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Hepatology Research 2015; 45: 1248–1250
doi: 10.1111/hepr.12490
Case Report
Living donor liver transplantation using a graft with periportal fibrosis Yusuke Mitsuka,1,2 Takuya Hashimoto,1 Takeshi Takamoto,1 Kazuto Inoue,1 Yoshikazu Maruyama,1 Satoshi Ogata,1 Michiharu Komatsu,3 Shu-ichi Ikeda,3 Tadatoshi Takayama2 and Masatoshi Makuuchi1 1
Department of Hepato-Biliary-Pancreatic-Transplantation Surgery, Japanese Red Cross Medical Center, and Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, and 2Third Department of Medicine, Shinshu University School of Medicine, Shinshu, Japan
3
A 57-year-old woman with familial amyloid polyneuropathy (FAP) was scheduled to undergo living donor liver transplantation (LDLT), but the operation was cancelled because the only potential donor had chronic alcohol-related liver disease. One year later, FAP-related neurological symptoms progressed rapidly, and emergency LDLT was planned. The donor’s hepatic function had returned to normal range after 1 year of abstinence. The left liver graft volume was equivalent to 37.7% of the standard liver volume (SLV) of the recipient. However, a liver biopsy revealed
mild fibrosis (score, F1). LDLT was successfully performed without any complications. The recipient’s neurological findings returned to normal. One year after LDLT, the liver graft volume was equivalent to approximately 90% of the SLV, and the fibrosis had improved. LDLT using a graft with a fibrosis score of up to F1 may be an acceptable alternative for recipients with normal hepatic function.
INTRODUCTION
However, extended criteria for LDLT remain unclear as compared with DDLT owing to concerns about the donor’s safety.5 We describe our experience with a patient who received a liver transplant from a donor who had a history of chronic alcohol-related liver disease (ALD) accompanied by periportal fibrosis as confirmed by liver biopsy. To our knowledge, this is the first time to document the postoperative course of a liver graft with fibrosis and the long-term pathological changes of the graft.
L
IVING DONOR LIVER transplantation (LDLT) is sometimes not performed because an appropriate donor is unavailable owing to problems with hepatic function, medical history and graft size. Grafts from deceased donors are predominantly used in most countries. Deceased donor liver transplantation (DDLT) is performed in only approximately 1% of all recipients of liver transplants in Japan. One solution to the shortage of liver grafts is to extend the donor criteria. However, extended criteria donors in DDLT remain controversial because they include factors such as advanced age, fatty liver, medical history such as systemic disease and abdominal surgery, and vascular anomalies.1,2 Therefore, extended donor criteria remain a matter of debate. Recently, DDLT has been performed using organs from extended criteria donors positive for hepatitis virus.3,4
Correspondence: Dr Masatoshi Makuuchi, Department of Hepato-BiliaryPancreatic-Transplantation Surgery, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. Email: masatoshi. [email protected] Received 25 September 2014; revision 28 December 2014; accepted 7 January 2015.
© 2015 The Japan Society of Hepatology
Key words: donor criteria, fibrosis, live donor
CASE REPORT
A
57-YEAR-OLD WOMAN was scheduled to undergo LDLT. She had a family history of familial amyloid polyneuropathy (FAP), which affected her parents, uncle, aunt, elder brother and niece. The FAP-related neurological findings included impaired sense of touch, pain and temperature in both lower legs and decreased deep tendon reflex. The donor was a 58-year-old man, 154 cm tall and weighed 56.7 kg (body mass index, 23.9%). He had consumed 90 g/day of alcohol for 24 years. The operation was postponed because the only potential donor, her husband, had chronic ALD and hypercholesterolemia. In the liver biopsy specimen obtained at the initial assessment, fibrosis with portal-to-portal and portal-to-central (P-C)
1248
Hepatology Research 2015; 45: 1248–1250
bridging were observed. The portal area was expanded by the infiltration of neutrophils and lymphocytes. There was 5–10% mild lipid deposition in the liver, while Mallory bodies and cellular ballooning were not observed (Fig. 1a). The Model for End-Stage Liver Disease (MELD) score was 6; however, her gait disorder was progressing, thus requiring that transplantation be performed as soon as possible. The donor subsequently abstained from alcohol for 1 year, and a slight recovery in the laboratory data was observed (the aspartate aminotransferase level was unchanged from 24 IU/L to 24 IU/L, while the alanine aminotransferase level decreased from 28 IU/L to 25 IU/L
Graft with periportal fibrosis
1249
and the γ-glutamyltransferase level decreased from 34 mU/L to 24 mU/L). In the second liver biopsy sample, slight liver fibrosis scored as F1 in the liver parenchyma remained; however, the portal P-C bridging was not found at the time of donation (Fig. 1b). The scheduled left liver graft volume was equivalent to 37.7% of the standard liver volume (SLV) of the recipient. This graft volume was adequate, but the presence of fibrosis in the scheduled liver graft did not meet the donor criteria at our hospital. Although liver grafts from donors with chronic ALD associated with fibrosis are usually excluded, the hepatic function was normal, with an indocyanine green retention rate at 15 min (ICG-R15) of 9.0% and a scheduled remnant liver volume of 66.5%, thus suggesting that the safety of the donor would not be compromised. Furthermore, because the primary disease of the recipient was FAP with normal hepatic function, we concluded that her husband was eligible as a donor. Therefore, this LDLT was approved by the Japanese Red Cross Medical Center ethics committee, and written informed consent was obtained from the patients. A left liver graft with the middle hepatic vein was harvested from the donor, who had no complications and was discharged on postoperative day 14. The liver function of recipient normalized within approximately a month. There were no significant complications observed in the recipient, and she was discharged after an appropriate postoperative follow up. The liver volume was equivalent to 83.6% of the SLV (777 cm3) 1 month after operation, further increasing to 90.3% (839 cm3) at 1 year, which is comparable with the volume after LDLT in patients without liver fibrosis.6 The disappearance of inflammatory cell infiltration in the small bile ducts and an amelioration of hepatic fibrosis in the graft were confirmed (Fig. 2).
DISCUSSION IVER GRAFTS WITH up to F1 fibrosis are marginally acceptable as donor organs, whereas those with F2 or more fibrosis should not be used for DDLT.7 Transplantation of liver grafts with mild fibrosis from donors who are positive for hepatitis C virus (HCV+) to HCV+ recipients results in outcomes comparable with those obtained when grafts negative for HCV are transplanted to HCV+ recipients.8,9 In contrast, persons with hepatic fibrosis are usually unacceptable as donors for LDLT. Liver grafts with fibrosis are assumed to carry increased risks of postoperative morbidity and mortality in LDLT, although the actual risks remain unclear owing to the paucity of adequate studies.10 However, we used a donor organ with a fibrosis score of F1
L
Figure 1 (a) In the liver biopsy specimen obtained at the initial assessment, fibrosis with portal-to-portal (P-P) bridging and mild portal-to-central bridging were observed. Findings of fibrosis clearly seen on Masson-trichrome staining. (b) Liver biopsy before transplantation revealed mild steatosis (5–10%). A view at lower magnification, fibrosis was scored as F1 on the basis of incomplete P-P bridging (original magnifications: [a] ×5; [b] ×5).
© 2015 The Japan Society of Hepatology
1250
Hepatology Research 2015; 45: 1248–1250
Y. Mitsuka et al.
although the regeneration rate may be related to the degree of hepatectomy.12 In our patient, the liver volume increased to approximately 80% and 90% of the SLV 1 month and 1 year after operation, respectively, thus indicating that the regeneration rate was comparable to that of normal transplanted liver grafts. Although further studies of LDLT using liver grafts with fibrosis are needed, our results suggest that LDLT using a graft with a fibrosis score of up to F1 may be an acceptable alternative for recipients with a normal hepatic function.
REFERENCES
Figure 2 Results of liver biopsy 1 year after transplantation, showing very mild fibrosis. Fibrosis as well as fatty liver had also improved (original magnification ×10).
because the recipient had FAP with normal liver function. The donor’s residual liver volume (66.5%) was adequate, and the ICG-R15 value (9.0%) was normal. On the basis of Makuuchi’s criteria, 33.5% of the liver can be safely resected from a donor with an ICG-R15 of 19% or less.11 The criteria used to determine liver graft volume in our hospital are as follows: (i) 30% or more residual liver for the donor; (ii) 35% or more SLV for recipients with a MELD score of less than 15; and (iii) 40% or more SLV for recipients with a MELD score of 15 or more. Therefore, a low risk for the donor and no critical issues for LDLT other than fibrosis were the primary reasons for using a liver graft from the scheduled donor. Auxiliary partial orthotopic liver transplantation (APOLT) was a useful option in the present case. The liver function in the donor recovered to within the normal range, pathological improvement was observed and the volume was 37.7% of the SLV, which was adequate. Moreover, the recipient had a healthy status in terms of the liver function except for FAP, and APOLT requires an additional operation. Therefore, we judged that conventional LDLT would be safe using a left liver graft in this patient. To our knowledge, a liver graft with fibrosis due to chronic liver disease has not been used previously as an extended criteria donor graft for LDLT. Although fibrosis was still seen on biopsy of the liver graft in the recipient 1 year after operation, its severity was very mild, and not only steatosis and inflammatory cell infiltration, but also fibrosis had improved. Liver regeneration has been reported to be inferior in patients with cirrhosis than in those without cirrhosis,
© 2015 The Japan Society of Hepatology
1 Barshesa NR, Horwitz IB, Franzini L, Vierling JM, Goss JA. Waitlist mortality decreases with increased use of extended criteria donor liver grafts at adult liver transplant centers. Am J Transplant 2007; 7(5): 1265–1270. 2 Mehrabi A, Fonouni H, Muller SA, J Schmidt. Current concepts in transplant surgery: liver transplantation today. Langenbecks Arch Surg 2008; 393: 245–60. 3 Maluf DG, Edwards EB, Kauffman HM. Utilization of extended donor criteria liver allograft: Is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient? Transplantation 2006; 82: 1653–57. 4 Silberhumer GR, Pokorny H, Hetz H et al. Combination of extended donor criteria and changes in the Model for End-Stage Liver Disease score predict patient survival and primary dysfunction in liver transplantation: a retrospective analysis. Transplantation 2007; 83(5): 588–92. 5 Trotter JF. Selection of donors for living donor liver transplantation. Liver Transpl 2003; 9: S2–S7. 6 Kobayashi T, Imamura H, Aoki T, Sugawara Y, Kokudo N, Makuuchi M. Morphological regeneration and hepatic functional mass after right hemihepatectomy. Dig Surg 2006; 23: 44–50. 7 Claire Melin, Ronald Miick, Young Nancy A, Ortiz J, Balasubramanian M. Approach to Intraoperative Consultation for Donor Liver Biopsies. Arch Pathol Lab Med 2013; 137(2): 270–4. 8 Testa G, Goldstein RM, Netto G et al. Long-term outcome of patients transplanted with livers from hepatitis C-positive donors. Transplantation. 1998; 65(7): 925–9. 9 Velidedeoglu E, Desai NM, Campos L et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation. 2002; 73(4): 582–7. 10 Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 2002; 12: 1114–1122. 11 Imamura H, Seyama Y, Kokudo N et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg 2003; 138(11): 1198–1206. 12 Kawasaki S, Makuuchi M, Ishizone S, Matsunami H, Terada M, Kawarazaki H. Liver regeneration in recipients and donors after transplantation. Lancet 1992; 3: 580–1.
Hepatology Research 2015; 45: 1248–1250
doi: 10.1111/hepr.12490
Case Report
Living donor liver transplantation using a graft with periportal fibrosis Yusuke Mitsuka,1,2 Takuya Hashimoto,1 Takeshi Takamoto,1 Kazuto Inoue,1 Yoshikazu Maruyama,1 Satoshi Ogata,1 Michiharu Komatsu,3 Shu-ichi Ikeda,3 Tadatoshi Takayama2 and Masatoshi Makuuchi1 1
Department of Hepato-Biliary-Pancreatic-Transplantation Surgery, Japanese Red Cross Medical Center, and Department of Digestive Surgery, Nihon University School of Medicine, Tokyo, and 2Third Department of Medicine, Shinshu University School of Medicine, Shinshu, Japan
3
A 57-year-old woman with familial amyloid polyneuropathy (FAP) was scheduled to undergo living donor liver transplantation (LDLT), but the operation was cancelled because the only potential donor had chronic alcohol-related liver disease. One year later, FAP-related neurological symptoms progressed rapidly, and emergency LDLT was planned. The donor’s hepatic function had returned to normal range after 1 year of abstinence. The left liver graft volume was equivalent to 37.7% of the standard liver volume (SLV) of the recipient. However, a liver biopsy revealed
mild fibrosis (score, F1). LDLT was successfully performed without any complications. The recipient’s neurological findings returned to normal. One year after LDLT, the liver graft volume was equivalent to approximately 90% of the SLV, and the fibrosis had improved. LDLT using a graft with a fibrosis score of up to F1 may be an acceptable alternative for recipients with normal hepatic function.
INTRODUCTION
However, extended criteria for LDLT remain unclear as compared with DDLT owing to concerns about the donor’s safety.5 We describe our experience with a patient who received a liver transplant from a donor who had a history of chronic alcohol-related liver disease (ALD) accompanied by periportal fibrosis as confirmed by liver biopsy. To our knowledge, this is the first time to document the postoperative course of a liver graft with fibrosis and the long-term pathological changes of the graft.
L
IVING DONOR LIVER transplantation (LDLT) is sometimes not performed because an appropriate donor is unavailable owing to problems with hepatic function, medical history and graft size. Grafts from deceased donors are predominantly used in most countries. Deceased donor liver transplantation (DDLT) is performed in only approximately 1% of all recipients of liver transplants in Japan. One solution to the shortage of liver grafts is to extend the donor criteria. However, extended criteria donors in DDLT remain controversial because they include factors such as advanced age, fatty liver, medical history such as systemic disease and abdominal surgery, and vascular anomalies.1,2 Therefore, extended donor criteria remain a matter of debate. Recently, DDLT has been performed using organs from extended criteria donors positive for hepatitis virus.3,4
Correspondence: Dr Masatoshi Makuuchi, Department of Hepato-BiliaryPancreatic-Transplantation Surgery, Japanese Red Cross Medical Center, 4-1-22 Hiroo, Shibuya-ku, Tokyo 150-8935, Japan. Email: masatoshi. [email protected] Received 25 September 2014; revision 28 December 2014; accepted 7 January 2015.
© 2015 The Japan Society of Hepatology
Key words: donor criteria, fibrosis, live donor
CASE REPORT
A
57-YEAR-OLD WOMAN was scheduled to undergo LDLT. She had a family history of familial amyloid polyneuropathy (FAP), which affected her parents, uncle, aunt, elder brother and niece. The FAP-related neurological findings included impaired sense of touch, pain and temperature in both lower legs and decreased deep tendon reflex. The donor was a 58-year-old man, 154 cm tall and weighed 56.7 kg (body mass index, 23.9%). He had consumed 90 g/day of alcohol for 24 years. The operation was postponed because the only potential donor, her husband, had chronic ALD and hypercholesterolemia. In the liver biopsy specimen obtained at the initial assessment, fibrosis with portal-to-portal and portal-to-central (P-C)
1248
Hepatology Research 2015; 45: 1248–1250
bridging were observed. The portal area was expanded by the infiltration of neutrophils and lymphocytes. There was 5–10% mild lipid deposition in the liver, while Mallory bodies and cellular ballooning were not observed (Fig. 1a). The Model for End-Stage Liver Disease (MELD) score was 6; however, her gait disorder was progressing, thus requiring that transplantation be performed as soon as possible. The donor subsequently abstained from alcohol for 1 year, and a slight recovery in the laboratory data was observed (the aspartate aminotransferase level was unchanged from 24 IU/L to 24 IU/L, while the alanine aminotransferase level decreased from 28 IU/L to 25 IU/L
Graft with periportal fibrosis
1249
and the γ-glutamyltransferase level decreased from 34 mU/L to 24 mU/L). In the second liver biopsy sample, slight liver fibrosis scored as F1 in the liver parenchyma remained; however, the portal P-C bridging was not found at the time of donation (Fig. 1b). The scheduled left liver graft volume was equivalent to 37.7% of the standard liver volume (SLV) of the recipient. This graft volume was adequate, but the presence of fibrosis in the scheduled liver graft did not meet the donor criteria at our hospital. Although liver grafts from donors with chronic ALD associated with fibrosis are usually excluded, the hepatic function was normal, with an indocyanine green retention rate at 15 min (ICG-R15) of 9.0% and a scheduled remnant liver volume of 66.5%, thus suggesting that the safety of the donor would not be compromised. Furthermore, because the primary disease of the recipient was FAP with normal hepatic function, we concluded that her husband was eligible as a donor. Therefore, this LDLT was approved by the Japanese Red Cross Medical Center ethics committee, and written informed consent was obtained from the patients. A left liver graft with the middle hepatic vein was harvested from the donor, who had no complications and was discharged on postoperative day 14. The liver function of recipient normalized within approximately a month. There were no significant complications observed in the recipient, and she was discharged after an appropriate postoperative follow up. The liver volume was equivalent to 83.6% of the SLV (777 cm3) 1 month after operation, further increasing to 90.3% (839 cm3) at 1 year, which is comparable with the volume after LDLT in patients without liver fibrosis.6 The disappearance of inflammatory cell infiltration in the small bile ducts and an amelioration of hepatic fibrosis in the graft were confirmed (Fig. 2).
DISCUSSION IVER GRAFTS WITH up to F1 fibrosis are marginally acceptable as donor organs, whereas those with F2 or more fibrosis should not be used for DDLT.7 Transplantation of liver grafts with mild fibrosis from donors who are positive for hepatitis C virus (HCV+) to HCV+ recipients results in outcomes comparable with those obtained when grafts negative for HCV are transplanted to HCV+ recipients.8,9 In contrast, persons with hepatic fibrosis are usually unacceptable as donors for LDLT. Liver grafts with fibrosis are assumed to carry increased risks of postoperative morbidity and mortality in LDLT, although the actual risks remain unclear owing to the paucity of adequate studies.10 However, we used a donor organ with a fibrosis score of F1
L
Figure 1 (a) In the liver biopsy specimen obtained at the initial assessment, fibrosis with portal-to-portal (P-P) bridging and mild portal-to-central bridging were observed. Findings of fibrosis clearly seen on Masson-trichrome staining. (b) Liver biopsy before transplantation revealed mild steatosis (5–10%). A view at lower magnification, fibrosis was scored as F1 on the basis of incomplete P-P bridging (original magnifications: [a] ×5; [b] ×5).
© 2015 The Japan Society of Hepatology
1250
Hepatology Research 2015; 45: 1248–1250
Y. Mitsuka et al.
although the regeneration rate may be related to the degree of hepatectomy.12 In our patient, the liver volume increased to approximately 80% and 90% of the SLV 1 month and 1 year after operation, respectively, thus indicating that the regeneration rate was comparable to that of normal transplanted liver grafts. Although further studies of LDLT using liver grafts with fibrosis are needed, our results suggest that LDLT using a graft with a fibrosis score of up to F1 may be an acceptable alternative for recipients with a normal hepatic function.
REFERENCES
Figure 2 Results of liver biopsy 1 year after transplantation, showing very mild fibrosis. Fibrosis as well as fatty liver had also improved (original magnification ×10).
because the recipient had FAP with normal liver function. The donor’s residual liver volume (66.5%) was adequate, and the ICG-R15 value (9.0%) was normal. On the basis of Makuuchi’s criteria, 33.5% of the liver can be safely resected from a donor with an ICG-R15 of 19% or less.11 The criteria used to determine liver graft volume in our hospital are as follows: (i) 30% or more residual liver for the donor; (ii) 35% or more SLV for recipients with a MELD score of less than 15; and (iii) 40% or more SLV for recipients with a MELD score of 15 or more. Therefore, a low risk for the donor and no critical issues for LDLT other than fibrosis were the primary reasons for using a liver graft from the scheduled donor. Auxiliary partial orthotopic liver transplantation (APOLT) was a useful option in the present case. The liver function in the donor recovered to within the normal range, pathological improvement was observed and the volume was 37.7% of the SLV, which was adequate. Moreover, the recipient had a healthy status in terms of the liver function except for FAP, and APOLT requires an additional operation. Therefore, we judged that conventional LDLT would be safe using a left liver graft in this patient. To our knowledge, a liver graft with fibrosis due to chronic liver disease has not been used previously as an extended criteria donor graft for LDLT. Although fibrosis was still seen on biopsy of the liver graft in the recipient 1 year after operation, its severity was very mild, and not only steatosis and inflammatory cell infiltration, but also fibrosis had improved. Liver regeneration has been reported to be inferior in patients with cirrhosis than in those without cirrhosis,
© 2015 The Japan Society of Hepatology
1 Barshesa NR, Horwitz IB, Franzini L, Vierling JM, Goss JA. Waitlist mortality decreases with increased use of extended criteria donor liver grafts at adult liver transplant centers. Am J Transplant 2007; 7(5): 1265–1270. 2 Mehrabi A, Fonouni H, Muller SA, J Schmidt. Current concepts in transplant surgery: liver transplantation today. Langenbecks Arch Surg 2008; 393: 245–60. 3 Maluf DG, Edwards EB, Kauffman HM. Utilization of extended donor criteria liver allograft: Is the elevated risk of failure independent of the model for end-stage liver disease score of the recipient? Transplantation 2006; 82: 1653–57. 4 Silberhumer GR, Pokorny H, Hetz H et al. Combination of extended donor criteria and changes in the Model for End-Stage Liver Disease score predict patient survival and primary dysfunction in liver transplantation: a retrospective analysis. Transplantation 2007; 83(5): 588–92. 5 Trotter JF. Selection of donors for living donor liver transplantation. Liver Transpl 2003; 9: S2–S7. 6 Kobayashi T, Imamura H, Aoki T, Sugawara Y, Kokudo N, Makuuchi M. Morphological regeneration and hepatic functional mass after right hemihepatectomy. Dig Surg 2006; 23: 44–50. 7 Claire Melin, Ronald Miick, Young Nancy A, Ortiz J, Balasubramanian M. Approach to Intraoperative Consultation for Donor Liver Biopsies. Arch Pathol Lab Med 2013; 137(2): 270–4. 8 Testa G, Goldstein RM, Netto G et al. Long-term outcome of patients transplanted with livers from hepatitis C-positive donors. Transplantation. 1998; 65(7): 925–9. 9 Velidedeoglu E, Desai NM, Campos L et al. The outcome of liver grafts procured from hepatitis C-positive donors. Transplantation. 2002; 73(4): 582–7. 10 Ryan CK, Johnson LA, Germin BI, Marcos A. One hundred consecutive hepatic biopsies in the workup of living donors for right lobe liver transplantation. Liver Transpl 2002; 12: 1114–1122. 11 Imamura H, Seyama Y, Kokudo N et al. One thousand fifty-six hepatectomies without mortality in 8 years. Arch Surg 2003; 138(11): 1198–1206. 12 Kawasaki S, Makuuchi M, Ishizone S, Matsunami H, Terada M, Kawarazaki H. Liver regeneration in recipients and donors after transplantation. Lancet 1992; 3: 580–1.
