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Hepatology Research 2015; 45: 1041–1046

doi: 10.1111/hepr.12445

Case Report

Successful resolution of very severe hepatopulmonary syndrome following adult-to-adult living donor liver transplantation: Report of two cases Toshimitsu Irei,1,2 Takashi Onoe,1,2 Lalit Kumar Das,1 Naoki Tanimine,1 Kohei Ishiyama,1 Kentaro Ide,1 Tsuyoshi Kobayashi,1 Hirotaka Tashiro1 and Hideki Ohdan1 1 Department of Gastroenterological and Transplant Surgery, Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, Hiroshima, and 2Institute for Clinical Research, National Hospital Organization Kure Medical Center/Chugoku Cancer Center, Kure, Japan

Hepatopulmonary syndrome (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Liver transplantation (LT) is a promising treatment for HPS; however, very severe HPS, which is defined by an arterial oxygen pressure (PaO2) of less than 50 mmHg and a right–left intrapulmonary shunt rate of more than 20%, may be a contraindication to LT, including living donor LT (LDLT). Here, we report two cases of decompensated liver cirrhosis with very severe HPS which were resolved after adult-to-adult LDLT including ABO-incompatible LDLT. Both patients required oxygen supportive therapy in combination with specialized respiratory care postoperatively, followed by improvement of oxygenation and substantial decreases of intrapulmonary

shunt rate. These findings suggest very severe HPS can be resolved by LDLT, including ABO-incompatible LDLT, and reduced graft volume did not impede the reversal of intrapulmonary shunting. Our current report may indicate that adultto-adult LDLT, including ABO-incompatible LDLT, is becoming an effective therapeutic method and prompt a review of previous reports as well as our own files with particular regard to the indication of LDLT for decompensated liver cirrhosis with very severe HPS.

INTRODUCTION

report the successful resolution of two cases of very severe HPS following adult-to-adult LDLT, including one case of ABO-incompatible LDLT.

H

EPATOPULMONARY SYNDROME (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Reports have shown that HPS may be treated with orthotopic liver transplantation (LT).1 Nonetheless, high mortality rates have been reported in patients with very severe HPS, which is defined by an arterial oxygen pressure (PaO2) of less than 50 mmHg and a right–left (R-L) shunt rate of more than 20%.2 Furthermore, only a few cases of adult-toadult living donor LT (LDLT) and no ABO-incompatible cases of patients with HPS have been reported. Here, we

Correspondence: Dr Takashi Onoe, Department of Gastroenterological and Transplant Surgery Applied Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima City, Hiroshima 734-8551, Japan. Email: [email protected] Received 26 May 2014; revision 8 October 2014; accepted 21 October 2014.

© 2014 The Japan Society of Hepatology

Key words: ABO-incompatible, hepatopulmonary syndrome, living donor liver transplantation

CASE REPORTS Patient 1

A

57-YEAR-OLD WOMAN was diagnosed with hepatitis C virus (HCV)-related cirrhosis. She had exertional dyspnea and was referred to our hospital for a detailed examination and further treatment. Blood tests and physical examination revealed liver cirrhosis with a Child–Turcotte–Pugh (CTP) classification of C and a calculated Model for End-Stage Liver Disease (MELD) score of 13. Arterial blood gas (ABG) analysis showed severe hypoxemia at room air (RA) (pH, 7.474; pCO2, 33.1 mmHg; pO2, 41.4 mmHg) and alveolar–arterial pO2 gradient (A-a DO2) was 67.3 mmHg (Table 1). Technetium-99m macroaggregated albumin perfusion (99mTc-MAA) scan showed a significant R-L shunt of 55%

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Hepatology Research 2015; 45: 1041–1046

Table 1 Pre- and postoperative results of pulmonary function test of two patients

Patient 1 Patient 2

Age, years

Sex

Primary disease

57 55

Female Male

HCV HCV

Pre-LDLT

Post-LDLT

A-a DO2 (mmHg, at RA)

PaO2 (mmHg, at RA)

PaO2 (mmHg, at 100% O2)

A-a DO2 (mmHg, at RA)

PaO2 (mmHg, at RA)

67.3 63.1

41.4 42.1

116.0 285.1

33.7 61.7

72.2 60.2

A-a DO2, alveolar-arterial oxygen difference; LDLT, living donor liver transplantation; PaO2, partial pressure of arterial oxygen; RA, room air.

(Fig. 1a). There was no evidence of primary cardiac or pulmonary disease. An abdominal computed tomography (CT) scan showed liver cirrhosis and growth of a splenorenal shunt suggesting severe portal hypertension (Fig. 2a,b). She was diagnosed with decompensated

a

liver cirrhosis complicated by very severe HPS. Oxygen therapy and pulmonary rehabilitation was introduced. The patient was referred to our department for LDLT and she underwent LDLT using the left lobe from her son. The graft–recipient weight ratio (GRWR) was

c Pre-LT

Pre-LT

Shunt:55.0% b

Shunt:35.8% d

Post-LT

Shunt:12.9%

© 2014 The Japan Society of Hepatology

Post-LT

Shunt:17.6%

Figure 1 Technetium-99m macroaggregated albumin perfusion (99mTcMAA) scan showing resolution of a right–left (R-L) shunt after living donor liver transplantation (LT) in two patients with severe hepatopulmonary syndrome. Pre- (top) and post-LT (bottom) 99mTc-MAA scan images of patients 1 (a,b) and 2 (c,d) are shown. Pre-LT 99mTc-MAA scan showed abnormal accumulations in both kidneys while post-LT images showed reduction of abnormal accumulation in kidneys. Indicated number represents shunt rate (%) which was calculated using the following equation: (whole-body count – lung count) × 100 / wholebody count.

Hepatology Research 2015; 45: 1041–1046

Figure 2 Abdominal computed graphy (CT) of patients 1 (a,b) (c,d). Abdominal CT showing liver cirrhosis (a,c) and growth splenorenal shunt (b,d).

Resolution of HPS following adult LDLT

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0.74%. At the time of the surgery, the pre-explant portal vein pressure was 25 mmHg, and it decreased to 18 mmHg after reperfusion. She received postoperative immunosuppressive therapy with tacrolimus, basiliximab and a small dose of steroids. After the LDLT, rehabilitation for respiratory dysfunction and inactivity was introduced immediately after surgery. Hypoxemia did not improve immediately after LDLT. We used the Trendelenburg position and lateral rotation during intubation and even after extubation for severe hypoxemia. Despite the graft functioning well after LDLT, she showed a persistent hypoxia and required oxygenation support for a few weeks after extubation. She did not experience any fatal perioperative complications, although she developed a focal pneumonia as well as a herpes zoster infection on her right leg, which were treated with antibiotic and antiviral drugs, respectively. Under frequent oxygen titration and physical rehabilitation, the oxygen requirement gradually decreased (Fig. 3a). The calculated R-L shunt rate dramatically resolved 2 months after LDLT (12.9%) (Fig. 1b). She was discharged on foot on postoperative day (POD) 71 with home oxygen therapy (HOT), which was discontinued 1 month after discharge. Interferon (IFN) and ribavirin therapy was introduced at 3 months after LDLT, and a sustained viral response was achieved.

Her liver graft continued to function well, without HPS or HCV recurrence, 48 months after the surgery.

Patient 2 A55-year-old man was diagnosed with HCV-related cirrhosis. He had received endoscopic sclerotherapy twice for esophageal varices. He presented with progressive exertional dyspnea and was referred to our hospital for a detailed examination and further treatment. Blood tests and a physical examination revealed liver cirrhosis with a CTP classification of B and a calculated MELD score of 13. An ABG test showed severe hypoxemia at RA (pH, 7.469; pCO2, 35.9 mmHg; pO2, 42.1 mmHg) and an A-a DO2 of 63.1 mmHg (Table 1). A 99mTc-MAA scan showed a significant R-L shunt of 35.8% (Fig. 1c) without any evidence of primary cardiac or pulmonary disease. An abdominal CT scan showed severe growth of a splenorenal shunt and dilatation of the umbilical vein suggesting severe portal hypertension (Fig. 2c,d). HOT was introduced for hypoxemia. However, his dyspnea gradually deteriorated. He was referred to our department for LDLT, and perioperative respiratory rehabilitation was introduced. He underwent an ABOincompatible LDLT (blood type A to O) using the right lobe from his wife.

© 2014 The Japan Society of Hepatology

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(a) 400

PaO2/FiO2 ratio

LDLT Extubation Pneumonia Discharge

Herpes zoster

300

Post-LT scintigram

200

100 0.5 1.0 0.6 Oral IPPV

0

0.4 Oral, nasal, oxygen tent

0

30

60

0.28 FiO2

71 (POD)

(b) 400

PaO2/FiO2 ratio

LDLT leukoencephalopathy

300 Extubation

Post-LT scintigram

Dead

any fatal surgery-related complications, although he developed leukoencephalopathy on POD 8. When he suffered from leukoencephalopathy, his respiratory function was transiently deteriorated and we applied non-invasive positive pressure ventilation (NIPPV) to him to support oxygenation. After introduction of NIPPV, his oxygen requirement gradually lessened along with improvement in his liver function (Fig. 3b). Six months after LDLT, his calculated R-L shunt rate and PaO2/FiO2 ratio markedly improved (17.5% and 254, respectively) (Fig. 1d) compared with those at preoperation. He continued rehabilitation using nasal oxygenation. However, he died of liver dysfunction 16 months after the LDLT resulting from HCV reinfection and rapid progression to cirrhosis despite IFN therapy from 7 months after the LDLT. There was no evidence showing a rebound of anti-blood group A antibody or humoral rejection.

200 IFN

DISCUSSION

Rivabirin

100 1.0 0.28 0.5

0.5

0.5

0.28

0.5 FiO2

Oral, nasal, NIPPV

0

0

90

180

270

360

459 (POD)

Figure 3 Schemas showing the clinical courses of patients 1 (a) and 2 (b). IFN, interferon; IPPV, invasive positive pressure ventilation; LDLT, living donor liver transplantation; NIPPV, non-invasive positive pressure ventilation; PaO2, partial pressure of arterial oxygen; POD, postoperative day.

We introduced desensitization therapy against B cells responding to blood group carbohydrates based on our preliminary result to avoid humoral rejection with antiCD20 monoclonal antibody (rituximab, 500 mg/body on POD-7 and 100 mg/body on POD 0), calcineurin inhibitor (CNI) (tacrolimus) and mycophenolate mofetil (MMF) at 7 days before LDLT.3 The natural antibody was removed by four plasma exchanges. His antiblood group A immunoglobulin M/G titer fell from ×64/×64 to ×2/×4 until LDLT. The calculated GRWR was 0.85 and the pre-explant portal vein pressure fell from 24 mmHg to 17 mmHg after reperfusion during LDLT. The patient received postoperative immunosuppressive therapy with tacrolimus, MMF and a low dose of steroids. Steroids were rapidly tapered because of the high HCV titer. After LDLT, respiratory and physical rehabilitation were immediately introduced at POD 1. After extubation on POD 3, he required oxygenation by an oral mask or nasal cannula. The patient did not have

© 2014 The Japan Society of Hepatology

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EPATOPULMONARY SYNDROME IS a progressive complication of end-stage liver disease that affects 10–30% of patients with cirrhosis and portal hypertension.4–6 The diagnostic criteria for HPS are: (i) chronic liver disease or portal hypertension; (ii) hypoxemia (PaO2 20 mmHg); and (iii) intrapulmonary vascular dilation or shunt.7 Some methods including pharmaceutical reagents (e.g. methylene blue, indomethacin, almitrine, octreotide), inhaled NO and transjugular intrahepatic portosystemic shunt placement were previously reported as effective treatments for HPS.8 However, those methods showed variable or only transient therapeutic efficacy.9 At present, LT has been recognized as the most promising and radical treatment for liver failure with HPS.10 The indication for LT in patients with very severe HPS (PaO2

Successful resolution of very severe hepatopulmonary syndrome following adult-to-adult living donor liver transplantation: Report of two cases.

Hepatopulmonary syndrome (HPS) is a severe complication in patients with chronic liver disease with poor prognosis. Liver transplantation (LT) is a pr...
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