Ebook Sherlock’s diseases of the liver and biliary system (13/E): Part 1

Part 1 book “Sherlock’s diseases of the liver and biliary system” has contents: Anatomy and function, liver function in health and disease, biopsy of the liver, coagulation in cirrhosis, acute liver failure, hepatic fibrogenesis, hepatic cirrhosis, hepatic encephalopathy in patients with cirrhosis,… and other contents.

Table of Contents 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 References 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 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 Chapter 7: Non invasive Assessment of Fibrosis and Cirrhosis Introduction The use of invasive and non invasive tests Non invasive tests: specifics Conclusions References Chapter 8: Hepatic Cirrhosis 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 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 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 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 Chapter 14: Gallstones and Benign Biliary Disease 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 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 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 Chapter 20: Enterically Transmitted Viral Hepatitis General features of enterically transmitted viral hepatitis Hepatitis A virus Hepatitis E virus References Chapter 21: Hepatitis B 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 History Hepatitis D virus (Table 22.1) Epidemiology Pathogenesis Modes of infection and clinical course Diagnosis Treatment Prevention References Chapter 23: Hepatitis C Introduction Epidemiology Virology Pathology and pathogenesis Diagnostic tests for hepatitis C Acute hepatitis C Chronic hepatitis C References 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 10 hybridization (FISH) and other DNA based methods may increase the diagnostic yield [66,67] but are not widely available Treatment of cholangiocarcinoma Curative treatment of established cholangiocarcinoma in PSC is hard to achieve, and the median survival is only around months Surgical resection or liver transplantation is a treatment option but only in highly selected patients [68] Palliative biliary stenting can relieve symptoms of cholestasis, and chemotherapy can be used following general guidelines for cholangiocarcinoma Screening for cholangiocarcinoma There are no evidence based screening strategies for the early detection of cholangiocarcinoma or gallbladder cancer in PSC An annual ultrasound scan to detect gallbladder polyps, combined with CA 19 measurement, is recommended Additional cross sectional imaging with MRI/MRC is increasingly used [51,63,64,69] Hepatocellular carcinoma surveillance should be performed according to standard guidelines as in patients with cirrhosis Elevated CA 19 levels may also be found in cases of cholestasis, bacterial cholangitis, and other malignancies, and reliance on CA 19 alone in the surveillance for cholangiocarcinoma in PSC is not recommended Colorectal carcinoma In established IBD associated with PSC, ileocolonoscopy with dye based chromoendoscopy and targeted biopsies is recommended every 1–2 years from the time of diagnosis of concurrent PSC and IBD [70] In appropriately trained hands, when there is quiescent disease and adequate bowel preparation, non targeted four quadrant biopsies are therefore not needed, yet are still commonly used [71] The risk of colorectal neoplasia may approach 15% at 10 years and 30% at 20 years after the diagnosis of IBD [72] An increased risk is also seen in patients with PSC with Crohn disease Colonic neoplasms in PSC have a predilection for the right side of the colon Colorectal carcinoma generally presents at a younger age in PSC associated IBD than in IBD without hepatobiliary disease (median age 39 versus 59 years) [5] 952 Liver transplantation PSC has been the main indication (15–20%) for liver transplantation in the Nordic countries for many years, and accounts for approximately 5–6% of all indications in Europe and the USA [52,73] Impaired quality of life, mainly due to refractory pruritus or recurrent bacterial cholangitis, may be an indication for transplantation in selected patients [74] Cholangiocarcinoma is generally considered a contraindication to liver transplantation Some centres transplant patients with PSC because of the finding of cholangiocellular dysplasia in biliary brush specimens (without evidence of tumour on imaging), with the aim of removing premalignant lesions or early stage cholangiocarcinoma and so prevent progression to invasive cancer [75] In a few centres, patients with early stage hilar cholangiocarcinoma are considered for liver transplantation, following an extensive preoperative protocol to reduce the tumour burden [68] Results after liver transplantation for PSC show year survival rates of approximately 85% To remove as much of the involved extrahepatic bile duct as possible, a hepaticojejunostomy has previously been the preferred surgical procedure In these cases, post transplant ERC has to be carried out by the balloon enteroscopy technique More recently, hepaticoduodenostomy has been used to re establish bile drainage and allow easier access for ERC The standard duct to duct biliary anastomosis is also sometimes performed if feasible Recurrent PSC in the allograft is classically diagnosed when cholangiographic findings (>90 days post transplant) and/or histological features of PSC are found that are compatible with PSC Post transplant causes of secondary sclerosing cholangitis need to have been excluded (Table 18.4) [76] With the current availability of MRC, it is now reasonable to require the presence of cholangiographic findings for the diagnosis The reported prevalence of recurrent PSC varies widely from around 6% up to 60%, with a median time to recurrence ranging from 8.5 to 68 months [77] An intact colon after liver transplantation and the presence of IBD have been proposed to increase the risk of PSC recurrence [78–80] The clinical implications of the latter observations are not clear, and colectomy prior to liver transplantation should not be performed unless otherwise 953 indicated Recurrent PSC is associated with reduced graft survival and an increased risk of death [80] Table 18.4 Diagnostic criteria for recurrent primary sclerosing cholangitis (PSC) following liver transplantation [76] (confirmed diagnosis of PSC prior to liver transplantation is a prerequisite) Cholangiographic Intra and/or extrahepatic biliary stricturing, criteria beading, and irregularity >90 days after liver transplantation Histological Fibrous cholangitis and/or fibro obliterative criteria lesions with or without ductopenia, biliary fibrosis/cirrhosis Exclusion criteria Hepatic artery thrombosis/stenosis (ischaemia) Anastomotic strictures alone Established ductopenic rejection Non anastomotic strictures before post transplantation day 90 ABO incompatibility Immunosuppression given after liver transplantation would be expected to reduce the disease activity in associated IBD, given that some of the immunosuppressive drugs used after transplant are effective treatments for IBD However, the course of IBD after liver transplantation has proven to be variable As a general rule, about one third of patients experience improvement in IBD, one third remain unchanged, and one third deteriorate It is recommended that aminosalicylate therapy is continued post transplant The risk of colorectal cancer after liver transplantation appears to be significantly higher in patients with PSC–IBD than in patients transplanted for non PSC indications [81] This risk may even be increased in patients with PSC–IBD after, as compared with before, transplantation [82], and surveillance colonoscopy should be performed annually (see the previous section) Secondary sclerosing cholangitis A broad range of conditions can give rise to similar cholangiographic and histological changes to those seen in PSC 954 (Table 18.1) [83] It is likely that the changes (Figs 18.2 and 18.4) represent chronic bile duct injury from any cause (‘cirrhosis of the bile ducts’) In making a diagnosis of PSC, such alternative causes need to be excluded Furthermore, some diseases may give rise to imaging features that may closely mimic PSC (Table 18.1) As in all areas of medicine, there should be a high index of suspicion for unusual explanations for common clinical syndromes, such as cholestasis Ischaemia‐ and trauma‐associated sclerosing cholangitis Unlike the hepatic parenchyma, which depends on dual blood flow from the portal vein and hepatic artery, the bile ducts rely on arterial blood flow to maintain their integrity Vascular insufficiency from a variety of causes (e.g thrombotic occlusion, vasculitis, circulatory shock) may result in ischaemic injury to the biliary tree that may persist and mimic PSC In many cases of trauma associated sclerosing cholangitis (violent or iatrogenic), the mechanism is also likely ischaemia rather than direct duct injury Ischaemic biliary lesions are a common complication (up to 10%) of liver transplantation A special case has been made for ‘sclerosing cholangitis of the critically ill’ (SCCI), which occurs in the context of a severe systemic inflammatory response syndrome (SIRS) with associated ischaemic biliary injury [84] These patients typically have extensive biliary cast formation requiring ERC and may show progressive features, sometimes requiring consideration for liver transplantation Infectious cholangitis Choledocholithiasis and associated severe cholangitis can lead to sclerosing cholangitis like changes in any individual In Asia, a related condition, recurrent pyogenic cholangitis (RPC), occurs endemically in rural areas The pathogenesis of RPC is not fully understood, but bile duct occlusion due to pigment stones and epithelial injury from Ascaris lumbricoides, Clonorchis sinensis, Opisthorchis viverrini, Opisthorchis felineus, or Fasciola hepatica is thought to play a role Patients with RPC are at risk of cholangiocarcinoma (5% of the cases), and abscess formation is frequently seen [85] Cholangiocarcinoma development is also seen 955 in chronic helminthic infections (Clonorchis sinensis and Opisthorchis viverrini in particular) Opportunistic infections Chronic opportunistic infections may occur in immunodeficiency syndromes Cholangiopathy associated with serious HIV infection, often due to Cryptosporidium parvum, Microsporidium or other opportunistic pathogens, has become rare with the use of novel antiretroviral regimens However patients with serious HIV infection and low CD4 counts are still at risk Sclerosing cholangitis has been reported to be the most common hepatobiliary disease in children with primary immunodeficiencies Drug‐related sclerosing cholangitis Direct toxicity due to hepatic artery drug injections is a very rare cause of sclerosing cholangitis [83] Chronicity and cholangiographic abnormalities have also been reported in patients with cholestatic drug induced liver injury [86] Sclerosing cholangitis in systemic inflammatory diseases Bile duct disease, which may mimic sclerosing cholangitis on cholangiography, occurs in the context of a variety of inflammatory and non inflammatory systemic conditions Examples include IgG4 associated systemic disease, sarcoidosis (which may also coexist with true PSC), histiocytosis X, and amyloidosis IgG4 associated systemic disease with cholangitis may mimic both PSC and cholangiocarcinoma (pseudotumour) – a differential diagnosis made difficult by the fact that some patients with PSC also have high levels of serum IgG4 Diagnostic criteria for IgG4 associated cholangitis are described in the following but nearly parallel HISORt criteria for diagnosing autoimmune pancreatitis [87] IgG4 associated cholangitis is considered in patients with two or more of the main manifestations (i.e elevated serum IgG4, suggestive pancreatic imaging findings, other organ involvement, and bile duct or papillary biopsy with >10 IgG4 positive 956 cells/high powered field) and a significant corticosteroid treatment response (i.e marked improvement of biliary strictures allowing stent removal, liver enzymes less than two times ULN and significant decreases in serum IgG4 and CA19 levels) There is a risk of relapse after stopping treatment, and many patients require long term immunosuppression [88] Biopsies of the duodenal papilla are easily taken [89], yet have only moderate diagnostic sensitivity Care must be taken to avoid injury to the papilla, which carries an increased risk of post procedural pancreatitis In the future, diagnosis of IgG4 associated sclerosing cholangitis may become easier with the implementation of new diagnostic algorithms and techniques [90,91] IgG4 associated sclerosing cholangitis should be borne in mind for any patient who does not fit the classic characteristics of PSC Of note, patients with PSC may sometimes have slightly elevated levels of serum IgG4 without fulfilling criteria of IgG4 associated cholangitis In these patients, corticosteroid treatment may not be effective References Molodecky NA, Kareemi H, Parab R et al Incidence of primary sclerosing cholangitis: a systematic review and meta analysis Hepatology 2011; 53: 1590–1599 Jepsen P, Gronbaek L, Vilstrup H Worldwide incidence of autoimmune liver disease Dig Dis 2015; 33(Suppl 2): 2–12 Kaplan GG, Laupland KB, Butzner D et al The burden of large and small duct primary sclerosing cholangitis in adults and children: a population based analysis Am J Gastroenterol 2007; 102: 1042–1049 Deneau M, Jensen MK, Holmen J et al Primary sclerosing cholangitis, autoimmune hepatitis, and overlap in Utah children: epidemiology and natural history Hepatology 2013; 58: 1392– 1400 Boonstra K, Weersma RK, van Erpecum KJ et al Population based epidemiology, malignancy risk, and outcome of primary sclerosing cholangitis Hepatology 2013; 58: 2045–2055 Bach JF Infections and autoimmune diseases J Autoimmun 957 2005; 25(Suppl): 74–80 Saarinen S, Olerup O, Broome U Increased frequency of autoimmune diseases in patients with primary sclerosing cholangitis Am J Gastroenterol 2000; 95: 3195–3199 Lunder AK, Hov JR, Borthne A et al Prevalence of sclerosing cholangitis, detected by magnetic resonance cholangiography, in patients with long term inflammatory bowel disease Gastroenterology 2016; 151: 660–669 Boberg KM, Bergquist A, Mitchell S et al Cholangiocarcinoma in primary sclerosing cholangitis: risk factors and clinical presentation Scand J Gastroenterol 2002; 37: 1205–1211 10 Soetikno RM, Lin OS, Heidenreich PA et al Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and ulcerative colitis: a meta analysis Gastrointest Endosc 2002; 56: 48–54 11 Brandt DJ, MacCarty RL, Charboneau JW et al Gallbladder disease in patients with primary sclerosing cholangitis AJR Am J Roentgenol 1988; 150: 571–574 12 Said K, Glaumann H, Bergquist A Gallbladder disease in patients with primary sclerosing cholangitis J Hepatol 2008; 48: 598–605 13 Bergquist A, Ekbom A, Olsson R et al Hepatic and extrahepatic malignancies in primary sclerosing cholangitis J Hepatol 2002; 36: 321–327 14 Harnois DM, Gores GJ, Ludwig J et al Are patients with cirrhotic stage primary sclerosing cholangitis at risk for the development of hepatocellular cancer? J Hepatol 1997; 27: 512–516 15 Boyer JL Bile formation and secretion Compr Physiol 2013; 3: 1035–1078 16 Trauner M, Fickert P, Wagner M MDR3 (ABCB4) defects: a paradigm for the genetics of adult cholestatic syndromes Semin Liver Dis 2007; 27: 77–98 17 Beuers U Drug insight: mechanisms and sites of action of 958 ursodeoxycholic acid in cholestasis Nat Clin Pract Gastroenterol Hepatol 2006; 3: 318–328 18 Hohenester S, Wenniger LM, Paulusma CC et al A biliary HCO3– umbrella constitutes a protective mechanism against bile acid induced injury in human cholangiocytes Hepatology 2012; 55: 173–183 19 Bjornsson E, Cederborg A, Akvist A et al Intestinal permeability and bacterial growth of the small bowel in patients with primary sclerosing cholangitis Scand J Gastroenterol 2005; 40: 1090– 1094 20 Grant AJ, Lalor PF, Salmi M et al Homing of mucosal lymphocytes to the liver in the pathogenesis of hepatic complications of inflammatory bowel disease Lancet 2002; 359: 150–157 21 Henriksen EK, Jorgensen KK, Kaveh F et al Gut and liver T cells of common clonal origin in primary sclerosing cholangitis– inflammatory bowel disease J Hepatol 2017; 66: 116–122 22 Riley TR, Schoen RE, Lee RG et al A case series of transplant recipients who despite immunosuppression developed inflammatory bowel disease Am J Gastroenterol 1997; 92: 279– 282 23 Karlsen TH Primary sclerosing cholangitis: 50 years of a gut liver relationship and still no love? Gut 2016; 65: 1579–1581 24 Kummen M, Holm K, Anmarkrud JA et al The gut microbial profile in patients with primary sclerosing cholangitis is distinct from patients with ulcerative colitis without biliary disease and healthy controls Gut 2016; 66: 611–619 25 Ellinghaus D, Jostins L, Spain SL et al Analysis of five chronic inflammatory diseases identifies 27 new associations and highlights disease specific patterns at shared loci Nat Genet 2016; 48: 510– 518 26 Liu JZ, Hov JR, Folseraas T et al Dense genotyping of immune related disease regions identifies nine new risk loci for primary sclerosing cholangitis Nat Genet 2013; 45: 670–675 959 27 Blechacz B, Gores GJ Cholangiocarcinoma: advances in pathogenesis, diagnosis, and treatment Hepatology 2008; 48: 308–321 28 Mendes FD, Levy C, Enders FB et al Abnormal hepatic biochemistries in patients with inflammatory bowel disease Am J Gastroenterol 2007; 102: 344–350 29 Hov JR, Boberg KM, Karlsen TH Autoantibodies in primary sclerosing cholangitis World J Gastroenterol 2008; 14: 3781–3791 30 Talwalkar JA, Angulo P, Johnson CD et al Cost minimization analysis of MRC versus ERCP for the diagnosis of primary sclerosing cholangitis Hepatology 2004; 40: 39–45 31 Dave M, Elmunzer BJ, Dwamena BA et al Primary sclerosing cholangitis: meta analysis of diagnostic performance of MR cholangiopancreatography Radiology 2010; 256: 387–396 32 Bjornsson E, Olsson R, Bergquist A et al The natural history of small duct primary sclerosing cholangitis Gastroenterology 2008; 134: 975–980 33 Boberg KM, Chapman RW, Hirschfield GM et al Overlap syndromes: the International Autoimmune Hepatitis Group (IAIHG) position statement on a controversial issue J Hepatol 2011; 54: 374–385 34 Bjornsson E, Chari S, Silveira M et al Primary sclerosing cholangitis associated with elevated immunoglobulin G4: clinical characteristics and response to therapy Am J Ther 2011; 18: 198– 205 35 Karlsen TH, Vesterhus M, Boberg KM Review article: controversies in the management of primary biliary cirrhosis and primary sclerosing cholangitis Aliment Pharmacol Ther 2014; 39: 282–301 36 Kim WR, Therneau TM, Wiesner RH et al A revised natural history model for primary sclerosing cholangitis Mayo Clin Proc 2000; 75: 688–694 37 de Vries EM, Verheij J, Hubscher SG et al Applicability and 960 prognostic value of histologic scoring systems in primary sclerosing cholangitis J Hepatol 2015; 63: 1212–1219 38 Ruiz A, Lemoinne S, Carrat F et al Radiologic course of primary sclerosing cholangitis: assessment by three dimensional magnetic resonance cholangiography and predictive features of progression Hepatology 2014; 59: 242–250 39 Ponsioen CY, Reitsma JB, Boberg KM et al Validation of a cholangiographic prognostic model in primary sclerosing cholangitis Endoscopy 2010; 42: 742–747 40 Eaton JE, Dzyubak B, Venkatesh SK et al Performance of magnetic resonance elastography in primary sclerosing cholangitis J Gastroenterol Hepatol 2016; 31: 1184–1190 41 Corpechot C, Gaouar F, El Naggar A et al Baseline values and changes in liver stiffness measured by transient elastography are associated with severity of fibrosis and outcomes of patients with primary sclerosing cholangitis Gastroenterology 2014; 146: 970– 979.e6 42 European Association for the Study of the Liver, Asociacion Latinoamericana para el Estudio del Higado EASL–ALEH Clinical Practice Guidelines: non invasive tests for evaluation of liver disease severity and prognosis J Hepatol 2015; 63: 237–264 43 Vesterhus M, Hov JR, Holm A et al Enhanced liver fibrosis score predicts transplant free survival in primary sclerosing cholangitis Hepatology 2015; 62: 188–197 44 Ponsioen CY, Chapman RW, Chazouillères O et al Surrogate endpoints for clinical trials in primary sclerosing cholangitis: review and results from an International PSC Study Group consensus process Hepatology 2016; 63: 1357–1367 45 Olsson R, Boberg KM, de Muckadell OS et al High dose ursodeoxycholic acid in primary sclerosing cholangitis: a year multicenter, randomized, controlled study Gastroenterology 2005; 129: 1464–1472 46 Poropat G, Giljaca V, Stimac D et al Bile acids for primary sclerosing cholangitis Cochrane Database Syst Rev 2011; (1): 961 CD003626 47 Carey EJ, Lindor KD Chemoprevention of colorectal cancer with ursodeoxycholic acid: cons Clin Res Hepatol Gastroenterol 2012; 36(Suppl 1): S61–S64 48 Lindor KD, Kowdley KV, Luketic VA et al High dose ursodeoxycholic acid for the treatment of primary sclerosing cholangitis Hepatology 2009; 50: 808–814 49 Chapman R Genome wide association studies in primary sclerosing cholangitis: still more questions than answers? Hepatology 2011; 53: 2133–2135 50 European Association for the Study of the Liver EASL Clinical Practice Guidelines: management of cholestatic liver diseases J Hepatol 2009; 51: 237–267 51 Lindor KD, Kowdley KV, Harrison ME ACG Clinical Guideline: primary sclerosing cholangitis Am J Gastroenterol 2015; 110: 646– 659; quiz 660 52 Lazaridis KN, LaRusso NF Primary sclerosing cholangitis N Engl J Med 2016; 375: 1161–1170 53 Tabibian JH, Talwalkar JA, Lindor KD Role of the microbiota and antibiotics in primary sclerosing cholangitis BioMed Res Int 2013; 2013: 389537 54 Farkkila M, Karvonen AL, Nurmi H et al Metronidazole and ursodeoxycholic acid for primary sclerosing cholangitis: a randomized placebo controlled trial Hepatology 2004; 40: 1379– 1386 55 Rahimpour S, Nasiri Toosi M, Khalili H et al A triple blinded, randomized, placebo controlled clinical trial to evaluate the efficacy and safety of oral vancomycin in primary sclerosing cholangitis: a pilot study J Gastrointest Liver Dis 2016;25: 457– 464 56 Chapman R, Fevery J, Kalloo A et al Diagnosis and management of primary sclerosing cholangitis Hepatology 2010; 51: 660–678 962 57 Zenouzi R, Weismuller TJ, Jorgensen KK et al No evidence that azathioprine increases risk of cholangiocarcinoma in patients with primary sclerosing cholangitis Clin Gastroenterol Hepatol 2016; 14: 1806–12 58 Hommes DW, Erkelens W, Ponsioen C et al A double blind, placebo controlled, randomized study of infliximab in primary sclerosing cholangitis J Clin Gastroenterol 2008; 42: 522–526 59 Meszaros M, Pageaux GP, Altwegg R Management of ulcerative colitis using vedolizumab after liver transplantation for primary sclerosing cholangitis J Crohn’s Colitis 2016; 10: 236 60 Stine JG, Wang J, Behm BW Chronic cholestatic liver injury attributable to vedolizumab J Clin Trans Hepatol 2016; 4: 277– 280 61 Beuers U, Kremer AE, Bolier R et al Pruritus in cholestasis – facts and fiction Hepatology 2014; 60: 399–407 62 Bergquist A, Glaumann H, Persson B et al Risk factors and clinical presentation of hepatobiliary carcinoma in patients with primary sclerosing cholangitis: a case–control study Hepatology 1998; 27: 311–316 63 Charatcharoenwitthaya P, Enders FB, Halling KC et al Utility of serum tumor markers, imaging, and biliary cytology for detecting cholangiocarcinoma in primary sclerosing cholangitis Hepatology 2008; 48: 1106–1117 64 Folseraas T, Boberg KM Cancer risk and surveillance in primary sclerosing cholangitis Clin Liver Dis 2016; 20: 79–98 65 Trikudanathan G, Navaneethan U, Njei B et al Diagnostic yield of bile duct brushings for cholangiocarcinoma in primary sclerosing cholangitis: a systematic review and meta analysis Gastrointest Endosc 2014; 79: 783–789 66 Moreno Luna LE, Kipp B, Halling KC et al Advanced cytologic techniques for the detection of malignant pancreatobiliary strictures Gastroenterology 2006; 131: 1064–1072 67 Timmer MR, Lau CT, Meijer SL et al Genetic abnormalities in 963 biliary brush samples for distinguishing cholangiocarcinoma from benign strictures in primary sclerosing cholangitis Gastroenterol Res Pract 2016; 2016: 4381513 68 Mansour JC, Aloia TA, Crane CH et al Hilar cholangiocarcinoma: expert consensus statement HPB (Oxford) 2015; 17: 691–699 69 Razumilava N, Gores GJ, Lindor KD Cancer surveillance in patients with primary sclerosing cholangitis Hepatology 2011; 54: 1842–1852 70 Annese V, Daperno M, Rutter MD et al European evidence based consensus for endoscopy in inflammatory bowel disease J Crohn’s Colitis 2013; 7: 982–1018 71 Kaminski MF, Hassan C, Bisschops R et al Advanced imaging for detection and differentiation of colorectal neoplasia: European Society of Gastrointestinal Endoscopy (ESGE) Guideline Endoscopy 2014; 46: 435–449 72 Claessen MM, Vleggaar FP, Tytgat KM et al High lifetime risk of cancer in primary sclerosing cholangitis J Hepatol 2009; 50: 158– 164 73 Fosby B, Melum E, Bjoro K et al Liver transplantation in the Nordic countries – An intention to treat and post transplant analysis from the Nordic Liver Transplant Registry 1982–2013 Scand J Gastroenterol 2015; 50: 797–808 74 Andersen IM, Fosby B, Boberg KM et al Indications and outcomes in liver transplantation in patients with primary sclerosing cholangitis in Norway Transplantation Direct 2015; 1(9): e39 75 Boberg KM, Jebsen P, Clausen OP et al Diagnostic benefit of biliary brush cytology in cholangiocarcinoma in primary sclerosing cholangitis J Hepatol 2006; 45: 568–574 76 Graziadei IW, Wiesner RH, Batts KP et al Recurrence of primary sclerosing cholangitis following liver transplantation Hepatology 1999; 29: 1050–1056 964 77 Fosby B, Karlsen TH, Melum E Recurrence and rejection in liver transplantation for primary sclerosing cholangitis World J Gastroenterol 2012; 18: 1–15 78 Alabraba E, Nightingale P, Gunson B et al A re evaluation of the risk factors for the recurrence of primary sclerosing cholangitis in liver allografts Liver Transpl 2009;15: 330–340 79 Hildebrand T, Pannicke N, Dechene A et al Biliary strictures and recurrence after liver transplantation for primary sclerosing cholangitis: a retrospective multicenter analysis Liver Transpl 2016; 22: 42–52 80 Ravikumar R, Tsochatzis E, Jose S et al Risk factors for recurrent primary sclerosing cholangitis after liver transplantation J Hepatol 2015; 63: 1139–1146 81 Sint Nicolaas J, de Jonge V, Steyerberg EW et al Risk of colorectal carcinoma in post liver transplant patients: a systematic review and meta analysis Am J Transplant 2010; 10: 868–876 82 Jorgensen KK, Grzyb K, Lundin KE et al Inflammatory bowel disease in patients with primary sclerosing cholangitis: clinical characterization in liver transplanted and nontransplanted patients Inflamm Bowel Dis 2012; 18: 536–545 83 Abdalian R, Heathcote EJ Sclerosing cholangitis: a focus on secondary causes Hepatology 2006; 44: 1063–1074 84 Kirchner GI, Rummele P Update on sclerosing cholangitis in critically ill patients Viszeralmedizin 2015; 31: 178–184 85 Kwan KE, Shelat VG, Tan CH Recurrent pyogenic cholangitis: a review of imaging findings and clinical management Abdom Radiol (NY) 2017; 42: 46–56 86 Gudnason HO, Bjornsson HK, Gardarsdottir M et al Secondary sclerosing cholangitis in patients with drug induced liver injury Dig Liver Dis 2015; 47: 502–507 87 Maillette de Buy Wenniger L, Rauws EA, Beuers U What an endoscopist should know about immunoglobulin G4 associated disease of the pancreas and biliary tree Endoscopy 2012; 44: 66– 965 73 88 Masamune A, Nishimori I, Kikuta K et al Randomised controlled trial of long term maintenance corticosteroid therapy in patients with autoimmune pancreatitis Gut 2017; 66: 487–494 89 Moon SH, Kim MH, Park DH et al IgG4 immunostaining of duodenal papillary biopsy specimens may be useful for supporting a diagnosis of autoimmune pancreatitis Gastrointest Endosc 2010; 71: 960–966 90 Doorenspleet ME, Hubers LM, Culver EL et al Immunoglobulin G4+ B cell receptor clones distinguish immunoglobulin G4 related disease from primary sclerosing cholangitis and biliary/pancreatic malignancies Hepatology 2016; 64: 501–507 91 Boonstra K, Culver EL, de Buy Wenniger LM et al Serum immunoglobulin G4 and immunoglobulin G1 for distinguishing immunoglobulin G4 associated cholangitis from primary sclerosing cholangitis Hepatology 2014; 59: 1954–1963 966 ... antivirals and immunosuppressants List of Illustrations Chapter 01 Fig 1. 1 Anterior view of the liver Fig 1. 2 Posterior view of the liver Fig 1. 3 Inferior view of the liver Fig 1. 4 The sectors of the. .. hepatic veins and portal veins are intertwined as the fingers of two hands [6] Fig 1. 6 Gallbladder and biliary tract Fig 1. 7 The surface marking of the liver Fig 1. 8 Surface markings of the gallbladder... 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