 'to': [101, 178, 270, 282, 287, 295, 361, 370, 402, 520, 564, 584, 609, 624, 638, 641, 772, 778, 794, 857, 926, 953, 999, 1039, 1059, 1195, 1378, 1400, 1462, 1497, 1514, 1637, 1672, 1721, 1750, 1773, 1777, 1848, 1850, 1918, 2002, 2010, 2188, 2278, 2325, 2469, 2842, 2871, 2943, 2960, 2981, 3016, 3069, 3301, 3794, 3840, 3900, 3933, 4101, 4203, 4245, 4422], 'establishing': [102], 'guidelines.': [103, 2838], 'They': [104, 279], 'are': [105, 224, 280, 292, 303, 430, 467, 518, 559, 600, 700, 713, 766, 818, 1136, 1285, 1936, 2095, 2142, 2276, 2355, 2432, 2460, 2583, 2701, 2711, 2726, 3571, 3613, 3649, 3708, 3721, 3979], 'based': [106, 304, 2654], 'on': [107, 122, 147, 162, 305, 874, 1411, 1505, 1641, 2221, 2655, 2963, 3458, 4212], 'following:': [109], '(1)': [110, 664, 1298], 'formal': [112], 'review': [113], 'analysis': [115, 3481], 'recently': [118], 'published': [119, 307], 'world': [120], 'literature': [121], 'topic;': [124], '(2)': [125, 673, 1309], 'College': [128], 'Physicians': [130], 'Manual': [131], 'Assessing': [133], 'Health': [134], 'Practices': [135], 'Designing': [137], 'Practice': [138, 153, 167, 192], 'Guidelines1;': [139], '(3)': [140, 684, 1317], 'policies': [142, 294], 'including': [143], 'AASLD': [145, 191, 2811, 2837], 'Policy': [146, 160], 'Development': [149], 'Use': [151, 164], 'Guidelines': [154, 193], 'Gastroenterological': [158], "Association's": [159], 'Statement': [161], 'Medical': [166], 'Guidelines2;': [168], '(4)': [170, 1325], 'experience': [172], 'authors': [175], 'in': [176, 220, 285, 298, 320, 333, 344, 393, 437, 453, 504, 574, 706, 750, 758, 798, 827, 847, 869, 878, 903, 911, 955, 960, 977, 1009, 1044, 1052, 1093, 1179, 1250, 1305, 1366, 1370, 1442, 1469, 1478, 1487, 1502, 1544, 1571, 1584, 1606, 1615, 1684, 1739, 1807, 1880, 1915, 1973, 1996, 2042, 2064, 2067, 2079, 2108, 2127, 2130, 2146, 2155, 2158, 2180, 2183, 2214, 2241, 2265, 2394, 2477, 2628, 2671, 2785, 2791, 2808, 2834, 2897, 2907, 2920, 2924, 2957, 3075, 3082, 3102, 3105, 3115, 3133, 3179, 3193, 3197, 3224, 3229, 3236, 3241, 3245, 3275, 3279, 3281, 3309, 3313, 3331, 3343, 3348, 3368, 3429, 3602, 3626, 3691, 3736, 3806, 3865, 3902, 3935, 4016, 4059, 4111, 4236, 4253], 'regard': [177], 'hemochromatosis.': [179, 1482, 2646], 'To': [180], 'more': [181, 865, 4038], 'fully': [182, 2043, 2071], 'characterize': [183], 'available': [185, 1847, 3795, 4383], 'evidence': [186, 237, 594, 1731, 2638, 2719, 4291], 'supporting': [187, 238], 'recommendations,': [189], 'Committee': [194], 'adopted': [196], 'classification': [198, 652], 'used': [199, 2807, 2833, 2973], 'Evaluation': [208], '(GRADE)': [209], 'workgroup': [210], 'with': [211, 348, 427, 471, 476, 567, 571, 587, 617, 708, 1078, 1138, 1200, 1240, 1255, 1352, 1357, 1568, 1602, 1701, 1747, 1792, 1900, 1929, 2074, 2101, 2165, 2237, 2339, 2347, 2466, 2496, 2555, 2594, 2616, 2625, 2637, 2689, 2709, 2739, 2746, 2752, 2774, 2948, 3031, 3084, 3107, 3144, 3157, 3199, 3334, 3405, 3438, 3500, 3508, 3516, 3632, 3693, 3837, 3927, 3943, 3973, 3986, 4000, 4123, 4161, 4177, 4193, 4266], 'minor': [212, 3032, 3734], 'modifications': [213], '(Table': [214, 662, 2204, 2289, 2384, 2426, 2860], '1).3': [215], 'The': [216, 234, 358, 385, 555, 650, 734, 864, 946, 1003, 1018, 1128, 1333, 1389, 1419, 1691, 1713, 1757, 2087, 2148, 2648, 2788, 2826, 2839, 3919, 4089, 4401, 4430], 'strength': [217], 'GRADE': [222], 'system': [223, 4403], 'classified': [225, 814], 'as': [226, 478, 815, 1108, 1429, 1822, 2476, 2525, 2529, 2623, 2737, 3036, 3038, 3360, 3498, 3698, 3710, 3741, 3861, 3906, 4024, 4303, 4326, 4328], 'strong': [227, 239], '(class': [228, 232], '1)': [229], 'or': [230, 240, 256, 341, 483, 603, 730, 802, 835, 1156, 1182, 1268, 1541, 1587, 1597, 1979, 2112, 2176, 2225, 2382, 2418, 2458, 2480, 2504, 2692, 2723, 2853, 2922, 3347, 3413, 3443, 3470, 3506, 3597, 3656, 3704, 3713, 3743, 3883, 3888, 4013, 4030, 4074, 4084, 4288, 4306], 'weak': [231, 241], '2).': [233], 'quality': [235], 'is': [243, 326, 329, 396, 440, 456, 542, 545, 636, 840, 892, 897, 923, 939, 951, 1005, 1014, 1037, 1056, 1176, 1232, 1253, 1426, 1449, 1460, 1484, 1490, 1500, 1518, 1533, 1559, 1661, 1719, 1744, 1853, 1967, 2015, 2023, 2028, 2035, 2062, 2077, 2153, 2320, 2534, 2602, 2653, 2768, 2802, 2828, 2844, 2863, 2882, 2900, 2934, 2941, 2954, 2995, 3121, 3292, 3383, 3465, 3565, 3575, 3587, 3600, 3624, 3635, 4223, 4250, 4313], 'designated': [244], 'one': [246, 436, 718, 725, 751, 2066, 2145, 2157], 'three': [248, 551, 556, 660, 1699], 'levels:': [249], 'high': [250, 2122, 3000], '(level': [251, 254, 258], 'A),': [252], 'moderate': [253], 'B),': [255], 'low-quality': [257], 'C).': [259], 'Intended': [260], 'use': [262], 'physicians,': [264], 'these': [265, 1245, 1526, 1869, 2084, 2297, 2430, 2456, 3043, 3627, 3676, 4092, 4213], 'suggest': [267], 'preferred': [268], 'approaches': [269], 'diagnostic,': [272], 'therapeutic,': [273], 'preventive': [275], 'aspects': [276], 'care.': [278], 'intended': [281], 'be': [283, 296, 1060, 1070, 1161, 1187, 1296, 1379, 1463, 2163, 2326, 2351, 2621, 2643, 2677, 2732, 3073, 3323, 3329, 3453, 3483, 3525, 3546, 3619, 3645, 3671, 3679, 3717, 3873, 3934, 4173, 4218, 4246, 4277, 4352, 4360, 4366, 4382], 'flexible': [284], 'contrast': [286], 'standards': [288], 'care,': [290], 'which': [291, 345, 438, 454, 938, 1374, 1499, 1761, 1995, 2340, 2667, 3890], 'inflexible': [293], 'followed': [297], 'every': [299], 'case.': [300], 'Specific': [301], 'relevant': [306], 'information.3,': [308], '4': [309, 4375], 'Hereditary': [310], 'hemochromatosis': [311, 820, 1231, 2061, 2203, 2349, 2425, 2448, 2652], '(HH)': [312], 'remains': [313], 'most': [315, 331, 523, 746, 1129, 2193, 2463, 3124, 3165, 3960, 4226], 'common,': [316], 'identified,': [317, 3638], 'genetic': [318, 569, 589, 615, 647, 1066], 'disorder': [319, 570, 590, 616, 1013, 2033], 'Caucasians.': [321], 'Although': [322, 2988], 'its': [323, 997, 1196, 1673, 2999], 'geographic': [324], 'distribution': [325, 947, 1034, 4339], 'worldwide,': [327], 'it': [328, 346, 1225, 1666, 2022, 2027, 2319, 2899, 2940, 2953, 3006, 3058, 3669, 4216], 'seen': [330, 475, 2041, 2063, 2078, 2143], 'commonly': [332], 'populations': [334], 'northern': [336], 'European': [337], 'origin,': [338], 'particularly': [339, 2393, 3342], 'Nordic': [340], 'Celtic': [342], 'ancestry,': [343], 'occurs': [347, 868, 1050, 1972], 'prevalence': [350, 3988, 4046], 'approximately': [352, 2065, 2156, 2244, 2271, 2513, 2522, 3769], '1': [353, 562, 4420], 'per': [354], '220-250': [355], 'individuals.5,': [356], '6': [357, 1631], 'pathophysiologic': [359, 1913], 'predisposition': [360], 'increased,': [362, 3614], 'inappropriate': [363], 'absorption': [364, 1301, 1548, 1573, 1609], 'dietary': [366, 1073, 1303, 1386], 'may': [368, 931, 1790, 1802, 2098, 2162, 2333, 3304, 3322, 3328, 3732, 3898, 3958, 4297], 'lead': [369, 793, 3899], 'development': [372, 1257, 1271, 3684], 'life-threatening': [374], 'complications': [375], 'cirrhosis,': [377, 2048, 2398, 3391, 3889, 3985, 4201], 'carcinoma': [379], '(HCC),': [380], 'diabetes,': [381, 2049], 'heart': [383, 2380, 2408], 'disease.': [384, 1146, 2263, 4294], 'principal': [386, 557, 1465, 1938], 'HFE': [387, 1322, 1337, 1349, 1392, 1409, 1695, 1717, 1734, 1742, 1762, 1770, 1787, 1799, 1820, 1841, 1846, 1859, 3479, 3559, 3829, 3852, 4105], 'gene': [388, 873, 881, 914, 979, 1679, 2102], 'defect': [389, 1114], 'was': [390, 1364, 2210, 3243, 3804, 4057, 4109], 'first': [391, 1334], 'described': [392, 4044], '1996,': [394], 'G-to-A': [398], 'missense': [399], 'mutation': [400, 705, 723, 867, 1022, 3480, 3538, 3830, 3853, 4106], 'leading': [401, 2009], 'substitution': [404], 'tyrosine': [406], 'cysteine': [408, 455], 'at': [409, 444, 460, 1826, 2782, 3549, 3651, 3724, 3980, 4006, 4373], 'amino': [410, 445, 461], 'acid': [411, 446, 462, 900, 1452], '282': [413], 'protein': [416, 534, 541, 1338, 1350, 1393, 1410, 1630, 1696, 1718, 1735, 1743], 'product': [417, 535], '(C282Y).7': [418], 'C282Y': [419, 477, 704, 722, 2125, 2274, 2591, 2690, 2928, 3004, 3180, 3251, 3289, 3432, 3595, 3639, 3778, 3971, 3998, 4042, 4237, 4274], 'homozygotes': [420, 2275, 3662, 3715, 3779, 3972, 3999, 4043], 'account': [421, 521], '80%-85%': [423], 'typical': [425], 'patients': [426, 566, 586, 643, 658, 692, 738, 1928, 2181, 2195, 2215, 2227, 2236, 2298, 2332, 2345, 2453, 2465, 2495, 2499, 2560, 2615, 2624, 2636, 2708, 2773, 2983, 3083, 3106, 3836, 3956, 4176, 4192, 4296], 'HH.8': [428], 'There': [429, 544, 1284, 2725], 'two': [431, 848, 859, 973, 1527], 'other': [432, 452, 494, 754, 1115, 1167, 1724, 1751, 2105, 2437, 3108, 3137, 3563, 3694, 3914, 4289], 'regularly': [433], 'identified': [434, 1949, 2213, 2230, 2240, 2501, 2561, 2582, 2713, 3520, 3557, 3709, 3776], 'mutations,': [435], 'substituted': [441, 457], 'histidine': [443], '63': [448], '(H63D),': [449], 'serine': [459], '65': [464], '(S65C).': [465], 'generally': [468, 2769, 3566, 3722], 'not': [469, 792, 1097, 1737, 2249, 2254, 2955, 3122, 3581, 3650, 3723, 4243], 'associated': [470, 1254, 1398, 1746, 1954, 2164, 2172, 2688, 3942], 'loading': [473, 774], 'unless': [474], 'compound': [480, 714, 2694, 3351, 3598], 'heterozygote,': [481], 'C282Y/H63D': [482, 2693, 3350], 'C282Y/S65C': [484], '(Fig.': [485, 1711], '1).': [486, 1712], 'Over': [487, 2967], 'last': [489], '10': [490, 2159, 2514, 2523, 2586], 'years,': [491, 2969], 'mutations': [492, 558, 749, 826, 930, 976, 987, 1026], 'genes': [495, 756, 829, 850, 1592], 'coding': [496], 'regulatory': [499, 1805], 'proteins': [500, 2106], 'have': [501, 578, 592, 613, 621, 645, 667, 676, 694, 740, 748, 805, 854, 1124, 1154, 1166, 1204, 1214, 1375, 1618, 1948, 2250, 2279, 2299, 2314, 2778, 2972, 3146, 3356, 3373, 3733, 3747, 3892, 3924, 3968, 4011, 4284, 4298, 4398], 'implicated': [503], 'inherited': [505, 668, 695, 741, 809, 1122], 'overload': [507, 597, 619, 655, 699, 745, 765, 796, 823, 1049, 1081, 1089, 1135, 1159, 1175, 1217, 1947, 2175, 2687, 3035, 3120, 3303, 3327, 3346], 'syndromes': [508, 656], '(e.g.,': [509, 2598], 'hepcidin,': [510, 1316, 1596], 'hemojuvelin,': [511, 1595], 'receptor': [513, 832, 1640, 1781], '2,': [514], 'ferroportin).': [516], 'thought': [519], 'non-HFE': [526], 'forms': [527, 696, 742, 810, 860, 1354], 'HH.9': [529], 'Schematic': [530], 'representation': [531], 'HFE.': [537], 'Most': [538], 'extracellular.': [543], 'short': [547], 'cytoplasmic': [548], 'tail': [549], 'extracellular': [552, 1692], 'alpha': [553], 'loops.': [554], 'identified.': [560], 'Stage': [561, 581, 606], 'refers': [563, 583, 608], 'those': [565, 585, 610, 665, 674, 769, 776, 803, 1164, 2738, 2745, 2751, 3499, 3507, 4206], 'no': [572, 2918, 2935, 3588], 'increase': [573, 1605, 2670], 'stores': [576, 2288, 3081], 'who': [577, 591, 599, 612, 644, 666, 675, 693, 712, 739, 804, 1095, 1102, 1148, 1153, 1165, 1203, 2216, 2454, 3707, 3957, 4195, 4207, 4272], '"genetic': [579], 'susceptibility."': [580], '2': [582, 833, 1867, 4426], 'phenotypic': [593, 2093, 3220], 'but': [598, 890, 1087, 1730, 2170, 2440, 3057, 4271, 4372], 'without': [601, 2113, 2171, 2718], 'tissue': [602, 628, 1326, 2173, 4350, 4380], 'organ': [604, 630, 2748, 3510], 'damage.': [605, 2177], '3': [607, 2793, 4428], 'individuals': [611, 801, 1077, 1137, 1199, 2160, 3186], 'deposition': [623, 1007], 'degree': [626, 3159, 4336, 4393], 'that': [627, 717, 906, 922, 954, 1027, 1068, 1180, 1229, 1294, 1347, 1391, 1454, 1620, 1722, 1733, 1795, 1814, 1855, 1922, 1968, 2034, 2192, 2331, 2447, 2614, 2730, 2771, 3148, 3262, 3294, 3375, 3647, 3673, 3719, 3749, 3970, 4189, 4220, 4362, 4412], 'damage': [631, 1921, 1952], 'occurs.': [632], 'organizational': [634], 'schema': [635], 'important': [637, 1432, 1476, 2322, 3860, 4227], 'allow': [639], 'clinicians': [640, 2324], 'categorize': [642], 'positive': [646, 3012, 3063, 3244], 'test': [648], 'results.': [649], 'current': [651], 'divides': [657], 'into': [659, 1492], 'groups': [661, 2729, 3496], '2):': [663], 'causes': [669, 678, 770, 1131, 1168, 1688, 1976], 'overload,': [672, 682, 784, 813, 1143, 3729], 'various': [677], 'secondary': [680, 763, 1125, 1133, 1170, 3033], 'small': [686, 710, 2294], 'miscellaneous': [687, 786, 1277], 'group.': [688], 'Approximately': [689], '85%-90%': [690], 'homozygous': [701, 2592, 3751], 'HFE,': [707, 1594], 'minority': [711], 'heterozygotes,': [715, 3041], 'meaning': [716], 'allele': [719, 726], 'H63D': [729, 3642, 3661, 3711, 3714], 'S65C': [732], 'mutation.': [733], 'remaining': [735], '10%-15%': [736], 'likely': [747, 2535], 'aforementioned': [755], 'involved': [757, 2107], 'homeostasis.9': [760], 'Causes': [761], 'divided': [767], 'between': [768, 1336, 1874, 2120], 'related': [771, 777, 3068], 'anemias,': [775], 'chronic': [779, 2402, 3092, 3110, 4307], 'disease,': [781, 2404, 2509, 2600], 'transfusional': [782, 1155, 1215], 'causes.': [787], 'Oral': [788], 'ingestion': [790], 'does': [791, 1736, 3891, 4242], 'except': [797], 'genetically': [799], 'predisposed': [800], 'ineffective': [806, 1139, 1201, 1564], 'erythropoiesis.': [807], 'Other': [808, 1275], 'non–HFE-related': [816, 1065, 3344], 'juvenile': [819, 862, 888], 'resulting': [824, 1569, 1604], 'from': [825, 972, 1163, 1344, 1553, 1574, 1581, 1842, 1889, 1902, 1924, 1987, 2185, 2804, 2830, 2865, 2884, 2903, 3961, 4368, 4417], '(TfR2),': [834], 'ferroportin': [836, 1025, 1030, 1517, 1613], '(SLC40A1).9': [837], 'Juvenile': [838], 'HH': [839, 921, 970, 1293, 1916, 2209, 2238, 2467, 2675, 2710, 3145, 3505, 3517, 3839, 4099, 4178, 4194], 'characterized': [841], 'rapid': [843], 'accumulation.': [845], 'Mutations': [846, 877, 910, 1583], 'different': [849, 2970], '(hemojuvelin': [851], 'hepcidin)': [853], 'shown': [856, 2917], 'cause': [858, 932, 3126, 3305], 'HH.14': [863], 'common': [866, 1130, 3125], 'hemojuvelin': [871], '(HJV)': [872], 'chromosome': [875], '1q.15': [876], 'hepcidin': [880, 1441, 1473, 1512, 1557, 1600, 1624, 1648, 1685, 1767, 1864], '(HAMP)': [882], 'also': [883, 1091, 1213, 3028, 4179, 4365], 'produce': [884, 915, 1992], 'form': [886, 919, 968, 1235], 'this': [891, 1012, 1099, 1273, 2242, 2931, 2962, 3320, 4052], 'much': [893, 1430], 'less': [894, 1431, 3052, 3859, 3947, 4209], 'common.14': [895], 'Hepcidin': [896, 1448, 1483, 1535], '25–amino': [899, 1451], 'peptide': [901, 1453], 'produced': [902], 'down-regulates': [907], 'absorption.': [909, 1388], 'TfR2': [913, 944, 1598, 1775, 1789, 1801, 1861], 'an': [916, 1083, 1112, 1475, 1823, 2280, 2390, 2669, 2945, 3128, 3176, 3317, 3335, 3357, 3384, 3406, 3556, 3576, 3981, 4405], 'autosomal': [917, 966], 'recessive': [918], 'clinically': [924], 'similar': [925, 952, 1038, 1720, 1749], 'HFE-related': [927, 956, 1040, 3838], 'HH.16': [928], 'abnormal': [933, 2218, 2484, 2617, 2775, 3466, 4075], 'sensing': [935], 'hepatocytes,': [937, 1877], 'predominant': [941, 1381], 'site': [942, 1382], 'expression.': [945, 1649, 1865], 'excess': [949, 1539, 4257], 'namely,': [958], 'primarily': [959, 1008, 1051], 'parenchymal': [962, 1045], 'cells.16': [963], 'A': [964, 2910, 3399, 4034, 4143], 'rare': [965, 1276, 2032], 'dominant': [967], 'results': [971, 1543, 1923, 3570], 'categories': [974, 1288], 'transporter': [983], 'protein,': [984, 1323], 'ferroportin.': [985, 1887], '"Loss-of-function"': [986], 'decrease': [988, 1599], 'cell': [990, 1421, 1528, 1828], 'surface': [991, 1508], 'localization': [992], 'ferroportin,': [994, 1498, 1515], 'thereby': [995, 1844, 2008], 'reducing': [996], 'ability': [998], 'export': [1000, 1524], 'iron.17,': [1001], '18': [1002], 'result': [1004, 1062, 1110], 'macrophages,': [1010], 'called': [1015], '"ferroportin': [1016], 'disease".': [1017], 'second': [1019, 1707, 2368, 2950], 'category': [1020], 'includes': [1023], '"gain-of-function"': [1024], 'abolish': [1028], 'hepcidin-induced': [1029], 'internalization': [1031], 'degradation18;': [1033], 'concentrating': [1042], 'predominantly': [1043, 1486], 'cells.': [1046], 'African': [1047, 1079], 'sub-Saharan': [1053], 'Africa': [1054], 'now': [1057, 1427, 2712], 'considered': [1058, 1377, 1461, 2030, 2352, 2451, 3874, 4278], 'abnormality': [1067], 'can': [1069, 1090, 1771, 2116, 2342, 2676, 2794, 2815, 3072, 3618, 3644, 3663, 3678, 3716, 3953, 4217, 4351, 4364], 'exacerbated': [1071], 'loading.19': [1075], 'Some': [1076], 'drink': [1082, 1098], 'iron-rich': [1084], 'fermented': [1085], 'beverage,': [1086], 'occur': [1092, 3690], 'people': [1094], 'do': [1096, 2961], 'beverage.19': [1100], 'Individuals': [1101, 1147], 'absorb': [1103], 'excessive': [1104, 4025], 'amounts': [1105, 2005, 4182], 'underlying': [1113], 'than': [1116, 2081, 2312, 2438, 2517, 2605, 3055, 3456, 3948, 3995, 4039], 'any': [1117, 2256, 3674], 'previously': [1120], 'mentioned': [1121], 'disorders': [1123, 1278], 'overload.20': [1127], 'erythropoiesis,': [1140, 1565], 'parenteral': [1141, 1157], 'receive': [1149], 'blood': [1150, 1181, 2539], 'transfusions': [1151], 'should': [1160, 1295, 2350, 2420, 2620, 2642, 2731, 3452, 3482, 3493, 3524, 3545, 3670, 3872, 4276, 4318, 4359, 4381], 'distinguished': [1162], 'overload.': [1172, 1260, 2766, 3659], 'Parenteral': [1173], 'always': [1177], 'iatrogenic,': [1178], '(given': [1184], 'parenterally)': [1185], 'must': [1186, 4172], 'ordered': [1188], 'health': [1191], 'care': [1192, 2489, 3227], 'provider': [1193], 'prior': [1194, 2932, 3793, 4100], 'administration.': [1197], 'Many': [1198, 2428], 'erythropoiesis': [1202], 'decreased': [1205, 1310, 1545, 1560, 2375], 'utilization': [1206], 'marrow': [1212], 'because': [1218, 2026, 2472, 2536, 3065, 3568, 3585, 4062], 'requirement': [1221], 'transfusions.20': [1223], 'Recently,': [1224], 'found': [1228, 1501, 2154, 2277, 3601], 'neonatal': [1230], 'actually': [1233], 'congenital': [1237, 1280], 'alloimmune': [1238], 'hepatitis': [1239, 3093, 3700], 'subsequent': [1241], 'deposition.21': [1243], 'In': [1244, 1555, 1784, 1927, 2491, 2875, 3113, 3164, 3182, 3215, 3253, 3435, 3992, 4051, 4344], 'cases,': [1246], 'immune-mediated': [1247], 'injury': [1249, 1327, 1978], 'fetus': [1252], 'Administration': [1261], 'intravenous': [1263], 'immunoglobulin': [1264], 'during': [1265, 2545], 'pregnancy': [1266, 2546], 'slows': [1267], 'prevents': [1269], 'condition.22': [1274], 'include': [1279, 4319], 'atransferrinemia': [1281], 'aceruloplasminemia.': [1283], 'four': [1286], 'main': [1287], 'pathophysiological': [1290], 'mechanisms': [1291, 1759], 'mentioned:': [1297], 'increased': [1300, 2004, 2286, 2315, 2658, 3079, 3589, 3982], 'upper': [1307, 2360, 3474, 4139], 'intestine,': [1308], 'expression': [1311, 1536, 1558, 1601, 1625, 1686, 2094, 3759], 'iron-regulatory': [1314, 1466], 'hormone': [1315], 'altered': [1319], 'function': [1320, 2777], 'fibrogenesis': [1329], 'induced': [1330, 1537], 'iron.': [1332], 'link': [1335], 'cellular': [1340, 1416, 4338], 'metabolism': [1342], 'resulted': [1343], 'observation': [1346, 1390], 'along': [1351], 'β2-microglobulin': [1353], 'complex': [1356, 1727, 1754, 1797, 1816, 1857], 'receptor-1': [1359], '(TfR1).23': [1360], 'physical': [1362, 2337, 2387, 2505, 3441], 'association': [1363], 'observed': [1365], 'cultured': [1367], 'cells': [1368, 1982, 2001], 'duodenal': [1371, 1875], 'crypt': [1372], 'enterocytes,': [1373, 1876], 'regulation': [1384, 1425, 1444, 1471, 1622, 1765], 'TfR1': [1395, 1818], 'were': [1396, 2239, 2500, 2521, 3271, 3786, 3819, 4094], 'physically': [1397, 1745], 'led': [1399], 'number': [1402], 'investigations': [1404], 'effect': [1407, 2550], 'TfR1-mediated': [1412], 'uptake': [1414], 'stores.24': [1418], '"crypt': [1420], 'hypothesis"': [1422], 'regarded': [1428], 'since': [1433], 'discovery': [1435], 'central': [1438], 'role': [1439, 1477, 1806], 'metabolism.': [1447, 1895], 'influences': [1455, 1763, 1863], 'systemic': [1456], 'status.25': [1458], 'It': [1459, 1495, 1852, 2097, 2767, 3291, 4358], 'hormone.': [1467], 'Alteration': [1468], 'plays': [1474], 'pathogenesis': [1480], 'expressed': [1485, 2072], 'hepatocytes': [1488, 1642, 1974, 1990, 4411], 'secreted': [1491], 'circulation.': [1494], 'binds': [1496, 1513, 1636], 'macrophages': [1503, 1879], 'basolateral': [1507], 'enteroctyes.': [1510], 'When': [1511, 2235, 2344, 3637, 4310], 'internalized': [1519], 'degraded': [1521], 'types': [1529], '(macrophages': [1530], 'enterocytes)': [1532], 'inhibited.26': [1534], 'inflammation': [1542], 'intestinal': [1546, 1607], 'diminished': [1550], 'release': [1552, 1578], 'macrophages.25': [1554, 1582], 'contrast,': [1556, 3993], 'deficiency,': [1563], 'hypoxia,': [1567], 'increases': [1570], 'intestine': [1576], 'human': [1585], 'disease': [1586, 2045, 2073, 2141, 2435, 2596, 2641, 3087, 3090, 3100, 3298, 3687, 3803, 3843, 4301], 'murine': [1588], 'knockouts': [1589], 'via': [1610], 'up-regulation': [1611, 1657], 'levels': [1614, 3270, 3355, 3612, 3818, 3952, 4067], 'enterocytes.25': [1616], 'Studies': [1617], 'revealed': [1619], 'iron-induced': [1621, 1656, 1969], 'involves': [1626], '(BMP6)-dependent': [1632], 'signaling': [1633, 1654, 1683], 'pathway.27': [1634], 'BMP6': [1635, 1653, 1663, 1671, 1682, 1808, 1892], 'specific': [1639], 'triggering': [1643], 'SMAD': [1644], 'protein–dependent': [1645], 'activation': [1646], 'Selective': [1650], 'inhibition': [1651], 'abrogates': [1655], 'hepcidin.27': [1659], 'Hemojuvelin': [1660], 'coreceptor,': [1664], 'facilitates': [1667], 'binding': [1669], 'receptor;': [1674], 'knockout': [1675], 'HJV': [1678], 'markedly': [1680], 'decreases': [1681], 'overload.28': [1690], 'domain': [1693], 'consists': [1697], 'loops': [1700], 'intramolecular': [1702], 'disulfide': [1703], 'bonds': [1704], 'within': [1705], 'third': [1709, 2370], 'loops7': [1710], 'structure': [1714], 'major': [1725, 1752, 1758, 1912], 'histocompatibility': [1726, 1753], 'class-1': [1728, 1755], 'proteins,': [1729], 'indicates': [1732], 'participate': [1738], 'antigen': [1740], 'presentation.29': [1741], 'β2-microglobulin,': [1748], 'molecules.': [1756], 'iron-dependent': [1764, 1950], 'remain': [1768], 'unclear.': [1769], 'bind': [1772, 1849], 'both': [1774, 1786, 3535], 'classic': [1779, 2197], 'TfR1.23,': [1782], '30': [1783], 'addition,': [1785, 4345], 'interact': [1791], 'suggesting': [1794], 'play': [1803], 'signaling.28': [1809], 'One': [1810, 1965], 'proposed': [1811], 'explanation': [1812], 'suggests': [1813], 'acts': [1821], 'sensor': [1825], 'membrane': [1829], 'hepatocyte.30': [1832], 'As': [1833], 'saturation': [1835], '(TS)': [1836], 'increases,': [1837], 'diferric': [1838], 'displaces': [1840], 'TfR1,': [1843], 'making': [1845], 'TfR2.': [1851], 'postulated': [1854], 'then': [1862, 3478, 3615, 3629], 'Figure': [1866], 'summarizes': [1868], 'interactions.31': [1870], 'Summary': [1871], 'interactions': [1873, 2100], 'homeostasis': [1882, 2110], 'regulated': [1883], 'hepcidin.': [1885], 'FPN,': [1886], '(Adapted': [1888], 'Camaschella': [1890], 'C.': [1891], 'orchestrates': [1893], 'Nat': [1896], 'Genet': [1897], '2009;41:386–388.': [1898], 'Used': [1899], 'permission': [1901], 'Nature': [1903, 1908], 'Genetics.': [1904], 'Copyright': [1905], '©': [1906], '2009,': [1907], 'Publishing': [1909], 'Group).': [1910], 'Another': [1911], 'mechanism': [1914], 'relates': [1917], 'overload.32': [1926], 'advanced': [1930, 2202, 3364, 3886, 4048, 4233], 'fibrosis': [1933, 2722, 3365, 3887, 4015, 4235], 'cirrhosis': [1935, 3367, 3428, 3897, 4012, 4124], 'pathological': [1939], 'findings.': [1940], 'Numerous': [1941], 'studies': [1942, 2220, 2486, 2619, 2780, 2971, 3141, 3372, 3634, 3746, 3827, 3967], 'using': [1943, 2913, 3021, 3489], 'experimental': [1944], 'oxidative': [1951], 'impairment': [1955], 'membrane-dependent': [1957], 'functions': [1958], 'mitochondria,': [1960], 'microsomes,': [1961], 'lysosomes.33,': [1963], '34': [1964], 'hypothesis': [1966], 'lipid': [1970], 'peroxidation': [1971], 'death.': [1980], 'Kupffer': [1981], 'become': [1983, 3858], 'activated': [1984], 'byproducts': [1985], 'released': [1986], 'injured': [1988], 'iron-loaded': [1989], 'profibrogenic': [1993], 'cytokines,': [1994], 'turn': [1997], 'stimulate': [1998], 'stellate': [2000], 'synthesize': [2003], 'collagen,': [2007], 'pathologic': [2011], 'fibrosis.32,': [2012], '35': [2013], 'Hemochromatosis': [2014], 'increasingly': [2016, 2211], 'being': [2017, 2212], 'recognized': [2018, 3293, 3672, 4361], 'clinicians.': [2020], 'Nonetheless,': [2021, 2318, 2587, 3132], 'still': [2024, 2321, 2715], 'underdiagnosed,': [2025], 'often': [2029, 2996], 'manifested': [2036], 'clinical': [2039, 2137, 2300, 2649, 3758, 3863, 3903, 4290], 'findings': [2040, 2200, 2338, 2388, 2506], 'established': [2044], 'consisting': [2046], 'skin': [2051, 2410], 'pigmentation': [2052], '(so-called': [2053], '"bronze': [2054], 'diabetes").': [2055], 'Genetic': [2056], 'susceptibility': [2057], '(C282Y': [2058], 'homozygosity)': [2059], '250': [2068], 'Caucasians;': [2069], 'however,': [2070], 'end-organ': [2075], 'manifestations': [2076, 2138, 2179, 2260, 2400, 2597], 'fewer': [2080, 3994], '10%': [2082], 'individuals.10,': [2085], '12': [2086], 'reasons': [2088], 'lack': [2091, 4273], 'unknown.': [2096], 'involve': [2099], 'products': [2103], '(with': [2111], 'mutation).': [2114], 'explain': [2117], 'discrepancy': [2119], 'incidence': [2123], 'homozygosity': [2126, 2691, 3596], 'Caucasians': [2128], '(one': [2129], '250)': [2131], 'versus': [2132, 2608], 'how': [2133], 'infrequently': [2134], 'full': [2136], '(approximately': [2144, 4135], '2500).': [2147], 'heterozygote': [2149, 3578], 'genotype': [2150, 3536], '(C282Y/wild': [2151], 'type)': [2152], 'elevated': [2166, 2281, 2663, 2946, 3074, 3129, 3177, 3272, 3318, 3336, 3407, 4064, 4261, 4267, 4285], 'serum': [2167, 2664, 2858, 2869, 2889, 3150, 3167, 3191, 3232, 3268, 3310, 3379, 3400, 3490, 3610, 3737, 3816, 3975, 4065, 4076, 4144, 4163, 4221, 4262, 4268], 'markers,': [2169], 'Clinical': [2178], 'reported': [2182, 2194, 3932], 'series': [2184, 2493], '1950s': [2187], '1980s': [2190], 'showed': [2191, 4188], 'had': [2196, 2217, 3204, 4125, 4149, 4168, 4200], 'symptoms': [2198, 2251, 2330, 2378, 2457, 2503], '3).36-38': [2205], 'By': [2206], '1990s,': [2208], 'routine': [2222, 4315], 'chemistry': [2223], 'panels': [2224], 'having': [2228, 2547, 3962], 'family': [2232, 2478, 2741, 3444, 3502, 3522], 'screening.39,': [2233], '40': [2234], 'way,': [2243], '75%': [2245], 'them': [2247], 'did': [2248, 2253], 'exhibit': [2255, 2334, 2455], 'end-stage': [2259], 'Currently,': [2264, 2462], 'large': [2266, 3217, 4181], 'population': [2267, 3228, 3766], 'screening': [2268, 2563, 3523, 3825, 3907], 'studies,': [2269, 2479, 2564, 4215, 4270], 'only': [2270, 2292, 3875], '70%': [2272, 4153], 'ferritin': [2282, 2316, 2665, 2859, 3050, 3130, 3151, 3168, 3192, 3233, 3269, 3337, 3354, 3380, 3401, 3451, 3471, 3611, 3622, 3817, 3951, 3976, 4002, 4066, 4145, 4164, 4222, 4249], 'level': [2283, 3377, 3402, 3409, 3623, 4003, 4146, 4165], 'indicative': [2284, 2433], '4),': [2290], 'percentage': [2295], 'consequences': [2301], 'storage': [2304], 'disease.6,': [2305], '10,': [2306], '12,': [2307], '41,': [2308], '42': [2309], 'More': [2310, 2553], 'men': [2311, 2527, 2572, 2579, 2606, 3237], 'women': [2313, 2510, 2570, 2581, 2593, 3242], 'levels.': [2317], 'aware': [2327], 'they': [2341, 3648, 3689, 3720, 3731, 4283], 'present.': [2343], 'present': [2346, 3330, 3805, 4110], 'symptoms,': [2348, 3440], 'when': [2353, 2452, 2498, 3688, 3815, 4175, 4248], 'there': [2354, 2520, 3586], 'complaints': [2356], 'fatigue,': [2358], 'right': [2359], 'quadrant': [2361], 'abdominal': [2362], 'pain,': [2363], 'arthralgias,': [2364], '(typically': [2365], 'metacarpophalangeal': [2371], 'joints),': [2372], 'chondrocalcinosis,': [2373], 'impotence,': [2374], 'libido,': [2376], 'failure': [2381], 'diabetes': [2383], '5).': [2385], 'Similarly,': [2386], 'enlarged': [2391], 'liver,': [2392], 'presence': [2396, 3426, 3882, 4081, 4231], 'extrahepatic': [2399], 'testicular': [2405], 'atrophy,': [2406], 'congestive': [2407], 'failure,': [2409], 'pigmentation,': [2411], 'changes': [2412], 'tarda': [2416], '(PCT),': [2417], 'arthritis': [2419], 'raise': [2421], 'suspicion': [2423], '6).': [2427], 'features': [2431, 3915], 'processes': [2436], 'hemochromatosis,': [2439, 2626], 'thoughtful': [2442], 'clinician': [2443], 'will': [2444, 3027, 3045], 'make': [2445], 'sure': [2446], 'signs': [2459], 'seen.': [2461], 'new': [2464], 'come': [2468], 'medical': [2470], 'attention': [2471], 'screening,': [2474], 'such': [2475, 2736, 3497, 3697, 3740, 3905, 4023, 4302], 'evaluation': [2482, 4317], 'laboratory': [2485], 'primary': [2488, 3226], 'physicians.': [2490], 'older': [2492], 'typically': [2511], 'presented': [2512], 'years': [2515, 3188, 3775], 'later': [2516], 'men,': [2518, 3276], 'times': [2524, 4137], 'many': [2526, 3750], 'presenting': [2528], 'women.': [2530, 2552], 'sex': [2532], 'difference': [2533], 'menstrual': [2538], 'loss': [2540, 2544], 'maternal': [2542], '"protective"': [2549], 'recently,': [2554], 'greater': [2557], 'proportion': [2558, 2589, 4409], 'age': [2566], 'diagnosis': [2568, 2650, 2843, 3867, 4010, 4097], 'equalized,': [2574], 'numbers': [2577], 'roughly': [2584], 'equivalent.6,': [2585], 'definite': [2595], 'arthritis)': [2601], 'significantly': [2603], 'lower': [2604, 3009], '(1%': [2607], '25%,': [2609], 'respectively).10': [2610], '1.': [2611], 'We': [2612, 3823], 'recommend': [2613, 3824], 'evaluated': [2622, 2644, 3787], 'even': [2627], 'absence': [2630, 3077, 3135, 3315, 3389, 3884, 4018, 4255], 'symptoms.': [2632], '(A)': [2633], '2.': [2634], 'All': [2635, 4121], '(1B)': [2647, 3462, 3485, 3512], 'documentation': [2656], 'stores,': [2660, 2850], 'demonstrated': [2661, 3147, 3374, 3969], 'levels,': [2666], 'reflects': [2668], 'content.': [2674], 'further': [2678, 2797, 2818, 2986, 3047, 3583], 'defined': [2679], 'genotypically': [2680], 'familial': [2683], 'occurrence': [2684], 'heterozygosity.': [2695], 'Serologic': [2696], 'markers': [2698, 2847, 3223, 3492], '(TS,': [2699], 'ferritin)': [2700], 'widely': [2702], 'available,': [2703], 'majority': [2706, 4090], 'while': [2714], 'asymptomatic': [2716, 4041], 'cirrhosis.': [2724, 4158, 4169], 'certain': [2727], 'high-risk': [2728, 3495], 'targeted': [2733], 'evaluation,': [2735], 'history': [2742, 3503], 'suspected': [2747, 3509], 'involvement,': [2749], 'chance': [2753], 'detection': [2754, 2926], 'biochemical': [2756, 3756], 'and/or': [2757], 'radiological': [2758], 'abnormalities': [2759, 3735], 'suggestive': [2760, 3439], 'possibility': [2763], 'recommended': [2770, 3526], 'all': [2772, 3528, 4114, 4119], 'done': [2781], 'some': [2783, 2796, 2817, 2876, 3039], 'point': [2784], 'their': [2786, 3798], 'evaluation.': [2787], 'algorithm': [2789, 2814, 2827], 'outlined': [2790], 'Fig.': [2792], 'direction': [2798, 2819], 'regarding': [2799, 2820], 'testing': [2800, 2821, 3560, 3584], 'modified': [2803, 2829], 'version': [2806, 2832], 'previous': [2810, 2836], 'guidelines.42': [2812], 'An': [2813, 4185], 'treatment': [2823], 'HH.': [2825, 3370, 3869], 'initial': [2840], 'indirect': [2846], 'namely': [2851], 'TS': [2852, 2862, 2947, 2980, 2991, 3024, 3178, 3201, 3449, 3742], 'unsaturated': [2854, 2893], 'iron-binding': [2855, 2873, 2880, 2894], 'capacity': [2856, 2881], '7).': [2861], 'calculated': [2864, 2883, 2901], 'ratio': [2867], 'total': [2872, 2879], 'capacity.': [2874], 'laboratories,': [2877], 'sum': [2886], 'capacity,': [2895], 'whereas': [2896], 'others,': [2898], 'indirectly': [2902], 'concentration': [2906, 3152, 4129], 'serum.': [2909], 'recent': [2911, 3765, 4035, 4214], 'study,': [2912, 4053], 'fasting': [2914, 2965], 'samples,': [2915], 'improvement': [2919], 'sensitivity': [2921, 3001, 4151], 'specificity': [2923, 3010, 4154], 'homozygotes.43': [2929], 'Accordingly,': [2930], 'recommendation': [2933], 'longer': [2936], 'absolutely': [2937], 'necessary,': [2938], 'although': [2939, 3730], 'advisable': [2942], 'confirm': [2944], 'determination': [2951], 'unreasonable': [2956], 'our': [2958], 'opinion': [2959], 'specimen.': [2966], 'variety': [2975, 3296], 'cutoff': [2977, 2990, 3018, 3023, 4070], 'values': [2978], 'identify': [2982, 3029, 3955], 'eligible': [2984], 'testing.': [2987], 'value': [2992, 3014, 3208, 3359], '45%': [2994, 3026, 3203, 3469], 'chosen': [2997], 'detecting': [3003], 'homozygotes,': [3005], 'predictive': [3013, 3207], 'compared': [3015, 4202], 'higher': [3017], 'values.': [3019], 'Thus,': [3020], 'persons': [3030], 'well': [3037, 4327], 'C282Y/wild-type': [3040], 'cases': [3044], 'require': [3046], 'evaluation.44': [3048], 'Serum': [3049, 3353, 3950], 'biological': [3053], 'variability': [3054], 'significant': [3061], 'false': [3062], 'rate': [3064], 'elevations': [3067], 'inflammation.': [3070], 'Ferritin': [3071], 'necroinflammatory': [3085], '(alcoholic': [3088], '[ALD],': [3091], 'B': [3094], 'C,': [3096], 'nonalcoholic': [3097], 'fatty': [3098, 4031], '[NAFLD]),': [3101], 'lymphomas,': [3103], 'nonhepatic': [3109], 'inflammatory': [3111, 3138], 'conditions.': [3112], 'fact,': [3114], 'general': [3117], 'population,': [3118], 'level.': [3131], 'processes,': [3139], 'several': [3140], 'families': [3143], 'provides': [3153, 3169], 'valuable': [3155], 'correlation': [3156], 'body': [3161], 'stores.': [3163, 4343], 'circumstances,': [3166], 'additional': [3170, 3358], 'confirmation': [3171], 'significance': [3174], 'homozygotes.': [3181, 4238], 'study': [3184, 3218, 3261, 3767, 4036, 4187], '<35': [3187], 'age,': [3190], 'normal': [3195, 3340, 3625], 'range': [3196, 3937], 'combination': [3198, 3447, 4086], '<': [3202], 'negative': [3206], '97%': [3210], 'excluding': [3212], 'overload.45': [3214], 'correlating': [3219], 'genotypic': [3222], 'California,': [3230], '>250': [3234], 'μg/L': [3235, 3240, 3274, 3278, 3382, 3404, 3978, 4005, 4148, 4167], '>200': [3239, 3277, 4131], '77%': [3246], '56%,': [3248], 'respectively,': [3249], 'homozygotes.12': [3252], 'HEIRS': [3255], '(HEmochromatosis': [3256], 'IRon': [3258], 'Overload': [3259], 'Screening)': [3260], 'screened': [3263], '99,711': [3264], 'North': [3265], 'participants,': [3267], '(>300': [3273], 'women)': [3280], '57%': [3282], 'female': [3284], '88%': [3286], 'male': [3288], 'homozygotes.6': [3290], 'conditions': [3299], 'unrelated': [3300], 'nonspecific': [3307], 'rise': [3308, 3321], 'ferritin,': [3311], 'nonspecific.': [3324], 'Conversely,': [3325], 'patient': [3333, 3437, 3515], 'heterozygote.46': [3352], 'predictor': [3362, 3386, 4228], 'confirmed': [3369], 'Several': [3371, 3966], '<1000': [3381, 4166], 'accurate': [3385], 'independent': [3392], 'duration': [3395], 'disease.47-49': [3398], '>1000': [3403, 3820, 3977, 4147], 'aminotransferase': [3408, 3411, 3415], '(alanine': [3410], '[ALT]': [3412], '[AST])': [3416], 'platelet': [3419], 'count': [3420], '<200': [3421], '×': [3422], '109/L': [3423], 'predicted': [3424], '80%': [3430], 'homozygotes.50': [3433], '3.': [3434], 'findings,': [3442], 'history,': [3445], 'obtained': [3454, 4353], 'rather': [3455], 'relying': [3457], 'single': [3460, 3551, 4225], 'test.': [3461], 'If': [3463, 3594, 3621], 'either': [3464], '(TS': [3467], '≥': [3468], 'above': [3472], 'limit': [3475, 4140], 'normal),': [3477], 'performed.': [3484], '4.': [3486], 'Diagnostic': [3487], 'strategies': [3488], 'target': [3494], 'involvement.': [3511], 'Once': [3513], '(proband),': [3521], 'first-degree': [3529, 3833], 'relatives.': [3530], 'For': [3531, 3553], 'ease': [3532], 'testing,': [3534], '(HFE': [3537], 'analysis)': [3539, 3831], 'phenotype': [3541], '(ferritin': [3542], 'TS)': [3544], 'performed': [3547, 4058, 4095, 4247], 'simultaneously': [3548], 'visit.': [3552], 'children': [3554], 'proband,': [3558, 3607], 'parent': [3564], 'recommended,': [3567], 'if': [3569, 3609, 4282], 'normal,': [3572], 'child': [3574], 'obligate': [3577], 'need': [3580, 4244], 'undergo': [3582], 'risk': [3590, 3652, 3725, 3983, 4021], 'loading.51': [3593], 'heterozygosity': [3599], 'adult': [3603], 'relatives': [3604, 3752, 3834], 'therapeutic': [3616], 'phlebotomy': [3617], 'initiated.': [3620], 'patients,': [3628], 'yearly': [3630], 'follow-up': [3631], 'indicated.': [3636], 'heterozygotes': [3640, 3643, 3712], 'reassured': [3646, 3718], 'developing': [3654], 'progressive': [3655, 3727], 'symptomatic': [3657], 'Occasional': [3660], 'develop': [3664], 'mild': [3665, 3928], 'overload.52': [3667], 'However,': [3668], 'genotypes': [3677], 'cofactor': [3681], 'conjunction': [3692], 'diseases': [3696], 'C': [3701], 'infection,': [3702], 'NAFLD.': [3705], 'Relatives': [3706], 'measurements': [3739], 'ferritin.': [3744], 'Family': [3745], 'concluded': [3748, 4219], 'probands': [3754], 'demonstrate': [3755], 'disease.53,': [3761], '54': [3762], 'Furthermore,': [3763], '30,000': [3770], 'Caucasian': [3771], 'subjects': [3772, 3785, 4061, 4122], 'aged': [3773], '40-69': [3774], '203': [3777], '(108': [3780], 'females,': [3781, 3813], '95': [3782], 'males).': [3783], 'sequentially': [3788], 'over': [3789], '12-year': [3791], 'period,': [3792], 'knowledge': [3796], 'genotype.': [3799], 'Documented': [3800], 'overload-related': [3802], '28%': [3807], 'males': [3809, 4115], '1%': [3811], 'especially': [3814], 'μg/L.10': [3821], '5.': [3822], '(iron': [3826], 'detect': [3841], 'early': [3842], 'prevent': [3845], 'complications.': [3846], '(1A)': [3847], 'Since': [3848], 'advent': [3850], 'analysis,': [3854], 'biopsy': [3856, 3871, 3923, 3931, 4056, 4241, 4281, 4312], 'tool': [3864], 'purpose': [3878], 'determining': [3880], 'prognostic': [3893], 'value.': [3894], 'Identification': [3895], 'adjustments': [3901], 'management,': [3904], 'HCC': [3909], 'esophageal': [3911], 'varices': [3912], '(and': [3913], 'portal': [3917], 'hypertension).55': [3918], 'risks': [3920], 'reviewed,': [3926], 'bleeding': [3929], 'after': [3930], '1%-6%,': [3939], 'mortality': [3941], 'complication': [3945], '1:10,000.56': [3949], 'help': [3954], 'benefit': [3959], 'biopsy.': [3965], '20%-45%.49,': [3990], '50': [3991], '2%': [3996], '<l000': [4004, 4251], 'time': [4008], 'bridging': [4014], 'another': [4020], 'factor': [4022], 'alcohol': [4026, 4258], 'consumption,': [4027], 'viral': [4028, 4308], 'hepatitis,': [4029], 'disease.47-50': [4033], '670': [4040], 'fibrosis.41': [4050], '350': [4060], '(using': [4068], '500': [4072], 'μg/L)': [4073], 'enzyme': [4078], 'results,': [4079], 'hepatomegaly,': [4083], 'these.': [4088], 'biopsies': [4093], 'availability': [4103], 'analysis.': [4107], 'Cirrhosis': [4108], '5.6%': [4112], '1.9%': [4117], 'females.': [4120], '(HIC)': [4130], 'μmol/g': [4132], 'dry': [4133, 4377], 'weight': [4134, 4378], 'seven': [4136], 'normal).': [4142], '100%': [4150], 'identification': [4156], 'No': [4159], 'subject': [4160], 'observations': [4171], 'tempered': [4174], 'consume': [4180], 'alcohol.': [4184], 'Australian': [4186], '>60%': [4190], 'consumed': [4196, 4208], '>60': [4197], 'g': [4198], 'alcohol/day': [4199], '<7%': [4204], 'alcohol.57': [4210], 'Based': [4211], 'Therefore,': [4239], 'μg/L,': [4252], 'consumption': [4259], 'enzymes.': [4264], 'Patients': [4265], 'homozygosity,': [4275], 'enzymes': [4287], 'non-HH': [4299], 'NAFLD,': [4304], 'hepatitis.': [4309], 'performed,': [4314], 'histopathologic': [4316], 'standard': [4320], 'hematoxylin–eosin': [4321], "Masson's": [4323], 'trichrome': [4324], 'stains': [4325, 4332], "Perls'": [4329], 'Prussian': [4330], 'blue': [4331], 'evaluating': [4334], 'portion': [4347], 'measurement': [4355], 'HIC.': [4357], 'HIC': [4363], 'measured': [4367], 'formalin-fixed,': [4369], 'deparaffinized': [4370], 'specimens,': [4371], 'least': [4374], 'mg': [4376], 'evaluation.58': [4385], 'Qualitative': [4386], 'semiquantitative': [4388], 'methods': [4389], 'grading': [4391], 'stainable': [4395], 'described.': [4400], 'Batts–Ludwig': [4402], 'uses': [4404], 'estimation': [4406], 'stain': [4413], 'iron,': [4415], 'ranging': [4416], 'solely': [4418], 'zone': [4419], '(periportal)': [4421], 'inclusion': [4423], 'zones': [4425], '(pericentral).': [4429], 'gr': [4431]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2082390213', 'counts_by_year': [{'year': 2024, 'cited_by_count': 38}, {'year': 2023, 'cited_by_count': 38}, {'year': 2022, 'cited_by_count': 69}, {'year': 2021, 'cited_by_count': 59}, {'year': 2020, 'cited_by_count': 51}, {'year': 2019, 'cited_by_count': 52}, {'year': 2018, 'cited_by_count': 53}, {'year': 2017, 'cited_by_count': 55}, {'year': 2016, 'cited_by_count': 55}, {'year': 2015, 'cited_by_count': 62}, {'year': 2014, 'cited_by_count': 38}, {'year': 2013, 'cited_by_count': 39}, {'year': 2012, 'cited_by_count': 24}], 'updated_date': '2024-12-18T00:17:13.668690', 'created_date': '2016-06-24'}
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