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Case Report
OGH Reports 2017; 6(2): 51-55
Peer Reviewed Journal in Oncology, Gastroenterology and Hepatology
www.oghreports.org | www.journalonweb.com/ogh
Uncommon cause for a common disease-Severe steatohepatitis
secondary to Ayurvedic ‘Man-Lion Tonic’
Cyriac Abby Philips1, Praveen Kumar2, Philip Augustine3, Pushpa Mahadevan4
ABSTRACT
Narasimha Rasayana (Sanskrit for ‘Man-Lion Tonic’) is a frequently prescribed Ayurvedic
herbal medicinal preparation in South India for treatment of fatigue, hair loss, rejuvenation
and weight gain in young men and women. The preparation is also considered, as per Vedic
medical literature known as Ashtanga Hridayam Uttara to improve fertility by acting as an
aphrodisiac. We present the interesting case of a young male, who consumed 2 tablespoons
(~15 grams) of the ‘Man-Lion Tonic’ daily for 2 years, presenting with loss of appetite and
well-being and elevated transaminases with liver histology showing overlapping features
unique to spectrum of acute alcohol liver injury not described with CAM before.
Key words: Steatohepatitis, Fatty liver disease, Complementary and alternative medicine,
Ayurveda, Drug induced liver injury, Hepatotoxicity.
Cyriac Abby Philips1,
Praveen Kumar2, Philip
Augustine3, Pushpa Mahadevan4
Department of Hepatology and Transplant Medicine, PVS Institute of Digestive Diseases, PVS Memorial Hospital,
Cochin, Kerala, INDIA.
2
Deparment of Gastroenterology,
Government Medical College, Thrissur,
Kerala, INDIA.
3
Department of Gastroenterology, PVS
Institute of Digestive Diseases, PVS Memorial Hospital, Cochin, Kerala, INDIA.
4
Deparment of Pathology, VPS Lakeshore Hospital, Cochin, Kerala, INDIA.
1
Correspondence
Cyriac Abby Philips
Philip Augustine Associates, PVS
Memorial Hospital Campus, Kaloor,
Cochin 682017, INDIA.
Phone: +919207745776
Email: [email protected]
History
• Submission Date: 23-11-2016;
• Review completed: 20-12-2016
• Accepted Date: 12-02-2017.
DOI : 10.5530/ogh.2017.6.2.15
Article Available online
http://www.oghreports.org
Copyright
© 2017 Phcog.Net. This is an openaccess article distributed under the terms
of the Creative Commons Attribution 4.0
International license.
OGH Reports, Vol 6, Issue 2, Jul-Dec, 2017
INTRODUCTION
Non-alcoholic fatty liver disease (NAFLD) is the
commonest cause of asymptomatic abnormal transaminases world-wide and of chronic liver disease in
the developing world, found in 17-30% of the population in Western countries. The well-known primary
causes of NAFLD are obesity, type II diabetes, dyslipidemia, and insulin resistance.[1] However, secondary
conditions that cause similar clinical and histologic
picture, should be considered in patients who present
with NAFLD without traditional risk factors. These
include disorders of lipid peroxidation such as, abetalipoproteinemia, hypobetalipoproteinemia, familial
combined hyperlipidemia; glycogen storage diseases,
lipodystrophy syndromes, hepatitis C infection, Wilson’s disease, total parenteral nutrition, severe weight
loss secondary to bariatric procedures, celiac disease,
drugs such as amiodarone, tamoxifen and anti-retroviral therapy.[2] Here we present the case of severe
drug induced steatohepatitis in a young man, who
consumed a commonly used complementary and
alternative medication, Narasimha Rasayanam or
‘Man-Lion’ Tonic for weight gain for 2 years, presenting with loss of appetite and well-being and elevated
transaminases for a period of 2 months’ duration and
in whom unique histology of liver injury not previously described with CAM was noted.
CASE REPORT
A 23-year-old non-alcoholic male without known
metabolic syndrome, was referred to our Liver Clinic
with a 2-month history of fatigue, loss of appetite and
well-being without nausea, diarrhoea, and abdominal pain. The patient reported no smoking, previous
liver disease, family history of liver diseases, blood
transfusion or exposure to toxins. His past medical
history was significant for consumption of herbal
complementary and alternative (CAM), known as
Narasimha Rasayana (Man-Lion Tonic, daily once,
approximately 15 g for 2 years) taken for weight gain
and ‘rejuvenation’. On physical examination, the
patient was alert, and oriented to time, place and
person without pallor, icterus, peripheral lymphadenopathy or stigmata of chronic liver disease.
His weight was 56 kg and height 168 cm, with body
mass index of 19.8 kg/m2. Liver span was 18 cm in
the right mid clavicular line. The laboratory evaluation revealed normal hemogram, total bilirubin
1.2 mg/dL with direct fraction 0.4 mg/dL, alanine
transaminase (ALT) 514 IU/L, aspartate transaminase (AST) 338 IU/L, normal serum protein, albumin and globulin, international normalized ratio
1.1 with normal renal function tests. C-reactive
protein level was mildly raised 12.3 mg/L (normal
0–5 mg/L). Results of serologic tests were negative
for hepatitis B surface antigen; anti-hepatitis B-core
Immunoglobulin (IgM and core total); anti-hepatitis
A and E virus IgM; anti-hepatitis C virus antibody;
anti-Cytomegalovirus IgM; anti-Epstein–Barr virus
IgM; anti-nuclear antibodies; anti-smooth-muscle
antibodies; anti-mitochondrial antibodies; and
anti-neutrophil cytoplasmic antibodies. Serum ferritin and ceruloplasmin levels were also normal. An
ultrasound and a computerized tomography (CT)
scan of the abdomen revealed only steatotic hepatomegaly and Shearwave elastography showed liver
stiffness of 9.2 kPa suggestive of F3 fibrosis. A percutaneous ultrasound guided plugged liver biopsy
revealed features suggestive of severe mixed macro
and micro-vescicular-steatosis (Figure 1A) with lobular inflammation, ballooned hepatocytes (Figure
Cite this article: Philips CA, Kumar P, Augustine P, Mahadevan P. Uncommon cause for a common disease-Severe steatohepatitis secondary to Ayurvedic ‘Man-Lion Tonic’. OGH Reports.
2017;6(2):51-5.
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Philips et al.: Severe steatohepatitis secondary to Man-Lion Tonic
Figure 1: Liver histopathology revealing features suggestive of severe mixed macro and micro-vescicular-steatosis (A, H&E 10x) with lobular
inflammation, ballooned hepatocytes (B, thin black arrow; H&E 40x), Mallory Denk bodies (B, thick black arrow; H&E 40x), micro-vescicular
steatosis related foamy degeneration (C, black arrow, H&E 40x) and periportal and preisinusoidal (or chicken wire fibrosis, D; Masson Trichrome,
20x) fibrosis suggestive of severe steatohepatitis.
1B, thin black arrow), Mallory Denk bodies (Figure 1B, thick black arrow), micro-vescicular steatosis related foamy degeneration (Figure 1D,
black arrow) and periportal and preisinusoidal (chicken wire) fibrosis
suggestive of severe steatohepatitis (NASH CRN activity grade 6/8 and
NASH CRN fibrosis stage 2). The patient was advised to stop the offending CAM, advised vitamin E and antioxidants, put on a low-fat diet and
advised daily activities in the form of brisk walking and treadmill exercises. On follow up after 4 weeks, his ALT and AST had decreased to 101
IU/L and 68 IU/L with improvement in well-being and appetite.
DISCUSSION
Narasimha Rasayanam or ‘Man-Lion Tonic’ is a commonly utilized
Ayurvedic herbal medicine in South India for treatment of a variety of
symptoms ranging from fatigue to loss of libido without scientific reasoning. The product is available over the counter and for purchase online. Advertisements and publicity about this product is rampant among
lower class and lower middle class population who opt for cheaper and
easy symptomatic treatment options without the need for investigational
expenditure. The ‘Man-Lion Tonic’ has 10 herbal ingredients (Table 1),
mixed in special proportions along with powdered iron alloy, water, honey and butter, heated till boiling and then cooled down to a semi-solid
consistency. Dosage is usually 1-2 tablespoons once or twice daily without a specified duration limit. The herbal components of this concoction
have a plethora of other non-medicinal uses such as being part of dyeing
agents, drill oil viscosity regulators, construction grade wall plaster stabilizer and marking inks.
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Excess alcohol consumption, glucocorticoids, total parenteral nutrition, amiodarone and methotrexate, chemotherapy associated steatosis
related to 5-fluorouracil, tamoxifen, irinotecan, cisplatin, and asparaginase are also causes of macrovesicular steatosis.[3] Valproate, tetracycline
(intravenous administration), aspirin, nucleoside reverse transcriptase
inhibitors, glucocorticoids, nonsteroidal anti-inflammatory drugs and
cocaine are causative agents. Drugs rarely associated with steatohepatitis are amiodarone, methotrexate tamoxifen, and irinotecan.[4, 5] It was
interesting to note that in our patient, histopathology showed foamy
degeneration of the hepatocytes. Foamy degeneration (AFD) of hepatocytes is classically seen in severe alcoholic fatty liver disease. It is closely
related to alcoholic fatty liver with jaundice (AFLJ). Both are defined by
steatosis involving > 75% of hepatocytes. In the latter, diffuse macrovesicular steatosis is noted in the presence of cholestasis. The histological
diagnosis of AFLJ requires exclusion of alcoholic hepatitis (AH; the absence of chicken wire fibrosis, neutrophilic inflammation, or MalloryDenk bodies) and is characterized by the presence of significant diffuse
microvesicular, foamy-appearing steatosis involving the perivenular and
often midzonal hepatocytes, similar to that seen in several non-alcoholic
liver injuries with abnormal mitochondrial fatty acid oxidation.[6] The
only report of CAM causing severe microvesicular steatohepatitis was
secondary to Margosa oil use.[7]
Schoepfer and colleagues reported 12 cases of toxic hepatitis implicating
Herbalife preparations (1998-2004) with 10 sufficiently documented to
permit causality analysis. In their cohort, liver histology showed hepatic
necrosis, marked lymphocytic/eosinophilic infiltration and cholestasis
patterns. Fulminant liver failure with explant showing giant cell hepatiOGH Reports, Vol 6, Issue 2, Jul-Dec, 2017
Philips et al.: Severe steatohepatitis secondary to Man-Lion Tonic
Table 1: Components of Narasimha Rasayanam (Man-Lion Tonic), their contents and non-medicinal uses. *
Ingredient
Common name/ Description
Content
Non Ayurvedic Properties
Leaves of Acacia catechu
Cutch tree or Black Cutch,
Arecanut tree
Rich in flavanols
Red colouring agent in Paan (betel leaf
with areca nut and tobacco chewed for its
stimulant and psychoactive effects)
Agent in dyeing and leather tanning
Preservative for fishing nets
Viscosity regulator for oil drilling
Leaves of Plumbago zeylanica
Ceeylon leadwort or Doctorbush
Plumbagin Organic hexane
compounds
Methanols
Plumbagin is genotxic and mutagenic
Used for treating canine distemper
Mosquito larvicide
Leaves of Dalbergia sissoo
Indian Rosewood
Rich in polyphenols
Molluscicide against eggs of freshwater snails
Juiced leaves and bark used as bonding agent
in construction grade wall plaster
Leaves of Pterocarpus marsupium
Indian Kino Tree or Malabar
Kino
Stillbenoids, natural phenols, rich in
resveratrol
Hypoglycemic agent
Causes weight loss and diarrhea when used
for longer periods
GlaxoSmithKline in 2010 suspended a
small clinical trial of SRT501, a resveratrol
compound due to adverse effects
Fruit of Terminalia chebula
Black Myrobalan (plum -like
fruit bearing tree)
Glycosides, triterpenes, gallic acid,
coumadins, tannins, phenols
No potential uses
Paste mixed with cattle urine used for
treatment of skin and genital infections and
ingested for respiratory infections in some
parts of India
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Philips et al.: Severe steatohepatitis secondary to Man-Lion Tonic
Fruit of Embelia ribes
False Black Pepper
Benzoquinones, alkaloids, resins and
tannins
Cyclodextrin-based polymers for therapeutic
delivery
As components of hydrogels
Leaves and fruit of Terminalia
bellirica
Bastard myrobalan
Beta-sitosterol, gallic acid, ellagic
acid, ethyl gallate, galloyl glucose
Used in volatile oil preparations
Fruit of Semecarpus anacardium
Marking – Nut Tree
Biflavonoids, phenolic complounds,
oxy-acids, non-volatile alcohols
Marking inks
Fixator agent for color dyes
Flowers of Clerodendrum serratum
Glory Bower or Bleeding Heart
flower
Flavanoids, terpenoids and steroids
None
Flowers of Eclipta prostate
False Daisy
Coumestans, polyacetylenes,
thiophene derivatives, steroids,
triterpenes, flavonoids
None
* Sources: Narasimha – Rasayanam - Retrieved from: http://www.bimbima.com/health/post/2016/02/23/narasimha-rasayanam-ingredients-and-uses-directions.
aspx; Baliga et al. Rasayana Drugs From the Ayurvedic System of Medicine as Possible Radioprotective Agents in Cancer Treatment. Integr Cancer Ther. 2013
Nov;12(6):455-63; Parasuraman S et al. Polyherbal formulation: Concept of ayurveda. Pharmacogn Rev. 2014 Jul-Dec; 8(16): 73–80; Dixit VK. Controversial
ayurvedic herbs. J Adv Pharm Technol Res. 2011 Apr-Jun; 2(2): 78–80.
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Philips et al.: Severe steatohepatitis secondary to Man-Lion Tonic
tis (GCH) occurred in one, while sinusoidal obstruction syndrome was
observed in another.[8] Very recently, Shetty and colleagues from India,
reported herbal medicine use as the cause of giant cell hepatitis in an
adult patient.[9]
In our patient, we noted a mixed macro and microvesicular pattern of
steatohepatitis with foamy degeneration and perisinusoidal fibrosis - a
histopathology pattern encompassing AFD, AFLJ and AH – which is not
described in literature, especially with CAM. We suspect that the presence of phytochemicals such as phenolic and carbolic compounds along
with alkaloids and tannins leading to mitochondriopathy, would have
caused a mixed pattern of injury similar to histopathology of acute alcoholic liver disease spectrum. Drug induced steatohepatitis is a rare form
of drug induced liver injury (DILI) and is regarded as an uncommon
cause of a common disease. The common histological patterns observed
in DILI are acute and chronic hepatitis, acute and chronic cholestasis,
and mixed cholestatic hepatitis. A Spanish group study on DILI noted
that only 2 out of the 110 cases on liver histopathology showed a predominant pattern of steatosis.[10] However, more recent data from the
Drug Induced Liver Injury Network (DILIN) concluded that although
this is rarely described as the dominant pattern, 26% of cases showed
some degree of steatosis and macrovesicular type as the predominant
pattern noted in over 70% of the cases.[11] In a study by Navarro et al on
liver injury from herbals and dietary supplements in the DILIN, majority of patients used products that contained vitamins, minerals and botanical extracts. Majority of the patients took non-body building supplements and 81% of the total number enrolled had identifiable ingredients.
[12]
Use of pure Ayurvedic products and related liver injury has not been
reported in any drug injury screening networks.
In recent years, it has been shown that some monomers and certain functional mixtures of herbs have potential uses in NAFLD treatment. Xiao
and colleagues carried out an extensive PubMed review on randomized
trials on several herbal derivatives under intense basic and/or clinical investigations relevant to treatment of NAFLD, such as wolfberry polysaccharides, garlic-derived monomers, red grape–derived resveratrol, and
milk thistle–derived substances. However, a more detailed mechanistic
research methodology and long-term clinical evaluations are needed for
their future applications.[13] Phytochemical such as Curcumin, Lycopene,
Resveratrol and Silymarin have been shown in indexed complementary
and alternative journal studies to have steatosis reversing effects. However, none of these studies are well designed and lacks scientific clinical assessment and proper study methodology.[14] Traditional medicinal systems such as Indian Ayurveda, Japanese Kampo and Traditional
Chinese medicine have reported on the therapeutic role of polyherbal
formulations in treating hepatic ailments including NAFLD. Not many
Ayurvedic formulations have been put for a scrutiny in the treatment of
NAFLD and widespread use of the same, targeting low costs and ‘potential safety’ because of natural ingredients invites acceptance without
scientific reasoning.[15] None of the phytochemical agents (except? Resveratrol) noted in the CAM used by our patient are validated in clinical
trials for safety and efficacy in treatment of NAFLD. Severe steatohepatitis secondary to Ayurveda medications in countries like India, might be
under reported as rampant use remains unchecked and under-evaluated.
Histopathological liver injury patterns overlapping multiple aetiologies
or and not specific to commonly described ones, should be thought of
secondary to drug use, especially CAM. Knowledge regarding local/alternative medical practices and timely liver biopsies can help clinch the
diagnosis in the absence of a strong clinical suspicion. Proper and de-
tailed declaration of ingredients by and intense role of government and
scientific regulatory agencies scrutiny of ‘alternate’ practice is called for.
CONCLUSION
Complementary and alternate medications produce a plethora of hepatic
injuries ranging from asymptomatic elevation of transaminases to severe
liver injury. Regulatory norms defining content and organotoxicity of
alternative medications need to be implemented through Government
participation. In patients of severe steatohepatitis, in the absence of traditional risk factors, drug history taking is of utmost importance.
ACKNOWLEDGEMENT
No Acknowledgement are declared.
CONFLICT OF INTEREST
No conflict of interest are declared.
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Cite this article: Philips CA, Kumar P, Augustine P, Mahadevan P. Uncommon cause for a common disease-Severe steatohepatitis
secondary to Ayurvedic ‘Man-Lion Tonic’. OGH Reports. 2017;6(2):51-5.
OGH Reports, Vol 6, Issue 2, Jul-JDec, 2017
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