Clinical Nutrition 36 (2017) 1239e1244

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Clinical Nutrition
journal homepage: http://www.elsevier.com/locate/clnu

Randomized Control Trials

n-3 fatty acid-based parenteral nutrition improves postoperative

recovery for cirrhotic patients with liver cancer: A randomized
controlled clinical trial
Binhao Zhang a, 1, Gang Wei a, 1, Rui Li b, Yanjun Wang a, Jie Yu a, Rui Wang a, Hua Xiao a,
Chao Wu a, Chao Leng a, Bixiang Zhang a, **, Xiao-ping Chen a, *
a
Institute of Hepato-Pancreato-Bililary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030,
China
b
Department of Oncology Center, Wuhan No. 11 Hospital Affiliated to Medical College, Wuhan University of Science and Technology, Wuhan, 430016, China

a r t i c l e i n f o s u m m a r y

Article history: Background & aims: A new lipid emulsion enriched in n-3 fatty acid has been reported to prevent hepatic
Received 20 December 2014 inflammation in patients following major surgery. However, the role of n-3 fatty acid-based parenteral
Accepted 4 August 2016 nutrition for postoperative patients with cirrhosis-related liver cancer is unclear. We investigated the
safety and efficacy of n-3 fatty acid-based parenteral nutrition for cirrhotic patients with liver cancer
Keywords: followed hepatectomy.
n-3
Methods: A prospective randomized controlled clinical trial (Registered under ClinicalTrials.gov Identi-
Parenteral nutrition
fier no. NCT02321202) was conducted for cirrhotic patients with liver cancer that underwent hepatec-
Cirrhosis
Liver cancer
tomy between March 2010 and September 2013 in our institution. We compared isonitrogenous total
Hepatectomy parenteral nutrition with 20% Structolipid and 10% n-3 fatty acid (Omegaven, Fresenius-Kabi, Germany)
(treatment group) to Structolipid alone (control group) for five days postoperatively, in the absence of
enteral nutrition.
Results: We enrolled 320 patients, and 312 (97.5%) were included in analysis (155 in the control group
and 157 in the treatment group). There was a significant reduction of morbidity and mortality in the
treatment group, when compared with the control group (total complications 78 [50.32%] vs. 46
[29.30%]; P < 0.001, total infective complications, 30 [19.35%] vs. 15 [9.55%]; P ¼ 0.014), overall mortality
(5 [3.23%] vs. 1 [0.64%]; P ¼ 0.210), and hospital stay (12.56 ± 3.21 d vs. 10.17 ± 3.15 d; P ¼ 0.018).
Conclusions: We found that addition of n-3 fatty acid-based parenteral nutrition significantly improved
postoperative recovery for cirrhotic patients with liver cancer following hepatectomy, with a significant
reduction in overall mortality and length of hospital stay.
© 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Abbreviations: ICGR15, indocyanine green retention rate at 15 min; ALT, alanine
aminotransferase; HBV, hepatitis B virus; FLR, future liver remnant; SLV, stan-
dardized liver volume; NRI, nutrition risk index; SGA, subjective global assessment;
HCC, hepatocellular carcinoma; Alb, Albumin; WBC, white blood cell; Hgb,
hemoglobin; PLT, platelets; TBil, total bilirubin; TC, total cholestrol; TG, triglyceride;
BUN, blood urea nitrogen; Cr, creatinine; DPT, variation of prothrombin time;
Hs-CRP, hypersensitive C-reactive protein.
* Corresponding author. Department of Surgery, Tongji Hospital, Tongji Medical
College, Huazhong University of Science and Technology, Wuhan, 430030, China.
Fax: þ86 27 83662851.
** Corresponding author. Hepatic Surgery Centre, Department of Surgery, Tongji
Hospital, Tongji Medical College, Huazhong University of Science and Technology,
Wuhan, 430030, China. Fax: þ86 27 83662851.
E-mail addresses: bixiangzhang@163.com (B. Zhang), chenxp@medmail.com.cn
(X.-p. Chen).
1
Binhao Zhang and Gang Wei contribute equally to this study.
1. Introduction
Liver cancer is one of the most prevalent life-threating diseases
in China, and hepatectomy is the major therapy for this malignancy
[1]. Many causes of liver cirrhosis may give rise to liver cancer and
the two conditions often occur together [2]. The postoperative re-
covery is poor for cirrhotic patients as compared with non-cirrhotic
patients [3]. While parenteral nutrition (PN) has been used as an
approach to prevent worsening malnutrition during the post-
operative phase, it may precipitate severe hepatic complications
and promote inflammation [4]. This leads to a surgical dilemma
balancing the increased morbidity and mortality as a result of
malnutrition against the morbidity of parenteral nutrition.

http://dx.doi.org/10.1016/j.clnu.2016.08.002
0261-5614/© 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
1240 B. Zhang et al. / Clinical Nutrition 36 (2017) 1239e1244
Malnourished patients have greater risk to develop post-
operative morbidity or mortality, when compared with the well-
nourished patients [5]. Furthermore, cirrhotic patients require 1.3
times the energy over the basal metabolic rate [6]. However, a
lower content of n-6 unsaturated FA in lipid emulsion than in
conventional pure soybean oil emulsion was suggested by the
ESPEN for cirrhotic patients [6]. There is a great need for a novel
lipid emulsion that causes minimal liver inflammation for the
postoperative management of cirrhotic patients with liver cancer.
A new lipid emulsion of n-6/n-3 fatty acid (FA) ratio 3:1 was
reported to attenuate proinflammatory responses in patients
following major surgery compared with traditional lipid emulsion
enriched in n-6 FA [7]. Research into the use of n-3 fatty acid
supplements generated conflicting results. In one study, n-3 fatty
acid supplements were not associated with improved outcomes
in elective colorectal cancer surgery [8]. Yet n-3 fatty acid
improved liver regeneration and functional recovery after hepa-
tectomy in mice with hepatic steatosis [9]. The following two
characteristics of n-3 fatty acid may explain its benefit for post-
operative recovery after major surgery: 1) A potential anti-
inflammatory effect caused by alteration in the generation of
anti-inflammatory 3-series eicosanoids [10,11]; 2) modulation of
the immune response by changing the membrane fluidity and
regulating gene transcription [12].
The role of n-3 fatty acid-based PN in major surgery is still
controversial. In this study, we tested the safety and efficacy of
postoperative use of n-3 fatty acid-based PN for malnourished
cirrhotic patients with liver cancer in a randomized controlled
clinical trial.
2. Methods
2.1. Study design and oversight
This study was a pragmatic, single center, parallel-group, pro-
spective, randomized, controlled clinical trial, and was approved by
the Ethics Committee for Clinical Pharmacology in Tongji Medical
College (Registered under ClinicalTrials.gov Identifier no.
NCT02321202). The State Key Project on Infectional Disease of
China and the Chinese Ministry of Public Health for Key Clinical
Projects funded this study. Written consent forms from the patients
were obtained before enrollment, and the patients had the right to
withdraw from the trial any time.
2.2. Study participants
Between March 2010 and September 2013, a total of 1086 pa-
tients with hepatic carcinoma were screened in this study in the
Hepatic Surgery Center of Tongji Hospital. Cirrhotic patients with
malnutrition and liver cancer scheduled for hepatectomy were
consecutively enrolled prior to surgery. Nutritional assessment was
performed at admission according to Subjective Global Assessment
(SGA) [13] and Nutrition Risk Index (NRI): 83.5e97.5 was consid-
ered as mildly malnourished, while <83.5 was considered as
severely malnourished [13,14]. NRI was calculated with the for-
mula: 1.519  serum albumin (Alb) (g/L) þ 0.417  (current weight/
usual weight)  100. Malnutrition was considered if the patients
met at least one of two criteria [14]: (1) NRI 100, (2) any two of the
following: current weight/ideal weight was 95%; serum Alb
35.0 g/L; or serum prealbumin was 200 mg/L.
Patients with the following characteristics were excluded: (1)
contraindication for hepatectomy, including gastrointestinal hem-
orrhage, severe hemorrhagic disorders, explicit acute nonspecific
infectious lesion, overt ascites, Child-Pugh Score C [15], indoc-
yanine green retention rate at 15 min (ICGR15) >30% [16], serum
HBV-DNA >106 copies/ml and serum alanine aminotransferase
(ALT) >2  ULN, serum triglycerides >2.0 mmol/L, circulatory
shock, stroke, acute myocardial infarction, renal failure, coma of
unknown cause; (2) pregnancy; (3) age of <18 y or >75 y; (4)
performed intraoperative ablation; (5) unresectable tumor during
operation; and (6) allergic reactions against fish or egg proteins.
One patient in the control group was lost to follow-up, owing to
invalid contact with an unknown reason. As a result, the percentage
of patient extent to follow up was 99.36% (155/156) in the control
group, and 100% (157/157) in the treatment group.
2.3. Study intervention
A total of 320 cirrhotic patients with liver cancer who under-
went hepatectomy were assigned to respective group by computer-
derived block randomization, using sealed non-transparent enve-
lopes with randomization number inside. There were totally 40
blocks, and every block contained 8 cases, including 4 cases in the
trial arm and other 4 cases in the control arm. Eight envelopes in
each block were prepared for every eight patients, and one enve-
lope was chosen by each patient. A researcher who had no
knowledge of this trial performed the randomization and alloca-
tion. The study was conducted in a double-blind fashion, with
treatments concealed from patients, the investigators, caregivers
and outcomes assessors. The lipid emulsion of treatment and
control group looked identical. The code was not accessible by the
investigators before the study completed, and was not broken until
statistical analyses were completed.
Associated therapy after admission was delineated in
Supplemental Table 1. PN was continuously administered through
an indwelling central venous catheter controlled by infusion pump
at least over 18 h daily, initiating from the operation day when
patients were hemodynamically stable. Glucose, lipid emulsion,
amino acids, vitamins and electrolytes were compounded in an
“All-In-One” manner. 20% Structolipid and 10% n-3 fatty acid
(Omegaven, Fresenius-Kabi, Germany), were applied to the n-3
fatty acid treated group, but only Structolipid (n-6 FA) to the control
group for 5 consecutive days postoperatively.
Non-protein energy requirement was defined as 25 Kcal/kg per
day. Glucose made up appropriately 60% of non-protein energy
requirements, and the remaining was provided by lipid emulsion.
The supply of glucose, lipid and amino acids was based on 3 g/kg,
0.8 g/kg and 1.2 g/kg per day, respectively [6]. The concentration of
amino acids, enriched in branched-chain amino acid, was 10.8%.
The n-6/n-3 FA ratio was 7:1 in the control group and 2:1 in the
treatment group, respectively.
2.4. Surgical outcomes, histological and biochemical markers
The evaluation of present hepatic function was based on Child-
Pugh scoring system [15]. Liver functional reserve estimation was
evaluated according to ICGR15 [16]. Future liver remnant (FLR)/
standardized liver volume (SLV) ratio >20% was considered safe
hepatectomy for patients with normal liver function, but >31% with
impaired liver function [17]. SLV was calculated according to the
following formula: 794.41 þ 1267.28  body surface area (m2)
[18].
Surgical trauma was evaluated by Surgical Stress Score (SSS)
[19], calculated by the formula: 0.342 þ 0.0139  blood loss/body
weight (g/kg) þ 0.0392  operation time (h) þ 0.352  extent of
skin incision (0 indicates a minor incision for laparoscopic or
thoracoscopic surgery including laparoscopic-or thoracoscopic-
assisted surgery; 1, laparotomy or thoracotomy alone; and 2, lap-
arotomy and thoracotomy). The severity of each complication was
classified according to Clavien's classification [11]. Briefly, the
 B. Zhang et al. / Clinical Nutrition 36 (2017) 1239e1244
classification of surgical complications was mainly based on
whether the patient required pharmacological treatment (grade II,
otherwise grade I), surgical, endoscopic or radiological intervention
(grade III), or presented life-threatening complication (grade IV), or
was dead (grade V).
Complete blood counts, biochemistry panels, and urinalyses
were performed to evaluate organ function and drug toxicity. The
blood samples were collected at 7:00 A.M. without food at day 0, 1,
3 and 5, and the urine samples were collected from day 0 to day 5.
Day 0 refers to the preoperative day proximal to the day of surgery.
The intake and loss of fluid were recorded daily during the post-
operative period.
Resected hepatic tissue specimen was implemented H&E
staining for the purpose of grading of activity and staging of fibrosis
for the patients of chronic viral hepatitis [20].
2.5. Outcome measures
We evaluated the clinical safety and effectiveness, including the
primary outcomes within 14 days and secondary outcome within
30 days after surgery. Surgeons independent of this study recorded
outcome measures. The primary outcomes were postoperative re-
covery, complications and duration of hospital stay. The definitions
of postoperative complications were guided by the reported liter-
ature [10], in accordance with authors' clinical practice. Secondary
outcome was surgical mortality within 30 days postoperatively.
Adverse events were monitored for 30 days.
2.6. Statistical analysis
The sample size of 142 in each group was calculated based on the
primary outcome, considering an 80% power and an alpha of 0.05 to
detect a 70% difference in the treatment group and a 50% difference in
the control group. The following calculation was used to calculate the
sample size: n1 ¼ n2 ¼ (ua/2 þ ub)2[p1  (1  p1) þ p2  (1  p2)]/
(p1  p2)2. Considering the loss of follow-up rate of 10% and some
unexpected events, the final sample size was assumed as 160 in each
group.
Continuous data sets were described as mean ± SD, and Student
t-test was used for analysis. Categorical data sets were reported as
proportions and analyzed by Chi-square test. The statistical analysis
was performed with the software SPSS 18.0 (Illinois, USA). P < 0.05
was considered statistically significant.
3. Results
3.1. Patients
From March 2010 and September 2013, we screened a total of
1086 cirrhotic patients with hepatic carcinoma in Tongji Hospital.
Of these patients, 320 were enrolled, and 7 of them subsequently
withdrew from the study, resulting in an intention-to-treat popu-
lation of 313 patients (156 in the control group and 157 in the
treatment group). One patient in the control group was lost to
follow-up within the 30 days postoperative study period for an
unknown reason. As a result, 155 (99.36%) patients in the control
group and 157 (100%) in the treatment group were included for
final outcome analysis (Fig. 1).
Preoperative baseline characteristics of the two groups were
similar in rates of age, sex, weight, Child-Pugh Score, serum HBsAg
and HBV-DNA status, FLR/SLV, serum biochemical parameters, Th/
Ts, NRI after PN and associated therapy after admission
(Supplemental Table 1).
1241
3.2. n-3 FA supplementation resulted in a reduction in complication
rates and postoperative admission
Among the 155 patients, 89 cases presented complications in
the control group, while only 58 in 157 patients had complications
in the treatment group (P ¼ 0.025). There was significant reduction
in overall complication rates in the treatment group, when
compared with control group (78 [50.32%] vs. 46 [29.30%];
P ¼ 0.000). There was a significant reduction in the incidence of
infective complications in the treatment group, when compared
with control group (30 [19.35%] vs. 15 [9.55%]; P ¼ 0.014). Post-
operative liver failure occurred in 7 patients in the control group
and 2 in the treatment group (P ¼ 0.170) (Table 2).
Consistent with this, patients in the treatment group had sig-
nificant shorter duration of hospital stay, when compared with the
control group (10.17 ± 3.15 d vs. 12.56 ± 3.21 d; P ¼ 0.018). Neither
group had significant adverse reactions to their nutritional
supplementation.
3.3. Patients in the treatment group had reduced postoperative
transaminase and increased serum pre-albumin
The intraoperative characteristics, including surgery time, he-
patic pedicle blocking time and blood loss, did not show any sig-
nificant difference between the control group and the treatment
group (Supplemental Table 1). The number of cases that had greater
than 3 segments resected was significantly more in the treatment
group compared with the control group (P ¼ 0.05). Conversely, the
number of cases that had fewer than one segment resected was
significantly less in the treatment group (P ¼ 0.005), when
compared with that in the control group (Supplemental Table 1).
There were 125 (80.65%) patients who were diagnosed as HCC in
the control group, and 135 (85.99%) in the treatment group, ac-
cording to the postoperative pathological results (Supplemental
Table 2). Based on the system of grading of activity and staging of
fibrosis [20], the number of patients with HCC graded G1 was 113
(90.40%) in the control group, 120 (88.89%) in the treatment group
(P ¼ 0.069), and staged S2 was 72 (57.6%), 81 (60.0%) respectively
(P ¼ 0.694).
From day 1 to day 5, we found 24 h-urine output was not sta-
tistically different, but from day 3 to day 5, the urinary albumin-
creatinine ratio (ACR) [12] was significantly lower in the treat-
ment group, when compared with the control group (P < 0.05)
(Supplemental Table 2). The volume of positive fluid balance in the
treatment group was significantly lower than that in the control
group (P ¼ 0.005). In addition, the emerging time of negative fluid
balance in the treatment group was significantly earlier, when
compared with that in the control group (P ¼ 0.001).
There was significant reduction in serum ALT at day 3 and 5 in
the treatment group when compared with control group, together
with a similar difference in serum hypersensitive C-reactive protein
(Hs-CRP) between the two groups at day 3 and day 5 (P ¼ 0.015 and
0.001, respectively) (Supplemental Table 2). The level of pre-
albumin at day 1 in the treatment group was lower than that in the
control group (P ¼ 0.056), but by day 5 it was significantly higher in
the treatment group (P ¼ 0.019). The value of variation of pro-
thrombin time (DPT) at day 5 was significantly higher in the
treatment group than that in the control group (P ¼ 0.004).
3.4. Secondary outcome
In keeping with a reduction in the postoperative complication
rates, we found a significant reduction in the postoperative mor-
tality in the treatment group, when compared with control group
(5 [3.23%] vs. 1 [0.64%]; P ¼ 0.210). There was no intraoperative
1242 B. Zhang et al. / Clinical Nutrition 36 (2017) 1239e1244

1086 Patients met inclusion criteria

572 Met exclusion criteria

301 Had contraindication
132 Intraoperative ablation
79 Unresectable liver cancer
during operation
60 Allergic reactions against
fish or egg proteins
1 Were eligible but did not
194
undergo randomization
96 Declined to give consent
28 Were unable to give consent
24 Were excluded by clinician
46 Were participating in
another study

320 Underwent
ent randomization
ran

160 Were
re assigned to 160 Were assigned
ass to
the control group the trial group

2 Did not receive 2 Did not receive

assigned nutritional assigned nutritional
support support
2 Requested removall 1 Requested removal
of all data of all data

156 Received
eived a
assigned 157 Received
eived assigned
a
nutritional support nutritional support

1 was lost to follow-up

p
before 30 days

155 were
re included
incl in 157 were
re included
incl in
outcome analysis outcome analysis

Fig. 1. Flow diagram of patients enrollment, allocation and follow-up.

Table 1
Postoperative complications according to Clavien classification.

Grade I Grade II Grade III Grade IV Grade V

Biliary leakage 17 1 3 0 0
Intra-abdominal haemorrhage 2 3 1 0 0
Upper gastrointestinal hemorrhage 0 4 2 0 0
Liver failure 0 0 0 6 3
Incision infection 0 24 0 0 0
Intra-abdominal infection 0 6 6 3 0
Pulmonary infection 0 8 4 0 0
Pleural effusion 15 9 0 0 0
Postoperative ileus 0 0 3 0 0
Respiratory distress 0 6 0 6 3
Sepsis 0 0 3 3 0
Shock 0 0 0 6 0
Total 34 64 22 24 6
 B. Zhang et al. / Clinical Nutrition 36 (2017) 1239e1244
death in either group. Three patients died from aggressive irre-
versible liver failure in the control group at postoperative day 5, 9,
11, respectively (Tables 1 and 2), while no death occurred in the
treatment group as a result of liver failure. Two patients in the
control group died from intra-abdominal infection. By contrast
there was a single death in the treatment group from respiratory
failure as a result of pulmonary infection.
4. Discussion
This study, for the first time, provided evidence that n-3 fatty
acid-based PN improved postoperative outcomes for cirrhotic pa-
tients with liver cancer followed hepatectomy.
The role of n-3 fatty acid-based nutrition in major surgery is still
controversial. Recent clinical trials reported that n-3 fatty acid
supplements was not associated with improved outcomes in elec-
tive colorectal cancer surgery [8], oesophagogastric cancer surgery
[21], and coronary artery bypass surgery [22]. However, a pro-
spective randomized controlled trial including 48 patients with
gastric tumor showed that n-3 fatty acid based PN reduced in-
flammatory complications after surgical resection [23]. For patients
after liver transplantation, postoperative n-3 FA based PN reduced
inflammatory complications and hospital stay [24]. In addition, n-3
fatty acid improved liver regeneration and functional recovery after
hepatectomy in mice with hepatic steatosis [9]. In this study we
found that n-3 fatty acid-based parenteral nutrition improved
postoperative recovery for cirrhotic patients with liver cancer
following hepatectomy, through a reduction in postoperative
complications, mortality and hospital stay. The treatment group
was associated with lower postoperative Hs-CRP, lower ACR and
ALT, a reduction in postoperative fluid overload associated with an
earlier postoperative diuresis.
For cirrhotic patients with liver cancer following hepatectomy,
we expected gastrointestinal function to recover after 3 days, dur-
ing which parenteral nutrition would be required. Cirrhotic pa-
tients are expected to require more energy compared with patients
without liver cirrhosis [6]. Therefore, parenteral nutrition was
applied for 5 consecutive days postoperatively in this study to
ensure recovery. The dose of lipid emulsion was calculated ac-
cording to energy requirement as described in the method.
According to the guidelines of the ESPEN for cirrhotic patients
[6], conventional pure soybean oil emulsion should not be routinely
applied in cirrhotic patients. In this study, patients from the control
arm received a lipid emulsion not composed exclusively by soybean
oil, but with parenteral nutrition containing Structolipid with lower
content of n-6 as control. This observation suggests that the
Table 2
Postoperative complications and mortality.
Control group (n ¼ 155)
Biliary leakage, no. (%) 12 (7.74)
Intra-abdominal haemorrhage, no. (%) 3 (1.94)
Upper gastrointestinal hemorrhage, no. (%) 2 (1.29)
Liver failure, no. (%) 7 (4.52)
Incision infection, no. (%) 15 (9.68)
Intra-abdominal infection, no. (%) 12 (7.74)
Pulmonary infection, no. (%) 6 (3.87)
Pleural effusion, no. (%) 15 (9.68)
Postoperative ileus, no. (%) 2 (1.29)
Respiratory distress, no. (%) 9 (5.81)
Sepsis, no. (%) 3 (1.94)
Shock, no. (%) 3 (1.94)
Total, no. (%) 78 (50.32)
Infection rate, no. (%) 30 (19.35)
Mortality, no. (%) 5 (3.23)
P value less than 0.05 was marked with bold font, indicating significance.
1243
benefits observed in surgical patients treated with parenteral reg-
imens containing fish oil is significant even when comparing it with
lipid emulsions containing lower amounts of n-6 fatty acids than
those provided by the conventional soybean oil lipid emulsion.
n-3 fatty acid, a fish oil, enriched in eicosapentaenoic acid and
docosahexaenoic acid, was reported to have anti-inflammatory
potential through regulating the arachidonic acid pathway and
producing 3-series prostaglandins, thromboxanes, and 5-series
leukotrienes [25]. This leads to a reduction in the generation of
proinflammatory cytokines, including IL-6, IL-8 and TNF-a, and in
turn a reduction in the incidence of postoperative hepatic inflam-
mation [26]. Alternatively, the presence of n-3 fatty acids have been
reported to change membrane fluidity through the regulation of
gene transcription such as sterol regulatory element-binding pro-
tein (SREBP)-1, protein acylation and calcium release [27].
Furthermore, a recent study reported that n-3 fatty acid signifi-
cantly decreases experimental hepatic steatosis and results in
reduced ischaemia/reperfusion injury following partial hepatec-
tomy [28].
There are several limitations in this study which need further
discussion and exploration. It is a single center report with limited
number of patients. Patients were evaluated over a relatively short
post operative period, although it is unlikely that in the long term
the benefit seen in the n-3 fatty acid treated group will be reversed.
In addition, this study leaves unanswered the question of the
mechanism by which n-3 fatty acid-based parenteral nutrition
helps to improve postoperative recovery for cirrhotic patients with
liver cancer although several mechanisms have been reported.
Either nutritional support or anti-inflammatory effect may
contribute to this result. Further study will be concentrated on
exploring the potential mechanism, by using animal models treated
with n-3 fatty acid-based parenteral nutrition. Finally, no enteral
nutrition was used in this clinical trial. We specially focused on
parenteral nutrition for cirrhotic patients with HCC followed hep-
atectomy, but did not investigate the role of early enteral nutrition
in this population.
In conclusion, this study provided evidence that n-3 fatty acid-
based parenteral nutrition is safe and improves postoperative re-
covery for cirrhotic patients with liver cancer following
hepatectomy.
Funding sources
This work is supported by the State Key Project on Inflectional
Disease of China (Grant No. 2012ZX10002016-004 and 2012ZX
10002010-001-004), the Chinese Ministry of Public Health for Key
Trial group (n ¼ 157) P Value
9 (5.73) 0.479
3 (1.91) 1.000
4 (2.55) 0.692
2 (1.27) 0.170
9 (5.73) 0.191
3 (1.91) 0.016
6 (3.82) 0.982
9 (5.73) 0.191
1 (0.64) 0.991
6 (3.82) 0.413
3 (1.91) 1.000
3 (1.91) 1.000
46 (29.30) 0.000
15 (9.55) 0.014
1 (0.64) 0.210
1244 B. Zhang et al. / Clinical Nutrition 36 (2017) 1239e1244
Clinical Projects (No. 439, 2010) to Prof Xiao-ping Chen, the Na-
tional Nature Science Foundation of China (No. 30973498 and
81072001) to Prof Bixiang Zhang, and the National Nature Science
Foundation of China (No. 81502524) to Dr Binhao Zhang.
Statement of authorship
Bixiang Zhang and Xiao-ping Chen designed this study and
drafted the manuscript. Binhao Zhang and Gang Wei performed the
major part of the study, including patient recruitment, data
acquisition and analysis, and manuscript drafting. Yanjun Wang
and Jie Yu performed the computer-generated randomization and
allocation, revised the manuscript critically for important intel-
lectual content. Rui Li, Rui Wang and Hua Xiao helped in patient
recruitment, data acquisition and analysis, and manuscript drafting.
Chao Wu and Chao Leng analyzed some data and revised the
manuscript. All authors approved the final version of the
manuscript.
Conflict of interest
The authors declare no conflict of interest.
Acknowledgements
We thank Dr. Arian Laurence from The Newcastle Upon Tyne
Hospitals NHS Foundation Trust, Freeman Hospital, Newcastle
Upon Tyne (UK), Dr. Dengping Ying from Chicago University, Dr.
Lishi Sun from University of Texas Health Science Center at San
Antonio and Dr. Wei Dong from University of Duisburg and Essen
for reviewing this manuscript and providing language assistance.
We also thank Dr. Ping Yin from Department of Epidemiology and
Biostatistics School of Public Health, Tongji Medical College,
Huazhong University of Science and Technology, provided assis-
tance for clinical trial design and statistical analysis.
Appendix A. Supplementary data
Supplementary data related to this article can be found at http://
dx.doi.org/10.1016/j.clnu.2016.08.002.
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