REVIEW JURNAL INTERNASIONAL IMUNOLOGI FARMASI

Tentang
The Hyperlipidemia Caused by Overuse of Glucocorticoid after Liver
Transplantation and the Immune Adjustment Strategy

Disusun Untuk memenuhi Tugas Individu

Mata Kuliah : Imunologi Farmasi
Dosen Pengampu : Apt. Tunjung Winarno, S.Farm

Disusun oleh:
Bella Suci Ramadhani (42118005)

PROGAM STUDI FARMASI

FAKULTAS SAINS DAN TEKNOLOGI
UNIVERSITAS PERADABAN
BUMIAYU
2020
Hindawi
Journal of Immunology Research
Volume 2017, Article ID 3149426, 5 pages
https://doi.org/10.1155/2017/3149426

Research Article
The Hyperlipidemia Caused by Overuse of Glucocorticoid after
Liver Transplantation and the Immune Adjustment Strategy

Xueqin Meng,1,2,3 Xinhua Chen,1,2,3 Liming Wu,1,2,3 and Shusen Zheng1,2,3

1 Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University, Hangzhou 310003, China

2
Key Laboratory of Combined Multi-Organ Transplantation, Ministry of Public Health, The First Affiliated
Hospital, Zhejiang University, Hangzhou 310003, China
3
The Department of Hepatobiliary and Pancreatic Surgery, The First Affiliated Hospital, Zhejiang
University, Hangzhou 310003, China
Correspondence should be addressed to Shusen Zheng; shusenzheng@zju.edu.cn

Received 29 July 2016; Revised 25 September 2016; Accepted 28 December 2016; Published 17 January 2017

Academic Editor: Andreia´ M. Cardoso

Copyright © 2017 Xueqin Meng et al. This is an open access article distributed under the Creative Commons Attribution License,
which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The overuse of glucocorticoid may cause the metabolic disorders affecting the long term outcome of liver transplantation. This study
aims to investigate the immune adjustment strategy by decreasing use of glucocorticoid after liver transplantation. The follow-up study
was carried out on liver function and lipid metabolism. This study included adult recipients of liver transplantation. There were 3
groups according to their use of glucocorticoid: long term (>3 months, = 18), short term (<3 months, = 20), and control group (no use
of glucocorticoid, radical hepatic resection, = 22). The laboratory results of liver function (AST/ALT ratio) and serum lipid were
compared 6 months after liver transplantation. AST/ALT ratio, the marker of liver function, showed no significant difference between
long and short term group ( > 0.05). The acute rejection had no significant difference between short and long term groups, while TG,
HDL, LDL, and glucose showed significant change in the long term group ( < 0.05). At 6 months af ter liver transplantation, the long
term group showed higher metabolic disorders ( < 0.05). The proper immune adjustment strategy should be made to avoid overuse of
glucocorticoid. It can decrease hyperlipidemia and other metabolic disorders after liver transplantation without increasing the acute
rejection or liver function damage.

1. Introduction transplant is considered a coronary heart disease high risk

After liver transplantation, the overuse of glucocorticoid will
cause glucocorticoid-related complications, such as new-onset
diabetes, hypertension, osteoporosis, growth retarda-tion, and
hyperlipidemia [1]. With the application of new potent
immune suppress agents, acute rejection after liver
transplantation is not the main factor affecting the prog-nosis
[2]. After raising the Hangzhou criteria, outcomes of liver
transplant in our center continued to improve in recent decade.
The liver transplantation recipients in 1-, 3-, and 5-year overall
survival rate achieved 90.41%, 78.04%, and 72.45% [3]. The
allograft-related perisurgery complications are decreasing.
Prevention of hyperlipidemia and other metabolic disorders
can decrease cardiovascular complications and improve the
long term outcomes. Liver
based on the National Cholesterol Education Program Expert
Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults [4]. T he study aims to compare the
different use of glucocorticoid and the impact on liver function
and hyperlipidemia after liver transplantation.
2. Materials and Methods
2.1. Patients. End-stage liver cirrhosis patients who had liver
transplantation were followed up. Liver disease pathology was
confirmed by laboratory examinations and liver biopsies. The
primary disease, surgery procedure, gender, and age in dif-
ferent groups were matched. The study was approved by the
Ethics Committee of the First Hospital of Zhejiang University.
2 Journal of Immunology Research

Table 1: The baseline and characteristics of patients.

Control without glucocorticoid Short term use of glucocorticoid Long term use of glucocorticoid
Number of patients 22 20 18
Time of glucocorticoid 0 <3 months >3 months
Gender (male/female) 10/12 11/10 10/8
Recipient age 52 ±8.3 53 ±7.4 48 ±5.1
MELD score 16.3 ±4.1 24.9 ±7.3 22.9 ±6.7
Surgery Hepatic resection Orthotopic liver transplantation Orthotopic liver transplantation
CSA No Yes Yes
BMI 24 ±3.4 26 ±1.4 28 ±1.1
Basic diseases Angioma Liver cirrhosis Liver cirrhosis

The details were present in Table 1. The 4

adrenocorticotropic hormone (ACTH) has been tested and
Cushing’s syndrome has been excluded.
3
We follow up the adult liver transplantation recipients

with the matched disease and surgeries. There were 3
groups according to their use of glucocorticoid: long term
(>3 months, = 18), short term (<3 months, = 20), and
control group (no use of glucocorticoid, radical hepatic
resection, and = 22). The laboratory results of liver
function, serum lipid, and metabolic disorder occurrence
were compared at 6 months after LT.
2.2. Immunosuppression Strategy. All transplantation recipi-
ents received immunosuppressants. The immunosuppressive
medications (cyclosporine/corticosteroid) were in early stage
after liver transplantation. We tried to cut off the time of
corticosteroids within 3 months. 1000 mg prednisolone on the
first day and 20 mg tapered to zero within the first 3 months.
2.3. Follow-Up Study. Adult recipients of liver transplan-
tation were followed up according to the time of taking
glucocorticoid: long term use of glucocorticoid (>3 month,
= 18), short term use of glucocorticoid (<3 month, =
20), and control group (no use of glucocorticoid, radical
hepatic resection, and = 22).
2.4. Laboratory Tests. Laboratory results of liver function and
metabolic function 6 months after LT were compared. Blood
samples following 12 h fasting and 2 h after dinner were
drawn from vein for adrenocorticotropic hormone (ACTH),
cortisol, glucose, and serum lipids (total cholesterol, LDL,
HDL, and triglyceride). ACTH was tested by electro-
chemiluminescence Elecsys ACTH immunoassay, ECLIIA,
(Roche Diagnostics, Mannheim, Germany) on E170 Model.
Cortisol was tested by a chemiluminescence assay (Bayer,
Shanghai, China) on the ACS180 SE Model. The biochemistry
exams were done by automated chemistry analyzer (Hitachi,
Tokyo, Japan) on Hitachi 7600-110 Model. The liver function
and lipids were tested by BECKMAN COULTER analyzer
(Beckman Coulter Diagnostics, CA, USA) on AU5811 Model.
We measured the new onset diabetes according to the
American Diabetes Association/World Health Organization
guidelines; new onset DM was defined as patient used to have
AST/ALT
2
1
0
Control Short term Long term
Use of glucocorticoid
Figure 1: The AST/ALT ratio in patients taking short term, long
term, and no glucocorticoid. Levels of AST/ALT ratio were
signif-icantly higher ( < 0.05) in patients who took glucocorticoid
no matter long term or short term compared with control. There
were no significant difference of AST between short or long term
groups. Data are expressed in AST/ALT which is a marker to
reflect liver function damage.
a normal fasting blood glucose, but after liver transplantation,
he/she has a fasting blood glucose of ≥7.00 mmol/L (1.26 g/L)
confirmed on at least 2 occasions or current treatment with an
oral antidiabetic drug or insulin. The pathological slides from
the biopsy were parallel to the liver function results.
2.5. Statistical Analysis. Data were expressed as mean ±SD.
For statistical comparison of values, Student’s -test was
used by software SPSS 17.0. values less than 0.05 were
deemed to indicate statistical significance.
3. Results
3.1. AST/ALT Ratio Significantly Changed in Patients Who
Took Glucocorticoid. T he 3 groups of patients who took glu-
cocorticoid at different times after liver surgery were shown in
Figure 1. There was no acute rejection in recipients, indicating
that the use of glucocorticoid helped the transplanted liver to
work properly and, as a results, patients survived. AST/ALT
ratio had no significant difference between short or long term
Journal of Immunology Research 3

Table 2: The complications in patients with use of glucocorticoid after liver transplantation.

Infection Wound nonhealing New onset diabetes Hypertension Acute rejection

Short term 3 2 3 2 2
Long term 10 7 11 9 3
2
5.238479 6.788542 5.553217 5.553217 0.015993
0.022093 0.009174 0.018447 0.018447 0.899364

Table 3: The baseline and characteristics of patients.

Control without Short term use of Long term use of

glucocorticoid glucocorticoid glucocorticoid
Number of patients 22 20 18
Time of glucocorticoid 0 <3 months >3 months
Glucose fasting (mmol/L) 4.9 ±1.3 5.1 ±0.7 5.3 ±1.1
Glucose 2 h after dinner (mmol/L) 6.9 ±0.7 7.1 ±0.7 9.3 ±2.6∗
ACTH 8 am (pmol/L) 6.5 ±0.4 7.2 ±0.7 7.9 ±0.3
HDL (high density lipoprotein, mmol/L) 1.49 ±0.31 1.29 ±0.24 0.99 ±0.21∗
LDL (low density lipoprotein, mmol/L) 2.29 ±0.81 2.71 ±0.53 3.09 ±0.74∗
TC (total cholesterol, mmol/L) 5.29 ±0.37 5.61 ±0.21 5.78 ±0.52

∗
< 0.05versus control group.

4 When comparing short term and long term use of glucocorti-

coid, short term group significantly had decreased TG versus
long term group ( < 0.05), indicating that cutting off the
3 overuse of glucocorticoid can effectively decrease TG.
TG(mol/L)

3.3. The Acute Rejection Occurrence. With development of

2 surgery skill and organ protection technology, acute rejection
becomes less common. All episodes of acute rejection in this
1 study occurred in the first 6 weeks in recipients with a donor
mismatches (Table 2). The prevalence of acute rejection was
10% in short term group versus 17% in long term group ( =
0 0.899364). Clinical symptoms were not typical. Laboratory
Control Short term Long term
tests on liver function were, for example, elevations AST
Use of glucocorticoid
(Figure 1). The diagnosis of acute rejection was confirmed by
Figure 2: The TG levels in patients taking short term, long term, needle biopsy. The histopathological findings in reports from
and no glucocorticoid. The quantitative evaluation of TG was Department of Pathology showed that acute rejection includes
analyzed and expressed in mol/L. TG significantly increased in predominantly mononuclear portal inflammation;
patients who took different time of glucocorticoid compared with subendothelial inflammation of portal and hepatic veins; and
the control group. When comparing short term and long term use bile duct inflammation and damage. The short and long term
of glucocorticoid, short term group significantly decreased versus groups had no significant difference in liver damage such as
long term group ( < 0.05). duct damages or unequivocal endotheliitis except some
inflammatory infiltration in long term group. There were no
visible steatosis cells in any groups (Figure 3).
groups, which indicates that the short use of glucocorticoid
less than 3 months can achieve the same immune effect as 3.4. The Metabolic Disorder Occurrence. Features of the
long term use of glucocorticoid longer than 3 months. metabolic disorders were found in patients 6 months after
transplantation (Tables 2 and 3). New onset diabetes rose
3.2. Cutting off the Overuse of Glucocorticoid Can Decrease from 15% in short term group to 61% in long term group (
TG. The quantitative evaluation of serum lipids was analyzed = 0.009174, Table 2); hypertension increased from 10% in
(Figure 2). TG significantly increased in patients who took short term group to 50% in long term group ( = 0.018447,
different time of glucocorticoid compared with the control Table 2). The long term group had significantly reduced
group ( < 0.05), indicating that the use of glucocorticoid can HDL and increased LDL and 2 h after dinner blood glucose
affect the lipid metabolism and lead to hyperlipidemia. (Table 3).
 4 Journal of Immunology Research

Control Short term Long term

Figure 3: The histopathological results. The biopsy from patients in short term, long term, and control groups was shown. The short term
indicates no significant difference from the control group while the long term group had sporadic inflammatory cells infiltration (the
arrow indicates the lymphocytes). There was no obvious steatosis in any groups.

3.5. The Occurrence of Glucocorticoid-Related Side Effects.
Occurrence of glucocorticoid-related side effects such as
infection and poor wound healing was found in patients
followed up >6 months after transplantation (Table 2). The
prevalence of infection rises from 15% in short term group to
56% in long term group ( = 0.022093). Poor wound healing
increased from 10% in short term group to 39% in long term
group ( = 0.087380). The reinfection with hepatitis B and the
infection with CMV have been excluded.
4. Discussion
Lipid metabolic disorders are becoming more common
after liver transplantation which affect the long term
morbidity and mortality as well as life quality. Some
patients do have the metabolic preconditions such as
overweight, diabetes, and cholestatic liver disease. The new
onset of metabolic disorders is often caused by the use of
immunosuppressant medications such as cyclosporine,
tacrolimus, and glucocorticoid which attack the insulin
signaling pathway by changing adipose enzymes [5].
We monitor patients’ liver function and lipid levels 6
months after transplant. The results indicate that avoiding
overuse of glucocorticoid can significantly decrease the
risk of hyperlipidemia in liver transplant recipients.
It has been well known that glucocorticoid inhibits
immune function. The metabolic side effects have been
noticed recently such as diabetes, hypertension, and hyper-
lipidemia [6].
Because acute rejection after liver transplantation gener-
ally occurred 2 weeks after liver transplantation, we suggest
early glucocorticoid withdrawal scheme to ensure a lower
rejection and minimize the amount of glucocorticoid. Our
clinical data suggest that the minimized use of glucocorticoid
did not increase the incidence of rejection but decreased
postoperative infection and poor wound healing. Quite dif-
ferent from some liver transplantation centers whose primary
liver diseases of liver transplantation are alcoholic cirrhosis,
HCV cirrhosis, and autoimmune liver disease, our center has
more than 90% of liver transplant recipients for HBV-related
diseases, with about 40% of hepatocellular carcinoma.
Overuse of glucocorticoid after liver transplantation for more
Journal of Immunology Research
than 1 year also causes the cancer and HBV recurrence [7,
8].
The blood glucose changes caused by the long term use
of steroid are different from type 1 and type 2 diabetes in
terms of etiology, clinical features, and treatment strategies.
One unique f inding is that the glucocorticoid-induced
blood glucose changes on fasting and randomly were
different. Because glucocorticoids were administered at
8:00 am, these patients’ fasting glucose was not affected.
But the 2 h blood glucose after dinner significantly
increased compared to control group.
Steroids have been used for the purpose of prevent-ing
rejection. However, steroid-related metabolic disorders, such
as hypertension, diabetes mellitus, hyperlipidemia, and
obesity, are causing concerns for its long term use. Hyper-
lipidemia significantly increases cardiovascular events. In
addition, the hyperlipidemia caused atherosclerosis, which can
reduce liver perfusion, resulting in deterioration of liver
function. Hyperlipidemia also participates in the chronic graft
rejection similar to the proliferate vascular disease.
Our result demonstrated that a short term use of steroid
(<3 months) was safe in patients undergoing LT for HBV-
related HCC. Liver function recovered significantly better
than those of long term use of steroid (>3 months).
The patients who had liver transplantation for their
autoimmune hepatitis do have difficulties stopping steroid
because the high chance of immune hepatitis recurrence. There
are a few patients who need to use steroid because of rejection.
When the acute rejection occurs, high dose steroid is still the
first line medicine. Other than the occasions mentioned above,
the majority of adult recipients can stop steroid safely within 3
months. Previous study [9] concluded that steroid tapering to 5
mg/day does not lead to graft loss and may decrease the
incidence and severity of late metabolic complications. When
there is no immune hepatitis nor acute rejection, the steroid
can be discontinued 14 d after liver transplantation when
immunosuppressive therapy based on FKS06+ MMF/CsA was
still maintained [10, 11].
5. Conclusion
Glucocorticoid after liver transplantation is one of the most
commonly used immunosuppressants, playing a very

important role in the prevention and treatment of acute
rejection. However, long term use of glucocorticoid has
many side effects. Early withdraw within 3 months can
decrease the risk of metabolic disorders.
Competing Interests
All the authors declare that they have no potential conflict
of interests.
Authors’ Contributions
5
[9] M. D. Stegall, G. Everson, G. Schroter, B. Bilir, F. Karrer, and I.
Kam, “Metabolic complications after liver transplantation: dia-
betes, hypercholesterolemia, hypertension, and obesity,” Trans-
plantation, vol. 60, no. 9, pp. 1057–1060, 1995.
[10] S. Marubashi, K. Dono, K. Amano et al., “Steroid-free living-
donor liver transplantation in adults,” Transplantation, vol.
80, no. 5, pp. 704–706, 2005.
[11] Q. Wei, X. Xu, C. Wang et al., “Efficacy and safety of a
steroid-free immunosuppressive regimen after liver
transplantation for hepatocellular carcinoma,” Gut and Liver,
vol. 10, no. 4, pp. 604– 610, 2016.

Shusen Zheng and Liming Wu conceived and designed the

experiments; Xueqin Meng, Xinhua Chen, and Liming Wu
collected samples; Xueqin Meng and Xinhua Chen per-
formed the experiment and analyzed data; and Xueqin
Meng and Xinhua Chen wrote the manuscript and
contributed equally to this paper.

Acknowledgments
The research is supported by National Natural Science
Foundation of China (81372425, 81401319, 81421062, and
91542205), Xinjiang Cooperation project (2014KL002),
and Zhejiang project (nos. 2013T301-15 and 2016C33145).

References
ˇ
[1] Z. Reiner, “Management of patients with familial
hypercholes-terolaemia,” Nature Reviews Cardiology, vol. 12,
no. 10, pp. 565– 575, 2015.
[2] X. Xu, D. Lu, Q. Ling et al., “Liver transplantation for hepato-
cellular carcinoma beyond the Milan criteria,” Gut, vol. 65,
no. 6, pp. 1035–1041, 2016.
[3] Z. Hu, J. Zhou, Z. Li et al., “Salvage liver transplantation for
recurrent hepatocellular carcinoma after liver resection:
retrospective study of the Milan and Hangzhou criteria,”
PLoS ONE, vol. 9, no. 1, Article ID e87222, 2014.
[4] A. Ayhan, C. Araz, O. Komurcu, S. Kaplan, A. Torgay, and M.
Haberal, “The evaluation of hemodynamic changes during the
reperfusion phase in adult living donor liver transplantations: the
role of cardiovascular problems,” Transplantation Proceed-ings,
vol. 47, no. 4, pp. 1199–1203, 2015.
[5] C. Huang, P. Chiu, H. Liu et al., “Clinical observations and treat-
ment of pediatric homozygous familial hypercholesterolemia due
to a low-density lipoprotein receptor defect,” Journal of Clinical
Lipidology, vol. 9, no. 2, pp. 234–240, 2015.
[6] S. Gebhardt, M. Jara, M. Malinowski et al., “Risk factors of
metabolic disorders after liver transplantation: an analysis of
data from fasted patients,” Transplantation, vol. 99, no. 6, pp.
1243–1249, 2015.
˚
[7] K. Nikkila,¨ F. Aberg, and H. Isoniemi, “Transmission of LDLR
mutation from donor through liver transplantation resulting in
hypercholesterolemia in the recipient,” American Journal of
Transplantation, vol. 14, no. 12, pp. 2898–2902, 2014.
[8] J. Chen, X. Xu, J. Wu et al., “T he stratifying value of hangzhou
criteria in liver transplantation for hepatocellular carcinoma,”
PLoS ONE, vol. 9, no. 3, Article ID e93128, 2014.

The Scientific
World Journal
Hindawi Publishing Corporation
http://www.hindawi.com
Journal of
Immunology Research
Hindawi Publishing Corporation
http://www.hindawi.com
PPAR Research
Hindawi Publishing Corporation
http://www.hindawi.com
Journal of
Ophthalmology
Hindawi Publishing Corporation
http://www.hindawi.com
Computational and
Mathematical
Methods in Medicine
Hindawi Publishing Corporation
http://www.hindawi.com
MEDIATORS of
INFLAMMATION
Gastroenterology Journal of
Research and Practice
Hindawi Publishing Corporation
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Diabetes Research
Hindawi Publishing Corporation
Disease Markers
Hindawi Publishing Corporation
Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014
International Journal of
Endocrinology
Hindawi Publishing Corporation
Volume 2014 http://www.hindawi.com Volume 2014
Submit your manuscripts at
https://www.hindawi.com
BioMed
Research International
Hindawi Publishing Corporation
Volume 2014 http://www.hindawi.com Volume 2014
Journal of
Obesity
Evidence-Based
Stem Cells Complementary and Journal of
International
Hindawi Publishing Corporation
Alternative Medicine
Hindawi Publishing Corporation Hindawi Publishing Corporation
Oncology
Hindawi Publishing Corporation
Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014 http://www.hindawi.com Volume 2014
Parkinson’s
Disease
Behavioural AIDS Oxidative Medicine and
Volume 2014
Neurology
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Research and Treatment
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
Cellular Longevity
Hindawi Publishing Corporation
http://www.hindawi.com Volume 2014
 REVIEW JURNAL
Judul Hiperlipidemia Disebabkan oleh Penggunaan Glukokortikoid
Berlebihan setelah Transplantasi Hati dan Strategi
Penyesuaian Kekebalan Tubuh
Jurnal Journal of Immunology Research
Download https://doi.org/10.1155/2017/3149426
Volume & Halaman
Tahun 2017
Penulis Xueqin Meng, Xinhua Chen, Liming Wu, and Shusen Zheng
Reviewer BELLA SUCI RAMADHANI (42118005)
Tanggal 07 Dec 2020

Abstrak Jurnal yang berjudul ‘’ Hiperlipidemia Disebabkan oleh Penggunaan

Glukokortikoid Berlebihan setelah Transplantasi Hati dan Strategi
Penyesuaian Kekebalan Tubuh’’ bertujuan untuk mengetahui
strategi penyesuaian kekebalan dengan mengurangi penggunaan
glukokortikoid setelah transplantasi hati. Studi lanjutan dilakukan
pada fungsi hati dan metabolisme lipid.

Pada jurnal ini penulisan jurnal hanya menggunakan satu Bahasa

yaitu Bahasa inggris. Secara keseluruhan isi dari abstrak ini
langsung menuju topik bahasan yang dibahas dalam jurnal ini, yang
menurut saya pembaca menjadi mudah memahami jurnal ini
Pengantar Pada bagian pengantar disampaikan bahwa Setelah transplantasi
hati, penggunaan glukokortikoid yang berlebihan akan
menyebabkan komplikasi terkait glukokortikoid, seperti diabetes
onset baru, hipertensi, osteoporosis, retardasi pertumbuhan, dan
hiperlipidemia. Dengan penerapan agen penekan kekebalan baru
yang kuat, penolakan akut setelah transplantasi hati bukanlah faktor
utama yang mempengaruhi prognosis. Setelah meningkatkan
kriteria Hangzhou, hasil transplantasi hati di pusat kami terus
meningkat dalam dekade terakhir. Penerima transplantasi hati dalam
tingkat kelangsungan hidup 1, 3, dan 5 tahun secara keseluruhan
mencapai 90,41%, 78,04%, dan 72,45%. Komplikasi perisurgery
terkait allograft menurun. Pencegahan hiperlipidemia dan gangguan
metabolisme lainnya dapat menurunkan komplikasi kardiovaskular
dan meningkatkan hasil jangka panjang. Transplantasi hati dianggap
 sebagai penyakit jantung koroner yang berisiko tinggi berdasarkan
Panel Pakar Program Pendidikan Kolesterol Nasional tentang
Deteksi, Evaluasi, dan Pengobatan Kolesterol Darah Tinggi pada
Orang Dewasa. Penelitian ini bertujuan untuk membandingkan
perbedaan penggunaan glukokortikoid dan pengaruhnya terhadap
fungsi hati dan hiperlipidemia pasca transplantasi hati.
Metode penelitian 1. Pasien

Pasien sirosis hati stadium akhir yang menjalani transplantasi hati

ditindaklanjuti. Patologi penyakit hati dikonfirmasi dengan
pemeriksaan laboratorium dan biopsi hati. Penyakit primer,
prosedur pembedahan, jenis kelamin, dan usia dalam kelompok
yang berbeda dicocokkan. Penelitian ini disetujui oleh Komite Etik
Rumah Sakit Pertama Universitas Zhejiang. Detailnya ada diTabel
1. Hormon adrenokortikotropik (ACTH) telah diuji dan sindrom
Cushing telah disingkirkan.

2. Strategi Imunosupresi

Semua penerima transplantasi menerima imunosupresan.

Pengobatan imunosupresif (siklosporin / kortikosteroid) berada
dalam tahap awal setelah transplantasi hati. Kami mencoba
memotong waktu pemberian kortikosteroid dalam waktu 3 bulan.
1000 mg prednisolon pada hari pertama dan 20 mg dikurangi
menjadi nol dalam 3 bulan pertama.

3. Studi Tindak Lanjut

Penerima transplantasi hati dewasa ditindaklanjuti sesuai dengan

waktu penggunaan glukokortikoid: penggunaan glukokortikoid
jangka panjang (> 3 bulan, n = 18), penggunaan glukokortikoid
jangka pendek (<3 bulan, n = 20), dan kelompok kontrol ( tidak
menggunakan glukokortikoid, reseksi hati radikal, dan n = 22).

4. Tes laboratorium

Hasil laboratorium dari fungsi hati dan fungsi metabolisme 6 bulan

setelah LT dibandingkan. Sampel darah setelah 12 jam puasa dan 2
 jam setelah makan malam diambil dari vena untuk hormon
adrenokortikotropik (ACTH), kortisol, glukosa, dan lipid serum
(kolesterol total, LDL, HDL, dan trigliserida). ACTH diuji dengan
electrochemiluminescence Elecsys ACTH immunoassay, ECLIIA,
(Roche Diagnostics, Mannheim, Jerman) pada Model E170.
Kortisol diuji dengan uji chemiluminescence (Bayer, Shanghai,
Cina) pada Model ACS180 SE. Ujian biokimia dilakukan oleh
penganalisis kimia otomatis (Hitachi, Tokyo, Jepang) pada Model
Hitachi 7600-110. Fungsi hati dan lipid diuji dengan penganalisis
BECKMAN COULTER (Beckman Coulter Diagnostics, CA, USA)
pada Model AU5811.

5. Analisis statistik

Data dinyatakan sebagai mean ± SD. Untuk perbandingan statistik

nilai, Student's t -test digunakan dengan software SPSS 17.0. Nilai P
kurang dari 0,05 dianggap menunjukkan signifikansi statistic.
Pembahasan Pada bagian pembahasan, sub pokok yang pertama dibahas adalah
Gangguan metabolisme lipid menjadi lebih umum setelah
transplantasi hati yang mempengaruhi morbiditas dan mortalitas
jangka panjang serta kualitas hidup. Beberapa pasien memang
memiliki prasyarat metabolik seperti kelebihan berat badan,
diabetes, dan penyakit hati kolestatik. Awitan baru gangguan
metabolisme sering disebabkan oleh penggunaan obat-obatan
imunosupresan seperti siklosporin, tacrolimus, dan glukokortikoid
yang menyerang jalur pensinyalan insulin dengan mengubah enzim
adiposa.

Kami memantau fungsi hati dan tingkat lipid pasien 6 bulan setelah
transplantasi. Hasil penelitian menunjukkan bahwa menghindari
penggunaan glukokortikoid secara berlebihan dapat secara
signifikan menurunkan risiko hiperlipidemia pada penerima
transplantasi hati. Diketahui bahwa glukokortikoid menghambat
fungsi kekebalan. Efek samping metabolik telah diketahui baru-baru
ini seperti diabetes, hipertensi, dan hyperlipidemia.
Sub yang kedua menjelaskan bahwa Karena penolakan akut setelah
transplantasi hati umumnya terjadi 2 minggu setelah transplantasi
hati, kami menyarankan skema penghentian glukokortikoid dini
untuk memastikan penolakan yang lebih rendah dan meminimalkan
jumlah glukokortikoid. Data klinis kami menunjukkan bahwa
penggunaan glukokortikoid yang diminimalkan tidak meningkatkan
kejadian penolakan tetapi menurunkan infeksi pasca operasi dan
penyembuhan luka yang buruk. Sangat berbeda dari beberapa pusat
transplantasi hati yang penyakit hati utamanya akibat transplantasi
hati adalah sirosis alkoholik, sirosis HCV, dan penyakit hati
autoimun, pusat kami memiliki lebih dari 90% penerima
transplantasi hati untuk penyakit terkait HBV, dengan sekitar 40%
dari karsinoma hepatoseluler . Penggunaan glukokortikoid yang
berlebihan setelah transplantasi hati selama lebih dari 1 tahun juga
menyebabkan kambuhnya kanker dan HBV.

Sub ketiga menjelaskan Perubahan glukosa darah yang disebabkan

oleh penggunaan steroid jangka panjang berbeda dari diabetes tipe 1
dan tipe 2 dalam hal etiologi, gambaran klinis, dan strategi
pengobatan. Satu temuan unik adalah perubahan glukosa darah yang
diinduksi glukokortikoid pada puasa dan secara acak berbeda.
Karena glukokortikoid diberikan pada jam 8 pagi, glukosa puasa
pasien ini tidak terpengaruh. Tetapi glukosa darah 2 jam setelah
makan malam meningkat secara signifikan dibandingkan dengan
kelompok kontrol.

Steroid telah digunakan untuk tujuan mencegah penolakan. Namun,

gangguan metabolisme terkait steroid, seperti hipertensi, diabetes
mellitus, hiperlipidemia, dan obesitas, menyebabkan kekhawatiran
untuk penggunaan jangka panjang. Hiperlipidemia secara signifikan
meningkatkan kejadian kardiovaskular. Selain itu, hiperlipidemia
menyebabkan aterosklerosis, yang dapat menurunkan perfusi hati,
yang mengakibatkan penurunan fungsi hati. Hiperlipidemia juga
berperan dalam penolakan cangkok kronis yang mirip dengan
 penyakit pembuluh darah yang berkembang biak.

Hasil kami menunjukkan bahwa penggunaan steroid jangka pendek

(<3 bulan) aman pada pasien yang menjalani LT untuk HCC terkait
HBV. Fungsi hati pulih secara signifikan lebih baik daripada
penggunaan steroid jangka panjang (> 3 bulan).

Para pasien yang menjalani transplantasi hati untuk hepatitis

autoimun mereka memang mengalami kesulitan untuk
menghentikan steroid karena tingginya kemungkinan kekambuhan
hepatitis imun. Ada beberapa pasien yang perlu menggunakan
steroid karena penolakan. Ketika penolakan akut terjadi, steroid
dosis tinggi masih menjadi obat lini pertama. Selain kejadian yang
disebutkan di atas, mayoritas penerima dewasa dapat menghentikan
steroid dengan aman dalam waktu 3 bulan. Penelitian sebelumnya
menyimpulkan bahwa pengurangan steroid menjadi 5 mg / hari
tidak menyebabkan kehilangan cangkok dan dapat menurunkan
insidensi dan keparahan komplikasi metabolik lanjut. Ketika tidak
ada hepatitis imun atau penolakan akut, steroid dapat dihentikan 14
hari setelah transplantasi hati ketika terapi imunosupresif
berdasarkan FKS06 + MMF / CsA masih dipertahankan.
Simpulan Glukokortikoid setelah transplantasi hati adalah salah satu
imunosupresan yang paling umum digunakan, memainkan peran
yang sangat penting dalam pencegahan dan pengobatan penolakan
akut. Namun, penggunaan glukokortikoid jangka panjang memiliki
banyak efek samping. Penarikan dini dalam waktu 3 bulan dapat
menurunkan risiko gangguan metabolisme.

Pada bagian kesimpulan, penulis membuktikan dan menjelaskan

bahwa Pada bagian kesimpulan ini penulis cukup baik dalam
menjelaskan, penulis lengkap dalam menyimpulkan keseluruhan isi
dari jurnal ini. Menurut saya hasil dalam penelitian ini sudah cukup
detail.
Kekuatan Penelitian 1. Teori dan analisis yang digunakan tepat
2. Analisisya mudah dipahami
 kesimpulan lengkap
Kelemahann Penelitian1. Bahasa yang digunakan penulis hanya menggunakan bahasa inggris.