Case Report
Open Access
Unusual Case of Simultaneous Acute Hepatitis and
Acute Pancreatitis in a Bodybuilder
Ravi Thanage1*, Sanjay Chandnani2, Vinay Zanwar3, Shubham Jain4, Samit Jain5,
Qais Contractor6 and Pravin Rathi7
1Senior Resident, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital, Mumbai, India. ORCID:
0000-0003-0669-2063.
2Senior Registrar, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0001-8270-7680.
3Senior Registrar, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0002-2512-0039.
4Senior Resident, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0001-9484-7568.
5Associate Professor, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0002-8097-5291.
6Associate Professor, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0001-7191-8589.
7Head of Department, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0002-1095-3652.
2Senior Registrar, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0001-8270-7680.
3Senior Registrar, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0002-2512-0039.
4Senior Resident, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai, India. ORCID: 0000-0001-9484-7568.
5Associate Professor, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0002-8097-5291.
6Associate Professor, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0001-7191-8589.
7Head of Department, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital Mumbai. India. ORCID: 0000-0002-1095-3652.
*Corresponding author: Ravi Thanage, D.M gastroenterology, Senior Resident, Department of Gastroenterology, Topiwala National Medical college and B.Y.L Nair hospital, Mumbai, India. ORCID: 0000-0003-0669-2063. Address: Room No: 202, New RMO hostel, Nair Hospital, Mumbai. Tel: 9028785843;E-mail:
@
Received: December 26, 2018; Accepted: December 31, 2018; Published: February 02, 2019
Citation: Ravi T, Sanjay C, Vinay Z, et al. (2019) Unusual Case of Simultaneous Acute Hepatitis and Acute Pancreatitis in a Bodybuilder.Gastroenterol Pancreatol Liver Disord 7(1): 1-3. DOI: 10.15226/2374-815X/7/1/001137
Introduction
The use of anabolic steroids is widespread, particularly among
bodybuilders. Most athletes have only a crude pharmacological
knowledge regarding these drugs and warnings of steroid misuse
are neglected. The illicit use of Androgenic Anabolic Steroids
(AAS) to obtain an athletic, healthy looking body can lead to
serious and often irreversible organ damage [1]. Anabolic steroids
with 17 alpha carbon substitutions have been associated with
a cholestatic injury with little hepatocellular injury. In the case
of hepatoxicity and severe cholestasis the prompt withdrawal
of the steroid and the administration of ursodeoxycholic acid
are recommended [2]. Steroid also is known to cause acute
pancreatitis which would result in acute onset abdominal pain
and vomiting. Possible mechanisms for drug-induced pancreatitis
include immune-mediated inflammatory response, direct cellular
toxicity, arteriolar thrombosis, and metabolic effects.
Case Report
A 22 years old male, physical trainer by profession, presented
with jaundice for 1 month. It was associated with generalized
pruritus and passage of clay colored stools with no prodromal
symptoms. He also had severe upper abdominal pain since 5
days which was of sudden onset, continuous, radiating to the
back. He was non-alcoholic with no major illness in the past.
On inquiry, he had no fever, abdominal distension, swelling of
feet, hemetemesis, malaena. He had anorexia and weight loss of
7 kilograms (10.14% of body weight) in one month. On further
inquiry, he gave a history of drug and supplement intake for
his bodybuilding profession for 2 months. He was receiving
intramuscular injections of testosterone complex 250 mg weekly
for 10 weeks along with injectable boldenone undecylenate 250
mg. He was also taking oxymetholone 50 mg once daily orally
initially for 7 days and then in gradually increasing doses every
6 hours over the next 3 weeks. He procured these medications
from an individual at the local gymnasium and was consuming
them till 3 weeks prior to his admission in the hospital. On
examination, he had icterus and scratch marks all over his body
associated with mild epigastric tenderness. Liver function tests
showed a cholestatic pattern and serum amylase was raised. The
bulky pancreas was noted on abdominal ultrasound. Computed
tomography of the abdomen revealed bulky heterogeneously
hypo enhancing edematous pancreas surrounded with free fluid
with normal pancreatic duct and no evidence of necrosis or
calcification (Figure 1). His Bedside Index of Severity in Acute
Pancreatitis (BISAP) was 0/5 and CT severity index 2/10. Other
etiologies of hepatitis were ruled out as serology for HBsAg, anti-
HCV, Hepatitis A and E was negative. As Drug-induced liver injury
is diagnosis by exclusion, autoimmune markers did. ANA, ASMA,
Anti LKM-1, were negative and serum IgG was normal. Serum
triglyceride, cholesterol and PTH were normal. He was managed
conservatively and abdominal pain subsided over a week.
Magnetic resonance cholangio pancreatography ( MRCP) done
for structural causes of pancreatitis revealed normal pancreatic
duct with no evidence of pancreatic edema and preserved
liver and biliary tree morphology. Liver biopsy revealed bland
cholestasis with no evidence of cellular infiltrate, steatosis or bile
duct proliferation (Figure 2). Patient recovered gradually, both
clinically and biochemically. He was asymptomatic at discharge.
He is on regular follow up and liver function tests are improving
(Table 1).
Figure 1: CT abdomen. Arrow showing bulky pancreas without any
peripancreatic fluid
Figure 2: Liver biopsy. Arrow showing cholestasis without inflammatory
cell (Bland cholestasis) 100 X magnification
Table 1: Trend of laboratory parameters during hospital stay and follow up
On admission |
1st week |
3rd week |
On discharge |
Follow up |
|
Total Bilirubin (mg%) |
3.83 |
13 |
21.1 |
4.7 |
2.3 |
Direct Bilirubin (mg%) |
3.16 |
8.61 |
12.6 |
2.2 |
1.99 |
AST(U/L) |
172 |
36 |
66 |
46 |
37 |
ALT(U/L) |
248 |
65 |
77 |
70 |
72 |
ALP(U/L) |
214 |
279 |
261 |
304 |
185 |
Amylase (U/L) |
360 |
372 |
782 |
136 |
|
INR |
1.00 |
1.00 |
1.00 |
1.1 |
1.00 |
AST- Aspartate Transaminase, ALT- Alanine transaminase, ALP- Alkaline phosphatase, INR- International normalised ratio
Discussion
Anabolic steroids with 17 alpha carbon substitutions have
been associated with a variety of cholestatic injury with little
hepatocellular injury. Cholestasis under these circumstances may
be secondary to the binding of drugs to canalicular membrane
transporters, accumulation of toxic bile acids from canalicular
pump failure, or genetic defects in canalicular transport proteins.
The US Food and Drug Administration (FDA) classified these
compounds as class III controlled substances in 1990, limiting
their use to specific indications such as replacement of male
sex steroids in men who have androgen deficiency, treatment of
certain rare forms of a plastic anemia, and the counteraction of
catabolic states such as trauma or HIV wasting [3].
Recently the number of cases of anabolic steroids induced liver toxicity has increased considerably due to the rise in the sales of nutritional supplements containing steroid based prohormone. Most cases of anabolic steroids induced cholestasis are not caused by direct hepatocellular damage but by an impaired biliary secretion. Simultaneous occurrence of hepatitis and pancreatitis is seen very rarely. Electron microscopy of rat livers following 17 carbon substituted anabolic steroid administration confirmed canalicular changes of dilation and loss of microvilli [4]. Cholestatic effects have been attributed to interference with bile flow with potential sites of anabolic injury at the canalicular, peri-canalicular microfibrillar network and the basolateral plasma membrane all resulting in canalicular contraction . The steroid-like agent, icterogenin, also leads to cholestasis and canalicular distortion, lending further support to this theory [5]. Steroids containing 17 alpha alkyl groups exhibit the greatest liver toxicity because of their slow metabolism. This side effect usually appears after 1-5 months of use. Drug-induced cholestasis can be of several varieties: bland, meaning that there is a limited injury to hepatocytes, inflammatory, sclerosing, or ductopenic (disappearance of bile ducts) [6]. Hepatic dysfunction often resolves quickly with the discontinuation of the anabolic steroid in anicteric cases and within months in patients presenting with icterus [7]. In patients without jaundice, a continuation of the offending agent has been noted to induce tolerance to the adverse effects of anabolic steroids with amelioration of hepatic enzymes levels [7]. There is no specific therapy for drug-induced liver injury and treatment is mainly supportive. Few have proposed the use of N-acetylcysteine in early liver failure [7]. Cholestyramine and ursodeoxycholic acid may decrease the pruritus. Rifampicin and naltrexone have been used for refractory pruritus. Albumin dialysis with the MARS system appears as a valuable therapeutic option for the management of anabolic steroids induced cholestasis not responding to medical therapy [8].
Our patient also had acute pancreatitis without any structural or metabolic cause. Exactly how anabolic steroids induce acute pancreatitis is unknown, but postulated mechanisms include immune-mediated inflammatory response, direct cellular toxicity, pancreatic ductal constriction, arteriolar thrombosis, and metabolic effects [9].
Simultaneous occurrence of both hepatitis and pancreatitis is very rare. Proper clinical history and drug history can alleviate the need for extensive work up. Proper education regarding the use and side effects of AAS might prevent such diseases.
Recently the number of cases of anabolic steroids induced liver toxicity has increased considerably due to the rise in the sales of nutritional supplements containing steroid based prohormone. Most cases of anabolic steroids induced cholestasis are not caused by direct hepatocellular damage but by an impaired biliary secretion. Simultaneous occurrence of hepatitis and pancreatitis is seen very rarely. Electron microscopy of rat livers following 17 carbon substituted anabolic steroid administration confirmed canalicular changes of dilation and loss of microvilli [4]. Cholestatic effects have been attributed to interference with bile flow with potential sites of anabolic injury at the canalicular, peri-canalicular microfibrillar network and the basolateral plasma membrane all resulting in canalicular contraction . The steroid-like agent, icterogenin, also leads to cholestasis and canalicular distortion, lending further support to this theory [5]. Steroids containing 17 alpha alkyl groups exhibit the greatest liver toxicity because of their slow metabolism. This side effect usually appears after 1-5 months of use. Drug-induced cholestasis can be of several varieties: bland, meaning that there is a limited injury to hepatocytes, inflammatory, sclerosing, or ductopenic (disappearance of bile ducts) [6]. Hepatic dysfunction often resolves quickly with the discontinuation of the anabolic steroid in anicteric cases and within months in patients presenting with icterus [7]. In patients without jaundice, a continuation of the offending agent has been noted to induce tolerance to the adverse effects of anabolic steroids with amelioration of hepatic enzymes levels [7]. There is no specific therapy for drug-induced liver injury and treatment is mainly supportive. Few have proposed the use of N-acetylcysteine in early liver failure [7]. Cholestyramine and ursodeoxycholic acid may decrease the pruritus. Rifampicin and naltrexone have been used for refractory pruritus. Albumin dialysis with the MARS system appears as a valuable therapeutic option for the management of anabolic steroids induced cholestasis not responding to medical therapy [8].
Our patient also had acute pancreatitis without any structural or metabolic cause. Exactly how anabolic steroids induce acute pancreatitis is unknown, but postulated mechanisms include immune-mediated inflammatory response, direct cellular toxicity, pancreatic ductal constriction, arteriolar thrombosis, and metabolic effects [9].
Simultaneous occurrence of both hepatitis and pancreatitis is very rare. Proper clinical history and drug history can alleviate the need for extensive work up. Proper education regarding the use and side effects of AAS might prevent such diseases.
Conflicts of interest
None to disclose.
Financial Disclosure
None to disclose.
Written informed consent obtained from the patient.
Written informed consent obtained from the patient.
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- Rosenfeld GA, Chang A, Poulin M, Kwan P and Yoshida E. Cholestatic jaundice, acute kidney injury and acute pancreatitis secondary to the recreational use of methandrostenolone: a case report. J. Med. Case Rep. 2011;5:138. Doi:10.1186/1752-1947-5-138.
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- Hu J, Zhang Q, Ren X, Sun Z and Quan Q. Efficacy and safety of acetylcysteine in “non-acetaminophen” acute liver failure: A meta-analysis of prospective clinical trials. Clinics and Research in Hepatology and Gastroenterology. 2015;39(5):594-599. Doi:10.1016/j.clinre.2015.01.003.
- Diaz FC, Saez-Gonzalez E, Benlloch S, Álvarez-Sotomayor D, Conde I and Polo B. et al. Albumin dialysis with MARS for the treatment of anabolic steroid-induced cholestasis. Ann. Hepatol. 2016;15(6):939-943. Doi:10.5604/16652681.1222114.
- Kaurich, Tracie. “Drug-Induced Acute Pancreatitis.” Proceedings (Baylor University. Medical Center) 21.1 (2008):21(1);77–81.