Liver Transplantation in a Monolung Patient: A Strategy of Sequential Treatments of Multiple Lung Tuberculosis Ca-vitations and Hepatocellular Carcinoma on Hepatitis B Related Virus Cirrhosis

doi:10.4236/ss.2011.25057

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Surgical Science, 2011, 2, 257-261

doi:10.4236/ss.2011.25057 Published Online July 2011 (http://www.SciRP.org/journal/ss)

Liver Transplantation in a Monolu ng Patient: A Strategy of

Sequential Treatments of Multiple Lung Tuberculosis

Cavitations and Hepatocellular Carc inoma on Hepatitis B

Related Virus Cirrhosis

Dino Donataccio1, Paola Del Bravo2, Albert o Masotto3, Marcello Ceola4, Francesco Calabrò5,

Matteo Donataccio1*

1Liver Transplant Unit, Ospedale Civile Maggiore, Verona, Italy

2 Infectious Disease Unit, Ospedale Po liclinico, Verona, Italy

3Gastroenterology Unit, Ospedale Sacro Cuore-Don Calabria, Negrar, It al y

4Anesthesia and Resuscitation Unit, Ospedale Civile Maggiore, Verona, Italy

5Thoracic Surgery Unit, Ospedale Civile Maggiore, Verona, Italy

E-mail: [email protected]

Received April 18, 2011; revised May 27, 2011; accepted June 8, 2011

Abstract

The presence of extrahepatic infection is a contraindication for liver transplantation, even more if supported

by an advanced pulmonary tuberculosis with persistent cavitation not curable with medical treatment. We

report a case of a young patient with hepatocellular carcinoma on hepatitis B virus related liver cirrhosis and

multiple lung tuberculosis cavitations. The patient was referred to our centre for liver transplantation. We

adopted a strategy with sequential treatments. First a left extra-pericardial pneumonectomy was performed

without opening the infected cavern, followed by a therapy with rifampicin, isoniazid and ethambutol for a

period of nine months. After the cure of tuberculosis, the monolung patient eventually was listed for liver

transplantation. An accurate planning of a multistep therapeutical strategy, an appropriate anesthetic man-

agement and a meticulous surgical technique allowed to successfully transplant a young patient suffering

from three life-threatening diseases: cavitary tuberculosis, hepatitis B virus cirrhosis and hepatocellular car-

cinoma. Thirty months after liver transplantation the patient is in good health, with normal liver function,

forced expiratory volume in one second of 42% (1.53 liters) and without any tuberculosis disease reactiva-

tion.

Keywords: Mycobacterium Tuberculosis, Infection, Pneumonectomy, Liver Disease, Liver Surgery

1. Introduction

Tuberculosis (TB) is a serious infection due to Myco-

bacterium Tuberculosis, with an estimated prevalence of

13.7 million cases world-wide [1]. The frequency of the

disease varies geographically, with particular regions

(Asia and Africa) having a higher prevalence than other

areas of the world [2]. Several factors place transplanted

patients at a greater risk of developing active TB. A pre-

vious TB infection increases the likelihood of TB devel-

oping after transplantation [3]. The number of pre-trans-

plant patients with a positive tuberculin skin test (TST)

underestimates the number of patients infected with TB

because end-stage liver disease may result in cutaneous

anergy, which decreases the sensitivity of the TST. Pa-

tients with compensated cirrhosis should be considered

for the treatment of TB. Patients with decompensated

cirrhosis should defer therapy to the period after trans-

plantation. Patients with active TB should not undergo

transplantation; exceptions might be considered for pa-

tients with well-controlled infections. In general, active

TB is an absolute contraindication for transplantation [4].

The presence of extrahepatic infection is a contraindica-

tion for liver transplantation, even more if supported by

an advanced pulmonary tuberculosis with persistent

cavitation not curable with medical treatment. The aim of

D. DONATACCIO ET AL.

258

this study was to demonstrate that liver transplantation,

usually contraindicated in presence of pulmonary tuber-

culosis with persistent cavitation, can be successfully

performed using such sequential treatments strategy.

2. Case Report

A 30 years old black man, born in Sub Saharan Africa,

with hepatocellular carcinoma (HCC) induced by hepati-

tis B virus (HBV) chronic liver disease was referred to

our centre for liver transplantation in April 2006.

In 2003 the patient underwent cholecystectomy and at

that time HBV related liver cirrhosis and active pulmo-

nary tuberculosis were diagnosed. Subsequently, pulmo-

nary TB was treated in Africa in 2003 with streptomycin

(STP), isoniazid (INH) and pyrazinamide (PZA) for two

months followed by INH and ethambutol (ETB) for one

month. The reason for the withdrawal of the anti TB

treatment was not clear. Two years later the patient was

treated again due to a relapse of TB with rifampicin

(RPM), ETB and ciprofloxacin (CIP) for eight months.

At the end of the treatment, a chest tomography revealed

cavitary evolution in the left lung, the largest cavitation

had a diameter of five centimeter with no signal of active

infection.

In January 2006 liv er cirrhosis was co mplicated by the

detection of two masses of HCC (VII and VIII seg ments,

both two centimeter in diameter) which were treated by

percutaneous ethanol injections. Subsequently, the pa-

tient was evaluated for a liver transplantation. In June

2006 during the pre-transplant assessment, a chest com-

puted tomography revealed a large parenchyma effusion

in the left lung (Figure 1) suggesting an active infection

that was a contraindication for liver tran splantation.

In December 2006 a relapse of HCC (VII segment

nodule) was treated by selective transarterial chemoem-

bolization using embosphere-biosphere gauge of 100 -

300 micron.

In January 2007, a computed tomography of the liver

revealed a residual of HCC (Figure 2); in addition, he

suffered a decompensation of the liver cirrhosis with

massive ascites, portal hypertension and esophageal

varices. At this time the patient was reconsidered for

liver transplantation with mayo end-stage liver disease

Figure 1. Chest computed tomography scan show pulmonary tuberculosis and left lung cavitation.

Figure 2. Abdomen co mpute d tomography sc an show liver cirrhosis and hepatocellular carcinoma.

D. DONATACCIO ET AL.259

(MELD) HCC 22 .

While the sputum culture was negative for acid-alcohol

resistant bacillus, based on a chest computed to mography

TB infection of the major pulmonary cavitation was still

present at lung framework. Therefore, we planned a

pre-transplant surgical treatment of the end-stage pul-

monary TB disease due to a major risk for relapse of

infection in post-transplant period.

In May 2007 a left extrapericardial pneumonectomy

was performed without opening the infected cavern and

with covering the bronchial stump with intercostal mus-

cle (Figure 3).

The histological examination described pulmonary

emphysema, with interstitial fibrosis and multiple granu-

lomatous giant cells lesions, sometimes necrotizing and

calcified. The Ziehl-Neelsen stain did not reveal acid-fast

bacilli.

Subsequently, a therapy with RPM, INH and ETB was

begun in October 2007.

The rationale for the third treatment was the non con-

ventional schedule of the previous treatments especially

for patients listed for liver transplantation and the high

suspicion of recurrence of disease despite the negative

culture for Koch’s bacillus. The treatment was well toler-

ated and prolonged until the liver transplantation for a

total period of nine months.

The patient was listed for transplantation in February

2008 with mayo end-stage liver disease (MELD) HCC

22, mild pulmonary hypertension with systolic pulmo-

nary artery pressure of 35 mmHg and diastolic pulmo-

nary pressure of 18 mmHg. Forced expiratory volume in

one second (FEV1) was 42% (1 .53 liters), left ventricu lar

ejection fraction (EF) 63%, estimated right ventricular

telesystolic pressure 37 mmHg and the patient at high

peri-operative risk (ASA IV).

Finally, the patient underwent liver transplantation in

June 2008 with a whole size graft from a deceased donor.

The liver transplantation was performed using a mini-

transplant procedure as described previously (Figure 4)

[5]. The total hepatectomy was performed preserving the

recipient’s vena cava and the graft was implanted using a

latero-lateral caval anastomosis.

The liver transplantation proceeded without any com-

plications with peri-operative hemodynamic stability.

Intra-operatively 3000 ml of crystalloid and 2000 ml of

fresh-frozen-plasma were given. No red blood cells

transfusions were infused during the surgical procedure.

Cold ischemia time was 330 minutes and warm ischemia

time 30 minutes.

The anesthesiologic management consisted of induc-

tion via TIVA method (propofol, remifentanil, cisatracu-

rium), cardiovascular monitoring via Swan-Ganz and

VigileoTM catheter and a lung protectiv e mechanical ven-

tilation. The combined use of different hemodynamic

monitoring enabled an accurate optimization of the

volemic expansion by adapting it to operating phases.

Central venous pressure (CVP) was 6 mmHg and pul-

monary capillary wedge pressure (PCWP) 12 mmHg.

The histological examination described macro and

micro nodular liver cirrhosis, with two poorly differenti-

ated (G3) hepatocellular carcinoma, which measured

three and two centimeter in diameter, respectively. These

masses of HCC were partially capsulated, with extensive

necrotic areas and vascular carcinomatous aspects.

The intensive care unit (ICU) stay lasted 4 days. The

patient was extubated six hours after operation and

started oral alimentation on the first post-operative day.

The whole hospital stay lasted two months and ascites

persisted for three months post-operatively.

After the transplantation we decided not to start with

INH prophylaxis according to previous reports of trans-

planted patients well treated for TB before [6].

Immunosuppression was based on low doses tac-

rolimus (blood trough level of 5 ng/ml) and steroids.

After thirty months the patient is in good health with nor-

mal liver function and without any tuberculosis disease

Figure 3. Chest computed tomography scan after left pneumonectomy and be fore liver transplantation.

D. DONATACCIO ET AL.

260

Figure 4. Minitransplant procedure with right subcostal

incision after 12 months of follow-up.

reactivation so far. No episodes of biopsy proven acute

cellular rejection was recorded .

3. Discussion

The management of TB disease in patients with end-stage

liver disease candidated for liver transplantation requires

a multidisciplinary approach to minimize the risk of drug

toxicity and relapse of disease in the post-transplant pe-

riod.

Reports in literature regarding transplanted patients

with recent history of active tuberculosis are scarce and

only describe patients who underwent liver transplanta-

tion because of hepatic failure due to anti TB treatment

[7,8]. Moreover, there is no universal consensus about the

prophylactic regimen following a documented TB disease

[6].

As reported in our case, the left lung was completely

affected by cavernous evolution of TB as confirmed by

histological report. Thus, the only possible treatment was

the surgical approach with a left pneumonectomy. On the

other hand, pneumonectomy involves important cardio-

respiratory changes that affect surgical and anesthetic

management of liver transplantation.

In our case, we have adopted an approach with se-

quential treatments, that combined with an appropriate

anesthetic management and a meticulous surgical tech-

nique allowed to successfully transplant a young patient

suffering from three life-threatening diseases: cavitary

tuberculosis, HBV cirrhosis and hepatocellular carci-

noma. Due to the concern of a possible reinfection, we

used a low dose immunosuppressive regimen (tacrolimus

dose of 1 mg per day with a blood trough level of 5

ng/ml, switched after two years to everolimus 1.5 mg per

day with a blood trough level of 4 ng/ml, and steroids 2.5

mg per day). Furthermore, an active surveillance al-

lowed us to preserve the patient from TB reinfection

without post-transplant therapy after thirty months fol-

low-up. Neither cases of liver transplantation in monolung

patients nor similar cases have been reported in the lite-

rature so far.

6. References

[1] WHO Report 2009, “Global Tuberculosis Control: Epi-

demiology, Strategy, Financing,” Geneva, World Health

Organization, 2009.

[2] A. Subramanian and S. Dorman, “Mycobacterium Tu-

berculosis in Solid Organ Transplant Recipients,”

American Journal of Transplantation, Vol. 9, No. s4,

2009, pp. S57-S62.

doi:10.1111/j.1600-6143.2009.02894.x

[3] J. M. Aguado, J. Torre-Cisneros, J. Fortun, N. Benito, Y.

Meije, A. Doblas, et al., “Tuberculosis in Solid-Organ

Transplant Recipients: Consensus Statement of the Group

for the Study of Infection in Transplant Recipients (GE-

SITRA) of the Spanish Society of Infectious Diseases and

Clinical Microbiology,” Clinical Infectious Diseases, Vol.

48, No. 9, 2009, pp. 1276-1284. doi:10.1086/597590

[4] B. R. Yehia and E. A. Blumberg, “Mycobacterium Tu-

berculosis Infection in Liver Transplantation,” Liver

Transplantation, Vol. 16, No. 10, 2010, pp. 1129-1135.

doi:10.1002/lt.22133

[5] M. Donataccio, G. Dalle Ore and D. Donataccio, “The

Ministransplant Procedure in Liver Transplantation,”

Acta Gastroenterol Belg, Vol. 73, No. 3, 2010, pp.

367-369.

[6] S. Nagai, Y. Fujimoto , K. Tair a, H. Egawa, Y. T akada, T.

Kiuchi, et al., “Liver Transplantation without Isoniazid

Prophylaxis for Recipients with a History of Tuberculo-

sis,” Clinical Transplantation, Vol. 21, No. 2, 2007, pp.

229-234. doi:10.1111/j.1399-0012.2006.00630.x

[7] R. Barcena, E. Oton, M. A. Moreno, J. Fortùn, M. Gar-

cia-Gonzalez, A. Moreno, et al., “Is Liver Transplanta-

tion Advisable for Isoniazid Fulminant Hepatitis in Ac-

tive Extrapulmonary Tuberculosis?” American Journal of

Transplantation, Vol. 5, No. 11, 2005, pp. 2796-2798.

doi:10.1111/j.1600-6143.2005.01065.x

[8] K. L. Nash, T. M. Yeung, P. J. Lehner, P. Gibbs and W. J.

Griffiths, “Orthotopic Liver Transplantation for Subacute

Hepatic Failure Following Partial Treatment of Isoni-

azid-Resistant Tuberculosis,” Transplant Infectious Dis-

ease, Vol. 10, No. 4, 2008, pp. 272-275.

doi:10.1111/j.1399-3062.2007.00277.x

D. DONATACCIO ET AL.

261

Abbreviations

TB: tuberculosis; TST: tuberculin skin test; HCC: hepa-

tocellular carcinoma; HBV: hepatitis B virus; STP:

streptomycin; INH: isoniazid; PZA: pyrazinamide; ETB:

ethambutol; RPM: rifampicin; CIP: ciprofloxacin.