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HEPATOMA (KARSINOMA HEPATOSELULER)

DEFINISI
Hepatoma (Karsinoma Hepatoseluler) adalah kanker yang berasal dari sel-sel
hati.

Hepatoma merupakan kanker hati primer yang paling sering ditemukan.


Karsinoma fibrolamelar merupakan jenis hepatoma yang jarang, yang
biasanya mengenai dewasa muda.
Penyebabnya bukan sirosis, infeksi hepatitis B atau C maupun faktor resiko
lain yang tidak diketahui.
PENYEBAB
Di daerah tertentu di Afrika dan Asia Tenggara, hepatoma lebih banyak
ditemukan dibandingkan dengan kanker hati metastatik dan merupakan
penyebab kematian yang utama.
Di daerah-daerah tersebut, terdapat angka kejadian infeksi hepatitis virus B
yang tinggi, yang meningkatkan resiko terjadinya hepatoma.
Infeksi menahun dari hepatitis C juga meningkatkan resiko terjadinya
hepatoma.
Bahan-bahan karsinogenik (penyebab kanker) tertentu juga menyebabkan
hepatoma.
Di daerah subtropis, dimana hepatoma banyak terjadi, makanan sering
tercemar oleh bahan karsinogenik yang disebut aflatoksin, yang dihasilkan
oleh sejenis jamur.
Di Amerika Utara, Eropa dan daerah lainnya dimana hepatoma jarang
ditemukan, sebagian besar penderita hepatoma adalah pecandu alkohol
dengan sirosis hati yang telah berlangsung lama.

Jenis sirosis lainnya juga berhubungan dengan hepatoma, tetapi sirosis bilier
primer memiliki resiko yang lebih rendah jika dibandingkan dengan sirosis
lainnya.
GEJALA
Biasanya gejala awal hepatoma adalah nyeri perut, penurunan berat badan
dan terdapatnya suatu masssa yang besar, yang dapat dirasakan/diraba di
perut kanan bagian atas.
Penderita yang sebelumnya menderita sirosis menahun, akan tampak sangat
sakit.
Pada umumnya terdapat demam.
Kadang gejala awalnya berupa nyeri perut akut dan syok, yang disebabkan
oleh pecahnya tumor atau perdarahan pada tumor
.
DIAGNOSA
Kadar alfa-fetoprotein darah pada penderita hepatoma tinggi.
Kadang pemeriksaan darah menunjukkan kadar gula darah yang rendah atau
peningkatan kadar kalsium, lemak atau sel darah merah.
Pada awalnya, gejala yang ada tidak cukup untuk mengarah pada diagnosis.
Tetapi jika teraba pembesaran hati, patut dicurigai suatu hepatoma, terutama
jika terdapat sirosis menahun.
Pada pemeriksaan dengan stetoskop, kadang terdengar suara bising (bruit
hepatik) dan suara gesekan (friction rubs).
USG dan CT Scan perut kadang dapat menemukan kanker yang belum
menimbulkan gejala.

Di beberapa negara, dimana banyak terdapat virus hepatitis B (misalnya di


Jepang), USG digunakan untuk menyaring penderita infeksi terhadap kanker
hati.
Arteriografi hepatik bisa menunjukkan hepatoma dan terutama dilakukan
sebelum pembedahan, untuk membantu menentukan lokasi yang pasti dari
pembuluh darah hati.
Biopsi jaringan hati dapat memperkuat diagnosis. Resiko terjadinya
perdarahan atau cedera lainnya pada saat melakukan biopsi pada umumnya
rendah.
PENGOBATAN
Kadang penderita dengan tumor yang kecil dapat sembuh dengan baik setelah
tumor diangkat melalui pembedahan.
Biasanya prognosis untuk hepatoma jelek karena tumor ditemukan pada
stadium lanjut.

HEPATOMA, THE SILENT KILLER


Netsains.Com Hepatoma atau Karsinoma hepatoseluler adalah tumor ganas
hati primer yang paling sering ditemukan daripada tumor ganas di hati
lainnya, seperti limfoma maligna, fibrosarkoma dan hemangioendotelioma.
Penyakit ini paling sering ditemukan di China dan kawasan Asia Tenggara.
Hepatoma selain sering menimbulkan gangguan faal pada hati, juga
membentuk beberapa jenis hormon yang dapat meningkatkan kadar
hemoglobin, kalsium, kolesterol dan alfa feto protein di dalam darah.
Gangguan faal hati menyebabkan peningkatan kadar SGOT, SGPT, fosfatase
alkali, laktat dehidrogenase, dan alfa L-fukosidase.
Pasien hepatoma 88% terinveksi virus hepatitis B atau C. Dan kedua virus ini
mempunyai hubungan yang erat dengan timbulnya hepatoma. Hepatoma
seringkali tidak terdiagnosis karena gejala karsinoma tertutup oleh penyakit
yang mendasari yaitu sirosis hati atau hepatitis kronik. Dan lebih dari 80%
pasien hepatoma menderita sirosis hati.
Dasar terapi dari hepatoma adalah operasi, terutama pada hepatoma kecil
yang diameternya kurang dari 5cm dan tunggal.
Tidak sedikit pakar berpendapat, untuk terapi hepatoma kecil cangkok hati
lebih baik daripada lobektomi. Dewasa ini hepatoma kecil disertai sirosis terapi
pilihan pertama adalah cangkok hati. Alasannya adalah, hepatoma yang
timbul diatas sirosis seringkali bersifat multifokal, bila direseksi satu, di
tempat lain akan timbul lagi. Sedangkan sirosis bersifat progresif, bila hanya
dilakukan lobektomi, tidak mungkin dapat menyembuhkan sirosis, bahkan
seringkali hipertensi portal dipersulit dengan pendarahan hebat dan kegagalan
fungsi hati.
Hepatoma atau karsinoma hepatoseluler biasa dan sering terjadi pada sirosis
hati yang merupakan komplikasi hepatitis virus kronik. Hepatitis kronik
adalah faktor resiko penting hepatoma, virus penyebabnya adalah virus
hepatitis B dan C.

Pada awalnya, gejala hepatoma tidak begitu tampak. Jika pun tampak,
biasanya sudah stadium lanjut dan harapan hidup pasien sekitar beberapa
minggu sampai beberapa bulan. Keluhan yang paling sering dirasakan oleh
pasien pada awalnya adalah berkurangnya selera makan, penurunan berat
badan, nyeri di perut kanan atas dan mata tampak kuning.
Untuk deteksi dan menegakkan diagnosis hepatoma pada pasien sirosis,
hepatitis B kronik, hepatitis C kronik, diperlukan pemeriksaan penunjang
seperti CT Scan dan USG. Pemeriksaan ini sangat membantu karena dapat
menemukan tumor yang masih berukuran kecil dan gejalanya tertutup oleh
sirosis hati ataupun hepatitis.
Kanker hati ini merupakan silent killer karena tidak ada gejala yang khas
sampai akhirnya pasien tahu bahwa tubuh sudah ada kanker hati bahkan
sudah sampai stadium ke stadium lanjut. Hepatoma tidak bisa diobati tetapi
hanya bisa mengurangi rasa sakit dan terapinya seperti yang telah disebutkan
diatas, yaitu cangkok hati.
Badan Kesehatan Dunia (WHO) menyebutkan hingga saat ini sekitar dua
milyar orang terinveksi hepatitis B (sebagai cikal bakal hepatoma) di seluruh
dunia dan 350 juta diantaranya berlanjut menjadi infeksi hepatitis B kronis.
Diperkirakan 600.000 orang meninggal dunia per tahun karena penyakit
tersebut. Di Indonesia, angka kematian infeksi hepatitis diperkirakan
mencapai 5-10 persen dari jumlah penduduk. (sumber: Republika 01
Februari 2011)
Prof. dr Ali Sulaiman, Sp PD.KGEH, guru besar dari divisi Hepatologi Fakultas
Kedokteran Universitas Indonesia menjelaskan, proses hepatitis menjadi
kanker boleh dibilang butuh waktu panjang. Di awal virus hepatitis B akan
masuk ke dalam tubuh yang kemudian virus tersebut merusak dan
merangsang sel-sel beraktivasi. Akibatnya sel-sel tersebut membentuk
benjolan pada hati yang bila dibiarkan akan menjadi sirosis hingga kanker
hati. Proses ini juga dipengaruhi gen dalam riwayat keluarga yang ternyata
memiliki keterkaitan penyakit hepatitis. Selain itu faktor lainnya adalah
obesitas, perlemakan hati, merokok, menkonsumsi alkohol dan pengguna
steroid anabolik jangka panjang.

Sebagian besar penderita kanker hati dan hepatitis merupakan kaum pria,
dengan data jumlah perbandingannya dengan perempuan sebesar 3:1 hingga
5:1. Penyebab pasti mengapa laki-laki lebih banyak menderita kanker hati
masih belum jelas betul. Namun diduga disebabkan adanya perbedaan
hormonal dan intensitas kegiatan laki-laki yang banyak menghabiskan waktu
diluar. Pendapat lain, mengatakan bahwa perempuan memiliki sistem
kekebalan tubuh yang lebih kuat dibanding laki-laki.
Pencegahan hepatoma adalah dengan mencegah penularan virus hepatitis B
ataupun C. Vaksinasi merupakan pilihan yang bijaksana, tetapi saat ini baru
tersedia vaksinasi untuk virus hepatitis B.
Penyakit yang telah banyak memakan korban ini, masih menjadi peristiwa
yang menakutkan karena virus yang menjadi penyebabnya belum bisa
sepenuhnya dijinakkan. Adalah benar bahwa mencegah adalah lebih baik
daripada mengobati. Karena itu, siapapun yang peduli terhadap keselamatan
jiwa memerlukan kewaspadaan kesehatan pribadi yang tinggi.
foto: klikdokter.com

ETIOLOGI
A.

Virus Hepatitis B

Hubungan antara infeksi kronik HBV dengan timbulnya hepatoma terbukti


kuat, baik secara epidemiologis, klinis maupun eksperimental. Sebagian besar
wilayah yang hiperendemik HBV menunjukkan angka kekerapan hepatoma
yang tinggi. Umur saat terjadinya infeksi merupakan faktor resiko penting
karena infeksi HBV pada usia dini berakibat akan terjadinya kronisitas.
Karsinogenitas HBV terhadap hati mungkin terjadi melalui proses inflamasi
kronik, peningkatan proliferasi hepatosit, integrasi HBV DNA ke dalam DNA sel
penjamu, dan aktifitas protein spesifik-HBV berinteraksi dengan gen hati.
Pada dasarnya, perubahan hepatosit dari kondisi inaktif menjadi sel yang aktif
bereplikasi menentukan tingkat karsinogenesis hati. Siklus sel dapat
diaktifkan secara tidak langsung akibat dipicu oleh ekspresi berlebihan suatu
atau beberapa gen yang berubah akibat HBV. Infeksi HBV dengan pajanan
agen onkogenik seperti aflatoksin dapat menyebabkan terjadinya hepatoma
tanpa melalui sirosis hati.1
B.

Virus Hepatitis C
Di wilayah dengan tingkat infeksi HBV rendah, HCV merupakan faktor

resiko penting dari hepatoma. Infeksi HCV telah menjadi penyebab paling
umum karsinoma hepatoseluler di Jepang dan Eropa, dan juga bertanggung
jawab atas meningkatnya insiden karsinoma hepatoseluler di Amerika Serikat,
30% dari kasus karsinoma hepatoseluler dianggap terkait dengan infeksi HCV.
Sekitar 5-30% orang dengan infeksi HCV akan berkembang menjadi penyakit
hati kronis. Dalam kelompok ini, sekitar 30% berkembang menjadi sirosis, dan
sekitar 1-2% per tahun berkembang menjadi karsinoma hepatoseluler. Resiko
karsinoma hepatoseluler pada pasien dengan HCV sekitar 5% dan muncul 30
tahun setelah infeksi. Penggunaan alkohol oleh pasien dengan HCV kronis
lebih beresiko terkena karsinoma hepatoseluler dibandingkan dengan infeksi
HCV saja. Penelitian terbaru menunjukkan bahwa penggunaan antivirus pada
infeksi HCV kronis dapat mengurangi risiko karsinoma hepatoseluler secara
signifikan.1,5

C.

Sirosis Hati

Sirosis hati merupakan faktor resiko utama hepatoma di dunia dan


melatarbelakangi lebih dari 80% kasus hepatoma. Penyebab utama sirosis di
Amerika Serikat dikaitkan dengan alkohol, infeksi hepatitis C, dan infeksi
hepatitis B. Setiap tahun, 3-5% dari pasien dengan sirosis hati akan menderita
hepatoma. Hepatoma merupakan penyebab utama kematian pada sirosis hati.
Pada otopsi pada pasien dengan sirosis hati , 20-80% di antaranya telah
menderita hepatoma.1,5
D.

Aflatoksin

Aflatoksin B1 (AFB1) meruapakan mikotoksin yang diproduksi oleh jamur


Aspergillus. Dari percobaan pada hewan diketahui bahwa AFB1 bersifat
karsinogen. Aflatoksin B1 ditemukan di seluruh dunia dan terutama banyak
berhubungan dengan makanan berjamur.1 Pertumbuhan jamur yang
menghasilkan aflatoksin berkembang subur pada suhu 13C, terutama pada
makanan yang menghasilkan protein. Di Indonesia terlihat berbagai makanan
yang tercemar dengan aflatoksin seperti kacang-kacangan, umbi-umbian
(kentang rusak, umbi rambat rusak,singkong, dan lain-lain), jamu, bihun, dan
beras berjamur.

Salah satu mekanisme hepatokarsinogenesisnya ialah kemampuan AFB1


menginduksi mutasi pada gen supresor tumor p53. Berbagai penelitian dengan
menggunakan biomarker menunjukkan ada korelasi kuat antara pajanan
aflatoksin dalam diet dengan morbiditas dan mortalitas hepatoma.1
E.

Obesitas

Suatu penelitian pada lebih dari 900.000 individu di Amerika Serikat


diketahui bahwa terjadinya peningkatan angka mortalitas sebesar 5x akibat
kanker pada kelompok individu dengan berat badan tertinggi (IMT 35-40
kg/m2) dibandingkan dengan kelompok individu yang IMT-nya normal.
Obesitas merupakan faktor resiko utama untuk non-alcoholic fatty liver
disesease (NAFLD), khususnya non-alcoholic steatohepatitis (NASH) yang dapat
berkembang menjadi sirosis hati dan kemudian berlanjut menjadi hepatoma.1

F.

Diabetes Mellitus

Tidak lama ditengarai bahwa DM menjadi faktor resiko baik untuk penyakit
hati kronis maupun untuk hepatoma melalui terjadinya perlemakan hati dan
steatohepatitis non-alkoholik (NASH). Di samping itu, DM dihubungkan
dengan peningkatan kadar insulin dan insulin-like growth factors (IGFs) yang
merupakan faktor promotif potensial untuk kanker. Indikasi kuatnya aasosiasi
antara DM dan hepatoma terlihat dari banyak penelitian. Penelitian oleh El
Serag dkk. yang melibatkan173.643 pasien DM dan 650.620 pasien bukan DM
menunjukkan bahwa insidensi hepatoma pada kelompok DM lebih dari dua
kali lipat dibandingkan dengan insidensi hepatoma kelompok bukan DM.1
G.

Alkohol

Meskipun alkohol tidak memiliki kemampuan mutagenik, peminum berat


alkohol (>50-70 g/hari atau > 6-7 botol per hari) selama lebih dari 10 tahun
meningkatkan risiko karsinoma hepatoseluler 5 kali lipat. Hanya sedikit bukti
adanya efek karsinogenik langsung dari alkohol. Alkoholisme juga
meningkatkan resiko terjadinya sirosis hati dan hepatoma pada pengidap
infeksi HBV atau HVC. Sebaliknya, pada sirosis alkoholik terjadinya HCC juga
meningkat bermakna pada pasien dengan HBsAg positif atau anti-HCV positif.
Ini menunjukkan adanya peran sinergistik alkohol terhadap infeksi HBV
maupun infeksi HCV

PEMERIKSAAN FAAL HATI

Banyak faal metabolik yang dilakukan oleh jaringan hati, maka ada banyak
pula, lebih dari 100, jenis test yang mengukur reaksi faal hati. Semuanya,
disebut sebagai "tes faal hati". Sebenarnya hanya beberapa yang- benar-benar
mengukur faal hati. Diantara berbagai tes tersebut tidak ada tes tunggal yang
efektif mengukur faal hati secara keseluruhan. Beberapa tes terlalu peka
sehingga tidak khas, sebagian lagi dipengaruhi pula oleh faktor-faktor di luar
hati, sebagian lagi sudah obsolete. Sebaliknya makin banyak tes yang diminta
maka makin besar pula kemungkinannya mendapatkan defisiensi biokimia.
Cara pemeriksaan shotgun semacam itu akan menimbulkan kebingungan.
Sebaiknya memilih beberapa tes saja.
Beberapa kriteria yang dapat dipakai adalah, antara lain, dapatnya dikerjakan
tes tersebut secara baik dengan sarana yang memadai, segi kepraktisan, biaya,
stress yang dibebankan kepada penderita, kemampuan diagnostik dari tes
tersebut, dan lain-lain. Pada pengujian kerusakan hati, gangguan biokimia
yang terlihat adalah peningkatan permeabilitas dinding sel, berkurangnya
kapasitas sintesa, terganggunya faal ekskresi, berkurangnya kapasitas
penyimpanan, terganggunya faal detoksifikasi peningkatan reaksi mesenkimal
dan imunologi yang abnormal.
Dengan melihat gangguan faal biokimia mana yang ingin diketahui dan
mempertimbangkan kriteria di atas maka testes yang ada dapat
dikelompokkan menurut suatu program bertahap.
I. Integeritas Sel
Enzim-enzim AST, ALT & GLDH akan meningkat bila terjadi kerusakan sel
hati. Biasanya peningkatan ALT lebih tinggi dari pada AST pada kerusakan
hati yang akut, mengingat ALT merupakan enzim yang hanya terdapat dalam
sitoplasma sel hati (unilokuler). Sebaliknya AST yang terdapat baik dalam
sitoplasma maupun mitochondria (bilokuler) akan meningkat lebih tinggi

daripada ALT pada kerusakan hati yang lebihdalam dari sitoplasma sel.
Keadaan ini ditemukan pada kerusakan sel hati yang menahun. Adanya
perbedaan peningkatan enzim AST dan ALT pada penyakit hati ini mendorong
para peneliti untuk menyelidiki ratio AST & ALT ini. De Ritiset al mendapatkan
ratio AST/ALT =0,7 sebagaibatas penyakit hati akut dan kronis. Ratio lni yang
terkenal dengan narna ratio De Ritis memberikan hasil <> 0,7 pada penyakit
hati kronis. Batas 0,7 ini dipakai apabila pemeriksaan
enzim-enzim tersebut dilakukan secara optimized, sedangkan apabila
pemeriksaan dilakukan dengan cara kolorimetrik batas ini adalah 1. Istilah
"optimized" yang dipakai perkumpulan ahli kimia di Jerman ini mengandung
arti bahwa cara pemeriksaan ini telah distandardisasi secara optimum baik
substrat, koenzim maupun lingkungannya. Enzim GLDH bersifat unikoluker
dan terletak di dalam mitochondria. Enzim ini peka dan karena itu baik untuk
deteksi dini dari kerusakan sel hati terutama yang disebabkan oleh alkohol,
selain itu juga berguna untuk diagnosa banding ikterus. Perlu diketahui
bahwa cortison dan sulfonil urea pada dosis terapi dapat menurunkan kadar
GLDH. Pemeriksaan enzim LDH total akan lebih bermakna apabila dapat
dilakukan pemeriksaan isoenzimnya yaitu LDH. Dalam hubungannya dengan
metabolisme besi, sel hati rnembentuk transferin sebagai pengangkut Fe dan
juga menyimpannya dalam bentuk feritin dan hemosiderin.
Cu terdapat di dalam enzim seruloplasmin yang dibentuk oleh hati. Kelebihan
Cu akan segera diekskeresi oleh hati. Perubahan kadar Fe dan / atau Cu pada
beberapa penyakit hati.
II. Faal Metabolisme/Ekskresi
Tes BSP (bromsulfonftalein), suatu zat warna, merupakan tes yang peka
terhadap adanya kerusakan hati. Diukur retensinya di dalam darah beberapa
waktu setelah disuntikkan intravena.
Di dalam darah ia diikat oleh albumin dan di "uptake" olehsel-sel hati,
dikonyugasi dan diekskresi melalui empedu. Pada penyuntikan 5 mg/kg berat
badan maka setelah 45 menit retensinya kurang dari 5% pada keadaan
normal.

Korelasinya baik dengan kelainan histopatologik. Tes ini berguna pada


hepatitis anikterus, mengetahui kerusakan setelah sembuh dari hepatitis,
sirosis hati, semua tingkat hepatitis kronik, tersangka perlemakan hati dan
keracunan hati. Namun tes ini kurang disenangi karena dapat timbul efek
samping, walaupun jarang, yang fatal seperti renjatan anafilaktis.
Akhir-akhir ini makin banyak dikerjakan pemeriksaan kadar asam empedu
dalam darah. Tes ini mempunyai makna seperti tes retensi BSP dan juga amat
peka terutama kadarnya 2 jam
setelah makan.
Kadar amonia mengukur faal detoksifikasi hati yang merubahnya menjadi
ureum. Faal ini baru terganggu pada kerusakan hati berat karena itu tes ini
baru berguna untuk mengikuti perkembangan sirosis hati yang tidak
terkompensir atau koma hepatikum. Kadarnya juga akan meningkat bila ada
shunt portokaval yang mem"by-pass" hati.
Tes toleransi galaktosa menguji kemampuan faal hati mengubah galaktosa
menjadi glukosa. Tes ini sudah jarang dilakukan.
III. Faal Ekskresi
Pemeriksaan kadar bilirubin serum terutama panting untuk membedakan
jenis-jenis ikterus. Pemeriksaan ini yang umumnya memakai metodik
Jendrassik dan Grof (1938) dapat di
pengaruhi oleh kerja fisik dan makanan tertentu seperti karoten, oleh karena
itu pengambilan sampel sebaiknya pagi hari sesudah puasa. Pada ikterus
prahepatik yang dapat disebabkan oleh proses hemolisis ataupun kelainan
metabolisme seperti sindroma Dubin-Johnson, ditemukan peningkatan dari
bilirubin bebas. Ikterus hepatik sebagai akibat kerusakan sel hati akan
meningkatkan baik bilirubin babas maupun bilirubin (diglukuronida) dalam
darah serta ditemukannya bilirubin (diglukuronida) didalam urin. Sedangkan
ikterus obstruktif, baik intra maupun ekstra hepatik, akan meningkatkan
terutama bilirubin diglukuronida di dalam darah dan urin. Kadar urobilinogen

dalam urin akan meningkat pada ikterus hepatik, sebaliknya ia akan menurun
atau tidak ada sama sekali pada ikterus obstruktif sesuai dengan derajat
obstruksinya.
Seperti telah disinggung sebelumnya pemeriksaan asam empedu makin
banyak dipakai sebagai tes faal hati. Pemeriksaan ini dimungkinkan untuk
dipakai di dalam klinik sejak ditemukannya metodik onzimatik yang relatif
sederhana dibandingkan metodik-metodik sebelumnya. Dalam keadaan normal
hanya sebagian kecil saja asam empedu terdapat di dalam darah sedangkan
sebagian besar di uptake oleh sel hati. Pada kerusakan sel hati, hati gagal
mengambil asam empedu, sehingga jumlahnya meningkat dalam darah.
Pemeriksaan ini seperti pemeriksaan BSP dapat mendeteksi kelainan hati yang
ri ngan disamping untuk follow up dan menguji adanya shunt port caval.
IV. Faal Sintesa
Albumin disintesa oleh hati. Pada gangguan faal hati kadarnya di dalam darah
akan menurun. Cara pemeriksaan yang banyak dipakai sekarang adalah cara
bromcresylgreen. Selain dengan cara di atas, penurunan kadar albumin juga
dapat diukur secara elektroforesa dengan peralatan khusus yang lebih mahal.
Selain dengan pemeriksaan albumin, pemeriksaan enzim cholinesterase(ChE)
juga dipakai sebagai tolok ukur dari faal sintesa hati. Penurunan aktivitas ChE
ternyata lebih spesifik dari pemeriksaan albumin, karena aktivitas ChE
kurang dipengaruhi faktor-faktor di luar hati dibandingkan dengan
pemeriksaan kadar albumin.
Penetapan masa protrombin plasma berguna untuk menguji sintesa faktorfaktor pembekuan II, VII, IX dan X. Semua pemeriksaan tersebut lebih
berguna untuk menilai atau membuat prognosa dari pada mendeteksi
penyakit hati kronis.
V. Proses Reaktif
Baik enzim GGT, AP, 5-NT maupun. LAP akan meningkat pada kelainan
saluran empedu Enzim-enzim cholestasis ini juga akan meningkat dalam

kadar yang lebih rendah pada kerusakan sel parenkin hati. Pemeriksaan GGT
pada saat ini merupakan pemeriksaan yang paling populer dari ketiga
pemeriksaan lainnya. Peningkatan aktivitas enzim ini sering merupakan tanda
pertama keracunan sel hati akibat alkohol. Disamping itu mengingat half-life
nya yang panjang peningkatan enzim ini sering merupakan abnormalitas
terakhir yang dijumpai pada proses penyembuhan kerusakan hati.
VI. Imunologi
Pemeriksaan TTT (tes turbiditas timol) merupakan salah satu tes labilitas yang
telah lama dikenal (sejak 1944). Mekanisme fisikakimia dari tes ini belum
jelas. Diketahui globulin akan mempermudah pembentukan presipitasi,
sedangkan albumin menghambat proses ini. Disamping itu trigliserida dan
khilomikron dapat menyebabkan tes TTT positip. Peningkatan dari TTT
kadang-kadang ditemukan sebelum terjadi kelainan pada hasil pemeriksaan
elektroforesa dan albumin. Tes labilitas yang lain adalah tes turbiditas zink
sulfat (Kunkel), Takata Ara, dan lain-lain. Sebenarnya tes-tes labilitas ini
bukan berdasarkan reaksi antigen antibodi, tetapi menggambarkan fraksifraksi protein.
Peningkatan dari globulin yang merupakan respon imunitas ini biasanya baru
ditemukan pada kerusakan hati yang kronis. Pada penyakit hati kronik
biasanya ditemukan peningkatan IgG. Peningkatan IgM menyolok pada
hepatitis type A, sedangkan untuk hepatitis type B yang menyolok biasanya
IgG.
Pemeriksaan AFP pada mulanya disangka adalah spesifik untuk karsinoma
hati primer (hepatoma), namun ternyata selain selain oleh sel tumor hati, AFP
juga adakalanya dibentuk oleh sel tumor pada saluran pencernaan. Denaan
cara radioimmunoassay atau enzyme immunoassay kadarnya hanya 20 mg/ml
dalam darah orang normal. Masih belum diketahui dengan jelas mekanisme
peningkatannya pada sel-sel tumor diatas. Bila kadarnya melebihi 3000 ng/ml
hampir dapat dipastikan diagnosa hepatoma. Kadar yang kurang dari itu
dapat juga dijumpai pada sirosis hati, hepatitis, kehamilan trimester ketiga,
teratoma, dll. Pemeriksaan AFP ini terutama dipakai untuk memonitor terapi

bedah ataupun khemoterapi karsinoma hati.


Ada pula beberapa antibodi yang berhubungan dengan penyakit hati. Antibodiantibodi yang ditetapkan secara immunofluorescence ini antara lain
antinuclear antibody (ANA) ditemukan pada hepatitis kronik aktif, anti
micochandrial antibody (AMA) dapat ditemukan pada hepatitis kronik aktif,
sirosis bilier dan cholestasis dan smooth muscle antibody (SMA) yang
ditemukan pada hepatitis virus akut.
Telah diketahui beberapa "seromarker" virus hepatitis A dan B. Untuk virus
hepatitis A dikenl HA Ag dan anti-HA. Untuk virus hepatits B dikenal HBsAg,
HBcAg, HBeAg, anti-HBc dan
anti-HBe. Pertanda serologik ini bermakna untuk menentukan etiologi,
mekanisme penularan, daya tular, tahap penyakit hepatitis dan penyakit hati
lainnya yang berkaitan serta prognosanya.
PENGGUNAAN DALAM KLINIK
Di klink pemeriksaan "faal" hati diperlukan untuk diagnosa adanya dan jenis
penyakit hati, diagnosa banding (ikterus, hepatomegali, asites, perdarahan
saluran pencernaan), menilai
beratnya penyakit, menilai prognosa dan mengikuti hasil pengobatan. Juga
diperlukan untuk penilaian prabedah serta pada keracunan obat-obatan.
Sebagai pedoman umum dapat dilakukan menurut beberapa prinsip praktis
seperti pemilihan tes haruslah menggambarkan berbagai macam tolok ukur
dari faal-faal hati, tes faal hati dilakukan secara serial untuk menilai
perkembangan penyakit dan juga semua tes tersebut harus ditafsirkan di
dalam keseluruhan konteks klinik. Juga harus dipahami bahwa tiap tes
laboratorium dapat saja tidak bebas dari kesalahan.
Pengertian menyeluruh diartikan mulai dari anamnesa, pemeriksaan fisik,
pemeriksaan laboratorik sampai pemeriksaan khusus. Pentingnya anamnesa
misalnya pada diagnosa druginduced hepatitis.

Dengan makin banyaknya pemakaian biopsi jarum, endoskopi, ultrasonografi,


scanning, arteriografi dan lain-lain untuk diagnosis tepat peranan diagnostik
dari tes-tes faal hati sekarang
ini sudah banyak berkurang. Walaupun demikian tes-tes ini masih berguna
untuk menyaring adanya penyakit hepatobilier, mengetahui beratnya dan
mengikuti kemajuannya.
Sherlock mengusulkan pola tes-tes faal hati yang paling berguna pada
beberapa jenis kelainan hepatobilier. Untuk diagnosa ikterus diusulkannya
fosfatase alkali, elektroforesa protein
serum dan enzim aminotransferase (AST, ALT), warna feses dari hari-kehari.
Penilaian beratnya kerusakan sel hati dilakukan dengan memeriksa secara
serial bilirubin serum, albumin,
aminotransferase dan masa protrombin setelah pemberian vitamin K.
Kerusakan sel hati yang minimal didiagnosa dengan mengamati kenaikan
kadar bilirubin serum dan aktivitas aminotransferase yang minimal. Bila
disebabkan oleh alkohol dilakukan dengan GGT.
Infiltrasi hati dipikirkan bila ada kenaikan aktivitas fosfatase alkali tanpa
ikterus.
Sebagai pemeriksaan penyaring Schmidt dan Schmidt mengusulkan
pemeriksaan 3 macam enzim, yaitu ALT untuk kerusakan sel hati, GGT untuk
kolestasis dan cholinesterase untuk faal sintesa hati.
Pemilihan macam tes faal hati apa saja yang diperlukan untuk setiap keadaan
dan jenis penyakit hepatobilier ini masih belum ada kesepakatan, Bermacammacam algoritme yang diusulkan dan penggunaan komputer telah dilakukan
pula. Untuk itu terlebih dahulu perlu dibakukan klasifikasi penyakit, metode
pemeriksaan laboratorium dan diagnostik lainnya kemudian diterapkan untuk
mendapatkan data asupan.
KEPUSTAKAAN
1. Raphael SS. Lynch's Medical Laboratory Technology, 3rd
ed.Philadelphia : WB Saunders Company, 1976 ; 212 - 236.

2. Bauer JD, Ackermann PG, Toro G. Clinical Laboratory Methods, 8thed,


Saint Louis. The CV Mosby Company, 1974 ; 434 - 447.
3. Henry JB. Todd - Sanford - Davidson.Clinical Diagnosis and
Managementby Laboratory Methods, 6th ed, Philadelphia : WB
SaundersCompany 1979; 305-383.
4. Isselbacher KJ, LaMont IT. Diagnostic procedures in liver disease.
1n:Isselbacher, Adams,Braunwald, Petersdorf, Wilson eds.
Harrison'sPrinciples of Internal Medicine. 9th ed. Tokyo : Mc GrawHillKogakusha Ltd., 1980 ; 1450.
5. Sherlock S.Diseases of the Liver and Biliary System, 6th ed. Fromedan
London : Butler & Tanner Ltd. 1981 ; 14 - 27.
6. Gotz W. Diagnosis of Hepatic Diseases, 1 st ed. Darmstadt : G-I-TVerlag
Ernst Giebeler, 1980 ; 19 - 44.
7. Schmidt E, Schmidt FW. Brief Guide to Practical Enzyme Diagnosis.2nd
ed Mannheim : Boehringer Mannheim GmBH, 1976 ; 73-76.
8. Henry RJ, Cannon DC, Winkelman JW. Clinical Chemistry, Principlesand
Technics, 2nd ed. Hagerstown : Harper and Row, 1974 ; 1009 - 1019.

Imaging in the Diagnosis, Staging, Treatment, and Surveillance of


Hepatocellular Carcinoma
1. Janio Szklaruk1,
2. Paul M. Silverman and
3. Chusilp Charnsangavej
+ Author Affiliations
1.

All authors: Division of Diagnostic Imaging, The University of Texas M. D.

Anderson Cancer Center, 1515 Holcombe Blvd., Box 57, Houston, TX


77030-4009.

Next Section
Hepatocellular carcinoma is the eighth most common malignancy worldwide.
This article will review the epidemiology, clinical presentation, staging,
pathology, laboratory findings, radiology, and treatment of hepatocellular
carcinoma.
Previous SectionNext Section
Epidemiology
Hepatocellular carcinoma represents 6% of all cancers and is the most common
primary hepatic malignancy worldwide. A geographic bias is seen, with an
increased incidence of hepatocellular carcinoma in the Far East, Southeast
Asia, and sub-Saharan Africa (90 cases per 100,000 population vs 2.4 cases
per 100,000 in the United States) [1,2,3,4].
The most important risk factors include cirrhosis and hepatitis B and C
viruses. Additional risk factors include hemochromatosis; excessive androgens;
1-antitrypsin deficiency; and exposure to aflotoxins, thorotrast, oral
contraceptives, and vinyl chloride [4]. The latter is associated with all types of
liver tumors, including angiosarcomas [5]. Hepatitis B virus is considered to be

the primary cause of 80% of cases worldwide. The peak age of incidence is 5070 years, with a male predominance of 4:1. The incidence in the United States
has increased approximately 70% during the past two decades, from 1.4 per
million in 1976-1980 to 2.4 per million in 1991-1995 [6]. Surveillance
Epidemiology and End Results of the National Cancer Institute evaluation of
7389 cases of hepatocellular carcinoma reported an improvement in the 1-year
survival rate from 14% to 23% during the same periods [1]. This improvement
is thought to be a reflection of the earlier detection of small resectable tumors,
a more aggressive surgical approach, and the wider availability of liver
transplantation. The 5-year survival rate has increased from 2% to 5%, and the
increase has resulted in a slight change in the still-very-low median survival
rate from 0.57 to 0.64 years.
Previous SectionNext Section
Clinical Presentation
Clinical manifestations are often masked by the presence of cirrhosis and or
chronic hepatitis. Common symptoms include abdominal pain, malaise,
fatigue, and weight loss (Table 1). The most common finding on physical
examination is an enlarged, irregular, and nodular liver. Jaundice and
abnormal findings of liver function tests may not be present until late in the
course of the disease because of the functional reserve of the liver. A number of
paraneoplastic manifestations of hepatocellular carcinoma, including
hypercalcemia and hyperglycemia, are directly or indirectly a result of tumor
secretion or synthesis [7]. Polycythemia occurs in fewer than 10% of patients.
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TABLE 1 Predominant Symptoms and Physical Signs in Patients with


Hepatocellular Carcinoma
Previous SectionNext Section

Staging
The staging of the disease is performed using the TNM system [8] (Fig.
1A,1B,1C,1D,1E,1F,1G,1H,1I,1J and Table 2). The primary lesion is defined by
tumor size, the number and location of lesions, invasion of vascular structures,
and biliary extension. In addition, this staging system addresses the presence
and location of regional nodal metastasis and the presence or absence of
distant metastases. The most common sites of metastatic disease are the lung
and bony skeleton. In the latest data analysis (1985-1996) from the National
Cancer Data Base, 4.6% of the patients were stage I; 13.7%, stage II; 23%,
stage III; 33.8%, stage IVA; and 23.9%, stage IVB [9].

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Fig. 1A. Staging of primary tumors. Illustrations show solitary tumors 2 cm


without (stage T1) (A) and with (stage T2a) (B) vascular invasion.

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Fig. 1B. Staging of primary tumors. Illustrations show solitary tumors 2 cm


without (stage T1) (A) and with (stage T2a) (B) vascular invasion.

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Fig. 1C. Staging of primary tumors. Illustration shows multiple tumors 2


cm that are limited to one lobe with no vascular invasion (stage T2b).

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Fig. 1D. Staging of primary tumors. Illustrations show solitary tumors >2 cm
without (stage T2c) (D) and with (stage T3a) (E) vascular invasion.

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Fig. 1E. Staging of primary tumors. Illustrations show solitary tumors >2 cm
without (stage T2c) (D) and with (stage T3a) (E) vascular invasion.

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Fig. 1F. Staging of primary tumors. Illustration shows multiple tumors 2


cm limited to one lobe with vascular invasion (stage T3b).

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Fig. 1G. Staging of primary tumors. Illustration shows multiple tumors >2
cm with or without vascular invasion (stage T3c).

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Fig. 1H. Staging of primary tumors. Illustration shows multiple tumors in


more than one lobe (stage T4a).

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Fig. 1I. Staging of primary tumors. Illustration shows multiple tumors with
invasion of major branch of hepatic or portal vein or of adjacent organs other
than gallbladder.

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Fig. 1J. Staging of primary tumors. Illustration shows segmental anatomy of


liver.
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TABLE 2 TNM Staging System Devised by the American Joint Committee


on Cancer [8]
New staging and scoring systems have recently challenged the widely accepted
TNM classification [10,11,12,13]. The Cancer of the Liver Italian Program has
developed a different scoring system that is based on Child-Pugh classification
[14]. This classification includes assessment of ascites, encephalopathy grade,
albumin level, prothrombin time, and bilirubin level [15]. The Cancer of the
Liver Italian Program staging for liver disease includes not only tumor
morphology but also -fetoprotein levels and grading of portal vein invasion (on
a score of 1-6). The Barcelona Clinic Liver Cancer group has also developed a
staging score for hepatocellular carcinoma that includes symptomatology and
vascular and extrahepatic invasion [13]. The Okuda staging system (I-III)
includes the presence of ascites, jaundice, and serum albumin levels [16].
The natural progression of hepatocellular carcinoma is well documented [16].
The overall median survival of hepatocellular carcinoma patients with no
treatment is reported to be 1.6-4.1 months for stages I and II and 0.8-2.4
months for stages III and IV [16, 17].
Previous SectionNext Section
Pathology
The gross pathology of hepatocellular carcinoma is a direct reflection of the
imaging findings. Hepatocellular carcinoma may appear as a unifocal mass,
multifocal nodules of variable size, or diffusely infiltrative. The tumor may
cause liver enlargement, and small nodules or diffuse patterns may be hidden
in a cirrhotic parenchyma. The tumor is paler than normal liver parenchyma
and in well-differentiated cases may have a greenish hue as a result of bile
accumulation.

Microscopically, tumors range from well differentiated to highly anaplastic [18].


Four histologic classifications are based on the structural organization:
trabecular, pseudoglandular, compact, and scirrhous, the trabecular pattern
being the most common. The pseudoglandular pattern has malignant
hepatocytes surrounding a lumen that may contain bile, with some of these
tumors having clear cells because of glycogen or fat. Scirrhous, the least
common pattern, contains fibrous stroma separating the tumor cell plates.
The development of hepatocellular carcinoma from premalignant lesions is
reported to occur in stages. The transformation usually begins in a cirrhotic
background, with regenerative nodules evolving into dysplastic nodules, and
the subsequent development of early hepatocellular carcinoma, which, if
untreated, becomes advanced carcinoma.
The fibrolamellar type of hepatocellular carcinoma has distinct clinical,
histologic, and prognostic features and a mean survival of 68 months compared
with conventional hepatocellular carcinoma. The fibrolamellar tumor is more
frequent in young patients who have no history of cirrhosis or chronic liver
disease.
Previous SectionNext Section
Laboratory Findings
Testing for the -fetoprotein level is the primary laboratory test for diagnosing
hepatocellular carcinoma (sensitivity, 80-70%; specificity, 90%). Values greater
than 400 ng/mL are most diagnostic [19]. Elevated -fetoprotein levels have
also been reported in yolk sac tumors, cirrhosis, massive liver necrosis, chronic
hepatitis, pregnancy, fetal distress, and fetal neural tube defects. Other tumor
markers with less sensitivity include des-gamma-carboxyprothrombin
(sensitivity, 58-91%; specificity, 84%), -L-fucosidase (sensitivity, 75%;
specificity, 70-90%), and isoenzymes of -glutamyl transferase (sensitivity, 60%;
specificity, 96%).
Previous SectionNext Section

Radiology
Radiography of the chest may show pulmonary and skeletal metastases (Fig. 2).
The right hemidiaphragm is elevated with hepatomegaly [19].

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Fig. 2. 79-year-old man who underwent hepatic resection for hepatocellular


carcinoma and tested positive for hepatitis D antibody. Chest radiograph shows
bilateral pulmonary metastases.
Sonography has been postulated as a screening imaging modality for
hepatocellular carcinoma in patients with a history of chronic liver disease
(hepatitis or alcohol abuse) [20]. However, the role of sonography in screening
has yet to be fully determined. The most common sonographic appearance of
small well-differentiated hepatocellular carcinoma (<3 cm) is a wellcircumscribed hypoechoic mass [20] (Fig. 3). However, sonography cannot
reliably distinguish hepatocellular carcinoma from other solid lesions in the
liver. The sonographic appearance in larger masses is variable and is related to
the presence of fat, calcium, and necrosis. The presence of compact cellular
elements, necrosis, or sinusoidal dilatation gives a hypoechoic appearance,
whereas the presence of hemorrhage, fatty change, or fibrosis is seen as a
hyperechoic mass. A surrounding capsule, when present, generally appears
hypoechoic (Fig. 4).

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Fig. 3. 50-year-old man with history of cirrhosis and hepatitis B and C.


Transverse sonogram shows hypoechoic mass (arrow) in right lobe of liver.

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Fig. 4. 61-year-old man with metastatic hepatocellular carcinoma.


Transverse sonogram of liver with sonographically guided biopsy shows
hyperechoic mass with hypoechoic capsule (arrow) in right lobe of liver.
Echogenic needle (arrowhead) is visualized.
Sonography is helpful in providing guidance for percutaneous biopsy and in
delivering therapy for a suspected liver mass (Fig. 4). Duplex and color Doppler
sonography can show hypervascularity and arteriovenous shunting. Doppler
and power Doppler sonography may play a role in differentiating hepatocellular
carcinoma from other small tumors. Doppler sonography of hepatic nodules
may play a role in selecting a nodule for biopsy in patients with hepatocellular
carcinoma that is suspected as a result of an elevated -fetoprotein level.
Sonographic contrast agents have shown promise in characterizing masses
suspected to be hepatocellular carcinoma [21]. A problem exists in
distinguishing regenerative nodules in cirrhosis from hepatocellular carcinoma.
Recently, Fracanzani et al. [22] evaluated contrast-enhanced Doppler
sonography in distinguishing early hepatocellular carcinoma from
nonmalignant nodules in cirrhosis. Those authors reported intratumoral
arterial blood flow in 95% of hepatocellular carcinomas versus 28% of
nonmalignant tumors. Doppler sonography may be a promising imaging

modality for this radiologic problem. In staging, sonography can provide


information regarding the size, number of lesions, and involvement of the
biliary tree, and can help in evaluating the portal vein, hepatic vein, and
inferior vena cava (Fig. 5A,5B). An intravascular arterial waveform indicates
neoplastic rather than bland thrombus. However, the lack of an arterial
waveform does not exclude tumor thrombosis.

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Fig. 5A. 50-year-old man with history of cirrhosis and hepatitis B and C.
Transverse color Doppler sonogram of right upper quadrant shows flow of
middle hepatic vein (white arrow), no flow in right hepatic vein (arrowhead),
and echogenic thrombus in inferior vena cava (black arrow).

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Fig. 5B. 50-year-old man with history of cirrhosis and hepatitis B and C.
Transverse color Doppler sonogram of right upper quadrant shows flow in right
main portal vein (arrow). Normal spectral waveform (arrowhead) is also shown.
Although many imaging modalities are essential in the diagnosis and staging of
hepatocellular carcinoma, CT is the most commonly used. On unenhanced CT,
hepatocellular carcinoma appears hypodense (Fig. 6) except in diffusely fatty
liver, where it may appear denser. Hemorrhage or calcifications may be detected

but are rare (5%). Fatty metamorphosis of hepatocellular carcinoma will appear
as areas of low attenuation.

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Fig. 6. 48-year-old woman with serology findings negative for hepatitis and
no history of alcohol abuse. Unenhanced CT scan of abdomen shows multiple
low-attenuation bilobar masses.
The CT evaluation of the liver in a patient with a clinical suspicion of
hepatocellular carcinoma should be performed at three stages of contrast
enhancement [23, 24]: the hepatic arterial phase at 20-30 sec after the
infusion of contrast material, an early parenchymal phase at 40-55 sec, and
the portal venous phase at 70-80 sec after the infusion of contrast material.
Hypervascular lesions are best viewed during the earlier phases of
enhancement. The rate of injection also plays a role in the sensitivity of CT to
liver lesions; a rate of 4-8 mL/sec is suggested. The added speed and flexibility
of multidetector CT (MDCT) allows high-quality, thin-section imaging and
permits three-dimensional reconstruction for preoperative vascular mapping.
Hepatocellular carcinoma predominately shows maximum enhancement during
the hepatic arterial phase (Fig. 7A,7B,7C). In the portal venous phase of
enhancement, the tumor will become hypoattenuating compared with the liver
as a result of rapid washout. Although most lesions have hyperdense
components in the early phase, a small percentage may be isodense or
hypodense after the administration of contrast material [25]. A heterogeneous
pattern of enhancement has been termed the mosaic pattern. Heterogeneous
attenuation may often be due to necrosis. When a capsule is present, it is
usually hypodense on the hepatic arterial phase, of mixed density on the portal

venous phase, and showing enhancement on the delayed images. Recent


studies have reported that delayed scans might increase confidence in the
detection of lesions [26] (Fig. 8A,8B).

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Fig. 7A. 74-year-old man with cirrhosis and history of alcohol exposure.
Unenhanced CT scan of liver shows exophytic mass (arrow) on segment VII.

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Fig. 7B. 74-year-old man with cirrhosis and history of alcohol exposure.
Contrast-enhanced CT scan of liver during late arterial phase shows multiple
enhancing masses (arrows).

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Fig. 7C. 74-year-old man with cirrhosis and history of alcohol exposure.
Contrast-enhanced CT scan of liver during venous delayed phase of
enhancement shows decreased contrast between lesion and liver.

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Fig. 8A. Axial CT scans of abdomen in 58-year-old man with hepatitis B.


Image obtained during late arterial phase of enhancement shows faint mass
(arrow) in liver segment VII.

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Fig. 8B. Axial CT scans of abdomen in 58-year-old man with hepatitis B.


Image obtained during delayed phase of contrast enhancement shows increase
in contrast (arrow) between low-attenuation hepatocellular carcinoma and liver
parenchyma.
In CT arterial portography, the portal system is opacified with contrast
material. CT will show relatively low attenuation of the hepatocellular
carcinoma because the blood supply is from the hepatic artery. CT arterial
portography is usually used in patients in whom the clinical suspicion of
hepatocellular carcinoma is high. This technique has been reported to be the
most sensitive technique for the detection of liver tumors, but it is invasive,
requiring catheter insertion (Fig. 9). Most recently, MDCT has provided highquality images and has generally supplanted CT arterial portography [27].

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Fig. 9. 46-year-old man with hepatitis B. CT angiogram of liver during portal


phase after direct infusion of contrast material into superior mesenteric artery
shows low-attenuation hepatoma (white arrow). Spleen (black arrow) is also low
in attenuation with respect to liver.
CT is highly accurate in staging hepatocellular carcinoma by detecting the
number of lesions and segments, regional adenopathy, vascular tumor invasion
(Fig. 10), and metastases [25, 28]. Distinction between bland thrombus and
tumor thrombus is not always possible, but the identification of thrombus
enhancement is indicative of tumor (Fig. 11A,11B). Indirect signs of a portal
vein diameter greater than 23 mm (Fig. 12) have been reported to have a low
(62%) sensitivity but 100% specificity for tumor thrombus [29]. Bile duct
obstruction is usually related to extrinsic compression on the biliary system by
the tumor or direct tumor extension into the biliary system. CT also plays a
major role in posttreatment evaluation and surveillance (Fig. 13), guidance for
biopsy of suspected recurrences, assessing regeneration of liver parenchyma
(Fig. 14A,14B), and follow-up after ablation when a change in enhancement
suggests tumor recurrence. CT is somewhat limited in assessing peritoneal
implants because of the presence of ascites related to the primary hepatic
disease.

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Fig. 10. 50-year-old man with history of hepatitis B and C, cirrhosis, and
portal hypertension. Delayed phase contrast-enhanced CT scan of liver shows
thrombus (white arrow) in proximal inferior vena cava. Primary tumor (black
arrow) is in segment VIII.

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Fig. 11A. 69-year-old man with alcohol cirrhosis. Arterial phase contrastenhanced CT scan of abdomen at level of main portal vein shows linear
enhancement of portal vein and ascites (arrow).

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Fig. 11B. 69-year-old man with alcohol cirrhosis. Late phase contrastenhanced CT scan of abdomen at same level as A shows washout of
enhancement in portal vein (arrow).

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Fig. 12. 51-year-old man with history of hepatitis C, cirrhosis, and


hemochromatosis. Delayed phase contrast-enhanced CT scan of abdomen
shows filling defect (arrow) in main portal vein. Note nodular contour of liver
that is consistent with cirrhosis.

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Fig. 13. 76-year-old woman with history of left hepatic lobectomy. Delayed
contrast-enhanced CT scan of abdomen shows recurrence of tumor (arrow)
adjacent to surgical margin.

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Fig. 14A. 50-year-old man with history of hepatitis B and C and cirrhosis.
Patient also had history of solid mass in lateral segment of left lobe of liver.
Delayed phase contrast-enhanced CT scans of abdomen obtained 5 days (A)
and 5 months (B) after radiofrequency ablation. Both images show change in
size and attenuation of treated area (arrows) in lateral segment of left lobe of
liver.

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Fig. 14B. 50-year-old man with history of hepatitis B and C and cirrhosis.
Patient also had history of solid mass in lateral segment of left lobe of liver.
Delayed phase contrast-enhanced CT scans of abdomen obtained 5 days (A)
and 5 months (B) after radiofrequency ablation. Both images show change in
size and attenuation of treated area (arrows) in lateral segment of left lobe of
liver.
MR imaging should include T1-weighted images, T2-weighted images with fat
suppression, and dynamic contrast-enhanced gradient-echo sequences of the
liver. The T1 technique is usually a breath-hold gradient-echo sequence with an
in-phase TE of 4.1 msec at 1.5-T field-strength magnet. The T2-weighted
sequences are obtained at two TE ranges (60-70 and 136-150 msec) for lesion
characterization. For T2-weighted sequences, a fast spin-echo sequence with fat
suppression is performed. The critical sequences in the detection of
hepatocellular carcinoma are the dynamic gadolinium-enhanced images [24,
30]. The arterial phase of enhancement may be the only phase in which a
tumor may be revealed (Fig. 15A,15B). On T1-weighted sequences,
hepatocellular carcinoma is usually hypointense to liver (Fig. 16A,16B,16C).
Areas of increased intensity may be due to fat, protein, or copper in the tumor
[31]. On T2-weighted sequences, the tumor is usually hyperintense to liver [32]
(Fig. 16A,16B,16C). Dynamic enhancement shows hyperintensity on the
hepatic arterial phase because of the hepatic artery supply [33, 34]. The
fibrous capsule shows low signal intensity on T1- and T2-weighted images and
enhancement on delayed contrast-enhanced images (Fig. 17A,17B). The tumor
may invade the portal vein, hepatic veins, or the biliary system (Figs. 18 and
19). The MR imaging biliary contrast agent, mangafodipir (Teslascan; NycomedAmersham, Oslo, Norway) is taken up by hepatocytes and well-differentiated
tumors (Fig. 16A,16B,16C). This technique can reveal lesions not visualized on
the unenhanced images [35]. MR imaging plays a role in postoperative
treatment. Tumor may recur locally or distant from the surgical site. After

successful ablation, patients with hepatocellular carcinoma show low-signalintensity areas on the T2-weighted protocol.

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Fig. 15A. 52-year-old man with history of hepatitis B and C. Axial twodimensional spoiled gradient-echo unenhanced MR image (TR/TE, 4.1/110)
shows faint hyperdense nodules (arrow) in right lobe of liver.

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Fig. 15B. 52-year-old man with history of hepatitis B and C. MR image from
same sequence as A during early phase of enhancement shows marked
enhancement of nodule (arrow) in segment VII.

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Fig. 16A. 74-year-old man with history of alcohol exposure. Axial spin-echo
T1-weighted MR image of liver (TR/TE, 600/8) without IV contrast material
shows low-signal-intensity mass (arrow) in segment V of liver.

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Fig. 16B. 74-year-old man with history of alcohol exposure. Axial fast spinecho T2-weighted MR image (136/68; echo-train length, 12) shows
hyperintense hepatocellular carcinoma (arrow).

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Fig. 16C. 74-year-old man with history of alcohol exposure. Axial spin-echo
T1-weighted MR image of liver (600/8) after administration of mangafodipir
(Teslascan; Nycomed-Amersham, Oslo, Norway) shows uptake of contrast
material, which suggests moderately to well-differentiated tumor (arrow).

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Fig. 17A. 73-year-old man with hepatitis C and cirrhosis. Axial fast spinecho T2-weighted MR image (TR/TE, 136/68; echo-train length, 12) of liver
shows tumor to be slightly hyperintense. Note thin low-signal-intensity capsule
(arrow).

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Fig. 17B. 73-year-old man with hepatitis C and cirrhosis. Delayed fatsaturated gadolinium-enhanced axial spin-echo T1-weighted MR image (TR/TE,
600/9) shows that hepatocellular carcinoma has low signal relative to liver.
Note enhancing capsule (arrow).

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Fig. 18. 72-year-old man with history of hepatitis C and cirrhosis. Axial
gradient-echo MR image (TR/TE, 110/4.1) during venous phase of
enhancement after dynamic administration of gadolinium shows filling defect
(arrow) in main left portal vein.

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Fig. 19. 61-year-old man with history of hepatitis B and cirrhosis. Axial
time-of-flight gradient-echo MR image (TR/TE, 50/4) of liver during arterial
phase of contrast enhancement shows filling defect (arrow) in inferior vena
cava.
Various groups have compared the sensitivity of imaging modalities for the
diagnosis and detection of hepatocellular carcinoma (Table 3). Although the
imaging modalities are similar, direct comparison is limited because the
sensitivity of detection depends on equipment, operator skill, and techniques.
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TABLE 3 Comparison in Radiology Literature of Sensitivities of CT,


Sonography, and MR Imaging in Diagnosing and Detecting Hepatocellular
Carcinoma
Angiography is a versatile technology that plays a role in the diagnosis when
coupled with CT arterial portography, pretreatment imaging, and treatment of
hepatocellular carcinoma. Angiography plays a role in the pretreatment of
patients with hepatocellular carcinoma with preoperative portal vein
embolization, which can improve the prognosis after right hepatectomy by the
development of compensatory liver hypertrophy [36] (Fig. 20A,20B,20C). The
hypertrophy may be adequate at 2-4 weeks after portal vein embolization [36].
Two major approaches to portal vein embolization are used: direct ileocolic vein
catheterization (requiring laparotomy) and the percutaneous approach.
Embolization agents include Gelfoam (Upjohn, Kalamazoo, MI), coils, thrombin,
cyanoacrylate, polyvinyl alcohol, microspheres, and absolute alcohol. No
specific agent has been shown to be superior. Portal vein embolization is used
when the remnant liver volume is 25% or less of the total liver volume in
patients without compromised liver function. In patients with compromised
liver function, portal vein embolization is used when the volume is 40% or less.

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Fig. 20A. 61-year-old man with serology findings negative for hepatitis B or C
and no history of alcohol abuse. Arterial phase contrast-enhanced CT scan
shows mass (arrow) in liver segment VII.

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Fig. 20B. 61-year-old man with serology findings negative for hepatitis B or C
and no history of alcohol abuse. Delayed phase contrast-enhanced CT scans
show coils (arrow, B) used in portal vein embolization (B), hypertrophy (arrow,
C) of left lobe of liver, and changes after trisegmentectomy (C).

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Fig. 20C. 61-year-old man with serology findings negative for hepatitis B or C
and no history of alcohol abuse. Delayed phase contrast-enhanced CT scans

show coils (arrow, B) used in portal vein embolization (B), hypertrophy (arrow,
C) of left lobe of liver, and changes after trisegmentectomy (C).
Angiography also plays an essential role in transarterial catheter embolization,
which is a selective catheterization of the branch of the hepatic artery feeding
the tumor (Fig. 21).

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Fig. 21. 61-year-old man with history of alcohol liver cirrhosis. Selected
image from digital subtraction angiography of right hepatic artery (white arrow)
shows catheter (black arrow) used for transarterial chemoembolization of tumor
(arrowhead) in right lobe of liver.
Previous SectionNext Section
Treatment
The treatment of hepatocellular carcinoma includes surgery, chemotherapy,
radiation, and combination therapies. In the period 1995-1996, the National
Cancer Data Bank reported that 17.7% of patients were treated with
chemotherapy alone, 17% with surgery alone, and 3.2% with radiation therapy
[9, 37].
Surgery is considered the best treatment option. Patients are surgical
candidates if their disease is stage I, II, or IIIA. Surgical removal may be
performed by either tumor resection or orthotopic liver transplantation [38, 39].
The reported 5-year survival rate of patients after orthotopic liver
transplantation ranges from 58% to 75% [38] (Table 4). The results in Table 4
are from a highly selected population. For resection, the 5-year survival rate
ranges from 35% to 51% (Table 4). The recurrence rate after resection in one

series was reported to be as high as 33%, with a recurrence rate of 3-17% for
orthotopic liver transplantation [40]. Factors considered in the selection of
candidates for surgery are liver function, bilobar disease, biliary obstruction,
venous tumor extension, nodal involvement, and metastasis.
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TABLE 4 Survival Rates Reported in Literature for Various Treatment


Modalities for Hepatocellular Carcinoma
The 5-year survival rate of unifocal tumors smaller than 5 cm was reported in
one series to be 63% [41]. That report noted that larger tumors were associated
with indicators of poor outcome such as absence of capsule, multiple nodules,
satellite nodules, and vascular invasion.
Percutaneous ethanol injection, transarterial catheter embolization,
cryoablation, and radiofrequency ablation are secondary treatment options for
hepatocellular carcinoma [42,43,44]. Percutaneous ethanol injection for tumor
ablation has been reported to be the most effective form of direct ablation for
hepatocellular carcinoma in lesions smaller than 3 cm and fewer than three in
number (5-year survival rate, 36-68%). Percutaneous ethanol injection is
contraindicated in the presence of gross ascites, bleeding, or obstructive
jaundice. Radiofrequency ablation is a therapeutic option for hepatocellular
carcinoma for tumors smaller than 3 cm and has a 5-year survival rate of 45%.
In comparison with percutaneous ethanol injection, radiofrequency ablation
achieved tumor necrosis in fewer sessions [45]. Cryotherapy is an alternative
treatment for solitary tumors of 3-6 cm. The 5-year survival rate is 20%.
Cryotherapy is contraindicated for lesions near major vessels. Transarterial
catheter embolization uses combination agents to compromise the flow of the
hepatic artery. The agents include gelatin (Gelfoam), iodized oil (Lipiodol
[Guerbet, Aulnay-sous-Bois, France]), and a cytotoxic agent. Retreatment can
be performed in 6-12 weeks. The 5-year survival rate is reported to be 6-22%
(Table 4). The selective nature of hepatic artery infusion of chemotherapy

minimizes adverse effects while maximizing drug delivery to the tumor. A


hepatic artery infusion pump may be implanted in a selected number of
patients. Agents used include 5-fluorouracil, floxuridine, doxorubicin,
mithoxantrone, epirubicin, and cisplatin [43]. Radiotherapy is a welldocumented treatment, and proton therapy has recently been implemented
[46].
Systemic chemotherapy has been used with single and multiple agents
including 5-fluorouracil, interferon, cisplatin, thalidomide, octreotide, and
tamoxifen [43, 47].
Previous SectionNext Section
Summary
Hepatocellular carcinoma is one of the most common malignancies worldwide.
Imaging plays an essential role in the detection, diagnosis, staging, treatment,
and surveillance of these patients. Reports to clinicians should include all
pertinent diagnostic information for staging, including lesion size, number,
location, and the presence of adenopathy, ascites, cirrhosis, vascular
involvement, biliary tree involvement, and metastases. Despite advanced
imaging techniques and the large number of therapeutic options, the 5-year
survival rate remains dismal. Close surveillance with imaging now affords the
opportunity to diagnose recurrences early and to apply the most effective
therapy.
Previous SectionNext Section
Footnotes

Address correspondence to J. Szklaruk.

Received December 11, 2001.

Accepted July 9, 2002.

American Roentgen Ray Society

Previous Section

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