Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_47_библиотеки_им_акад_М_И_Перельмана
.pdf
386
3. Broussolle E, Trocello JM, Woimant F, Lachaux A, Quinn N.Samuel Alexander Kinnier Wilson.
Wilson’s disease, Queen Square and neurology. Rev Neurol. 2013 Dec;169(12):927–35.
4. Ferenci P, Ott P.Wilson’s disease: fatal when overlooked, curable when diagnosed. J Hepatol.
2019 Jul;71(1):222–4.
5. Scheinberg IH, Sternlieb I.Wilson disease and idiopathic copper toxicosis. Am J Clin Nutr.
1996 May;63(5):842S–5S.
6. Sternlieb I, Scheinberg IH.Radiocopper in diagnosing liver disease. Semin Nucl Med. 1972
Apr;2(2):176–88.
7. Hellman NE, Gitlin JD. Ceruloplasmin metabolism and function. Annu Rev Nutr.
2002;22:439–58.
8. Knopfel M, Solioz M. Characterization of a cytochrome b(558) ferric/cupric reductase
from rabbit duodenal brush border membranes. Biochem Biophys Res Commun. 2002 Feb
22;291(2):220–5.
9. Ohgami RS, Campagna DR, McDonald A, Fleming MD.The Steap proteins are metalloreduc-
tases. Blood. 2006 Aug 15;108(4):1388–94.
10. Lee J, Pena MM, Nose Y, Thiele DJ.Biochemical characterization of the human copper trans-
porter Ctr1. J Biol Chem. 2002 Feb 8;277(6):4380–7.
11. Molloy SA, Kaplan JH.Copper-dependent recycling of hCTR1, the human high afnity cop-
per transporter. J Biol Chem. 2009 Oct 23;284(43):29704–13.
12. Petris MJ, Smith K, Lee J, Thiele DJ.Copper-stimulated endocytosis and degradation of the
human copper transporter, hCtr1. J Biol Chem. 2003 Mar 14;278(11):9639–46.
13. Clifford RJ, Maryon EB, Kaplan JH.Dynamic internalization and recycling of a metal ion
transporter: cu homeostasis and CTR1, the human cu(+) uptake system. J Cell Sci. 2016 Apr
15;129(8):1711–21.
14. Lutsenko S, Barnes NL, Bartee MY, Dmitriev OY.Function and regulation of human copper-
transporting ATPases. Physiol Rev. 2007 Jul;87(3):1011–46.
15. Harrison MD, Jones CE, Dameron CT. Copper chaperones: function, structure and copper-
binding properties. J Biol Inorg Chem. 1999 Apr;4(2):145–53.
16. La Fontaine S, Mercer JF.Trafcking of the copper-ATPases, ATP7A and ATP7B: role in cop-
per homeostasis. Arch Biochem Biophys. 2007 Jul 15;463(2):149–67.
17. Vairo FPE, Chwal BC, Perini S, Ferreira MAP, de Freitas Lopes AC, Saute JAM.A system-
atic review and evidence-based guideline for diagnosis and treatment of Menkes disease. Mol
Genet Metab. 2019 Jan;126(1):6–13.
18. Greenough M, Pase L, Voskoboinik I, Petris MJ, O’Brien AW, Camakaris J.Signals regulat-
ing trafcking of Menkes (MNK; ATP7A) copper-translocating P-type ATPase in polarized
MDCK cells. Am J Physiol Cell Physiol. 2004 Nov;287(5):C1463–71.
19. Nyasae L, Bustos R, Braiterman L, Eipper B, Hubbard A.Dynamics of endogenous ATP7A
(Menkes protein) in intestinal epithelial cells: copper-dependent redistribution between two
intracellular sites. Am J Physiol Gastrointest Liver Physiol. 2007 Apr;292(4):G1181–94.
20. Veldhuis NA, Gaeth AP, Pearson RB, Gabriel K, Camakaris J.The multi-layered regulation of
copper translocating P-type ATPases. Biometals. 2009 Feb;22(1):177–90.
21. Kim BE, Nevitt T, Thiele DJ.Mechanisms for copper acquisition, distribution and regulation.
Nat Chem Biol. 2008 Mar;4(3):176–85.
22. Liu N, Lo LS, Askary SH, Jones L, Kidane TZ, Trang T, etal. Transcuprein is a macroglobulin
regulated by copper and iron availability. J Nutr Biochem. 2007 Sep;18(9):597–608.
23. Moriya M, Ho YH, Grana A, Nguyen L, Alvarez A, Jamil R, et al. Copper is taken up ef-
ciently from albumin and alpha2-macroglobulin by cultured human cells by more than one
mechanism. Am J Physiol Cell Physiol. 2008 Sep;295(3):C708–21.
24. Prohaska JR. Role of copper transporters in copper homeostasis. Am J Clin Nutr. 2008
Sep;88(3):826S–9S.
25. Carr HS, Winge DR.Assembly of cytochrome c oxidase within the mitochondrion. Acc Chem
Res. 2003 May;36(5):309–16.
N. V. Bergasa
https://t.me/medicina_free
387
26. Schaefer M, Hopkins RG, Failla ML, Gitlin JD. Hepatocyte-specic localization and
copper-dependent trafcking of the Wilson's disease protein in the liver. Am J Phys. 1999
Mar;276(3):G639–46.
27. Kelly EJ, Palmiter RD.A murine model of Menkes disease reveals a physiological function of
metallothionein. Nat Genet. 1996 Jun;13(2):219–22.
28. Bull PC, Thomas GR, Rommens JM, Forbes JR, Cox DW. The Wilson disease gene is a
putative copper transporting P-type ATPase similar to the Menkes gene. Nat Genet. 1993
Dec;5(4):327–37.
29. Petrukhin K, Fischer SG, Pirastu M, Tanzi RE, Chernov I, Devoto M, etal. Mapping, cloning
and genetic characterization of the region containing the Wilson disease gene. Nat Genet. 1993
Dec;5(4):338–43.
30. Tanzi RE, Petrukhin K, Chernov I, Pellequer JL, Wasco W, Ross B, etal. The Wilson disease
gene is a copper transporting ATPase with homology to the Menkes disease gene. Nat Genet.
1993 Dec;5(4):344–50.
31. Davies LP, Macintyre G, Cox DW. New mutations in the Wilson disease gene, ATP7B: impli-
cations for molecular testing. Genet Test. 2008;12(1):139–45.
32. Ferenci P.Regional distribution of mutations of the ATP7B gene in patients with Wilson dis-
ease: impact on genetic testing. Hum Genet. 2006 Sep;120(2):151–9.
33. Merle U, Weiss KH, Eisenbach C, Tuma S, Ferenci P, Stremmel W.Truncating mutations in
the Wilson disease gene ATP7B are associated with very low serum ceruloplasmin oxidase
activity and an early onset of Wilson disease. BMC Gastroenterol. 2010 Jan 18;10:8.
34. Thomas GR, Forbes JR, Roberts EA, Walshe JM, Cox DW.The Wilson disease gene: spectrum
of mutations and their consequences. Nat Genet. 1995 Feb;9(2):210–7.
35. Shah AB, Chernov I, Zhang HT, Ross BM, Das K, Lutsenko S, etal. Identication and anal-
ysis of mutations in the Wilson disease gene (ATP7B): population frequencies, genotype-
phenotype correlation, and functional analyses. Am J Hum Genet. 1997 Aug;61(2):317–28.
36. Kegley KM, Sellers MA, Ferber MJ, Johnson MW, Joelson DW, Shrestha R. Fulminant
Wilson's disease requiring liver transplantation in one monozygotic twin despite identical
genetic mutation. Am J Transplant. 2010 May;10(5):1325–9.
37. Gromadzka G, Rudnicka M, Chabik G, Przybylkowski A, Czlonkowska A.Genetic variabil-
ity in the methylenetetrahydrofolate reductase gene (MTHFR) affects clinical expression of
Wilson's disease. J Hepatol. 2011 Oct;55(4):913–9.
38. Schiefermeier M, Kollegger H, Madl C, Polli C, Oder W, Kuhn H, etal. The impact of apo-
lipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson's
disease. Brain. 2000 Mar;123(Pt 3):585–90.
39. Gu M, Cooper JM, Butler P, Walker AP, Mistry PK, Dooley JS, etal. Oxidative-phosphorylation
defects in liver of patients with Wilson's disease. Lancet. 2000 Aug 5;356(9228):469–74.
40. Mordaunt CE, Kieffer DA, Shibata NM, Czlonkowska A, Litwin T, Weiss KH, et al.
Epigenomic signatures in liver and blood of Wilson disease patients include hypermethylation
of liver-specic enhancers. Epigenetics Chromatin. 2019 Feb 1;12(1):10.
41. Scheinberg IHaS, I.Wilson’s disease. Philadelphia: W B Saunders; 1984.
42. Coffey AJ, Durkie M, Hague S, McLay K, Emmerson J, Lo C, etal. A genetic study of Wilson’s
disease in the United Kingdom. Brain. 2013 May;136(Pt 5):1476–87.
43. Ohura T, Abukawa D, Shiraishi H, Yamaguchi A, Arashima S, Hiyamuta S, etal. Pilot study of
screening for Wilson disease using dried blood spots obtained from children seen at outpatient
clinics. J Inherit Metab Dis. 1999 Feb;22(1):74–80.
44. Hahn SH, Lee SY, Jang YJ, Kim SN, Shin HC, Park SY, etal. Pilot study of mass screening for
Wilson’s disease in Korea. Mol Genet Metab. 2002 Jun;76(2):133–6.
45. Sandahl TD, Laursen TL, Munk DE, Vilstrup H, Weiss KH, Ott P.The prevalence of Wilson
disease. An update. Hepatology. 2019 Aug 26.
46. Pster ED, Karch A, Adam R, Polak WG, Karam V, Mirza D, etal. Predictive factors for sur-
vival in children receiving liver transplants for Wilson's disease: a cohort study using European
liver transplant registry data. Liver Transpl. 2018 Sep;24(9):1186–98.
12
Wilson’s Disease
https://t.me/medicina_free
388
47. Walshe JM.Wilson’s disease; new oral therapy. Lancet. 1956 Jan 7;270(6906):25–6.
48. Walshe JM.Cause of death in Wilson disease. Mov Disord. 2007 Nov 15;22(15):2216–20.
49. Walshe JM.Wilson’s disease presenting with features of hepatic dysfunction: a clinical analy-
sis of eighty-seven patients. Q J Med. 1989 Mar;70(263):253–63.
50. Gollan JL, Gollan TJ.Wilson disease in 1998: genetic, diagnostic and therapeutic aspects. J
Hepatol. 1998;28(Suppl 1):28–36.
51. Bearn AG, Mc KV.Azure lunulae; an unusual change in the ngernails in two patients with
hepatolenticular degeneration (Wilson’s disease). J Am Med Assoc. 1958 Feb 22;166(8):904–6.
52. Harry J, Tripathi R. Kayser-Fleischer ring. A pathological study. Br J Ophthalmol. 1970
Dec;54(12):794–800.
53. Steindl P, Ferenci P, Dienes HP, Grimm G, Pabinger I, Madl C, etal. Wilson’s disease in
patients presenting with liver disease: a diagnostic challenge. Gastroenterology. 1997
Jul;113(1):212–8.
54. Litwin T, Langwinska-Wosko E, Dziezyc K, Czlonkowska A.Sunower cataract: do not forget
Wilson’s disease. Pract Neurol. 2015 Oct;15(5):385–6.
55. Langwinska-Wosko E, Litwin T, Dziezyc K, Czlonkowska A.The sunower cataract in Wilson’s
disease: pathognomonic sign or rare nding? Acta Neurol Belg. 2016 Sep;116(3):325–8.
56. Machado A, Chien HF, Deguti MM, Cancado E, Azevedo RS, Scaff M, etal. Neurological
manifestations in Wilson’s disease: report of 119 cases. Mov Disord. 2006 Dec;21(12):2192–6.
57. Soltanzadeh A, Soltanzadeh P, Nassi S, Ghorbani A, Sikaroodi H, Lot J.Wilson’s disease: a
great masquerader. Eur Neurol. 2007;57(2):80–5.
58. Zimbrean PC, Schilsky ML. Psychiatric aspects of Wilson disease: a review. Gen Hosp
Psychiatry. 2014 Jan-Feb;36(1):53–62.
59. Ferenci P, Czlonkowska A, Merle U, Ferenc S, Gromadzka G, Yurdaydin C, etal. Late-onset
Wilson’s disease. Gastroenterology. 2007 Apr;132(4):1294–8.
60. Kim JW, Kim JH, Seo JK, Ko JS, Chang JY, Yang HR, etal. Genetically conrmed Wilson
disease in a 9-month old boy with elevations of aminotransferases. World J Hepatol. 2013 Mar
27;5(3):156–9.
61. Jones EA, Clain D, Clink HM, MacGillivray M, Sherlock S.Hepatic coma due to acute hepatic
necrosis treated by exchange blood-transfusion. Lancet. 1967 Jul 22;2(7508):169–72.
62. Ritt DJ, Whelan G, Werner DJ, Eigenbrodt EH, Schenker S, Combes B.Acute hepatic necrosis
with stupor or coma. An analysis of thirty-one patients. Medicine. 1969 Mar;48(2):151–72.
63. Jones EA, Bergasa NV. Fulminant hepatic failure. In: Taylor RW, Shoemaker WC, editors.
Critical care state of the art Fullerton. Fullerton, CA: The Society of Critical Care Medicine;
1991. p.509–39.
64. Lee WM, Squires RH Jr, Nyberg SL, Doo E, Hoofnagle JH.Acute liver failure: summary of a
workshop. Hepatology. 2008 Apr;47(4):1401–15.
65. Nazer H, Ede RJ, Mowat AP, Williams R.Wilson’s disease: clinical presentation and use of
prognostic index. Gut. 1986 Nov;27(11):1377–81.
66. Dhawan A, Taylor RM, Cheeseman P, De Silva P, Katsiyiannakis L, Mieli-Vergani G.Wilson’s
disease in children: 37-year experience and revised King's score for liver transplantation. Liver
Transpl. 2005 Apr;11(4):441–8.
67. Korman JD, Volenberg I, Balko J, Webster J, Schiodt FV, Squires RH Jr, etal. Screening
for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests.
Hepatology. 2008 Oct;48(4):1167–74.
68. Ishak KG.Metabolic errors and liver disease. In: Roderick NM, MacSween PPA, Scheuer PJ,
Burt AD, Portmann BC, editors. Pathology of the liver. Edinburgh: Churchill Livingstone;
1994. p.123–218.
69. Sternlieb I, Feldmann G. Effects of anticopper therapy on hepatocellular mitochondria in
patients with Wilson’s disease: an ultrastructural and stereological study. Gastroenterology.
1976 Sep;71(3):457–61.
70. European Association for Study of L.EASL clinical practice guidelines: Wilson’s disease. J
Hepatol. 2012 Mar;56(3):671–85.
N. V. Bergasa
https://t.me/medicina_free
389
71. Roberts EA, Schilsky ML.American Association for Study of liver D. diagnosis and treatment
of Wilson disease: an update. Hepatology. 2008 Jun;47(6):2089–111.
72. Prashanth LK, Sinha S, Taly AB, Vasudev MK.Do MRI features distinguish Wilson’s disease
from other early onset extrapyramidal disorders? An analysis of 100 cases. Mov Disord. 2010
Apr 30;25(6):672–8.
73. Litwin T, Dziezyc K, Poniatowska R, Czlonkowska A.Effect of liver transplantation on brain
magnetic resonance imaging pathology in Wilson disease: a case report. Neurol Neurochir Pol.
2013 Jul-Aug;47(4):393–7.
74. Poujois A, Woimant F.Wilson’s disease: a 2017 update. Clin Res Hepatol Gastroenterol. 2018
Dec;42(6):512–20.
75. Ludwig J, Moyer TP, Rakela J.The liver biopsy diagnosis of Wilson’s disease. Methods in
pathology. Am J Clin Pathol. 1994 Oct;102(4):443–6.
76. Ferenci P, Caca K, Loudianos G, Mieli-Vergani G, Tanner S, Sternlieb I, etal. Diagnosis and
phenotypic classication of Wilson disease. Liver Int. 2003 Jun;23(3):139–42.
77. Nicastro E, Ranucci G, Vajro P, Vegnente A, Iorio R. Re-evaluation of the diagnos-
tic criteria for Wilson disease in children with mild liver disease. Hepatology. 2010
Dec;52(6):1948–56.
78. Sternlieb I.Wilson’s disease and pregnancy. Hepatology. 2000 Feb;31(2):531–2.
79. Brewer GJ, Johnson VD, Dick RD, Hedera P, Fink JK, Kluin KJ.Treatment of Wilson’s dis-
ease with zinc. XVII: treatment during pregnancy. Hepatology. 2000 Feb;31(2):364–70.
80. Brewer GJ.Zinc and tetrathiomolybdate for the treatment of Wilson’s disease and the potential
efcacy of anticopper therapy in a wide variety of diseases. Metallomics. 2009;1(3):199–206.
81. Bandmann O, Weiss KH, Kaler SG.Wilson’s disease and other neurological copper disorders.
Lancet Neurol. 2015 Jan;14(1):103–13.
82. Nishito Y, Kambe T.Absorption mechanisms of iron, copper, and zinc: an overview. J Nutr Sci
Vitaminol. 2018;64(1):1–7.
83. Weiss KH, Thurik F, Gotthardt DN, Schafer M, Teufel U, Wiegand F, etal. Efcacy and safety
of oral chelators in treatment of patients with Wilson disease. Clin Gastroenterol Hepatol.
2013 Aug;11(8):1028–35 e1-2.
84. Brewer GJ, Askari F, Dick RB, Sitterly J, Fink JK, Carlson M, etal. Treatment of Wilson’s
disease with tetrathiomolybdate: V. control of free copper by tetrathiomolybdate and a com-
parison with trientine. Transl Res. 2009 Aug;154(2):70–7.
85. Linn FH, Houwen RH, van Hattum J, van der Kleij S, van Erpecum KJ.Long-term exclusive
zinc monotherapy in symptomatic Wilson disease: experience in 17 patients. Hepatology. 2009
Nov;50(5):1442–52.
86. Weiss KH, Gotthardt DN, Klemm D, Merle U, Ferenci-Foerster D, Schaefer M, et al.
Zinc monotherapy is not as effective as chelating agents in treatment of Wilson disease.
Gastroenterology. 2011 Apr;140(4):1189–98 e1.
87. Iorio R, D’Ambrosi M, Marcellini M, Barbera C, Maggiore G, Zancan L, etal. Serum transam-
inases in children with Wilson’s disease. J Pediatr Gastroenterol Nutr. 2004 Oct;39(4):331–6.
88. Brewer GJ, Dick RD, Yuzbasiyan-Gurkin V, Tankanow R, Young AB, Kluin KJ.Initial therapy
of patients with Wilson’s disease with tetrathiomolybdate. Arch Neurol. 1991 Jan;48(1):42–7.
89. Brewer GJ, Dick RD, Johnson V, Wang Y, Yuzbasiyan-Gurkan V, Kluin K, etal. Treatment of
Wilson’s disease with ammonium tetrathiomolybdate. I.Initial therapy in 17 neurologically
affected patients. Arch Neurol. 1994 Jun;51(6):545–54.
90. Dziezyc K, Karlinski M, Litwin T, Czlonkowska A. Compliant treatment with anti-copper
agents prevents clinically overt Wilson’s disease in pre-symptomatic patients. Eur J Neurol.
2014 Feb;21(2):332–7.
91. Walshe JM, Dixon AK. Dangers of non-compliance in Wilson’s disease. Lancet. 1986 Apr
12;1(8485):845–7.
92. Holscher S, Leinweber B, Hefter H, Reuner U, Gunther P, Weiss KH, et al. Evaluation of
the symptomatic treatment of residual neurological symptoms in Wilson disease. Eur Neurol.
2010;64(2):83–7.
12
Wilson’s Disease
https://t.me/medicina_free
390
93. van Meer S, de Man RA, van den Berg AP, Houwen RH, Linn FH, van Oijen MG, etal. No
increased risk of hepatocellular carcinoma in cirrhosis due to Wilson disease during long-term
follow-up. J Gastroenterol Hepatol. 2015 Mar;30(3):535–9.
94. Pfeiffenberger J, Mogler C, Gotthardt DN, Schulze-Bergkamen H, Litwin T, Reuner U, etal.
Hepatobiliary malignancies in Wilson disease. Liver Int. 2015 May;35(5):1615–22.
95. Ferrarese A, Morelli MC, Carrai P, Milana M, Angelico M, Perricone G, etal. Outcomes of
liver transplant for adults with Wilson’s disease. Liver Transpl. 2020 Jan;4
96. Guillaud O, Dumortier J, Sobesky R, Debray D, Wolf P, Vanlemmens C, et al. Long term
results of liver transplantation for Wilson’s disease: experience in France. J Hepatol. 2014
Mar;60(3):579–89.
97. Garoufalia Z, Prodromidou A, Machairas N, Kostakis ID, Stamopoulos P, Zavras N, etal. Liver
transplantation for Wilson’s disease in non-adult patients: a systematic review. Transplant
Proc. 2019 Mar;51(2):443–5.
N. V. Bergasa
https://t.me/medicina_free
391© The Author(s), under exclusive license to Springer-Verlag London Ltd., part
of Springer Nature 2022
N. V. Bergasa (ed.), Clinical Cases in Hepatology,
https://doi.org/10.1007/978-1-4471-4715-2_13
Chapter 13
Tumors oftheLiver
NoraV.Bergasa
A 46-year-old man was referred to the hepatology clinic because of a liver mass
found on a liver sonogram to investigate right upper quadrant pain. The patient did
not have comorbidities. At the visit, the patient reported that the pain had resolved
itself spontaneously. The physical exam and the hepatic panel were normal.
Magnetic resonance imaging (MRI) to evaluate the mass further revealed nd-
ingsconsistent with a hemangioma (Fig.
13.1). The patient is doing well.
Patients may be referred to hepatology for the evaluation of liver tumors often
found incidentally through liver imaging studies for indications not related to sus-
pected liver disease [1]. This chapter introduces the general approach topatients
with liver tumors, which maynot include therapeutic intervention or mayrequire
aggressive diagnostic evaluation and treatment.
In the absence of liver disease, a liver lesion found in a patient incidentally has a
high probability of being benign. The most common are liver cysts, hemangiomata,
and focal nodular hyperplasia [2]. In contrast, in a patient with cancer, a liver mass
may be a metastasis from extrahepatic malignancy, in a patient with cirrhosis, hepa-
tocellular carcinoma (HCC) has to be excluded [
3], in patients with primary scleros-
ing cholangitis, a mass may be from cholangiocarcinoma (CCA) [4]. Thus, knowing
the context in which a mass develops in the liver is fundamental to creating an
investigational plan.
The radiographic characteristics of liver lesions can help in developing an inves-
tigational plan. The uid inside a liver lesion may be revealing of a cyst or abscess;
the features of blood ow into the mass can be diagnostic for HCC [3].
N. V. Bergasa (*)
Department of Medicine, H+H/Metropolitan, New York, NY, USA
New York Medical College, Valhalla, NY, USA
Hepatology, H+H/Woodhull, Brooklyn, NY, USA
https://t.me/medicina_free
392
Simple Hepatic Cysts
The prevalence of simple liver cysts in the general population has been reported in
the range of 2.5–18% [5–8], and they aremore common in women than in men.
Although many hepatic cysts are not associated with symptoms, if they are large,
abdominal pain, a palpable mass, and hepatomegaly are documented [9, 10].
Gamma-glutamyl transpeptidase (GGTP) has been reported as high in some series
[11], but, in general, the serum liver prole tends to normalin association with liver
cysts. On liver sonogram, simple cysts are seen as anechoic spaces, lled with uid
[5–8]. MRI reveals hepatic cysts as water-lled, well-dened lesions that do not
enhance in association with intravenous gadolinium-based contrast agents.
Congenital hepatic cysts tend to occur in the right hepatic lobe most commonly and
arise from biliary ducts not communicating with the biliary system [11].
Histologically, the epithelium of hepatic cysts is most frequently cuboidal [9]. Most
liver cysts are not associated with complications; however, serious complications
have been documented from large cysts. They include hemorrhage, rupture into the
abdominal cavity or bile duct, infection, and cholestasis from compression of bile
ducts [11]. Treatment consists of aspiration, which is associated with recurrence of
the cyst in most cases, or surgical resection, including cyst fenestration and excision.
Polycystic Liver Disease
Patients with polycystic kidney disease may have liver cysts; however, isolated
polycystic liver disease (PCLD) is a condition separate from polycystic kidney dis-
ease and is not associated with renal cysts or cerebral aneurysms [12].
PCLD is dominantly inherited. It is dened as the presence of more than 20 cysts
in the liver [12].
Fig. 13.1 An axial T2
weighted magnetic
resonance image from a 46
year old man showing a
lobular mass of increased
signal intensity in the right
hepatic lobe (arrow)
indicative of stagnant
blood ow consistent with
a hemangioma.
N. V. Bergasa
https://t.me/medicina_free
393
PCLD is associated with germline mutations in the PRKCSH gene, which codes
for hepatocystin. In association with the mutation, hepatocystin does not assemble
with the glucosidase II alpha subunit, thus, it was suggested that altered endoplas-
mic reticulum processing in the regulation of cell proliferation may contribute to the
pathogenesis of this disease [13].
Mutations in the SEC63 gene, which codes for a component of the protein trans-
location machinery in the endoplasmic reticulum (ER) are also associated with
PLD.These ndings were interpreted to suggest that the cotranslational protein-
processing pathways are fundamental in maintaining the epithelial luminal structure
and implicate noncilial ER proteins in human polycystic disease [14].
Heterozygous loss-of-function mutations were identied in ALG8, GANAB, and
SEC61B, which encode fundamental proteins in the biogenesis pathway of the
endoplasmic reticulum. The inactivation of these genes invitro was associated with
defective maturation and trafcking of polycystin-1, considered a fundamental fac-
tor in cyst pathogenesis [15].
Liver cysts can grow leading to symptoms including pain, and early satiety, or
may becomplicated by infection or intraluminal bleeding, which are indications for
treatment [12].
Somatostatin analogs decrease cAMP, suppressing bile duct proliferation, and
inhibit the production of certain growth factors [12]. In this group,lanreotide was
reported to reduce the volume of polycystic liver in a placebo-controlled study;
however, the reduction was small and it is recommended for patients in whom risk
factors impede surgical intervention [12]. Surgical treatment includes fenestration,
usually done laparoscopically, and liver resection, which may be required in cases
of multiple small cysts difcult to fenestrate [12]. The combination of cyst fenestra-
tion and hepatic resection was associated with improvement in the quality of life in
a prospective study from the United States between 2014 and 2018 that included
eighteen patients [16]. In extreme cases, liver transplantation is an alternative, if
liver function is predicted to be poor from resection [12]. The reported estimated
survival at 1 and 5years was calculated as 93% and 92%, respectively, for patients
undergoing liver transplantation [12].
Hydadtic Cysts
Echinococcal infection is a cause of hepatic cysts. Echinococcosis is a zoonotic
infection caused by the ingestion of the larvae of the cestode species of the genus
Echinococcus [17, 18]. The liver is one of the most commonly affected organs, in
which it manifests as cystic lesions.
The incidence of human disease has been reported to exceed 50 per 100,000
person-years in areas where it is endemic, with a prevalence of 5–10% reported in
Peru, Argentina, east Africa, and China [19]. The prevalence of echinococcosis
increases with age, and the disease is more prevalent in women than in men.
13 Tumors oftheLiver
https://t.me/medicina_free
394
Cystic echinococcosis tends to occur in rural areas where sheep and other herbi-
vores live in proximity with dogs, which, like other carnivores, are denitive hosts.
Close contact between dogs and human beings is the reason for transmission, which
is fecal-oral by the accidental ingestion of eggs from dogs’ feces, e.g., contaminated
foodstuff [20]. Human beings are considered accidental or aberrant hosts, and they
are highly unlikely to be involved in disease transmission [18].
Carnivores, including dogs, are the denitive hosts, and herbivores, including
sheep, goats, and cattle, are intermediate hosts. They maintain the parasite by har-
boring the larval stage of the parasite named metacestode. The egg-producing stage
of the cestode happens in the small intestine of the denitive host, which carries
hundreds of egg-producing worms. The eggs are excreted in the stool of the deni-
tive host and are infective upon release. In the target organ, a hydatid cyst or meta-
cestode develops and from it, protoscolices bud from the germinal layer and grow
within the cyst. When the denitive host ingests these, they evaginate, attach them-
selves to the intestinal mucosae, and evolve to adults over weeks. Thousands of
protoscolices can bud from a single cyst, and each protoscolex can turn into an adult
worm when ingested by a denitive host. Secondary echinococcosis can occur when
uid from a cyst is spilled into a cavity, e.g., the abdominal cavity, leading to new
cyst formation. All mammals in which metacestodes develop act as intermediate
hosts; however, not all intermediate hosts can sustain the life cycle (Fig. 13.2).
Human beings are considered accidental hosts and are not considered to be able to
transmit the infection [18].
Most echinococcal cysts are single and tend to be located in the right lobe. Most
patients are asymptomatic and are often diagnosed incidentally by radiographic
studies (Fig.13.3). Rupture of this type of cyst can be associated with anaphylaxis,
stressing the importance of not aspirating liver cysts’ contents, in the absence of
absolute exclusion of an echinococcal etiology. Documented complications from
echinococcal cysts include communication of the hydatid cyst with luminal struc-
tures including the biliary tract [21], intestine, and bronchial tree, or compression of
their compression in cases of large cysts [18].
Diagnostic serology, the most common being ELISA, is reported as positive in
70% of the patients, with subsequent testing used for conrmation [22, 23].
Surgical excision is the standard treatment for hydatid cysts; medical therapy
with mebendazole or albendazole is an alternative. Small cysts and those not associ-
ated with complications can be watched over time. It is recommended to consult
local experts or liver centers prior to any intervention.
Liver Abscess
Liver abscesses tend to occur in the right lobe of the liver, from streaming via the
portal vein from intra-abdominal infections including appendicitis and diverticuli-
tis; however, a recent retrospective review reported that nearly half of the patients
identied did not have any comorbidities in association with their liver abscesses
N. V. Bergasa
https://t.me/medicina_free
395
[24]. Bacteremia and direct extension from the biliary tree in cholangitis can also
result in liver abscesses. A history of travel to areas where amebiasis is common is
fundamental in the diagnosis, as radiological features do not offer specic ndings
to differentiate bacterial versus amebic abscesses, for which specic antibiotic treat-
ment is required.
a
b
c
d
e
f
g
h
Fig. 13.2 The adult Echinococcus granulosus (a) lives in the small intestine of the denitive host
(dog). Gravid proglottids release eggs (b), which are infectious, and are fecally excreted. Eggs
hatch in the intestine of the intermediate host (i.e. human beings, cattle, sheep) and release six-
hooked oncospheres (c) that pierce the intestinal wall traveling through the vascular system to vari-
ous organs including liver and lungs, where the oncospheres develop into a thick-walled hydatid
cyst (d), which enlarges itself producing protoscolices and daughter cysts that occupy the cavity of
the the cyst (e and f). The denitive host is infected by ingesting the cyst-containing organs of an
infected intermediate host. After ingestion, the protoscolices with invaginated heads (g) evaginate
(h) and attach to the intestinal mucosa and mature to adulthood (a) in 32 to 80 days. Human beings
are aberrant intermediate hosts who get infected by ingesting eggs. Oncospheres are released in the
intestine and hydatid cysts develop in several organs, including the liver (Fig.13.3). Protoscolices
create secondary cysts in other parts of the body if the main cyst ruptures (Illustration by Martha
M.Dao, Graphic (+WEB) DesignMMD).
13
Tumors oftheLiver
https://t.me/medicina_free
Соседние файлы в папке Библиотека им академика М.И. Перельмана