Liver Involvement in Autosomal-Dominant Polycystic Kidney Disease
Therapeutic Dilemma
DOMINIQUE CHAUVEAU,
FADI FAKHOURI and
JEAN-PIERRE GRÜNFELD
Department of Nephrology, INSERM U507,
Hôpital Necker, Paris, France.
Correspondence to Dominique Chauveau, Service de
Néphrologie,
Hôpital Necker, 149 rue de
Sèvres, 75015 Paris, France. Fax: 00 331 4449
5450; E-mail:
dominique.chauveau{at}nck.ap-hop-paris.fr
Liver involvement is the most frequent extrarenal manifestationin
autosomal-dominant polycystic kidney disease (ADPKD). Livercysts are
responsible for most hepatic complications, but otherliver changes may
occasionally be encountered, including congenitalhepatic fibrosis and
segmental dilation of the biliary tract.Both molecular and cellular changes
implicated in liver cystogenesishave recently been enlightened by advances in
genetics of ADPKDand the development of genetically modified animal models.
Althoughmost patients with ADPKD report no liver symptoms, some experience
chronicmanifestations related to progressive increase of the polycystic
liver.Ultimately, disability may severely affect their quality oflife. In
addition, a few develop acute complications that followa life-threatening
course. An armamentarium of surgical proceduresmay now be offered to the most
disabled patients, includingliver resection or transplantation. Because early
complicationsand mortality after either procedure remain frequent, the
hazardsof surgery have to be balanced against benefits; therefore,selection
of the optimum therapy still remains a challenge.This article focuses on
ADPKD patients with symptomatic liverinvolvement and provides guidelines for
therapy in polycysticliver disease (PLD).
In the general population, the prevalence of simple liver cystsdetected by
ultrasonography increases with age, reaching 4%at approximately 70 yr of age.
Paralleling findings on simplecysts in the kidney, most liver cysts are
solitary, but twoor three cysts are found in one fourth of the patients with
simplenonparasitic hepatic cysts. Polycystic liver as an isolateddisease may
be sporadic or dominantly inherited. Because nolarge systematic screening for
liver and renal cysts has beenperformed in relatives of the patients with
PLD, the respectiveprevalence of the hereditary and sporadic forms is not
known.In most cases, PLD is related to ADPKD and is linked eitherto
PKD1 (the main locus responsible for the disease) or to
PKD2.The isolated form of autosomal dominant PLD has been firmly
establishedas a distinct inherited disorder unlinked to PKD1 or
PKD2 (1).
In ADPKD, liver cysts seem to develop later than renal cysts.
Cross-sectionalstudies by ultrasonography or enhanced computed tomography
(CT)scan demonstrate a steady increase in frequency with advancingage.
Although liver cysts are very rare for people younger than20 yr, their
prevalence increases from 20% in the third to 70%in the seventh decade of
life, reaching a plateau beyond thisthreshold
(2). Why liver cysts do not
develop in some elderlyADPKD patients remains unknown. It is interesting that
CT scanquantitation in PLD has demonstrated no decrease in liver parenchymal
volumebut rather an increase in liver cyst volume
(3). Whether subtledifferences
regarding liver phenotype, such as age at onsetor prevalence, exist among
PKD1 and PKD2 families warrants furtherinvestigation.
Women are more prone to liver cystic involvement than are men.Liver cysts
are not only recognized earlier but also are morenumerous and larger in
females than in males. In the UnitedStates, it was found that the number of
pregnancies correlateswith the number of hepatic cysts. In addition, previous
useof estrogens was identified as a risk factor for harboring livercysts. In
postmenopausal women, a case-control study documentedthat a 1-yr course of
Premarin is associated with a 7% increasein liver volume resulting from
parallel changes of cystic andparenchymal volumes in the treatment group
versus a -2% changein the control group
(4). Whether use of nonequine
estrogens,as is currently practiced in most European countries, carriesa
similar risk is not known.
A minority of ADPKD patients develop massive cystic involvementof the
liver. Most are women. Familial aggregation for massiveliver cystic disease
is rare. Symptomatic PLD may occur in veryyoung women and contrast with the
mildness of renal involvement.For instance, in our experience, summarized in
1997 and basedon 37 ADPKD patients with massive hepatomegaly, 35 were females
andonly 1 of 110 ADPKD relatives had experienced symptomatic PLD
(5).Median age at first
hospitalization for liver symptoms was 46yr (range, 23 to 64 yr), and renal
involvement was extremelyheterogeneous; 47% of the patients had serum
creatinine below120 µmol/L, 22% had moderate to severe renal failure,and
21% were on regular dialysis. In contrast to the North Americandata, we found
that numerous pregnancies or use of estrogen-containingcontraceptives as not
a prerequisite for massive liver diseasebecause four women (11%) had never
used contraceptives and seven(20%) had never been pregnant. In summary,
epidemiologic evidencesuggests that a specific mutation is not implicated in
the liverphenotype in most cases but that the latter is strongly influenced
bythe hormonal environment.
Before identification of the primary molecular mechanism ofcystogenesis
(see below), PLD was regarded as a disorder ofthe development of small
intralobular bile ducts. Embryologicstudies suggest an abnormality of
remodeling of the ductal plate.Actually, liver cysts in ADPKD patients arise
from two differentstructures. Intrahepatic cysts originate from biliary
microhamartomas.The latter represent overgrowth of bile ductules. While
growing,they become disconnected from the bile ducts from which theyderive,
although the epithelial lining retains the distinctivecharacteristics of
biliary epithelia. These cysts are mostlylocated in the peripheral portions
of the liver, exhibitingan intraparenchymatous location on contrast-enhanced
CT. Theirdiameter varies from less than 5 mm to more than 10 cm. It is
surprisingthat peribiliary glands that surround large intrahepatic bileducts
also undergo cystic dilation in polycystic patients
(6).The corresponding cysts
typically are tiny and are located inthe hepatic hilum or surround the larger
portal tract.
Clonality in Liver Cysts and Lessons From Knockout Mice
Basic research has generated relevant techniques and informationregarding
liver cyst formation and progression. Immortalizedepithelial cell lines from
normal human intrahepatic biliaryepithelium and from ADPKD liver cysts is a
valuable tool todetermine how the function of the biliary epithelium is
alteredin ADPKD and how pharmacologic agents may prevent cyst development
(7).The pattern of expression
of polycystin-1 and polycystin-2 inliver cysts and kidney cysts is very
similar. Most liver cystsstained positive, and there was a striking
coincidence of expressionof the two polycystins; for example, each
polycystin-2—negativecyst in a PKD2 patient also lacked
polycystin-1 (8). Inactivating
somaticmutations have been found in liver cyst epithelia, like in renal
cysts,supporting the "two-hit" model as a unifying mechanism of
cystogenesis(9). Heterozygous
mice with targeted mutations in Pkd1
(10)or Pkd2
(11) develop liver cysts that
are indistinguishablefrom those found in ADPKD patients. In contrast,
homozygousmice that die in utero or early in the postnatal period
havea normal biliary system and no liver cysts, suggesting thatPkd1
and Pkd2 are required in the maintenance but not in theformation of
biliary ducts. These homozygous mice have renal(and pancreatic) cysts,
showing that as in human disease, livercysts develop later in life than do
kidney cysts. These resultssuggest that Pkd1± or
Pkd2± mice provide a relevantmodel of the
pathophysiology of ADPKD.
The risk of suffering a complication related to PLD is ill-defined.No
accurate assessment of its prevalence is available. Fifteenyears ago, in the
predialysis era, very little attention waspaid to liver complications, apart
from sporadic complicationsmentioned in case reports. In a first attempt to
delineate liverlesions in ADPKD patients on renal replacement therapy, we
wereimpressed by the severity of hepatic complications. Hepaticcyst
infection or cholangiocarcinoma was responsible for 10%of deaths, most
occurring in patients on regular dialysis
(12).In the most recent
period, it was shown that liver complicationshave a limited impact on outcome
and are less frequent on renalreplacement therapy than expected on the basis
of these earlyobservations
(2). A large experience in the
management of massivePLD has accumulated in several surgical series. We have
documenteda trend toward earlier liver morbidity, as exemplified by younger
ageat hospitalization for liver complications (19 to 64 yr) andless severe
renal involvement, with a 21% rate of patients onrenal replacement therapy.
Although recruitment bias may accountfor this trend, it is also possible that
changes in the exposureto estrogens have modified the natural history of
PLD.
Acute Complications of PLD
While most patients with polycystic liver have a "huge, silent,and
durable liver" (12),
those with PLD mostly complain of pain.Acute pain usually denotes acute
complication (see Table 1).
Rightabdominal pain and fever in the ADPKD patient should promptthe
physician to rule out infection of the right kidney andto consider infection
of a liver cyst. Concurrent elevationof liver enzymes is often found in the
latter. Approximately50% of the infections are nosocomial and complicate
percutaneousliver cyst fluid aspiration
(5). Spontaneous infection
predominantlyaffects patients on dialysis. Localization of the infected
cyst(s)may be difficult. The physician has to rely on imaging techniques.The
causative microorganism should be identified by blood cultureor puncture of
the suspected cyst. The physician should usea combination of antibiotics,
relying on drugs with proven penetrationin cysts, such as ciprofloxacin
(13) or amikacin
(5), and possiblyceftriaxone,
which is concentrated in bile. Drainage is nota prerequisite, but if
treatment with antibiotics fails, percutaneousdrainage or hepatic resection
should be considered (2,
13).Severe hemorrhage of
liver cysts may present with symptoms thatmimic those of an infected liver,
but this complication occursless frequently in our experience. Magnetic
resonance imagingdifferentiates best the hemorrhagic liver cyst from the cyst
withother complications, because it is associated with a hyperintensesignal
in T-1 and T-2 images. On very rare occasions, acutepain is associated with
torsion or rupture of massive livercyst with hemoperitoneum
(14).
Table 1. Liver complications in autosomal-dominant polycystic kidney
disease
Chronic Complications: PLD and the Massive Polycystic Liver
Chronic symptoms related to huge polycystic liver include abdominal
heavinessor distension, and intermittent or continuous pain. Mechanical
compressiondisplaces adjacent organs, including gut, diaphragm, and abdominal
wall,and is responsible for early satiety, dyspnea, abdominal hernias,and
uterine prolapse. At the end of the spectrum, extreme disability,
malnutrition,and physical exhaustion may be present.
In contrast to progressive deterioration of renal function overdecades,
hepatic function remains unaffected whatever the sizeof the liver. This is
ascribed to the preservation of liverparenchyma. Symptoms of liver failure
should prompt investigationfor a diagnosis other than PLD. However, in
massive PLD, moderateincreases in serum -glutamyl transferase or
alkaline phosphataseranging between 2 and 5 times the upper limit of normal
rangeare noted in two thirds and half of the patients, respectively.Serum
levels of aminotransferase or bilirubin are elevated infewer than 20% of the
cases. In addition, a poor nutritionalstatus is not rare in these patients,
as assessed by serum albuminand total cholesterol
(5,
15).
Complications Superimposed on Massive PLD
Ascites and variceal bleeding are uncommon in the polycysticpatient. The
initial workup should include routine analysisof the ascitic fluid, when
present, to rule out an infectiveprocess and endoscopic examination of the
upper gastrointestinaltract. If portal hypertension is diagnosed, then three
diagnosesshould be considered
(16). First, when few or no
liver cystsare demonstrable in the patients before 30 yr of age, congenital
hepaticfibrosis (see below) or liver cirrhosis should be suspected.Second,
mechanical compression of portal venous flow by livercysts may affect the
main portal vein or intrahepatic portalradicles causing portal hypertension.
In rare cases, varicealbleeding was the presenting symptom. Finally, when a
huge cysticliver is present (Figure
1), hepatic venous outflow obstruction(HVOO) is the most likely
diagnosis. In that case, obstructionis due to compression of hepatic veins or
of the inferior venacava or both by one or multiple cysts. At least 30
patientswith PLD and HVOO have been reported, most of them in threeseries
(5,
17,
18). Twenty-seven of them had
polycystic kidneys.Ascites is exudative and intractable. The high protein
contentof the ascitic fluid has been ascribed to high permeabilityof the
dilated sinusoidal walls to proteins. In rare cases,hepatic vein thrombosis
may be superimposed. Histologically,extensive sinusoidal dilation is found.
In addition, the lumenof small supralobular branches of the hepatic veins may
be narrowedor occluded by organized thrombi
(18).
Figure 1. Contrast-enhanced computed tomography (CT) scan showing massive polycystic
liver disease (PLD) with diffuse small cysts but a single large cyst and
ascites in a 57-yr-old female ADPKD patient. Only the caudate lobe was spared.
Serum creatinine was 105 µmol/l.
How can one diagnose hepatic venous outflow obstruction? Dopplerultrasound
and CT easily show compression of hepatic veins andthe inferior vena cava by
voluminous cysts in posterior location.Evidence of hepatic venous outflow
obstruction can be obtained
(1)by hemodynamic
studies showing a pressure gradient across thesite of obstruction,
(2) by cavography
demonstrating compressionand collateral circulation
(16),
(3) or by evidence of
hepaticvein occlusion. Magnetic resonance imaging permits assessmentof
patency and flow direction in the hepatic or portal veinsas well as the
inferior vena cava in PLD patients
(17).
Jaundice is rare and suggests bile duct compression in the portahepatis.
Low cardiac output with recurrent hypotension duringthe hemodialysis session
may be related to compromised bloodflow in the inferior vena cava as the
result of compressionby a cyst. Acute hepatic vein thrombosis and Budd-Chiari
syndromehave been reported after uni- or bilateral nephrectomy in ADPKD
patients(19). Progressive
hepatic failure has also been reported recently,but the underlying mechanism
remains unclear (20).
Complications Unrelated to Liver Cysts Congenital Hepatic Fibrosis. Congenital hepatic fibrosis (CHF)is a
constant feature of the recessive form of PKD. Nevertheless,CHF has now been
recognized in more than 20 patients with ADPKD.All cases reported so far
concerned PKD1 families (21).
In contrastto renal cystic disease, vertical transmission of liver
involvementwas not observed in these families, but some siblings were
affected.The molecular mechanism of such phenotypic variability has notbeen
elucidated (22). In CHF,
portal hypertension may be presentin early childhood or before 25 yr of age.
Spleen enlargementand variceal bleeding are prominent findings. If present,
ascitesis transudative. Liver cysts were detected in only two casesof CHF.
CHF may be associated with focal or diffuse cystic dilationof the segmental
bile ducts (Caroli's syndrome), which is wellvisualized by cholangio-CT or
Magnetic resonance cholangiography.Conventional treatment of portal
hypertension, including nonselectiveß-blockers, is indicated in these
patients.
Malignant Tumors. A few cases of cholangiocarcinoma have been
identified(12). An intriguing
association of malignant liver cysts andpancreatic cystadenocarcinoma has
been reported in two sisterswith ADPKD
(23).
Striking advances in liver surgery and transplantation havebeen made
recently, but the selection of the appropriate approachremains a challenge.
It has become appealing to reduce liversize in the most severely affected
patients, but surgery carriesa significant risk. There is no consensus
concerning the selectionof the patients, the optimal timing, and the best
mode of therapy.One should evaluate the patient for the presence of
discomfortand physical impairment related to liver size, superimposedliver
complications, and renal function, and overall physicalcondition should be
assessed. Finally, limitations and complicationsof surgery must be discussed
with the patient.
Aspiration of Cyst Fluid
Percutaneous aspiration should always be combined with sclerotherapyusing
alcohol or minocycline to minimize recurrence as a resultof fluid secretion
by the cyst wall. Sustained improvement isobserved in half of the patients,
and a second attempt is effectivein half of those with primary failure. Cyst
infection and peritonealor biliary leak of alcohol are the major risks of the
technique.Sclerotherapy should be considered if a limited number (fewerthan
5) of large cysts have to be treated
(Figure 2). It usuallyoffers
temporary relief.
Figure 2. Contrast-enhanced CT scan before (A) and 6 mo after (B) successful alcohol
sclerotherapy of two liver cysts responsible for painful protrusion underneath
the sternum.
Stenting
In selected patients, judicious stenting may reestablish flowpatency and
abolish pressure gradient as a result of cyst compressionin the portal or the
caval circulation. Percutaneous portalvenous stenting and transhepatic
portosystemic shunt (TIPS)were used in two patients who had contraindication
to majorliver surgery and who had variceal bleeding and refractory ascites,
respectively.Inferior vena cava stenting has also been used successfully
(Figure 3).
Figure 3. (A) Cavogram showing extrinsic compression of the inferior vena cava by a
liver cyst at the level of the hepatic vein. A pressure gradient of 12 mmHg
was documented across the segment compressed by the cyst. (B) Stenting of the
vena cava restored patency and achieved immediate relief of symptoms.
Cyst Fenestration
Resection or fenestration of the cyst wall has long been thestandard
treatment of symptomatic PLD
(24). It is mostly usedfor
superficial cysts. Large cysts in anterior, lateral, oreven superior location
expose a great proportion of their wall
(Figure 4).In contrast,
resection or fenestration is not effectivefor small cysts within the
parenchyma, which expose little oftheir surface. For instance, 5 of 13
patients treated by Fargeshad multiple small cysts and experienced
unsatisfactory results(24).
Postoperative ascites is the most common complication.After broad unroofing
of the cysts, fluid is secreted into theperitoneal cavity but it is readily
absorbed. Ascites occursif the daily rate of secretion exceeds the resorption
capacityof the peritoneum, i.e. approximately 900 ml in patients
withnormal renal function. Treatment of ascites is troublesome,especially in
patients with chronic renal failure, in whom ascitesmay follow a protracted
course. Some surgeons are reluctantto insert suction drains because they can
promote peritonealinfection. Diuretics may be effective. Repeated
paracentesisis often required. Anecdotal reports suggest that cimetidineor
somatostatin analogs may be of value by decreasing fluidsecretion
(25). Apart from ascites,
complications also includeinjuries to blood vessels or bile ducts adjacent to
the wallof the cysts. For experienced liver surgeons, fenestration isa
low-risk therapy. Nevertheless, in the long term, symptomsrecur in 23 to 57%
of cases (24,
26). Laparoscopic fenestration
hasbeen performed in PLD (27,
28). Advantages include rapid
recoveryand fewer postoperative adhesions. In the largest series, 11of 13
patients experienced initial improvement, but symptomsrecurred in 8 of them
within 6 to 24 mo. Recurrence occurredlater in patients in whom large cysts
predominated.
Figure 4. Contrast-enhanced CT scan of the abdomen showing few massive cysts in the
right lobe of the liver in a 46-yr-old female ADPKD patient with mild renal
involvement. Fenestration of the two largest cysts achieved long-lasting
improvement.
Cyst fenestration should be performed in symptomatic patientswith few
superficial large cysts (>5 cm in size except inposterior location) and
with moderate renal failure (serum creatinine< 200 µmol/L). Relief of
symptoms is usually achieved,morbidity is low, but recurrence is the rule.
When possible,the laparoscopic approach is recommended because it reduces
subsequentadhesions and can be repeated.
Liver Resection
Liver resection is more risky, because cysts distort the anatomyof the
liver. One attempts to remove the most affected cysticsegments, as assessed
by CT scan. An average of three to fourliver segments are usually removed by
anatomic or nonanatomicresection
(15,
22,
29). Transverse hepatectomy
has also beenrecently advocated in cases in which cysts are primarily located
inthe anterior segments (30).
Parenchymal transection is thencombined with fenestration of cysts.
Concomitant fulgurationof opened cystic cavities is achieved by using
electrocauteryor argon-beam coagulation. Even in the hands of experienced
liversurgeons, liver resection in PLD carries a substantial risk.Cumulative
data from series including at least five patientssuggest a mortality rate of
up to 42% (mean, 7.5%) (Table
2).Morbidity was reported in 37 to 83% of cases, including
ascites,hemorrhage, biliary leak, infection, and, more rarely, pancreatitis
(25,
30)or acute Budd-Chiari
syndrome (30). Renal function
is usuallynot permanently compromised by the surgical procedure. Liver
functionremains unaffected. Most symptoms related to hepatomegaly resolve,
andlimitation in daily activities as well as nutritional statusimprove
(15,
25,
26,
29,
31). Preoperative ascites
related tohepatic venous outflow obstruction may resolve
(15). Unfortunately,disabling
and long-lasting postoperative ascites is frequent,especially in patients
with severe renal failure or on hemodialysis.In three of our patients,
ascites disappeared only after paracentesiscombined with reinjection of the
ascitic fluid in the venousline during the dialysis session, or after renal
transplantation,respectively
(29).
Table 2. Results of liver resection in polycystic liver
diseasea
In the long run, almost all patients experience sustained improvement
(Figure 5)despite early
complications. In the largest series published,mean liver volume as estimated
by CT scan decreased from 9357cm3 to 3567 cm3 after
liver resection (15). Of note,
liver volumeremained stable postoperatively in almost all patients. However,
wehave observed marked enlargement of the liver in a 34-yr-oldwoman as a
result of expansion of residual cysts that requireda second resection 4 yr
after an initial successful procedure.Such late recurrence was also observed
in the youngest of the31 patients operated on at the Mayo Clinic
(15). Overall, massive
polycysticenlargement by small cysts is better treated by liver resection
thanby fenestration alone. As patients with severe renal failureseem to be
at higher risk of severe complications, we advocateconsidering liver
resection when serum creatinine is still below200 µmol/L.
Figure 5. CT before (top) and one year after (below) liver resection in a 46-yr-old
female ADPKD patient. Note enlarged left kidney.
Liver Transplantation
For diagnoses other than PLD, 1- and 5-yr survival rates afterliver
transplantation exceed 85 and 70% in most centers. Advancedrenal failure
before transplantation adversely affects postoperativesurvival. After
transplantation, the quality of life is excellentfor most recipients. In the
long run, immunosuppression canbe safely withdrawn in a minority of patients.
Liver transplantationis a drastic solution for the eradication of symptoms in
massivePLD. It has been rarely used in the treatment of PLD, becausepatients
typically present with preserved hepatocellular function.Excluding anecdotal
reports, six series of PLD patients treatedby liver transplantation are
available (Table 3). Among 51
patients,most had cystic kidneys, 90% were female. Before liver
transplantation,all had disabling PLD with severe reduction of normal
activities,and half of the patients had undergone cyst aspiration and/or
surgicalprocedures, without long-term improvement. A single patientpresented
with liver failure secondary to concomitant chronichepatitis B
(32). Combined liver/kidney
transplantation wasperformed in 22 patients (44% of cases). Combining all
series,mean follow-up was 4 yr (range, 0 to 11). Among the 51 patients,the
1-yr mortality rate was 18%. Most early deaths occurredwithin 2 mo after
transplantation and similarly affected liverand liver/kidney recipients.
Mortality was mainly the resultof severe superimposed infections in patients
whose conditionwas poor before transplantation
(33,
34). Two additional patients
died15 and 24 mo after combined liver/kidney transplantation. Theaverage
morbidity rate as a result of surgical complicationswas 42%. It was even
higher in patients in whom surgical procedureshad been performed before
transplantation.
Table 3. Characteristics of liver transplantation in 51 autosomal-dominant
polycystic kidney disease patients with polycystic liver disease
During a short follow-up (less than 18 mo), the course of renalfunction
after isolated liver transplantation in seven ADPKDpatients remained
unchanged in two and deteriorated in fivepatients. The mean decrease in
glomerular filtration rate was15 ml/min per year (7 to 37 ml/min per year),
and three patientsrequired hemodialysis within 3 to 5 yr. The rate of decline
wasthus higher than expected in ADPKD patients (-5 ml/min per year).These
data are consistent with an early decline in glomerularfiltration rate that
is found in liver transplant recipientswho do not have ADPKD, i.e.
minus 40 to 50% as early as 6 moafter transplantation
(35). In the subgroup of ADPKD
patientstreated with liver/kidney transplantation, accurate estimationof
renal function at transplantation is available in only ninepatients; three
were on regular dialysis, and the remainingpatients had moderate to severe
renal failure. The rationalefor preemptive renal transplantation in PLD
patients beforeend-stage renal failure has been reached was the fear that
administrationof cyclosporine A or FK506 would hasten the decline of renal
functionand precipitate the need for dialysis
(36). In addition, kidney
graftsurvival is significantly higher in liver/kidneys recipientsas compared
with kidney recipients alone, as the liver allograftprotects the kidney from
acute rejection (37). Is this
immunologicadvantage an argument for combined transplantation in patients
withPLD and renal cysts? Probably not. It is difficult to monitorthe renal
graft after preemptive kidney transplantation whilenative kidneys are still
present. Not unexpected, the diagnosisof acute rejection or graft thrombosis
has repeatedly been delayedin such patients
(32). Accordingly, several
authors warn againstpreemptive renal transplantation in PLD patients, at
least whenrenal failure is still mild to moderate.
Isolated orthotopic liver transplantation should be consideredin ADPKD
patients with severly disabling PLD when patients havediffuse cystic
involvement and portal hypertension or poor liverfunction or when liver
resection has failed or cannot be used
(Figure 6);ideally, it should
be performed before patients are in poorphysical condition. Combined
liver/kidney transplantation shouldbe restricted to patients with advanced
renal failure.
Figure 6. Contrast-enhanced CT scan of the abdomen in a 39-yr-old female patient with
ADPKD and massive polycystic liver disease with portal hypertension. Note
gastric compression and displacement of the inferior vena cava (top, left),
but only mild renal cystic disease. Liver transplantation was successful in
achieving long-term symptomatic relief.
Considerable insight into the pathogenesis and natural historyof PLD in
patients with ADPKD have been gained during the past2 decades. In the future,
clear identification of genetic andenvironmental modifiers will increase
understanding of the developmentand growth of liver cysts and help to
identify patients whoare at risk for developing an extreme liver phenotype.
In themeantime, for patient with massive liver cystic disease, itis
imperative to develop rational guidelines to establish theindications for
liver resection and liver transplantation, respectively,as well as their
optimal timing.
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Top
Introduction
Epidemiology
-glutamyl transferase or
alkaline phosphatase ranging between 2 and 5 times the upper limit of normal
range are noted in two thirds and half of the patients, respectively. Serum
levels of aminotransferase or bilirubin are elevated in fewer than 20% of the
cases. In addition, a poor nutritional status is not rare in these patients,
as assessed by serum albumin and total cholesterol
(5,
15). 
