British Columbia Medical Journal - May 2010: Liver transplantation: Current status in British Columbia
Mazhar Haque, MBBS, FRACP, Charles H. Scudamore, MD, FRCSC, Urs P. Steinbrecher,
MD, FRCPC, Stephen W. Chung, MD, FRCSC, Andrzej K. Buczkowski, MD, FRCSC,
Siegried R. Erb, MD, FRCPC, Eric M. Yoshida, MD, FRCPC
Current status in
While the number of liver transplants performed across North
America has increased, there has been an even greater increase in
the number of patients who are on a liver transplant wait list.
he first successful human liv- Today orthotopic liver transplan-
ABSTRACT: Orthotopic liver trans-
plantation has become an accepted er transplant was performed tation (OLT) has become an accepted
treatment for patients with acute or by Dr Thomas Starzl and his treatment for patients with acute or
chronic decompensated liver dis- colleagues in 1968 in Colorado on an chronic decompensated liver disease
ease of various causes. In British 18-month-old child who survived of various causes, as well as a form of
Columbia, liver transplantation has 400 days. Despite improved technical gene replacement therapy for several
been performed since 1989. Today aspects of transplant surgery, the 1-year systemic metabolic diseases in the
up to 35% of all transplantations are survival rates were not above 35% in absence of structural liver disease. In
done in patients with hepatitis C. the 1960s and 1970s, mainly because BC this most notably takes the form of
While there are few absolute con- of graft failure due to allograft rejec- urea cycle defects in adolescence.5
traindications to transplantation, tion. A major breakthrough in the field Approximately 400 liver transplants
there are some relative ones, includ- was the development of calcineurin are performed in Canada every year.
ing age and certain comorbidities. inhibitors, with a landmark paper In British Columbia liver transplanta-
After transplantation, the primary reporting 11 of 12 patients alive 1 year tion has been available since 1989.
care provider has an important role post-transplant on cyclosporine-based The number of transplants performed
to play in surveillance and treatment immunosuppresion.1 The availability increased from 3 in 1989 to 47 in 2008.
of the patient’s global health needs. of tacrolimus as an alternative to
Although post-transplant survival cyclosporine2 and the introduction of Dr Haque is a hepatology fellow in the
has been excellent, a tragic dispari- other immunosuppressive agents, in- Division of Gastroenterology at the Universi-
ty exists between organ availability cluding biologicals and mycopheno- ty of British Columbia. Dr Scudamore is
and need, which results in a 30% late mofetil, as well as refinements of an associate professor of surgery in the
mortality rate on the liver transplant surgical techniques, intensive care, Department of Surgery at UBC. Dr Stein-
wait list in BC. Careful patient selec- and diagnostic modalities, have led brecher is a professor of medicine in the Divi-
tion and optimal organ allocation is to current 1-year survival rates of 85% sion of Gastroenterology at UBC. Dr Chung
critical given the scarcity of this life- to 95% and 5-year survival rates of is a professor of surgery in the Department
saving resource. 75% after liver transplantation in BC of Surgery at UBC. Dr Buczkowski is a clini-
( Figure 1 ).3 In contrast, the expected cal associate professor of surgery in the
survival of a patient with Child class Department of Surgery at UBC. Dr Erb is a
C cirrhosis is in the order of 20% to clinical assistant professor of medicine in the
30% at 1 year. In addition to the sur- Division of Gastroenterology at UBC. Dr
vival benefit, liver transplantation Yoshida is a professor of medicine and head
provides patients with a distinct of the Division of Gastroenterology at UBC.
improvement in quality of life.4 All are affiliated with BC Transplant.
www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 203
Liver transplantation: Current status in British Columbia
100% Careful patient selection and proper
organ allocation are critical given the
90% scarcity of this life-saving resource.
The transplant team has an ethical
obligation to act in the best interests
of both the individual patient referred
for assessment and the entire group
of patients who are in need of trans-
plantation. 6 A successful outcome
Patient survival depends on optimal patient selection
Graft survival and timing.
0 1 2 3 4 5 6 7 8 9 10 General considerations
Years post-transplant A patient should be considered for
liver transplantation if this option
extends life expectancy and improves
Figure 1. Patient and graft survival for first liver transplants in BC, 1995–2004. quality of life beyond the expectation
Source: BC Transplant of the natural history of the underly-
ing liver disease. Current candidate
selection in BC occurs in two stages.
In the first stage, patients are asses-
sed to see if they are suitable to be
“activated” on the waiting list, and in
the second stage a decision is made
140 regarding which patient will receive a
120 given donor organ.
100 During assessment, scoring sys-
tems are used to determine patient sta-
tus and suitability. One of these sys-
35 36 32 tems is the model for end-stage liver
40 disease (MELD), which was original-
20 ly developed to estimate procedure-
0 related mortality in patients undergoing
2003 2004 2005
transjugular intrahepatic portosystem-
Referrals Transplants ic shunts.7 Today MELD is the most
commonly used prognostic model for
estimating disease severity and sur-
Figure 2. Number of referrals vs number of transplants in BC, 2003–2005.
vival in end-stage liver disease. It has
Source: BC Transplant
been prospectively validated in sever-
al patient populations and is currently
Initial referrals for liver transplant are on a liver transplant wait list. BC used by most transplant centres in the
assessment usually come from com- Transplant data for the number of world. The MELD score is based on
munity specialists with expertise in referrals for transplantation and the laboratory values for serum bilirubin,
the area who have decided that there number of transplants performed re- serum creatinine, and international
are no options other than transplanta- flect the situation across North Amer- normalized ratio (INR) in a log-
tion. While the number of liver trans- ica, and mean longer waiting times for transformed equation where Ln is
plants has increased across North very ill patients ( Figure 2 ). In recent the natural logarithm: (3.8[Ln serum
America, there has been a greater years the rate of death on the wait list bilirubin (mg/dL)] + 11.2[Ln INR] +
increase in the number of patients who has been approximately 30%. 9.6[Ln serum creatinine (mg/dL)] + 6.4).
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Liver transplantation: Current status in British Columbia
High MELD scores are associated with
a poor short-term prognosis. (An online
Acute fulminant Other Autoimmune chronic
MELD calculator that accepts SI units hepatitis 9% active hepatitis
is accessible at www.mdcalc.com/ 8% 6%
meld.) One of the requirements for Tumor
1% Chronic hepatitis
listing in the United Network for Type B
Organ Sharing in the US is a MELD Other chronic 10%
score of at least 14. With scores lower diseases
than 14, short-term prognosis without
transplantation is predicted to be Primary
similar or better than that with trans- cholangitis
plantation. Conversely, 3-month sur- 3%
vival drops to less than 20% in patients Primary Type C
with a MELD score of 40. Some of cirrhosis Cirrhosis alcoholic
these patients may be too sick for 12% 10%
The Child-Turcotte-Pugh (CTP)
is another scoring system for quanti- Figure 3. Liver transplants in BC by primary diagnosis, 2003–2005.
fying the severity of liver disease. It Source: BC Transplant
scores five variables: ascites, serum
albumin, bilirubin, INR, and encepha-
lopathy. CTP is less useful for assign- patients the best chance for a favor- ribavirin is associated with sustained
ing priority on a transplant wait list able outcome. virological response of approximately
because two of the parameters (ascites 27% (23% to 31%).12 Use of growth
and encephalopathy) are subjective. Chronic hepatitis C factors to support the hematological
Furthermore, it has not been validated Up to 35% of all liver transplantations parameters may improve compliance
as a reliable indicator of short-term are done in patients with chronic and success of antiviral therapy after
prognosis. For those reasons, MELD hepatitis C–related liver disease. Re- transplant.9 Immunoglobulin therapy
is now the only scoring system used in currence of HCV infection in the for HCV has been found to be inef-
the United States for allocating organs transplanted organ is universal,9,10 but fective.13
from deceased liver donors. In BC we the rate of progression is quite vari-
consider the global clinical assess- able. About 20% of patients develop Chronic hepatitis B
ment of the candidate as well as rapidly progressive fibrosis that may Significant improvements have been
MELD and CTP scores when allocat- lead to graft failure within a few years made recently in the treatment of
ing a donor organ. Patients who re- of transplantation. However, most chronic hepatitis B infection; howev-
ceive organs in BC have usually been studies show 5-year survival rates in er, liver transplantation remains the
diagnosed with the conditions and dis- HCV-positive recipients to be similar only option for many patients with
eases described below ( Figure 3 ). to those in HCV-negative recipients. end-stage liver disease due to HBV.
Some of these patients will have rela- After the incorporation of hepati-
Fulminant hepatic failure tively quiescent disease for many tis B immunoglobulin (HBIG) along
Fulminant hepatic failure (FHF) is the years, but in general the rate of fibro- with combination antiviral therapy,
acute onset of liver failure with devel- sis progression is faster in the trans- the 1- and 5-year survival rates of
opment of encephalopathy in a short planted liver than in the native liver. patients transplanted for HBV equals
period of time. Despite the differences Successful treatment of HCV before that of non-HBV transplant patients.14
in etiology, the progression of FHF is transplantation usually prevents post- Several reports show a combination
similar in all cases.8 Without liver operative recurrence but is often not of lamivudine and low-dose intramus-
transplantation, patients with FHF feasible. Unfortunately, antiviral treat- cular HBIG are effective in prevent-
will either have a complete recovery ment after liver transplantation is ing allograft reinfection by HBV at
of liver function or will die. Early often poorly tolerated.11 The combina- higher intravenous doses.15 Studies
referral to a transplant centre gives tion treatment of peginterferon and have also suggested that the rate of
www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 205
Liver transplantation: Current status in British Columbia
reinfection can be reduced further if non-ALD are comparable.18,19 waiting for an organ. Bridging mod-
the anti-HBs titers are kept consis- All Canadian transplant centres, alities such as transcatheter arterial
tently above 500 IU/L.16 A recent study as well as most American centres, chemoembolization, radiofrequency
of intramuscular low-dose HBIG (400 require a documented 6-month mini- ablation, percutaneous ethanol injec-
to 800 IU daily for 1 week then month- mum period of supervised abstinence tion, and surgical resection are also
ly) plus lamivudine (100 mg daily) in association with some form of alco- used in carefully selected patients.
following liver transplantation show- hol rehabilitation before transplanta-
ed patient survival was 92% at 1 year tion. Like BC, many centres expect Autoimmune hepatitis
and 88% at 5 years. A higher HBV patients to sign a contract to maintain Autoimmune hepatitis (AIH) is an ex-
DNA titer at baseline was associated abstinence. Six months of abstinence cellent indication for liver transplan-
with an increased risk of recurrence. with a good social support system is tation. Five-year patient and graft sur-
There is no consensus on the most associated with a favorable outcome.20 vival after liver transplantation range
appropriate initial antiviral therapy. A A 6-month abstinence requirement from 83% to 92%.25 There is a high
combination of lamivudine and ade- also gives patients a chance to recov- prevalence of autoimmune liver dis-
fovir/tenofovir, as well as entecavir, er spontaneously from advanced liver ease, specifically AIH and primary
along with HBIG is currently used in disease and thereby avoid transplanta- biliary cirrhosis (PBC), among British
our centre. Combination therapy allows tion. When transplantation is neces- Columbia’s First Nations people.26
more rapid viral suppression and min- sary, abstinence also affects immedi- Patients with autoimmune liver
imizes the risk of drug resistance when ate postoperative outcome. disease may have fairly rapid clinical
compared with using each of these decompensation after a long period of
drugs alone. Active immunization Hepatocellular carcinoma disease stability. Such episodes may
using standard hepatitis B vaccines Hepatocellular carcinoma (HCC) is not be well tolerated and thus permit
has been explored as an alternative to one of the most common cancers little time to undertake pre-transplant
lifelong HBIG prophylaxis. Unfortu- worldwide and is the most frequent assessment. Liver transplantation is
nately, anti-HBs titers achieved in the primary malignancy of the liver. It indicated for patients who are refrac-
responders were low despite the use ranks third among causes of cancer- tory to or intolerant of immunosup-
of higher doses and multiple courses related deaths. In the US, there has pressive therapy and develop end-
of vaccine.17 been a 70% increase in HCC over a stage liver disease. A subset of patients
20-year period, which is likely due to may present with fulminant hepatitis
Alcoholic liver disease the HCV epidemic,21 and similar trends and liver failure. All patients with ful-
Alcoholic liver disease (ALD) is the have been projected in a Canadian minant disease should be transferred
third most common indication for study.22 It is not uncommon to find to a liver transplant centre for moni-
liver transplant in British Columbia HCC in patients with viral hepatitis or toring and management. The rate of
and the second leading cause for trans- alcoholic liver disease during pre- acute and chronic allograft rejection
plant after viral hepatitis in many transplant assessment. Only selected and steroid-resistant rejection is high-
western countries, although the ALD patients with HCC who meet accept- er among AIH post-transplant patients.
group often has additional primary able criteria (Milan criteria) are con- The recurrence rate of primary dis-
liver disease causes (e.g., hepatitis C). sidered for transplant. ease is also higher—at least 17%.27
Due to the lack of consensus on a def- Vascular invasion is the most im-
inition for “relapse,” there is discrep- portant prognostic factor for HCC and Primary biliary cirrhosis
ancy among published reports of post- is present in up to 50% of tumors PBC is one of the most common indi-
transplant alcoholism relapse rates, greater than 5 cm.23 HCC is an aggres- cations for liver transplantation in
which range from less than 10% to sive tumor. The wait list dropout rate British Columbia and the rest of the
90%.18 as a result of tumor progression western world. The current 5-year sur-
Transplantation for alcoholic liver beyond acceptable criteria is between vival rate for liver transplant because
disease in an era of organ shortage and 5% and 20%.24 To overcome this prob- of PBC is 80% to 90%.28 Management
against a background of recidivism lem, a MELD score of 22 is automat- of progressive PBC requires predict-
raises both ethical and clinical con- ically assigned to high-risk HCC ing the prognosis and optimal time for
cerns. However, survival rates follow- patients (solitary lesions 2 to 5 cm or transplantation. A model developed at
ing liver transplant for both ALD and up to three lesions of 3 cm) currently the Mayo Clinic that does not require
206 BC MEDICAL JOURNAL VOL. 52 NO. 4, MAY 2010 www.bcmj.org
Liver transplantation: Current status in British Columbia
liver biopsy has been used for predic- Metabolic diseases tions in the recent past may no longer
tion.29 Prognosis is predicted from the Liver transplantation may play a vital even qualify as relative contraindica-
patient’s age, serum bilirubin, and role in the management of hemochro- tions. Current absolute contraindica-
al bumin concentrations, the pro- matosis, Wilson’s disease (WD), and tions include uncontrolled infection,
thrombin time, and the presence of alpha-1 antitrypsin deficiency. Liver extrahepatic malignancy, severe cardio-
edema. Of these variables, serum transplantation is the only effective pulmonary comorbidity, noncompli-
bilirubin concentration is the most option for those with WD who present ance, active substance abuse, advanced
heavily weighted. Patients should be with acute liver failure. It is also indi- hepatoma, and cholangiocarcinoma.
referred for transplant assessment cated for all patients with WD who Relative contraindications include
when their serum bilirubin concen- have decompensated liver disease un- extreme age and difficult psychoso-
tration approaches 100 µmol/L and responsive to medical therapy. Liver cial factors.
before it reaches 150 µmol/L.30
Primary sclerosing cholangitis
Liver transplantation is the treatment
of choice for patients with end-stage At present there are relatively few
primary sclerosing cholangitis (PSC). absolute contraindications to liver
Five-year survival after transplanta-
tion is as high as 85%.31 As it has for transplantation. Conditions that were
PBC, the Mayo Clinic has devised a considered as absolute contraindications
model for predicting lifespan in prima-
ry sclerosing cholangitis. It includes in the past may no longer even qualify as
age, serum bilirubin, serum albumin, relative contraindications.
serum AST, and a history of variceal
bleeding.32 The model suggests that
liver transplantation be undertaken
when the estimated 6-month survival
is less than 80%. A generally accepted transplantation corrects the hepatic A retrospective study of BC Trans-
list of indications in PSC also includes metabolic defects of WD and may nor- plant data collected from 1997 to 2001
quality-of-life issues such as intract- malize extrahepatic copper metabo- reveals that 150 of 737 patients re-
able itch or fatigue. lism.36 One-year survival following ferred for assessment were considered
Recurrence of PSC following liv- liver transplantation ranges from 79% unsuitable. Of these, 74 patients (49%)
er transplantation in up to 20% of to 87%. Data collected between 1997 were found unsuitable on medical
patients has been reported in several and 2006 from the United Network for grounds. The most common cause for
studies.33 The diagnosis of recurrence Organ Sharing indicate that recipients medical unsuitability was no need for
is based upon consistent findings on with a diagnosis of hemochromatosis liver transplant—29 patients (39%).
liver biopsy and cholangiography in had 1-, 3-, and 5-year survival rates Other medical causes included hepa-
the absence of other conditions that comparable to that of all other trans- toma or extrahepatic malignancy—20
could lead to similar findings, such as plant recipients.37 Transplantation may patients (27%)—and multisystem fail-
hepatic artery thrombosis, dominant also cure the underlying metabolic ure—12 patients (16%). Psychosocial
anastomotic stricture, or ABO blood disorder of alpha-1 antitrypsin defi- contraindication accounted for 73
group mismatched liver allograft. ciency since the metabolic defects patients (49%). Within this group,
The risk of cholangiocarcinoma is reside within the liver.38 failure to meet minimal alcohol absti-
increased in PSC patients, with report- nence criteria excluded the largest
ed life-time prevalence rates varying Contraindications number of patients (39, 53.4%) fol-
from 5% to 20%.34 Several reports and challenges lowed by unsatisfactory social sup-
have suggested that the incidence of At present there are relatively few port (12, 16.4%), medical noncompli-
colon cancer is increased in patients absolute contraindications to liver ance (10, 13.7%), and active substance
with ulcerative colitis and PSC who transplantation. Conditions that were abuse (6, 8.2%).39
undergo liver transplantation.35 considered as absolute contraindica-
www.bcmj.org VOL. 52 NO. 4, MAY 2010 BC MEDICAL JOURNAL 207
Liver transplantation: Current status in British Columbia
HIV vival in a study among HIV patients tive complications than a deceased
Prior to the introduction of highly was similar to that among age and race donor transplant. There are also sig-
active antiretroviral therapy (HAART), comparable patients without HIV.42 nificant risks to the donor that must be
the transplantation outcomes for pa- British Columbia is one of the few addressed when considering risks and
tients with human immunodeficiency centres in Canada that have been rou- benefits of LDLT versus deceased
virus infection were unfavorable.40 tinely assessing HIV patients with donor liver transplantation.
Because HIV and HCV have similar end-stage liver diseases for transplan-
tation. Complex drug interactions, Retransplantation
immunosuppressive dosing, and the Currently, retransplantation accounts
possibility of HCV recurrence are the for almost 10% of all liver transplants.
main issues that require the special Retransplantation is effective in the
Patients progressing consideration of an experienced mul- setting of primary nonfunction. Sur-
tidisciplinary team. vival after retransplantation for late-
beyond their 1-year
onset graft failure is less than after ini-
post-transplant Age tial transplantation.44 The outcome of
Transplantation in extreme-age pa- retransplantation for recurrent HCV is
anniversary will mostly
tients, either very young or old, is dif- poor and this remains a controversial
be stable and will need ficult. However, the age boundary is subject.
ever-changing. It has been reported
their primary care
that there are no differences in post- Role of the primary
providers to actively transplant outcomes in older versus care physician
younger patients in several centres. Primary care physicians play a very
Transplant can be successfully per- important role in liver transplantation.
surveillance and formed in patients as old as 70. In BC All physicians in BC need to under-
the general philosophy is to consider stand that the role of BC Transplant is
treatment of their
the “biological age” rather than the limited to assessment and investiga-
global health needs. “chronological age.” tion for transplant suitability and fea-
sibility in the pre-transplant period.
Comorbidities As pre-transplant referrals arise from
It is part of the assessment process to all regions of BC and the Yukon, it is
evaluate any existing comorbidity and not possible for the Liver Transplant
transmission routes, 16% to 29% of decide whether it increases surgical Program to assume primary and sec-
HIV-infected patients have coinfec- and anesthetic risk. Cardiovascular ondary care of these patients, so the
tion with hepatitis C.41 While survival and pulmonary morbidity, including community primary care physicians
of HIV infection is improving on coronary artery disease, need careful and specialists still need to follow
HAART, hepatitis-related end-stage consideration. Potential surgical prob- these patients. Post-transplant, the
liver disease has become a major lems such as portal vein thrombosis Liver Transplant Program follows all
cause of morbidity and mortality in and other anatomical difficulties re- patients carefully and manages all
this group. Patients with HIV and sulting from previous abdominal surg- post-transplant complications. How-
HCV coinfection progress faster to eries and trauma are also carefully ever, patients progressing beyond
cirrhosis than patients with HCV explored. their 1-year post-transplant anniver-
alone; the morbidity and mortality risk sary will mostly be stable and will
of end-stage liver disease and hepato- Living donor liver need their primary care providers to
cellular carcinoma is also increased. transplantation actively participate in surveillance
Patients can be considered for In response to the growing shortage and treatment of their global health
transplantation with a current CD4 of organs from deceased donors, adult needs.
count of more than 200 per mL, low living donor liver transplantation
HIV viral load, and limited oppor- (LDLT) was introduced in 1998.43 This Conclusions
tunistic complications with standard is a technically demanding procedure Over the past 20 years liver transplan-
listing criteria. The cumulative sur- and carries higher risks of postopera- tation has evolved in BC from a pro-
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Liver transplantation: Current status in British Columbia
cedure considered experimental to 506) and cyclosporine for immunosup- dian transplant hepatology workshop.
standard therapy for patients with end- pression in liver transplantation. N Engl J Can J Gastroenterol 2006;20:725-734.
stage liver disease. Today the main Med 1994;331:1110-1115. 10. Gane EJ, Portmann BC, Naoumov NV, et
limitation is the tragic disparity be- 3. Walker SR, Parsons DA, Coplestons P, et al. Long-term outcome of hepatitis C
tween organ availability and organ al. The Canadian Organ Replacement infection after liver transplantation. N
need. Given the scarcity of available Register. Clin Transpl 1996:91-107. Engl J Med 1996;334:815-820.
donor organs and the physiologically
demanding nature of every liver trans-
plant operation, candidates need to be
evaluated carefully for medical and
psychological comorbidities to im-
prove the post-transplant outcome. Given the scarcity of available donor
Although not all patients referred for
liver transplantation can undergo liver organs and the physiologically demanding
transplantation, the Liver Transplant nature of every liver transplant operation,
Program ensures that all are treated
fairly. candidates need to be evaluated carefully
to improve the post-transplant outcome.
On the 20th anniversary of the Liver Trans-
plant Program, the authors sincerely thank
the staff of the BC Transplant Society; the
nurses of the Solid Organ Transplant Ward,
the Solid Organ Transplant Clinic, the 4. Hunt CM, Tart JS, Dowdy E, et al. Effect 11. Watt KD, Lyden ER, McCashland TM.
Department of Pharmacy, the intensive of orthotopic liver transplantation on Poor survival after liver retransplantation:
care unit and the operating room staff of employment and health status. Liver Is hepatitis C to blame? Liver Transpl
the Vancouver General Hospital, and the Transpl Surg 1996;2:148-153. 2003;9:1019-1024.
staff of the Fraser Valley Transplant Clinic. 5. Sirrs S, Yoshida E, Wong L, et al. Ortho- 12. Rodriguez-Luna H, Khatib A, Sharma P, et
The authors especially thank the living relat- topic liver transplantation in a patient with al. Treatment of recurrent hepatitis C
ed donors and the families of the cadaver- carbamyl phosphate synthetase defi- infection after liver transplantation with
ic organ donors, without whom lifesaving ciency and cystic fibrosis. Paediatr Child combination of pegylated interferon
liver transplantation would not be possible. Health 2003;8:497-498. alpha2b and ribavirin: An open-label
6. Yoshida EM. Selecting candidates for series. Transplantation 2004;77:190-194.
Competing interests liver transplantation: A medical ethics 13. Davis GL, Nelson DR, Terrault N, et al. A
Dr Steinbrecher served on an Astellas Phar- perspective on the microallocation of a randomized, open-label study to evaluate
ma advisory board for clinical trials in 2009 scarce and rationed resource. Can J Gas- the safety and pharmacokinetics of
and received a liver transplant fellow troenterol 1998;12:209-215. human hepatitis C immune globulin
stipend from 2004 to 2009. Dr Yoshida has 7. Kamath PS, Wiesner RH, Malinchoc M, (Civacir) in liver transplant recipients.
received honoraria and unrestricted re- et al. A model to predict survival in Liver Transpl 2005;11:941-949.
search grants from a range of pharmaceu- patients with end-stage liver disease. 14. Steinmuller T, Seehofer D, Rayes N, et al.
tical companies, including Roche, Scher- Hepatology 2001;33:464-470. Increasing applicability of liver transplan-
ing-Plough, Gilead, and Novartis. 8. Ostapowicz G, Fontana RJ, Schiodt FV, tation for patients with hepatitis B-relat-
et al. Results of a prospective study of ed liver disease. Hepatology 2002;35:
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