Đang tải... (xem toàn văn)
Part 2 book “Sherlock’s diseases of the liver and biliary system” has contents: Autoimmune hepatitis and overlap syndromes, enterically transmitted viral hepatitis, drug - induced liver injury, iron overload states, wilson disease, nutrition and chronic liver disease, the liver in the neonate, in infancy, and childhood,… and other contents.
Chapter 19 Autoimmune Hepatitis and Overlap Syndromes Ashnila Janmohamed and Gideon M Hirschfield Centre for Liver Research, NIHR Biomedical Research Centre, University of Birmingham, Birmingham, UK LEARNING POINTS Autoimmune hepatitis (AIH) is an immune mediated liver disease that can present in all ages and races and both sexes Disease presentation is variable, ranging from asymptomatic disease to fulminant liver failure There is an absence of a specific diagnostic marker, hence diagnosis is made by exclusion of alternative liver disease and precipitants, for example, drugs and viruses Clinically, AIH is characterized by raised serum alanine aminotransferase, hypergammaglobulinaemia, autoantibodies, and interface hepatitis Seropositivity for autoantibody subclassifies disease into two distinct entities: antinuclear and/or smooth muscle antibodies (type disease) and anti liver kidney microsomal and/or liver cytosol (type disease) The cornerstone of therapy is immunosuppression using corticosteroids and azathioprine with the majority of patients achieving remission, reflecting that AIH is normally treatment responsive Liver transplantation is indicated in patients who present with fulminant liver failure or have end stage liver disease Lack of response to immunosuppression should prompt confirmation of compliance, exclusion of alternative/additional aetiology such as primary biliary or primary sclerosing cholangitis, and initiation of second line 967 therapy if appropriate Lack of standardization of second line therapy in AIH demonstrates an ongoing need for new and more rational therapies Introduction Autoimmune hepatitis (AIH) is a heterogeneous immune mediated liver disease that, in most cases, has effective treatment when diagnosed promptly and treated judiciously with classical immunosuppression focused on corticosteroids and azathioprine The spectrum of presentation alongside the absence of clear pathophysiology and non specific diagnostic markers results in a chronic, rare, and progressive immune mediated liver disease, which has ongoing unmet needs Clinically, in its classical form, patients with AIH are characterized by raised serum alanine transaminase (ALT) activity, hypergammaglobulinaemia, non organ specific autoantibodies, and a chronic relapsing hepatitis, associated with a plasma cell hepatic infiltrate Exclusion of drug precipitants (prescribed, ‘over the counter’, or herbal), alternative aetiologies of liver disease and confirmation of negative viral studies are always required (Fig 19.1) 968 Fig 19.1 Evaluating a patient with autoimmune liver disease ALP, alkaline phosphatase; ALT, alanine transaminase; AST, aspartate transaminase; ANAs, antinuclear antibodies; AMAs, antimitochondrial antibodies; MRCP, magnetic resonance cholangiopancreatography; MRI, magnetic resonance imaging; PBC, primary biliary cholangitis; PSC, primary sclerosing cholangitis; γ GT, γ glutamyltransferase; SMAs, anti smooth muscle antibodies Historical perspective Appreciation for an autoimmune aetiology in chronic hepatitis emerged in the 1940s as Waldenström recognized the relevance of hypergammaglobulinaemia in chronic hepatitis, and Kunkel et al [1] described a persistent liver disease predominantly in young females with hypergammaglobulinaemia, alongside extra hepatic symptoms including rash, arthralgia, fever, and amenorrhoea Subsequent observations reporting the presence of lupus erythematosus cells and antinuclear antibodies (ANAs) led to the suggestion of an immune mediated disease prompting treatment with cortisone, which resulted in marked symptomatic improvement, suggesting an important inflammatory component to 969 this disease Prolonged immunosuppressive therapy with corticosteroids and azathioprine, offered to patients from the 1960s onwards, proved effective and remains standard therapy [2–4] The term autoimmune hepatitis was applied in 1965 by Cowling and Mackay, and endorsed globally in 1993 Disease overview Clinical manifestations These range from asymptomatic through to fulminant hepatic failure Although most patients present when symptomatic (fatigue, arthralgia, anorexia, jaundice), others are diagnosed incidentally The prevalence, clinical presentation, and outcome of AIH vary between ethnic groups and geographical regions, and clinicians should be mindful of this AIH is more common and severe in North American Aboriginals/First Nations populations compared with predominately Caucasians, non First Nations populations [5] Cirrhosis at presentation is more frequent in black North American patients with AIH than white North Americans [6] They are also younger at presentation, similar to patients from Brazil and Argentina, and have poorer prognosis [5] Africans, Asians, and Arabs have an earlier disease onset than people from Northern Europe Along with Alaskan natives, they additionally appear to have a higher frequency of cholestatic laboratory findings and acute icteric disease Similarly, patients of Hispanic origin tend to present aggressively both biochemically and histologically and have a very high prevalence of cirrhosis and cholestatic features Serology Serological patterns of autoreactivity permit two major classifications: type 1, characterized by ANAs and/or anti smooth muscle antibodies (SMAs), and type 2, characterized by anti liver/kidney microsomal type (anti LKM 1) and/ or liver cytosol type (anti LC 1) antibodies [5] Epidemiology Patients of all ages and races and both genders can develop AIH AIH is considered rare, as its prevalence ranges from 16 to 18 cases 970 per 100 000 inhabitants in Europe Higher prevalence rates have been reported in areas with stable ‘populations’ (where both growth rates and relative age distribution not change with time) A large nationwide population study in Denmark, assessing the incidence and prevalence of AIH over a 20 year period between 1994 and 2013, demonstrated that the incidence of AIH had increased markedly over the study time period Between 1994 and 2012, the incidence rate had nearly doubled, reaching a point prevalence in 2012 of 23.9 per 100 000 [7] Natural history Sherlock’s follow up study, in which 44 patients, diagnosed between 1963 and 1967, were randomly allocated into control and treatment (prednisolone) groups, provides stark natural history data for patients with severe disease Ten year survival data demonstrated significantly improved survival in the treatment group, where 63% of patients were alive at 10 years (median survival 12.2 years), compared with 27% (median survival 3.3 years) in the control group (Fig 19.2) 971 Fig 19.2 Later results of the Royal Free Hospital trial of prednisolone in chronic autoimmune hepatitis Note the improved survival in the treated group Source: Kirk et al 1980 [36] Reproduced with permission of BMJ Publishing Biological determinants of disease Immunobiology Hepatic immunological tolerance is maintained in numerous ways, including (a) antigen priming in the liver, (b) sinusoidal tolerance and T regulatory cell (Treg) induction, and (c) hepatic stellate cell induced effector T cell apoptosis and generation of myeloid derived suppressor cells [8] Loss of tolerance is precipitated through various events, which collectively culminate in a common final pathway towards liver injury Evidence implies that both 972 innate and adaptive immune systems are involved in AIH Data demonstrate a genetic predisposition, strongly associated with the HLA locus, systemic immunoregulatory changes notably affecting Treg function, and immune restricted responses to target antigens Microscopic evaluation of the liver demonstrates an autoaggressive cellular immune attack with lymphocytes, macrophages, and plasma cells forming a dense portal mononuclear cell infiltrate involving surrounding parenchyma to varying degrees (interface hepatitis) Immunohistochemical studies have revealed a predominance of αβ T cells, the majority being CD4 helper T cells and a sizeable minority being CD8 cytotoxic suppressor T cells Other cells present include natural killer (NK) cells, monocytes/macrophages, and γδ T and B cells Antigen restricted immune mediated injury is driven through a combination of cellular and antibody mediated immunological attack against liver specific targets Th1, Th2, and Th17 cells interact to generate disease Th1 cells enhance HLA class I expression and induce expression of HLA class II molecules on hepatocytes, Th2 cells favour autoantibody production by B lymphocytes and Th17 cells play a role in organ specific autoimmune inflammation (Fig 19.3) 973 Fig 19.3 Diagrammatic representation of immunopathogenesis of autoimmune hepatitis A, a self antigenic peptide is presented to an uncommitted T helper (Th0) lymphocyte within the HLA class II molecule of an antigen presenting cell (APC) Th0 cells become activated and, depending on the cytokine milieu in the microenvironment, differentiate into Th1, Th2, and Th17 cells, initiating a series of immune reactions B, Th1 secrete IL2 and IFN γ, which stimulate cytotoxic T lymphocytes (CD8), enhance expression of class I, induce expression of class II HLA molecules on hepatocytes, and activate monocytes/macrophages (M0/Mφ) which in turn release TNF α and IL1 C, Th2 cells secrete IL4, IL10, and IL13, which induce the maturation of B cells in to plasma (P) cells D, expansion of plasma cells results in excess production of immunoglobulins, which bind to normal membrane constituents of the hepatocytes, inducing complement activation, engagement of natural killer (NK) cells, and hepatocyte death E, Th17 cells release IL17, IL23, and IL6 IL17 induces IL6 expression in hepatocytes, which in turn further stimulates Th17 cells Depending on the state of the immune system and IL6 production, a reciprocal relationship is thought to exist between Th17 cells and T regulatory (Treg) cells F, Tregs are derived from Th0 cells in the presence of transforming growth factor (TGF β) A considerable number of IL17 (a potent pro inflammatory cytokine) producing cells can also be present in the inflammatory infiltrate of the livers of patients with AIH The role of Th17 cells in AIH is incompletely understood IL17 produced by Th17 cells has been shown to induce IL6 (pro /anti inflammatory cytokine) expression in hepatocytes, stimulating Th17 cells further, resulting in a positive feedback loop between Th17 cells and hepatocytes and exacerbating the inflammatory process Depending on the state of the immune system and IL6 production, a reciprocal relationship is thought to exist between Th17 cells and Tregs in both development pathways and function Studies have shown that Tregs in AIH are reduced in number and function with decreased proliferative activity in response to stimulation Their ability to produce IL10 (anti inflammatory cytokine) has been shown to be impaired, contributing to a functional impairment [9] Tregs were found to have both impaired suppressive capacity and increased susceptibility to apoptosis 974 following contact with hepatic microenvironment that was rich in pro inflammatory cytokines but deficient in IL2 Exogenous IL2 reversed these effects, suggesting a possible mechanism to explain Treg dysfunction in inflamed tissue such as in AIH IL2 supplementation in addition to Treg therapy is an experimental paradigm being explored potentially to restore immune homeostasis in autoimmune liver diseases (AILDs) [10] In contrast, some studies have demonstrated no differences in the frequency and function of peripheral Tregs in AIH In one study, intrahepatic Tregs were noted to be increased in untreated type AIH whereas immunosuppression resulted in a disproportionate loss [11] The role of B cells in AIH remains unclear They are mainly responsible for antibody production Although AIH is characterized by the presence of autoantibodies, they are not generally disease specific, nor they correlate with disease severity or outcome B cells can act as antigen presenting cells (APCs) and modulate immune responses by cytokine production Preclinical and clinical studies investigating the effect of B cell depletion in AIH have produced contradictory results, although in many patients a clear response has been noted [12,13] B cell activating factor (BAFF) is a cytokine that influences B cell survival and maturation and plays a role in immune regulation Early conference proceedings have shown that patients with AIH have significantly elevated serum BAFF concentrations that correlate with transaminase activity, whereas corticosteroid therapy markedly reduces BAFF levels Genetics and AIH Genetic associations with AIH that are confirmed include common genetic variation in (a) HLA and (b) SH2B3, alongside (c) very rare coding variants in AIRE and GATA2 HLA loci and AIH The first genome wide association study (GWAS) of patients with type AIH in the Netherlands confirmed the strong involvement of the major histocompatibility complex region [14] and identified HLA DRB1*03:01 as a primary susceptibility genotype and HLA DRB1*04:01 as secondary In European and North American Caucasians, HLA A1 B8, HLA DRB1*03:01, and HLA DRB1*04:01 are associated with type AIH ad DRB1*03, DRB1*07, 975 and DQB1*02:01 with type Those over 60 years of age are more likely to have the HLA DRB1*04 allele, which is associated with less severe disease, whereas HLA A1 B8 DR3 haplotype is over represented in men with AIH and strongly associated with early disease onset and relapse [15] The presence of HLA DRB1*03 is associated with failure to respond to treatment and a more severe disease course HLA associations vary around the globe and may explain some disease presentation differences For example, in Japan and Argentina HLA DRB1*04:05 is associated with AIH, in Brazil HLA DRB1*13:01 and DRB3*01 are associated with disease, and among Mestizo Mexicans HLA DRB1*04:04 is predominant Non‐HLA loci and AIH GWAS identified the first non HLA genetic AIH risk factor; SH2B3, a protein that acts as a negative regulator of T cell activation, tumour necrosis factor (TNF) and janus kinase and signalling, and also plays a critical role in hematopoiesis It is also associated with other autoimmune diseases such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), type diabetes mellitus, and coeliac disease Other non HLA genes associated with AIH susceptibility include autoimmune regulator type (AIRE 1), a transcription factor that regulates clonal deletion of autoreactive T cells A single coding mutation of this transcription factor results in a severe autoimmune polyglandular syndrome type (APS1) Patients with APS1 suffer from mucocutaneous candidiasis and a number of organ specific autoimmune diseases, including AIH Recently, a mutation in GATA2, another haematopoietic transcription factor, has been shown to be associated with AIH, further highlighting relevant mechanisms of liver injury, notably Treg dysfunction [16] Environmental and drug triggers In patients with a presumed underlying genetic predisposition, environmental toxins such as drugs and viral infections may be presented immunologically in a manner that precipitates molecular mimicry Drugs can induce both immunologically mediated hepatocellular 976 WILEY END USER LICENSE AGREEMENT Go to www.wiley.com/go/eula to access Wiley’s ebook EULA 2211 目录 Cover Preface to the Thirteenth Edition Preface to the First Edition Chapter 1: Anatomy and Function Development of the liver and bile ducts Anatomy of the liver Functional liver anatomy: sectors and segments Anatomical abnormalities of the liver Anatomy of the biliary tract (Fig 1.6) Surface marking (Fig 1.7, Fig 1.8) Methods of examination Microanatomy of the liver Hepatic ultrastructure (electron microscopy) and organelle functions Functional heterogeneity of the liver (Fig 1.20) Dynamics of the hepatic microenvironment in physiology and disease (Fig 1.21) Hepatocyte death and regeneration (Fig 1.22) References Chapter 2: Liver Function in Health and Disease Bilirubin metabolism (see Chapter 13) Bile acids Lipid and lipoprotein metabolism Amino acid metabolism Plasma proteins Carbohydrate metabolism Markers of hepatocellular injury: the serum transaminases Markers of cholestasis: alkaline phosphatase (ALP) and gamma‐glutamyl transferase (GGT) Haematology in liver disease Effects of ageing on the liver 2212 96 98 100 100 101 104 107 109 112 115 116 124 134 135 137 140 147 151 154 160 166 169 175 176 178 182 185 References 186 Chapter 3: Biopsy of the Liver Selection and preparation of the patient Techniques Risks and complications Sampling variability Naked‐eye appearances Preparation of the specimen Interpretation: a stepwise diagnostic approach Indications (Table 3.4) [5] Special methods [34] References Chapter 4: Coagulation in Cirrhosis Introduction Normal coagulation pathways: a hepatologist’s perspective The coagulation system in cirrhosis Bleeding and thrombosis in cirrhosis Clinical laboratory tests of the coagulation system in cirrhosis Conclusion References Chapter 5: Acute Liver Failure Definition Epidemiology and aetiologies (Fig 5.1, Table 5.1) Clinical features Initial investigations Complications and management of acute liver failure Specific therapies Prognosis Liver transplantation (Chapter 37) Conclusion References Chapter 6: Hepatic Fibrogenesis Introduction 195 196 198 205 212 213 214 215 217 221 223 229 229 231 236 237 241 244 244 250 251 252 258 260 264 275 278 281 284 284 293 293 2213 Natural history of hepatic fibrosis Cellular and molecular features of hepatic fibrosis (Fig 6.2) Clinical aspects of hepatic fibrosis Emerging antifibrotic targets and strategies References 294 295 309 310 311 Chapter 7: Non‐invasive Assessment of Fibrosis and Cirrhosis 319 Introduction The use of invasive and non‐invasive tests Non‐invasive tests: specifics Conclusions References Chapter 8: Hepatic Cirrhosis 320 321 325 340 340 351 Definition Causes of cirrhosis Anatomical diagnosis Reversible cirrhosis Clinical cirrhosis: compensated versus decompensated Prognosis (Child–Pugh score, MELD, UKELD) Clinical and pathological associations Management Acute‐on‐chronic liver failure References Chapter 9: Ascites 352 354 356 361 361 364 365 384 386 393 401 Mechanisms of ascites formation Clinical features Differential diagnosis Spontaneous bacterial peritonitis (Table 9.3) Treatment of cirrhotic ascites Hyponatraemia Refractory ascites Hepatorenal syndrome Prognosis References 2214 404 409 415 416 421 431 434 438 446 447 Chapter 10: Hepatic Encephalopathy in Patients with Cirrhosis Clinical Features [1–3] Classification [2,4] Prevalence and consequences Diagnosis [30] Diagnostic comorbidities, confounders, and alternatives Pathogenesis Management [4] Prevention [4] References Chapter 11: Portal Hypertension in Cirrhosis Introduction Pathophysiology and rational basis of therapy Evaluation and diagnosis Natural history and prognosis Management Treatment of portal hypertension according to clinical scenarios References Chapter 12: Vascular Disorders of the Liver and Extrahepatic Portal Hypertension Hepatic artery occlusion Aneurysms of the hepatic artery Hepatic arterioportal fistula Hepatic vascular malformations in hereditary haemorrhagic telangiectasia Congenital portosystemic shunts – Abernethy malformation Budd–Chiari syndrome – hepatic venous outflow tract obstruction Extrahepatic portal vein obstruction – portal vein thrombosis and portal cavernoma in the absence of cirrhosis Portal vein thrombosis in patients with cirrhosis Idiopathic non‐cirrhotic intrahepatic portal hypertension Hypoxic hepatitis 2215 462 463 466 470 471 481 484 501 515 516 530 530 543 550 564 568 578 590 599 600 602 604 606 609 612 619 626 628 633 Congestive cardiac hepatopathy Non‐obstructive sinusoidal dilation (NOSD) and peliosis References Chapter 13: Jaundice and Cholestasis Introduction Mechanics of bile formation Syndrome of cholestasis Causes of isolated hyperbilirubinaemia Causes of cholestatic and hepatocellular jaundice Bile duct and hepatocellular diseases Consequences of cholestasis and their management Investigation of the jaundiced patient Decisions to be made in the jaundiced patient Management of cholestatic disorders References 635 638 641 653 653 657 668 670 677 680 683 691 700 700 701 Chapter 14: Gallstones and Benign Biliary Disease 713 Introduction Imaging the gallbladder and biliary tract Gallstones Symptoms and complications of gallstones Cholecystectomy Complicated acute gallbladder disease Percutaneous cholecystostomy Asymptomatic gallbladder stones Non‐surgical treatment of gallstones in the gallbladder Common bile duct stones Acute gallstone pancreatitis Large common duct stones Mirizzi syndrome Intrahepatic gallstones Haemobilia Functional gallbladder and sphincter of Oddi disorders Other gallbladder pathologies Relationships to malignant change 713 715 726 737 742 747 748 749 750 751 756 756 758 761 761 763 765 775 2216 Benign biliary strictures Anastomotic strictures following biliary surgery IgG4‐related sclerosing cholangitis Chronic pancreatitis References Chapter 15: Malignant Biliary Diseases Carcinoma of the gallbladder Carcinoma of the bile duct (cholangiocarcinoma) Other biliary malignancies Metastases at the hilum Ampullary and periampullary carcinomas Conclusion References Chapter 16: Fibropolycystic Liver Diseases and Congenital Biliary Abnormalities Overview Polycystic liver disease Fibropolycystic diseases Autosomal recessive polycystic kidney disease Congenital hepatic fibrosis Caroli disease [58] Microhamartomas (von Meyenberg complexes) Choledochal cysts Solitary non‐parasitic liver cyst Congenital anomalies of the biliary tract References Chapter 17: Primary Biliary Cholangitis Clinical features Diagnosis Epidemiology Aetiology and pathogenesis Management Prognosis References 776 783 785 786 788 813 813 817 831 831 831 843 843 851 852 856 865 866 868 872 877 878 884 885 894 903 904 905 916 916 921 925 925 2217 Chapter 18: Sclerosing Cholangitis Introduction Primary sclerosing cholangitis Secondary sclerosing cholangitis Sclerosing cholangitis in systemic inflammatory diseases References Chapter 19: Autoimmune Hepatitis and Overlap Syndromes Introduction Disease overview Biological determinants of disease Disease presentation Laboratory features Imaging Liver biopsy and histological features Differential diagnosis Diagnostic dilemmas Making a diagnosis in practice Management strategies Pretreatment and on‐treatment considerations Treatment challenges and alternative agents Pregnancy and autoimmune hepatitis The elderly and autoimmune hepatitis Childhood‐onset autoimmune hepatitis Autoimmune hepatitis and liver transplantation Overlap syndromes Conclusion References 933 933 937 954 956 957 967 968 970 972 977 980 985 986 993 995 996 999 1007 1008 1009 1010 1011 1012 1013 1021 1021 Chapter 20: Enterically Transmitted Viral Hepatitis 1028 General features of enterically transmitted viral hepatitis Hepatitis A virus Hepatitis E virus References 1028 1039 1049 1055 2218 Chapter 21: Hepatitis B 1065 Introduction Hepatitis B virus Immune response and mechanisms of hepatic injury Epidemiology Prevention Diagnosis Clinical manifestations Natural history Treatment HBV and HCV coinfection (also see Chapter 23) HBV and HDV coinfection HBV and HIV coinfection References Chapter 22: Hepatitis D 1066 1066 1072 1073 1076 1081 1088 1090 1097 1111 1112 1112 1113 1130 History Hepatitis D virus (Table 22.1) Epidemiology Pathogenesis Modes of infection and clinical course Diagnosis Treatment Prevention References Chapter 23: Hepatitis C 1131 1131 1134 1136 1137 1146 1148 1154 1155 1163 Introduction Epidemiology Virology Pathology and pathogenesis Diagnostic tests for hepatitis C Acute hepatitis C Chronic hepatitis C References 1163 1164 1167 1169 1171 1174 1175 1213 2219 Chapter 24: Drug‐Induced Liver Injury Introduction Epidemiology Complications of DILI Classification of hepatotoxicity Drug metabolism and pharmacokinetics Hepatic drug metabolism Molecular mechanisms in drug‐induced liver injury Non‐genetic risk factors for DILI Diagnosis of DILI Medical management Pharmacogenetic risk factors Potential immunological mechanisms in idiosyncratic DILI Liver injury from specific drugs References Chapter 25: Alcohol and the Liver Introduction Alcohol metabolism Pathogenesis Susceptibility Histological features Clinical features Clinical syndromes Prognosis Treatment Conclusions References 1237 1237 1238 1240 1242 1243 1244 1246 1249 1251 1260 1260 1262 1263 1279 1300 1301 1301 1304 1308 1310 1317 1323 1326 1329 1333 1334 Chapter 26: Iron Overload States Normal iron physiology Iron overload and liver damage Genetic haemochromatosis Other iron storage diseases References 1341 1343 1350 1350 1366 1369 2220 Chapter 27: Wilson Disease 1377 Molecular genetics: pathogenesis Pathology Clinical picture Laboratory tests Genetic strategies Diagnostic difficulties Treatment (Table 27.1) Prognosis Non‐Wilsonian copper‐related cirrhosis References Chapter 28: Non‐Alcoholic Fatty Liver Disease Introduction Further definitions, terminology, and diagnosis Liver biopsy, classification of NAFLD, and non‐invasive markers of NASH and fibrosis Clinical features Laboratory testing Epidemiology Ethnic variation in NAFLD Pathogenesis of NASH Natural history of NAFLD (Fig 28.9) NAFLD and hepatocellular carcinoma (HCC) Therapy for non‐alcoholic fatty liver disease Other forms of NAFLD References Chapter 29: Nutrition and Chronic Liver Disease Introduction Epidemiology and general characteristics Causes of malnutrition Consequences of malnutrition Diagnosis and assessment Treatment and management References 2221 1378 1381 1385 1392 1394 1394 1395 1401 1402 1402 1412 1413 1414 1416 1420 1422 1423 1424 1424 1434 1437 1437 1443 1445 1459 1459 1461 1462 1465 1467 1477 1480 Chapter 30: Pregnancy and the Liver Introduction Normal physiology in pregnancy Pregnancy‐related liver diseases Pre‐existing liver diseases and pregnancy Liver transplantation and pregnancy Liver disease coincidentally arising with pregnancy Conclusion References Chapter 31: The Liver in the Neonate, in Infancy, and Childhood Investigation of liver disease in children Neonatal jaundice Neonatal unconjugated hyperbilirubinaemia (Tables 31.2, 31.3) Neonatal liver disease (conjugated hyperbilirubinaemia) Neonatal hepatitis Inherited disease in the neonate Genetic cholestatic syndromes Structural abnormalities: biliary atresia and choledochal cyst Acute liver failure in infancy Liver disease in older children Metabolic disease in older children Cirrhosis and portal hypertension Liver transplantation Tumours of the liver (see also Chapters 35 and 36) References 1487 1488 1489 1490 1501 1507 1508 1510 1510 1524 1525 1528 1528 1533 1538 1543 1551 1556 1561 1568 1572 1586 1587 1590 1592 Chapter 32: The Liver in Systemic Diseases 1609 Collagen‐vascular and autoimmune disorders Hepatic granulomas Sarcoidosis The liver in endocrine disorders Amyloidosis Porphyrias The liver in haemolytic anaemias 1610 1613 1619 1624 1627 1634 1641 2222 The liver in myelo‐ and lymphoproliferative disease [102] Bone marrow transplantation Lymphoma Extramedullary haemopoiesis Rare haematological disorders that may involve the liver Lipid storage diseases Non‐metastatic complications of malignancy References 1651 1652 1655 1661 1663 1663 1669 1669 Chapter 33: The Liver in Infections 1684 Introduction Jaundice of infections Pyogenic liver abscess Hepatic amoebiasis Tuberculosis of the liver Hepatic actinomycosis Syphilis of the liver Perihepatitis Leptospirosis Relapsing fever Lyme disease Rickettsial infections Fungal infections Schistosomiasis (bilharzia) Malaria [113] Kala‐azar (visceral leishmaniasis) Echinococcosis (hydatid disease) Ascariasis Strongyloides stercoralis Trichinosis Toxocara canis (visceral larva migrans) Liver flukes References 1684 1685 1685 1693 1699 1702 1703 1705 1706 1712 1713 1713 1715 1717 1724 1725 1727 1740 1743 1743 1744 1744 1747 Chapter 34: Imaging of the Liver and Diagnostic Approach of Space‐Occupying Lesions 2223 1762 Ultrasound Computed tomography Magnetic resonance imaging Radioisotope scanning Positron emission tomography MR spectroscopy Conclusions and choice of imaging technique References Chapter 35: Benign Liver Tumours Diagnosis of focal liver lesions Hepatocellular lesions Biliary and cystic lesions Mesenchymal tumours References 1762 1766 1770 1777 1778 1778 1779 1779 1783 1785 1785 1799 1802 1805 Chapter 36: Primary Malignant Neoplasms of the Liver 1814 Hepatocellular carcinoma Intrahepatic cholangiocarcinoma Other malignant neoplasms of the liver Other sarcomas References 1814 1846 1850 1852 1852 Chapter 37: Hepatic Transplantation 1873 Selection of patients (Table 37.1) Candidates (Table 37.2) Absolute and relative contraindications (Table 37.4) General preparation of the patient Donor selection and operation The recipient operation (Fig 37.3) Immunosuppression Postoperative course Post‐transplantation complications (Table 37.9) Conclusion Acknowledgement References 2224 1874 1879 1892 1894 1896 1898 1905 1908 1909 1930 1930 1931 Chapter 38: Hepatic Transplantation and HBV, HCV, and HIV Infections Introduction Hepatitis B and liver transplantation Hepatitis C and liver transplantation HIV and liver transplantation References Index End User License Agreement 2225 1948 1949 1950 1960 1978 1983 2003 2211 ... one of the treatment endpoints [20 ] The presence of autoantibodies without other features of AIH is not diagnostic of AIH, and conversely their absence does not preclude a diagnosis of AIH in the. .. coding variants in AIRE and GATA2 HLA loci and AIH The first genome wide association study (GWAS) of patients with type AIH in the Netherlands confirmed the strong involvement of the major histocompatibility... demonstrated that the incidence of AIH had increased markedly over the study time period Between 1994 and 20 12, the incidence rate had nearly doubled, reaching a point prevalence in 20 12 of 23 .9 per 100