Author
Information
(Professor.
Department of Obstetrics and Gynecology, Seth
G.S. Medical
College and K.E.M
Hospital , Mumbai , India
Abstract
An
interesting case of hyperemesis gravidarum with elevated hepatic
aminotransferases is reported. Despite complete cessation of vomiting the
patient’s liver aminotransferases kept rising. All investigations to detect any
underlying liver disease were futile. She eventually responded to oral
administration of a multivitamin.
Introduction
Hyperemesis
gravidarum is pernicious vomiting of pregnancy that can lead to dehydration,
ketoacidosis of starvation, alkalosis, electrolyte imbalance, weight loss,
altered liver or renal function and Wernicke’s encephalopathy.[1] It
can result in deficiency of vitamins and nutrients due to reduced intake or
poor absorption. B complex vitamins are important coenzymes in enzymatic
reactions. They are required for normal energy metabolism, thiamine more than
the others. Wernicke encephalopathy is a well documented complication of
thiamine deficiency in patients of hyperemesis gravidarum.
Case Report
Twenty one
year old Gravida 1 presented with a complaint of hyperemesis gravidarum at 8
weeks of pregnancy. She had had persistent vomiting for one week. She was admitted, kept nil by mouth and was
infused with intravenous crystalloids including Ringer lactate solution.
Doxylamine and pyridoxine were administered at 8 hour intervals orally with
sips of water. On admission her pulse rate was 96/min., BP was 90/60 mm of Hg,
tongue was moist, respiratory rate was 18/min. Her uterus was anteflexed, soft
and corresponding to 8 weeks size. Her laboratory parameters were as follows:
Hb 11.5 g/dl, WBC 7600/mm3. TSH was 1.35 μIU/mL, random blood
sugar was 110 mg%, uric acid 3.2 mg%, BUN 11 mg%, serum creatinine 0.8 mg%,
SGOT 115 U/L, SGPT 91 U/L, serum electrolytes within normal limits. Urinary
ketones were small. After admission the patient had no further episodes of
vomiting and she was started on dry carbohydrate diet after 24 hours and oral
doxylamine and pyridoxine were continued three times a day. As her liver
enzymes were marginally elevated they were repeated. Her serial serum hepatic
aminotransferases levels are shown in the table below.
Serial laboratory serum hepatic
aminotransferases
levels
Parameter
|
2nd
Jan 14
Day 1
|
Day 3
|
Day 6
|
Day 9
|
Day 12
|
Day 15
|
Day 17
|
Day 81
|
SGOPT
U/L
|
115
|
131
|
145
|
182
|
240
|
127
|
83
|
25
|
SGPT U/L
|
91
|
166
|
190
|
227
|
278
|
201
|
149
|
7
|
Her serum
bilirubin, creatinine, BUN, electrolytes, coagulation profile were normal on
serial measurements. The liver enzymes showed a rising trend. The patient had
no further episodes of vomiting. Her condition was stable and she was
tolerating dry solids orally. She was continued on oral doxylamine and
pyridoxine three times a day. A coexisting liver disorder was suspected. A
gastroenterologist’s opinion was obtained. As per his advise, viral markers, ultrasound
(USG) abdomen, ANA, Anti-ds DNA and Anti smooth muscle antibody testing (ASMA)
were obtained. All viral markers (HbsAg, HCV, HIV, IgM HbcAb, and IgM HEV) were
negative. Autoimmune markers like ANA, Anti-ds DNA, and ASMA (Interglandular
Actin Fibers, Muscularis Mucosa, Muscle layers of blood vessels) were all
negative. USG abdomen was normal. Liver was normal in size and echo texture.
Hepato- portal color Doppler was also normal. Hepatic veins were normal. Middle
and lower hepatic vein had common ostia. Right hepatic vein was normal. Spleen
was normal. As the liver enzymes showed a rising trend over 12 days and all
tests indicating any other liver pathology were negative we were in a dilemma
about terminating her pregnancy. However before that we decided to give a
multivitamin orally. The contents of that multivitamin were vitamin B1 10mg,
vitamin B2 10 mg, Nicotinamide 100 mg, vitamin B6 3 mg, calcium pantothenate 50
mg, Folic acid 1.5 mg, vitamin B12 15 mcg, vitamin C 150 mg. We gave her one
tablet of this multivitamin daily and then repeated the liver enzymes after 3
days. The liver enzymes gradually decreased and normalized over the next 15
days. The patient was discharged after a stay of 19 days. The pregnancy is
ongoing and is uncomplicated.
Discussion
Nausea
vomiting is common is the first trimester of pregnancy. Incidence of
hyperemesis gravidarum is about 0.1-2% pregnancies.[1] Of these
about 50% patients have evidence of liver dysfunction as evidenced by deranged
liver aminotransferases.[2] The liver enzymes normalize after
vomiting resolves. If liver dysfunction persists an underlying liver pathology
is to be evaluated.[3] In our patient despite having no vomiting her
liver enzymes kept deteriorating. All investigations to detect any underlying
viral, autoimmune or ischemic pathology were done but no cause for the rising
aminotransferases could be found. B group of vitamins act as a cofactor in many
of the chemical reaction in the liver. Use of thiamine for prevention of
Wernicke’s encephalopathy is well documented.[4] B complex vitamins
have a wide role in enzymatic, non enzymatic regulatory roles. Thiamine is an
important cofactor in energy metabolism and is naturally present in the liver.[5]
One of the hypothesis of alteration of liver function in patients of
hyperemesis is the affect on the fatty acid oxidation in the mitochondria. Starvation
also results in increase in circulating fatty acids due to increased lipolysis.[2]
Thiamine pyrophosphate, a derivative of thiamine, is required for the
carbohydrate metabolism and the Kreb’s cycle. Deficiency of this vitamin may
increase the fatty acid metabolism.[6] Niacin is supposed to reduce
the triglyceride and secretion of very low density and low density lipoproteins.[7]
Riboflavin is believed to be involved in the biosynthesis of coenzyme A
reducing the oxidative stress.[8]
Administration of the B complex tablet in this case may have corrected the energy metabolism and
reduced the fatty acid metabolism allowing the liver enzymes to correct
themselves. It may be worth trying to administer a multivitamin tablet in cases
of hyperemesis gravidarum patients who fail to recover their liver function
despite cessation of vomiting. This may
be because the deficiency of the one or more components of the B group of
vitamins, especially where they are not stored in the body like thiamine, may
persist due to inadequate dietary intake even after vomiting stops. However, we
noted a significant decline in the liver enzymes on continuous administration
of the B complex tablet in our patient.
Conclusion
B complex
administration in intractable elevation of liver aminotransferases is worth a
trial especially in those cases of hyperemesis gravidarum whose liver function
continues to deteriorate even after control of vomiting and no other cause for
the abnormal liver function is detected.
References
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Kuşcu N K, Koyuncu F; Hyperemesis gravidarum:
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http://emedicine.medscape.com/article/254751-workup
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