Komokata et al. Surgical Case Reports(2020) 6:131
https://doi.org/10.1186/s40792-020-00898-7

CASE REPORTOpen AccessCentral hepatectomy for hepatocellular
carcinoma in a patient with anti-Gerbich
antibody
Teruo Komokata1* , Maki Inoue1, Bibek Aryal1, Hiroto Yasumura1, Chinami Mori2, Mituharu Nomoto2,
Mamoru Kaieda1 and Shuichi Hanada3

Abstract
Background: Anti-Gerbich (Ge) alloantibody against high-frequency erythrocyte antigen is extremely rare. Owing toincomplete evidence regarding the degree and severity of adverse events induced by hemolytic transfusion reactions,the transfusion management often remains cumbersome in these patients. We report an anti-Ge alloantibody positive
patient with hepatocellular carcinoma (HCC) who underwent central hepatectomy (CH) without the need for an
allogeneic blood transfusion.
Case presentation: A 76-year-old Japanese woman was diagnosed with HCC measuring 9.5 × 8.0 cm in segments 4,5, and 8 of the liver. This patient with anti-Ge alloantibody had a history of two pregnancies without transfusion. CH
was planned, and based on the suggestion from the multidisciplinary team meeting, preoperative autologous
donation (PAD) and acute normovolemic hemodilution (ANH) were performed. CH was successfully performed byusing CUSA and Thunderbeat® with Pringle maneuver and infra-hepatic inferior vena cava clamping without
perioperative need for an allogeneic blood transfusion. She has been alive without recurrence after a follow-up periodof 45 months.
Conclusion: To our knowledge, this is the first case report of hepatectomy in a patient with anti-Ge alloantibody. A
multidisciplinary team approach, PAD and ANH, and bloodless liver surgical techniques appear to be useful for major
hepatectomy in patients with extremely rare blood type.
Keywords: Anti-Gerbich Antibody, Central hepatectomy, Preoperative autologous donation, Acute normovolemic
hemodilution, Hepatocellular carcinoma

Background
Gerbich (Ge) is known to be a high-prevalence erythrocyte antigen that is present in more than 99% of the
population [1]. Transfusion management in patientswith positive anti-Ge alloantibody is complex in a surgical setting often requiring blood transfusion. A diverse
clinical significance of anti-Ge alloantibody has been described; however, the degree and severity of adverse
events induced by hemolytic transfusion reactions* Correspondence: komokata.teruo.je@mail.hosp.go.jp
1
Department of Surgery, National Hospital Organization Kagoshima Medical
Center, Kagoshima, Japan
Full list of author information is available at the end of the article(HTRs) after incompatible transfusion are not precisely
clear in the published literature [2].
Central hepatectomy (CH) is one of the technicallychallenging hepatectomies that is classified as a major
liver resection based on Couinaud’s classification, and isalso described as a high complexity liver resection [3].
Given the anatomical proximity of lesions to major hepatic veins, presence of two transection planes and larger
exposed raw surface area, CH appears to be associatedwith increased risk of intra-operative blood loss andblood transfusion ratio [4, 5].
We describe an anti-Ge alloantibody positive patientwith hepatocellular carcinoma (HCC) who had a© The Author(s). 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License,
which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give
appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate ifchanges were made. The images or other third party material in this article are included in the article's Creative Commonslicence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commonslicence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain
permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

Komokata et al. Surgical Case Reports(2020) 6:131

Page 2 of 7

successful central hepatectomy without the need of anallogeneic blood transfusion.

Case presentation
A 76-year-old Japanese woman was referred to our department for evaluation of a mass in the middle sectionof the liver. She had no subjective symptoms and a mass
was incidentally identified by an ultrasonography on her
routine medical check-up. Her medical history included
moderate to severe aortic stenosis, atrial fibrillation
under warfarin, and mild chronic kidney disease. On
presentation, her hemoglobin (Hb) level was 11.5 mg/
dL, hematocrit (Ht) was 36%, and platelet count was
199,000/μl. Her total bilirubin was 0.6 mg/dl, aspartate
aminotransferase (AST) was 59 U/l. alanine aminotransferase (ALT) was 19 U/l, albumin was 4.08 g/dl, andprothrombin time (PT) was 51% (INR 1.54) with warfarin use. A computed tomography (CT) scan and amagnetic resonance image (MRI) demonstrated a large
tumor of 9.5 cm in diameter in the segment 4 (S4), 5(S5), and 8 (S8) of the liver (Fig. 1). The serum alphafetoprotein (AFP) level was 54 ng/ml and protein induced by vitamin K absence or antagonist II (PIVKA-II)level was 210,000 mAU/ml. Hepatitis C virus antibody
was positive and hepatitis B virus antigen was negative.
She denied history of alcohol intake. Her Child-Pughgrade was corresponding to A with a score of point six
and indocyanine green retention rate at 15 minutes was
15.8%. With the diagnosis of hepatitis C virus (HCV)-induced hepatocellular carcinoma, CH without caudate
lobectomy was planned. The remnant liver volume(RLV) was estimated to be 633 mL on a threedimensional volume analyzer (SYNAPSE VINCENT;FUJIFILM Medical Co., Tokyo, Japan). The standard

Fig. 1 Computed tomography (CT) demonstrating a large tumor(9.5 cm in diameter) in the medial and anterior segments of the liver

liver volume (SLV) was estimated to be 942 mL by the
Urata formula [6]. The RLV/SLV ratio was estimated to
be 67%.
She had a history of two pregnancies with no historyof blood transfusion. She was group B and RhD-positive
as classified by ABO and Rh respectively. A preoperative
antibody test using a polyethylene glycol/Coombs
showed 3+ reactivity with all 11 panel cells (Table 1).
However, additional identification test using an enzyme
card revealed no reaction. The autocontrol and direct
antiglobulin test were negative. Suspecting the existenceof an antibody to a high-prevalence antigen, further tests

Table 1 Result of antibody screening
Rh-hrCell # Rh-hr

D C E cKELL
e f

CW V K k

DUFFY

KIDD

Xg

LEWIS

MNS

Kpa Kpb Jsa Jsb Fya Fyb Jka Jkb Xga Lea Leb S s

PLutheran Results

M N P1 Lua Lub PEG/
Coombs1

R1wR1 + + 0 0 + 0 +0 0 + 0

+

0

+

+

0

+

+

+

0

+

0 + +

+ +

0

+

3+

2

R1R1

0 + + 0

+

nt

+

0

+

+

0

0

+

0

+ + +

+ +

0

+

3+

3

R2R2

+ 0 + + 0 0 0

0 + + 0

+

nt

+

+

+

0

+

+

0

0

0 + +

0

+

0

+

3+

4

R0r

+ 0 0 + + + 0+ 0 + 0

+

0

+

0

0

+

0

0

0

0

+ + +

+ +

0

+

3+

5

r’r

0

+ 0 + + + 0

0 0 + 0

+

0

+

+

+

+

+

0

+

0

+ + +

0

+

0

+

3+

6

r”r

0

0 + + + + 0

0 0 + 0

+

0

+

0

+

0

+

+

0

+

+ + +

+ +

0

+

3+

7

rr

0

0 0 + + + 0

0 + + +

+

0

+

0

+

+

+

+

0

+

+ + +

+ +

0

+

3+

8

rr

0

0 0 + + + 0

0 0 + 0

+

nt

+

0

+

+

0

+

+

0

0 + 0

+ +

0

+

3+

+ + 0 0 + 0 0

9

rr

0

0 0 + + + 0

0 0 + 0

+

nt

+

+

+

0

+

+

0

+

+ 0 +

0

0

0

+

3+

10

rr

0

0 0 + + + 0

0 0 + 0

+

0

+

+

0

+

+

0

0

+

0 + 0

+ 0

0

+

3+

11

R1R1

+ + 0 0 + 0 0

0 0 + 0

+

nt

+

0

+

0

+

+

0

+

+ 0 +

0

+

+

3+

+

Autocontrol 0
nt not tested, PEG polyethylene glycol

Komokata et al. Surgical Case Reports(2020) 6:131

on erythrocyte antigens and antibodies were requested
from the reference laboratory (the Kyusyu Blood Centerof the Japanese Red Cross Society in Fukuoka, Japan)
where the anti-Ge antibody with titer of 32 was detected.
Negative results for Ge antigen were also shown using
sera including anti-Ge. Results from additional blood
type antigen test other than those for the Ge antigens
were as follows: C+c+E+e+, M+N+, S−s+, Le(a−b−), P2,
Fy(a+b−), Jk(a−b+), Di(a−b+), Xg(a+), Jr(a+). There wasneither frozen blood stored nor Ge negative donor registered in Japan. There were no other Ge negative members in her family.
The management of the patient was intensively discussed with a multidisciplinary team of experts from thedepartments of hematology, clinical laboratory, oncology, hepatology, radiology, and anesthesiology. Since it
was hard to predict the degree and severity of adverse
events related to HTRs by incompatible transfusion, preoperative autologous donation (PAD) and acute normovolemic hemodilution (ANH) were planned to avoid
perioperative allogenic blood transfusion as far as possible. After explaining the risks and benefits of the surgical intervention with the possibility of incompatible
transfusion to the patient, she agreed to proceed for thesurgery. A total of 800 ml autologous blood was preserved preoperatively under erythropoietin therapy,
epoetin beta 6000 IU intravenous administration threetimes a week, supplemented by the daily administrationof iron. Warfarin was interrupted 4 days before surgery,
subsequently intravenous unfractionated heparin wasstarted at 10,000 units per day, and stopped 6 h before
surgery.
Several measures were incorporated after the induction of general anesthesia. These included insertion of
Swan-Gantz catheter for evaluation of cardiac function
for moderate to severe aortic stenosis; insertion of a flexible double lumen catheter for continuous hemodiafiltration (CHDF) in preparation to deal acute HTRs
preceded by an unanticipated transfusion; a collection of
700 ml autologous blood as ANH; and a “stand-by” set
up of intraoperative cell salvage. Surgery was performed
through an inverted T-shaped incision. The tumor was
located in the S4, S5, and S8 of the liver (Fig. 2a). First, acholecystectomy with an insertion of a 6 Fr. tube via acystic duct for post-hepatectomy bile leakage test was
performed, and was followed by the dissection of thehepatic hilum. The middle hepatic artery and the anterior branch of the right hepatic artery originated from thesuperior mesenteric artery were ligated and divided.
Infra-hepatic inferior vena cava (IVC) above the confluence of the left renal vein was encircled by a cotton tapewith a tourniquet (Fig. 2b). Mobilization of the right lobeof the liver was performed with the division of the rightcoronary, triangle, and the hepato-renal ligaments, while

Page 3 of 7

Fig. 2 Intra-operative finding. a An elastic hard expanding tumor in
the segments 4, 5, and ventral site of the segment 8. b Hepatic
hilum dissection and encircling of the infra-hepatic IVC with a tape.
RHA: right hepatic artery; LHA: left hepatic artery; CHD: common
hepatic duct; PV: portal vein; IVC: inferior vena cava. c Completion of
the central hepatectomy without the caudate lobectomy of the liver

the short hepatic veins were not divided. Liver transection was performed with Thunderbeat® (TB) (Olympus
Medical Systems Corp., Tokyo, Japan) and a cavitron
ultrasonic surgical aspirator (CUSA) along with theKomokata et al. Surgical Case Reports(2020) 6:131

Pringle maneuver in cycles of clamp/unclamp time of
15/5 min. After intravenous administration of 100 mg ofhydrocortisone, parenchymal transection was initiatedjust right to the falciform ligament, during which inflow
structures of S4 arising off of the hilar plate were ligatedand divided. During the transection of parenchyma on
this plane, down to the para-caval portion of the caudate
lobe, we encountered a longitudinal split injury on thedorsal side of the middle hepatic vein at the confluenceof one of the drainage veins from S4B. The liver wastransected just left to the right hepatic vein by using TB
alone under simultaneous Pringle maneuver and infrahepatic IVC clamping, while preserving hemostasis withdigital compression of the injured portion. The middle
hepatic vein was clamped about 2 cm distal from its
root, divided, and double ligated at the proximal site.
Glissonian pedicles of S5 and S8 was double ligated anddivided, respectively, and a CH without caudate lobectomy was performed (Fig. 2c). However, a small portionof S8 and S4B was spared. Frozen sections of the surgical margins revealed negative margins. Hemostasis of
the transection line was achieved with suture ligationand soft coagulation. Bile leakage test was performed byusing indigocarmine dye. TachosilⓇ was applied to theraw surface and a closed suction drain was placed. The
estimated blood loss was 1380 ml without requiring intraoperative cell salvage and an allogenic blood transfusion. The operative time was 260 min. The weight ofPage 4 of 7

resected liver specimen was 342 g. The peri- and intraoperative course of Hb and Ht values with description of
PAD and ANH under erythropoietin therapy was demonstrated in Fig. 3. Pathologically, the tumor was foundto be a moderately differentiated HCC measuring 9.5 ×
8.0 cm with negative surgical margins (Fig. 4).
On postoperative day (POD) 1, the Hb level was 8.7
mg/dl and the Ht was 27%. The total bilirubin was 0.7
mg/dl, AST was 621 U/l, ALT was 451 U/l, and PT was
67% (INR 1.27). Anticoagulation therapy was resumed
on POD 2 after confirming the absence of bleeding complications. The postoperative course was uneventful except for congestive heart failure classified as grade II by
Clavien-Dindo classification [7]. On POD 18, the patient
was discharged from the hospital with her Hb level, 9.8
mg/dl; Ht, 32%; total bilirubin, 0.6 mg/dl; AST, 29 U/l;
ALT, 40 U/l and PT, 50% (INR: 1.56). She is alive withno sign of recurrence after 45 months after surgery.

Discussion
In this report, we demonstrated how CH for HCC could
be successfully performed in a patient with positive antiGe alloantibody without the need for allogeneic bloodtransfusion. A multidisciplinary team approach tailoredwith utmost technical adjustments appears to be crucial
in this challenging and high-risk surgery.
Preoperative management included PAD [8] facilitatedby erythropoietic therapy with recombinant humanFig. 3 Peri- and intra-operative course of Hb and Ht values with description of PAD and ANH under erythropoietin therapy. Hb: hemoglobin; Ht:
hematocrit; PAD: preoperative autologous donation; ANH: acute normovolemic hemodilution; Pre: preoperative day; DOS: day of surgery; Nadir:intraoperative hemoglobin nadir; Recovery: in recovery roomKomokata et al. Surgical Case Reports(2020) 6:131

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Fig. 4 Pathological finding of the specimen. a The tumor macroscopically showed a confluent multinodular type. b The tumor was moderately
differentiated hepatocellular carcinoma (Hematoxylin and eosin staining)erythropoietin supplemented by daily administration ofiron [9, 10]. The patient underwent 2 times of PAD as
often as once a week with 400 ml withdrawal of whole
blood until 72 h before surgery [11]. In addition, extensive discussions regarding the natural course of the disease [12], the treatment options [13], the standard
surgical strategies, the expected intraoperative blood loss[5], and the prediction and preparation for adverse
events in case of incompatible blood transfusion [2] arepivotal. We had three separate meetings and repeatedly

discussed all the details with the patient and the team
before we agreed to proceed for the surgery.
The intraoperative transfusion management included
measures to avoid and at the same time, prepare, for incompatible transfusion; autologous blood collection as
ANH immediately prior to operation [14]; setting forblood salvage with a cell saver [15]; insertion of a flexible
double lumen catheter for CHDF [16]. ANH is known to
be one of the best strategies to prevent perioperative red
blood cells (RBCs) transfusion; however, the amount ofKomokata et al. Surgical Case Reports(2020) 6:131

blood withdrawal, leading hemodilutional coagulopathy
and fluid overload remain major concern [14]. The withdrawal volume of whole blood as ANH was determinedby the anesthesiological team according to estimation of
initial blood volume (65 ml/kg) and initial and target
hemoglobin. Thus, 700 ml of blood to be collected wasdetermined by the formula [17]: V = EBV × (Hi–Hf)/Hav,
where V was the volume of blood to be withdrawn (700ml in this case), EBV was the estimated blood volume ofthe patient (2860 ml in this case), Hi was the initialhematocrit before the procedure (32% in this case), Hf
was the target final hematocrit after hemodilution (25%in this case), and Hav was the average of the Hi and Hf(28.5% in this case). In fact, her Hb level during liver resection immediately after hepatic vein injury dropped up
to 6.2 g/dl. Autologous blood reinfusion was also performed under preference by anesthesiologists based on
the Hb level, hemodynamics, and the progression statusof the operation. We escaped using blood salvage system
as many onco-surgeons are reluctant to use the bloodfor the theoretical risk of tumor dissemination [18].
However, surgeon should decide to use or spare the cellsalvage depending on the patients’ condition, as no concrete evidence on the sequelae of the salvaged blood incancer patients exists. Acute and delayed HTRs by incompatible transfusion in patients with anti-Ge alloantibody have not been well-documented. While there werea few reports documented on successful transfusion of
Ge-positive RBCs to patients with an anti-Ge alloantibody [19, 20], Baughn and colleagues reported a case of
acute HTRs induced by multiple transfusion [2]. Taking
into consideration the possibility of life-threating complications by acute HTRs such as vital shock, renal failure and disseminated intravascular coagulation, we
inserted a flexible double lumen catheter and prepared
for CHDF along with steroid and immunoglobulin.
The surgical strategy included precise surgical techniques with careful dissection; meticulous hemostasis;anesthesiologist-guided low central venous pressure during liver transection; bloodless liver transection with
Pringle maneuver and infra-hepatic IVC clamping; anduse of TB with CUSA. The liver transection time fromthe beginning of the parenchyma resection to the removal of the specimen of liver in the patient was 45
min. With this experience, we have been advocating thisprocedure (TB liver transection under simultaneousPringle maneuver and infra-hepatic IVC clamping) for
especially high complexity major liver resection [21, 22].
Postoperative management included the continuationof erythropoietic therapy supplemented with the dailyadministration of iron and reinstitution of anticoagulation therapy. A decline in postoperative serum Hb and
Ht levels without active evidence of bleeding until POD
3 after liver resection was reported [23]. Careful

Page 6 of 7

observation and continuation of erythropoietic therapy
are recommended, even if the patient does not have any
obvious symptoms of anemia [9]. Early reinstitution of
anticoagulation therapy was also essential in this elderly
patient. On POD 2, heparin was restarted after confirming the absence of bleeding complications and wasswitched to warfarin to prevent thromboembolic complications such as major adverse cardiovascular events,
cerebrovascular stroke, pulmonary embolism, or portal
vein thrombus [24].

Conclusions
To our knowledge, this is the first case report of hepatectomy in a patient with anti-Ge alloantibody. A multidisciplinary tailored approach remains crucial in establishinga concrete treatment and management modality. PAD
and ANH with perioperative erythropoietic therapy combined with bloodless liver resection should be advocatedduring major hepatectomy in patients with extremely rare
blood type.
Abbreviations
Ge: Gerbich; HTRs: Hemolytic transfusion reactions; CH: Central hepatectomy;
HCC: Hepatocellular carcinoma; Hb: Hemoglobin; Ht: Hematocrit;
AST: Aspartate aminotransferase; ALT: Alanine aminotransferase;
PT: Prothrombin time; INR: International normalized ratio; CT: Computed
tomography; MRI: Magnetic resonance image; S: Segment; AFP: Alphafetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II;
HCV: Hepatitis C virus; RLV: Remnant liver volume; SLV: Standard liver volume;
PAD: Preoperative autologous donation; ANH: Acute normovolemic
hemodilution; CHDF: Continuous hemodiafiltration;; IVC: Inferior vena cava;
TB: ThunderbeatⓇ; CUSA: Cavitron ultrasonic surgical aspirator;
POD: Postoperative day
Acknowledgements
None
Authors’ contributions
All authors participated in the operation or management of the patient inthis case report. TK, HY, BA, and MK performed the operation. TK, MI, and BA
drafted and revised the manuscript. The authors read and approved the final
manuscript.
Funding
No funding was obtained from the private or public sector for this research.
Availability of data and materials
Not applicable
Ethics approval and consent to participate
Not applicable
Consent for publication
The patient provided consent for publication.
Competing interests
The authors declare that they have no competing interests.
Author details
1
Department of Surgery, National Hospital Organization Kagoshima Medical
Center, Kagoshima, Japan. 2Department of Clinical Laboratory, National
Hospital Organization Kagoshima Medical Center, Kagoshima, Japan.
3
Department of Hematology, National Hospital Organization Kagoshima
Medical Center, Kagoshima, Japan.

Komokata et al. Surgical Case Reports(2020) 6:131

Received: 1 April 2020 Accepted: 5 June 2020

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