CONTOH CASE REPORT
L-ornithin L-aspartate in Hepatic
Encephalopathy due to Liver Cirrhosis
1Suzanna Ndraha, 2Marcellus Simadibrata
|
1 Department of Internal
Medicine, Faculty of Medicine, University of Indonesia
2 Division of
Gestroenterology, Department of Internal Medicine, Faculty of Medicine,
University of Indonesia
|
Abstrak
Pasien laki-laki 62 tahun dibawa ke ruang gawat
darurat RS Tebet Jakarta dengan keluhan utama penurunan kesadaran sejak 6 jam sebelumnya. Dia telah diketahui menderita penyakit liver sirosis
sejak 6 tahun, akibat hepatitis B. Beberapa hari sebelumnya pasien makan banyak
putih telur dan ikan karena tahu albumin darahnya rendah Pada pemeriksaan fisik
didapatkan keadaan gizi kurang, kesadaran delir, ada flapping tremor. Encefalopati hepatikum ditegakkan berdasarkan
hasil critical flicker test (CFF) yang
rendah (33,8 ± 0,58 Hz),
dan kadar amonia darah yang tinggi (189
mmol/L). Pasien
mendapatkan diet 35 kcal/kg per hari dan
protein 1.5 g/kg/ha ri. L-ornithine L-aspartate diberikan untuk menurunkan
ammonia darah dan meningkatkan angka critical
flicker test. Dalam pemantauan selajutnya didapatkan pasien membaik,
kesadaran berangsur normal, critical
flicker test (CFF) meningkat dan ammonia darah menurun.
Key words: sirosis hati, ensefalopati, L-ornitin
L-aspartat, critical flicker test, kadar ammonia darah
Abstract
A 62-year-old man was brought into emergency room of
Tebet Hospital Jakarta, Indonesia, with chief complaint of reduced consciousness
since 6 hours before admission. He had been diagnosed as liver cirrhosis for 6
years, due to chronic hepatitis B infection. Several days prior to admission he
took high protein diet, in order to reach normal blood albumin level. Physical
examination revealed unconsciousness and flapping tremor. Hepatic encephalopathy
was confirmed with critical flicker test (CFF) less than normal (33,8 ± 0,58 Hz), and blood ammonia level
higher than normal (189 mmol/L).
He was treated with diet 35
kcal/kg per day and protein 1.5 g/kg/day,
L-ornithine L-aspartate to decrease blood ammonia and improve the critical
flicker test. During the treatment, the patient’s condition improved, level of consciousness
improved to normal, critical flicker test (CFF) increased and blood ammonia
level decreased.
Key words: liver
cirrhosis, hepatic encephalopathy, L-ornithine L-aspartate, critical flicker
test, blood ammonia level
Introduction
. Liver cirrhosis
is the end of various type of liver disease, it can evoke various complications
such as reduce of liver synthetic function (coagulopathy), reduce liver
capability for detoxification (Hepatic Encephalopathy), and portal hypertension
with all its complications [1,2]. Hepatic Encephalopathy (HE) is one
of all liver cirrhosis that brings high morbidity and mortality effect. The
incidence rate of HE in liver cirrhosis are various from 30-45% [3] and also
50-70% [4], where most of it considered as minimal HE.
Increases of ammonia level
in the blood, among others is the effect of over intake protein and
gastrointestinal bleeding, until now is considered to have the major role in HE
pathogenesis [4,5]. Due to that, the management of HE especially tend to reduce
the amount of ammonia in the blood, besides to overcome the initiating factor.
The efforts to reduce the amount of ammonia in the blood are done by giving
lactulose, antibiotics for intestine sterilization, and constrict the protein
intake. Constricting protein intake in HE nowadays is becoming a controversy,
cause it can worsen malnutrition [6]. Few research reports that malnutrition can
increase mortality rate in liver cirrhosis [6,7]. Contrariwise
nutrition improvement can increase muscle mass, which is needed for ammonia
detoxification. For the nutrition improvement a diet 25-35 kcal/Kg per day and
protein 1-1.5g/Kg/day is suggested.
L-ornithine-L-aspartate (LOLA)
nowadays started to be used to overcome EH cause its proven can reduce ammonia
level in the blood [8], LOLA stimulates the urea cycle and glutamine synthesis,
which is the important mechanism in ammonia detoxification [9,10]. With the
intake of LOLA intend to reduce the ammonia level in the blood, so that it is
unnecessary to constrict protein intake in liver cirrhosis patient with
malnutrition.
This article reports the case
of hepatic encephalopathy which is treated with L-ornithine-L-aspartate (LOLA)
and given 35 kcal/kg/day diet and 1.5g/kg/day protein.
.
Case
Patient is a 62 years old man who was brought
in the emergency ward with chief complaint of reduced consciousness which
manifested as having difficulty in speaking since 6 hours prior to hospital
admission. From his present history of illness, patient has been experiencing
fatigue and loss of balance since 3 days prior to admission. Furthermore,
patient constantly feels drowsy therefore his sleeping hours have increased in
both duration and frequency and family members are often unable to comprehend
what the patient says. 6 hours prior to admission, he was unable to recognize
the people around him, further deterioration of speech skills therefore family
members decided to bring him to the emergency ward of RS Tebet Jakarta.
Patient was diagnosed with liver cirrhosis
due to hepatitis B infection 6 years prior to admission. His symptoms were
swollen abdomen and feet which resolved every time he received medications from
the doctor. He always performed his check-up routinely every month up to this incident;
furthermore, he also pays high attention on his daily diet which was
specifically recommended by a nutritionist. However, since several days prior
to admission, patient’s serum albumin level had been low, therefore his wife
decided to add more fish into his daily diet.
During physical examination in the emergency
ward, patient was deemed with severely ill condition, delirious. His body
height was 168 cm; his weight was at 62 kg and mid arm muscle circumference (MAMC) of 228 mm. He had normal blood
pressure, no signs of fever, however abnormalities were found in his eyes which
had anemic conjunctiva and icteric sclera. Other abnormalities seen were spider nevi on the chest and palmar erythem on his extremities. In
addition, collateral veins were discovered on his abdomen with enlarged spleen
up to shuffner II, with no signs of ascites or extremity edema, and a flapping tremor was also noticeable.
Laboratory results on admission showed a
condition of pancytopenia (Hb 11,7 g/dl, leukocyte 3270/uL, platelets
65.600/uL, LED 50 mm/jam. Electrolyte balance and prothrombine time were under
normal limits. Albumin 2,4 g/dl, total bilirubin 1,98 mg/dl, SGOT 75 iu/L, SGPT
32 iu/L. Urinalysis tests showed no abnormalities and were under normal limits.
Current
working diagnosis on arrival is hepatic encephalopathy due to increased protein
intake on cirrhotic patient due to chronic hepatitis B infection. Pancytopenia
was suspected due to hypersplenism with liver cirrhosis. To confirm this
diagnosis, USG of the abdomen is planned to confirm the cirrhosis, blood
ammonia level as well as critical
flicker test (CFF) to confirm hepatic encephalopathy. Patient is given a diet of 2100 calories
daily with 90 grams protein along with substituted multiple chained amino acids
(AARC), L-ornithine L-aspartate (HepamerzÒ) I.V.
20 grams of (4 ampoules) /day in 250 ml of infuse line for 5 days and
later replaced with oral route dose of 3 x 6 gram for 2 weeks in order to
reduce the ammonia levels in the blood. Lactulose of PO 4 x 15 ml is
administered to facilitate transit to reduce further breakdown of ammonia.
During the follow up, we
acquired the abdominal USG results which confirmed the diagnosis of liver
cirrhosis and splenomegaly with minimal ascites. Ammonia level shows 189 mmol/L (normal
< 50 mmol/L), CFF 33,8
± 0,58 Hz (normal
≥ 39 Hz). These results further strengthen the diagnosis of hepatic encephalopathy
on liver cirrhosis. After 2 days of treatment, patients condition improved with
increased consciousness level up to fully alert (compos mentis), and no flapping tremor was noticeable. Repeated
measurement of blood ammonia levels shows an improvement (reduction up to155mmol/L) and
furthermore, CFF has increased up to 38.8 ± 0.62 Hz.
Discussion
This is a case of liver cirrhosis with the
complication of encephalopathy due to excessive protein intake. Excessive protein intake is one of several initiating
factor of HE that cause increased ammonia production [11]. Encephalopathy
diagnosis was proven with the increased of ammonia level, supported the theory
that acknowledge that ammonia hold an important role in the HE mechanism.
Laboratory results shown 2,4 g/dl albumin level, 1,98 mg/dl total bilirubin
level, normal prothrombine time, minimal ascites (under control) and minimal
encephalopathy shown that liver function level of the patient is classified as
Child Pugh B so the possibility of HE due to endogen factor is not likely.
Flicker test nowadays
considered as a sensitive test, simple, and reliable to diagnose minimal HE in
liver cirrhosis [12, 13]. The Critical Flicker Test (CFF) of 33,8 ± 0,58 Hz in this
patient showed the existence of HE cause by increased ammonia level due to
increased protein intake priory.
The patient has 22, 7 kg/m2 BMI (Body Mass Index) that shows normal
nutritious, but apparently from MAMC shows that actually the patient has
started to undergo minor malnutrition. It was known that the weight of liver
cirrhosis patients is more affected by ascites and edema, therefore calculation
and measurement using MAMC is more suggested to evaluate nutrition status [14].
Patient is treated with 2100 calories diet, 90 gram of protein with branch
chain amino acid (BCAA) substitute, in order to maintain the nutrition status.
To overcome the risk of increasing ammonia level, patient is given L-ornithine-L-aspartate
(LOLA) 20 g intravenous (4 ampoules dissolved in 250 cc carrier solution over 4
hours) for 5 days followed by L-ornithine-L-aspartate granules 6 g three times
daily for 2 weeks. It appears that the diet treatment given to this patient did
not worsen EH, in this circumstance maybe cause of LOLA treatment that helps
decreasing the plasma ammonia level.
Conclusion
This case reports liver cirrhosis that nutrition status was measured base
on MAAC, EH was diagnosed based on CFF (critical
flicker test), then for this case, patient is given appropriate diet according
to the nutrition status to avoid worsening of the malnutrition. However, EH is
improving due to LOLA treatment which can reduce plasma ammonia level.
References
1.
Munoz SJ. Hepatic Encephalopathy. Med Clin N Am. 2008;
92:795–812
2.
Kusumobroto HO. Sirosis hati. Dalam Sulaiman HA, Akbar HN, Lesmana LA, Noer HMS.
Buku Ajar Ilmu Penyakit Hati. 1st ed. Jakarta: Jayabadi;
2007. p.335-45
3.
Kim WR, Brown RS, Terrault NA, El-Serag H. Burden of
Liver Disease in the United States: Summary of Workshop. Hepatology. 2002;36(1):227-42
4.
Poordad FF. Review article: the burden of hepatic
encephalopathy. Aliment Pharmacol Ther. 2006; 25 (Suppl. 1): 3–9
5.
Kramer L,
Tribl B, Gendo A, Zauner C, Schneider B, Ference P. et al. Partial Pressure of Ammonia
Versus Ammonia in Hepatic Encephalopathy. Hepatology 2000;31:30-34.
6.
Norenberg MD, Jayakumar AR, Rama Rao KV, Panickar
KS. The peripheral
benzodiazepine receptor and neurosteroids in the pathogenesis of hepatic
encephalopathy and amonia neurotoxicity. In Häussinger, Kircheis G, Schliess F.
Hepatic Encephalopathy and nitrogen metabolism. The Netherlands: Springer;
2006. p. 143-59
7.
Abdo AA. An evidence-based update on hepatic
encephalopathy. Saudi J Gastroenterol 2006;12:8-15
8.
Anne S
Henkel and Alan L Buchman. Nutritional support in patients with chronic liver
disease. Nature clinical practice. Gastroenterology and hepatology. 2006;3(4): 202-09
9.
Kircheis
G, Häussinger D. Management of Hepatic Encephalopathy. Conference Proceedings.
Journal of Gastroenterology and Hepatology 2002;17:S260-7
10. Rees
C J, Oppong K, Al Mardini H, Hudson M, Record C O. Effect of L-ornithine-L
aspartate on patients with and without TIPS undergoing glutamine challenge: a
double blind, placebo controlled trial. Gut 2000;47:571–574
11. Santiago
J. Munoz, MD. Hepatic Encephalopathy.
Med Clin N Am 2008; 92:795–812.
12.
Kircheis
G, Wettstein M, Timmermann L, Schitzler A, Häussinger D. Critical Flicker
Frequency for quantification of low grade hepatic encephalopathy. Hepatology
2002;35:357-66
13. Gomez MR. Critical flicker frequency:
It is time to break down barriers surrounding minimal hepatic encephalopathy. Journal
of Hepatology 2007;47:10–11
14. Kalaitzakis E, Olsson R,
Henfridsson P, Hugosson I, Bengtsson M, Jalan R. et al. Malnutrition and
diabetes mellitus are related to hepatic encephalopathy in patients with liver
cirrhosis. Liver International 2007;27(9):1194-201
Case report ini dipublikasi di majalah ACTA MEDICA Vol 42 • No 3 • Juli 2010 hal 158-161
