Jaundice is one of the earliest diseases known to mankind. The present article documents the history of documentation of Jaundice and its various subtypes. Thus, this brief review serves, in-part, as one ready reference for history of Jaundice.

1. Jaundice: A brief historical perspective

2. Review Article
Jaundice: A brief historical perspective
C.D. Poduri a,b,*
a
Formerly Assistant Professor (2002e2005), Department of Biotechnology at the Indian Institute of Technology (IIT),
Guwahati, India
b
Formerly Assistant Professor (2006e2012), Department of Biotechnology, Jaypee University of Information
Technology (JUIT), Waknaghat, HP, India
a r t i c l e i n f o
Article history:
Received 28 April 2014
Accepted 13 May 2014
Available online xxx
Keywords:
Hepatitis
History
Jaundice
Liver
a b s t r a c t
Jaundice is one of the earliest diseases known to mankind. The present article documents
the history of documentation of Jaundice and its various subtypes. Thus, this brief review
serves, in-part, as one ready reference for history of Jaundice.
Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.
The Talmud describes Jaundice as a sign of causeless hatred.1
Earliest references to jaundice, other than those depicted in
the popular Babylonian Talmud/Sumerian Tablets, are found
in Ebers papyrus,2
and then in the Ayurveda. The English
translators of Ebers papyrus claim that it is a 1500BC docu-
ment wherein references to the first dynasty are found. This
dates the written contents to around 3400BC, whence it will
precede Ayurveda (3000BC)3
by at least 400 years. It may be
noted that Ayurveda is practised even today and is continu-
ously evolving. This situation makes it difficult to specify the
exact date when the treatments of jaundice entered Ayurveda.
Despite an error in attributing the date, Issac Asimov con-
siders the Ebers papyrus as the first surviving account of
medical remedies in his book ‘Chronology of Science and
Discovery’.4
Subsequent other major references to jaundice
are found in the works of Hippocrates (460BCe370BC).5,6
Despite this, the readers must keep in mind that just as un-
derstanding of solar system by the scientific community
underwent a change of concepts from geo-centrism (Earth-
centred) to helio-centrism (Sun-centred), medical community
in the late 1800s underwent a paradigm shift from hepato-
centrism to cardio-centrism.
The words hepatic, liver and jaundice have their origins in
Greek, Sanskrit and Old French respectively.7,8
For an inter-
esting discussion on etymology of the words ‘hepatic’ and
‘liver’, and their historical usage, the readers are asked to
consult an interesting article by Riva and colleagues in the
journal of hepatology.8
Subsequent letters in the same journal
take the discussion on this topic to a crescendo.9,10
As per the
online etymology dictionary, ‘Jaundice’ has its origin in circa
1300AD in the Old French word ‘jaunis’ that meant ‘yellow-
ness’, and the word ‘jaunis’ itself is derived from an earlier
French word ‘jalnice’.11
Researchers prior to 1800s had little idea about the type
of Jaundice they were describing. Effects of alcohol were
first described by Addison in 1836.12
By 1937, i.e., a hundred
* Flat No. 501, Highlight Haveli, Street No. 6, Habsiguda, Hyderabad (Deccan) 500 007, India. Tel.: þ91 9492891303 (mobile).
E-mail address: cdpoduri@gmail.com.
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.elsevier.com/locate/apme
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e4
Please cite this article in press as: Poduri CD, Jaundice: A brief historical perspective, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.05.014
http://dx.doi.org/10.1016/j.apme.2014.05.014
0976-0016/Copyright © 2014, Indraprastha Medical Corporation Ltd. All rights reserved.

3. years later, the effects of halothane based anaesthetics on
liver were apparent.13
Autoimmune hepatitis (AIH), previ-
ously referred to as Chronic Active Hepatitis (CAH), was
originally described in 1940s. However, only in 1950 it was
considered to be autoimmune in nature. The nomenclature
AIH which was proposed in 1965 was approved in the year
1993.14
Put simply, the case of AIH and CAH was akin to
‘phthisis’ and ‘tuberculosis’ wherein the authors ended up
describing the same disease but were using different
terminology.
The concept of obstructive jaundice came up in the year
1935 with Whipple.15
The terms infective hepatitis (in En-
gland) and infectious hepatitis (in USA) were first used in the
years 1939 and 1943 respectively.16
Prior to this, jaundice as an
adverse effect of vaccination was noted as early as 1885 by
Lu¨ hrman.17,18
McDonald, in the year 1908, suggested that
jaundice may probably be caused by an agent much smaller
than a bacterium.19
Only in the year 1923 it was hypothesized
that a virus might be involved.17
World War II (WWII) threw open the field with regard to
hepatitis. During WWII, it is estimated that approximately 16
million people were killed as a consequence of hepatitis.18
This situation led to serious research not only on vaccine
induced hepatitis but on other types as well. By 1947, based on
the studies in volunteers, it was apparent that there were two
types of hepatitis: epidemic/infectious hepatitis and serum
hepatitis (SH). Whereas epidemic hepatitis had a short incu-
bation period, long incubation period was the hall mark of SH.
In 1953, World Health Organization (WHO) recommended
usage of the terms hepatitis A for infectious hepatitis and
hepatitis B for SH.17
Discovery of the respective viruses,
however, had to wait at least a decade in each of the cases.20,21
Needless-to-say, the Hippocratic corpus described epidemic
jaundice.
By 1974, it was apparent that there was a third virus other
than Hepatitis A virus (HAV) and Hepatitis B virus (HBV),
whence it was referred to as non-A, non-B hepatitis
(NANBH).22
Subsequent animal model research showed
clearly that there are at least two distinct forms of NANBH.23
Perhaps Hepatitis C virus (HCV) represents the first of these
two. The manner of discovery of HCV using reverse-
transcription of the viral nucleic acid represents one major
breakthrough in the field of biomedical biotechnology.24
However, this virus continues to remain an enigma to re-
searchers, and the diagnosis of this virus is typically by the
detection of virus specific antibodies using Enzyme linked
immunosorbent assays (ELISA), and/or by amplifying the viral
nucleic acid by reverse transcription polymerase chain reac-
tion (RT-PCR).
Massive epidemics of viral hepatitis between 1950e1970
in India, China and the adjoining regions led to identifica-
tion of Hepatitis E virus (HEV).18
The actual discovery of HEV
is credited to two groups of investigators. One of them,
Khuroo and colleagues, is from India,25
and the other group,
Balayan et al, is from Russia.26
The process of identification
of HEV by ingestion of infected material by Balayan is
indeed heroic and makes interesting stuff for Hollywood
story writers.
The year 1977 also marked the discovery of Hepatitis D
virus (HDV). With the observation that this virus requires the
presence of HBV as helper virus, and the fact that HBV is
vaccine preventable, HDV obviously became a neglected
disease.18
1995 saw the discovery of yet another virus that
targets liver, the GB virus e C, increasing the repertoire of
hepatitis viruses.27
Two years later in 1997, a seventh virus
the transfusion-transmitted virus (TTV) was identified in
patients with non-A-B-C-G hepatitis.28
Given the fact that
both GBV-C and TTV are transmissible by contaminated
blood and related fluids, Bendinelli et al,29
suggest that TTV
might be the other virus originally predicted by Shimizu et al,
in 1979.30
Needless-to-say, the period between the years
1950e2000 can easily be considered as the Era of Viral Hepa-
tides, whence as many as seven viruses that cause hepatitis
and target liver have been discovered and described. All of
this is summarized as Fig. 1.
Per se the underlying cause of jaundice is difficult to iden-
tify symptomatically. Thus, based on the symptoms alone, it
is difficult to differentiate between AIH and viral hepatides or
drug induced liver diseases. Complicating this scenario is the
discovery of seven viruses that target liver exclusively.
Fig. 1 e Milestones in Jaundice research and documentation.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e42
Please cite this article in press as: Poduri CD, Jaundice: A brief historical perspective, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.05.014

4. Therefore laboratory diagnosis and/or histologic examination
to exclude various possibilities become mandatory. Molecular
diagnosis of the causative agent, if involved, is essential prior
to the start of relevant treatment in viral hepatides. Prominent
strategies among these include the development and avail-
ability of cost-effective reagents, highly sensitive ELISA and
the hyper specific RT-PCR. Numerous variants of ELISA and
polymerase chain reaction (PCR) are available in the market
today. Many advanced research laboratories and hospitals, in
fact, have their own in-house variants of ELISA and PCR.
Involvement of PCR in medical diagnosis, via real time PCR,
permits quantification of the actual viral load, an essential
requirement for monitoring the response to treatment
imparted.
Despite what has been described here, a number of other
viruses like the cytomegalovirus (CMV) and the EpsteineBarr
virus (EBV), which usually do not target the liver, cause
jaundice later in their infection cycle. Additionally, pathogens
like Plasmodium sp., a protozoan which typically causes ma-
laria, and Leptospira interrogans, a gram-negative spirochaete
which causes Leptospirosis, can also cause jaundice during
the course of their infection. It may be noted that Malaria and
Leptospirosis are common in tropical countries. Because the
symptoms overlap, for various pathogens, exclusion labora-
tory diagnosis, as mentioned earlier, becomes mandatory for a
better management of jaundice. For HAV, HBV and HEV a
vaccine is available. Although, these may not be available
globally at present, the actuality that a vaccine is available
indicates that the cases of viral hepatides may come down in
future.
Conflicts of interest
The author has none to declare.
List of abbreviations1
AIH autoimmune hepatitis
BC before Christ
CAH Chronic Active Hepatitis
ELISA Enzyme linked immunosorbent assay
GBV-C Hepatitis GB virus e C
HAV Hepatitis A virus
HBV Hepatitis B virus
HCV Hepatitis C virus
HDV Hepatitis D virus
HEV Hepatitis E virus
NANBH non-A, non-B, hepatitis
PCR polymerase chain reaction
RT-PCR reverse transcription polymerase chain reaction
SH serum hepatitis
sp. species
TTV transfusion-transmitted virus
USA United States of America
WHO World Health Organization
WWII World War II
r e f e r e n c e s
1. Rabbi Dr. I. Epstein. Babylonian Talmud: Tractate Shabbath Folio 33a
[Internet]; 2003 [Updated 2003; Cited 2014-Jan-20]. Available
from: www.come-and-hear.com/shabbath/shabbath_33.
html#33a_53.
2. Bryan Cyril P. The Papyrus Ebers [translated from the Germen
version]. Letchworth, Herts, UK: The Garden City Press Ltd.;
1930.
3. Complementary and Alternative Supportive Care (CASC).
About Ayurveda [Internet]; 2014 [Cited 2014-Jan-20]. Available
from: casc.uchc.edu/ayurveda.
4. Asimov Issac. Asimov's Chronology of Science & Discovery.
London, UK: Grafton Books; 1989.
5. Schmid Rudi. History of viral hepatitis: a tale of dogmas and
misinterpretations. J Gastroenterol Hepatol. 2001;16:718e722.
6. Bynum William. The History of Medicine e A Very Short
Introduction. New York, USA: Oxford University Press Inc.; 2008.
7. Definition of Icterus; 2013 [Internet]. [Updated 2013-Aug-28;
Cited 2014-Feb-9]. Available from: www.medterms.com/
script/main/art.asp?articlekey¼3890.
8. Riva Michele Augusto, Riva Enrica, Spicci Mauro,
Strazzabosco Mario, Giovannini Marcello, Cesana Giancarlo.
"The city of hepar": rituals, gastronomy, and politics at the
origins of the modern names for the liver. J Hepatol.
2011;55:1132e1136.
9. Roffi Luigi. Liver in mythology: a different version of Tityos'
myth. J Hepatol. 2012;57:699e710.
10. Riva MA. Liver, snakes and myths. J Hepatol. 2012;57:711.
11. Jaundice (n.); 2001e2014 [Internet]. [Cited 2014-May-08]. Online
Etymology Dictionary. Available from: www.etymonline.com.
12. Lieber Charles S, Jones Don P, DeCarli Leonore M. Effects of
prolonged ethanol intake: production of fatty liver despite
adequate diets. J Clin Invest. 1965;44(6):1009.
13. Fairlie CW, Barss TP, French AB, Jones CM, Beecher HK.
Metabolic effects of anaesthesia in man IV: comparison of
effects of certain anaesthetic agents on normal liver. N Engl J
Med. 1951;244:615.
14. Invernizzi Pietro, Mackay Ian R. Historical reflections on
autoimmune hepatitis. World J Gastroenterol.
2008;14(21):3292e3300.
15. van der Gaag NA, Kloek JJ, de Castro SMM, Busch ORC, van
Gulik TM, Gouma DJ. Preoperative biliary drainage in patients
with obstructive jaundice: history and current status. J
Gastrointest Surg. 2009;13:814e820.
16. Kahak Elaine. The liver: a brief historical perspective. In:
Demetrious AA, Watanabe FD, eds. Support of the Acutely
Failing Liver. 2nd ed. USA: Landes Bioscience and
Eurekah.com; 2000.
17. Thomas Roger E, Lorenzetti Diane L, Spragins Wendy.
Mortality and morbidity among military personnel and
civilians during the 1930s and World War II from
transmission of hepatitis during yellow fever vaccination:
systemic review. Am J Public Health. 2013;103(3):e16ee29.
18. Trepo Christian. A brief history of hepatitis milestones. Liver
Int. 2014;34(s1):29e37.
19. Schmid R. Viral hepatitis: dogmatism revisted. Trans Am Clin
Climatol Assoc. 1986;97:53e57.
20. Feinstone SM, Kapikian AZ, Purcell RH. Hepatitis A: detection
by immune electron microscopy of virus like antigen
associated with acute illness. Science. 1973;200:365e373.
21. Blumberg BS, Sutnik AI, London WT. Hepatitis and leukemia:
their relation to Australia antigen. Bull N Y Acad Med.
1968;44(12):1566e1586.
22. Prince AM, Grady GF, Hazzi C, et al. Long incubation post
transfusion hepatitis without serological evidence of
exposure to hepatitis B virus. Lancet. 1974;304(7875):241e246.1
Other abbreviations carry their usual significance.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e4 3
Please cite this article in press as: Poduri CD, Jaundice: A brief historical perspective, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.05.014

5. 23. Bradley DW, Maynard JE, Popper H, et al. Post transfusion
non-A, non-B hepatitis: physicochemical properties of two
distinct agents. J Infect Dis. 1983;148(2):254e265.
24. Choo Qui-Lim, Kuo George, Weiner Amy J, Overby Lacy R,
Bradley Daniel W, Houghton Michael. Isolation of a cDNA
clone derived from a blood-borne non-A, non-B viral hepatitis
genome. Science. 1989;244(4902):359e362.
25. Khuroo M, Deurmeyer W, Zargar S, Ahanger MA, Shah MA.
Acute sporadic non-A non-B hepatitis in India. Am J Epidemiol.
1983;118:360e364.
26. Balayan M, Andajaparidze A, Savinskaya SS, et al. Evidence
for a virus in non-A non-B hepatitis transmitted via the fecal-
oral route. Intervirology. 1983;20(1):23e31.
27. Simons JN, Pilot-Matias TJ, Leary TP, et al. Identification of
two flavivirus-like genomes in the GB hepatitis agent. Proc
Natl Acad Sci U S A. 1995;92:3401e3405.
28. Nishizawa T, Okamoto H, Konishi K, Yoshizawa H,
Miyakawa Y, Mayumi M. A novel DNA virus (TTV) associated
with elevated transaminase levels in posttransfusion
hepatitis of unknown etiology. Biochem Biophys Res Commun.
1997;241(1):92e97.
29. Bendinelli M, Pistello M, Maggi F, Fornai C, Freer G,
Vatteroni ML. Molecular properties, biology and clinical
implications of TT virus, a recently identified widespread
infectious agent of humans. Clin Microbiol Rev.
2001;14(1):98e113. http://dx.doi.org/10.1128/CMR.14.98-113.
2001.
30. Shimizu YK, Feinstone SM, Purcell RH, Alter HJ, London WT.
Non-A, non-B hepatitis: ultrastructural evidence for two
agents in experimentally infected chimpanzees. Science.
1979;205(4402):197e200.
a p o l l o m e d i c i n e x x x ( 2 0 1 4 ) 1 e44
Please cite this article in press as: Poduri CD, Jaundice: A brief historical perspective, Apollo Medicine (2014), http://dx.doi.org/
10.1016/j.apme.2014.05.014

6. Apollohospitals:http://www.apollohospitals.com/
Twitter:https://twitter.com/HospitalsApollo
Youtube:http://www.youtube.com/apollohospitalsindia
Facebook:http://www.facebook.com/TheApolloHospitals
Slideshare:http://www.slideshare.net/Apollo_Hospitals
Linkedin:http://www.linkedin.com/company/apollo-hospitals
Blog:Blog:http://www.letstalkhealth.in/