1. NAFLD Epidemic in India
SP Singh

2. NAFLD Epidemic in India:
Why this Brouhaha?

6. • Non-alcoholic fatty liver disease is fast
becoming one of the top concerns for
clinicians due to the obesity epidemic and
it's potential to progress to advanced liver
disease which significantly impacts on
overall liver-related mortality.
• This data highlights a serious concern for
the future, and the enormous increasing
health burden of NAFLD.

7. • If the obesity epidemic is anything to go
by, the U.S. NAFLD epidemic may have a
ripple effect worldwide.
• It is imperative that health systems
continue to drive effective educational
programmes to reinforce awareness
among the general public to alert them of
the risks of obesity and promote the
importance of diet and exercise.

8. NAFLD Epidemic in India:
What is an Epidemic?
Is it not Endemic?

9. EPIDEMIC
The “unusual” occurrence in a community or region of
disease, specific health-related behaviour or other
health-related events clearly in excess of “expected
occurrence”.
ENDEMIC
It refers to the constant presence of a disease or
infectious agent within a given geographic area or
population group, without importation from outside.
HYPERENDEMIC
The term expresses that the disease is constantly
present at a high incidence and/or prevalence rate and
affects all age groups equally.

10. PANDEMIC
n
“An epidemic usually affecting a large
proportion of the population, occurring
over a wide geographic area such as a
section of the nation, the entire nation,
a continent or the world”.

11. NAFLD Epidemic in India:
Why should there be one?

12. NAFLD
The Metabolic Syndrome is synonymous to an iceberg with NAFLD above
the surface but a group of other key cardiovascular disease risk factors
lurking below.

13. The prevalence of insulin resistance is 2 - 3
fold higher in Asian-Indians (59%) compared
with other ethnic groups [20%-33%]
• Misra A, Misra R, Wijesuriya M, Banerjee D. The
metabolic syndrome in South Asians: Continuing
escalation & possible solutions. Indian J Med Res
2007;125:345-54.
• Petersen KF, Dufour S, Feng J, Befroy D, Dziura
J, Dalla Man C, Shulman GI. Increased
prevalence of insulin resistance and nonalcoholic
fatty liver disease in Asian-Indian men. Proc Natl
Acad Sci U S A:103:18273-7.

15. The prevalence of insulin resistance was 2- to 3-fold higher
in the Asian-Indians compared with all other ethnic groups.

16. Nearly 95% subjects had at least one abnormal
parameter. The prevalence of MS was found to be 20%

19. India is home to thirty-five million people with diabetes - nearly 15
percent of the global diabetes burden - and projections show that
this will increase to seventy million by 2025.

21. Childhood Obesity in India

23. The first Indian Test team at Lord’s, 1932. It was captained by
the legendary C.K. Nayudu

24. Recent T-20 Champions

25. NAFLD Epidemic in India:
Is there one?

26. What is the current burden of
NAFLD in India?
• There are not many reports on NAFLD
emanating from India.
• Published data on the prevalence of NAFLD
in India is still very scanty.
• The few studies on the prevalence of NAFLD
in India are based on ultrasonography to
detect fatty liver.

28. US Based Prevalence Studies
• Singh SP, Nayak S, Swain M, Rout N, Mallik RN,
Agrawal OP, et al. Prevalence of nonalcoholic fatty liver
disease in coastal eastern India: a preliminary
ultrasonographic survey. Trop Gastroenterol
2004;25:76-79.
• Singh SP, Nayak SN, Swain M, Agrawal OP, Meher C,
Rao MVK, et al. US study of prevalence of NAFLD in
coastal eastern India. Indian J Gastroenterol
2004;23(Suppl 2):A47.
• Amarapurkar D, Kamani P, Patel N, Gupte P, Kumar P,
Agal S, Baijal R, Lala S, Chaudhary D, Deshpande A.
Prevalence of non-alcoholic fatty liver disease:
population based study. Ann Hepatol 2007;6:161-3.

30. Trop Gastroenterol 2004;25:76-79.
• The first study from coastal eastern India
showed that the prevalence of NAFLD as
detected by US was as high as 24.5%.
• The majority [three fifths] of persons with
NAFLD were from the rural countryside.
• The number of male subjects was
disproportionately high.
• Males appeared to have a greater predilection
for fatty liver.

31. Indian J Gastroenterol
2004;23(Suppl 2):A47
• Another study on the prevalence of NAFLD by
the same group was published in abstract form.
• This study was also based on the US of 639
patients attending Gastroenterology OPD for
evaluation of different GI and hepatic
complaints.
• The subjects included 337 males and 302
females.
• Fatty liver was diagnosed by ultrasonography in
138 (21.6 %) of the 639 persons.

33. • In this population based study from Western
India by Amarapurkar et al, the prevalence
of NAFLD was around 18.9% in the adult
population confirming the “commonness” of
NAFLD in Indians.
• NAFLD was more prevalent in males than
females (24.6% vs 13.6%, p < 0.001)

35. NAFLD Prevalence in urban South Indians
• Overall prevalence of NAFLD was 32% (men:
35.1%, women: 29.1%, p = 0.140).
• Prevalence of NAFLD (54.5%) was higher in
subjects with DM compared to those with
prediabetes (IGT or IFG) (33%), isolated IGT
(32.4%), isolated IFG (27.3%) and normal glucose
tolerance (NGT) (22.5%).
• NAFLD is present in a third of urban Asian Indians
and its prevalence increases with increasing
severity of glucose intolerance and in MS.

37. • A total of 1,911 individuals were analyzed, 7% of
whom were overweight and 11% of whom had
abdominal obesity.
• The prevalence of NAFL, NAFL with elevated ALT, and
cryptogenic cirrhosis was 8.7%, 2.3%, and 0.2%,
respectively.
• 75% of NAFL subjects had a BMI <25 kg/m2, and 54%
were neither overweight nor had abdominal obesity.

38. Kolkata NAFL Study
• Most of the NAFLD subjects (75%) were
not overweight.
• 103/164 (63%) had normal BMI (18.5-
24.9 kg/m2).
• 20/164 (12%) were underweight (BMI
<18.5 kg/m2.

39. HISTOLOGY BASED
NAFLD PREVALENCE

40. • Singh SP, et al. Prevalence of fatty liver in fatal traffic
casualties in coastal Orissa. J Gastroenterol Hepatol
2004;19 (Suppl): A838.
• Singh SP, et al. A study of the prevalence of fatty liver
disease (NAFLD) in fatal traffic casualties in coastal
Orissa. Orissa Medical Journal 2004; 23:13-15.
• Bal MS, et al. Pathological findings in liver autopsy.
JIAFM, 2004; 26:55-57.
• Amarapurkar D, Ghansar T. Fatty liver: experience
from western India.
Ann Hepatol 2007;6:37-40.
• Singh SP, et al. Assessment of ultrasonography as a
tool for diagnosis of fatty liver. Orissa Medical Journal
2002;21:56-58.

41. Available at: http://medind.nic.in/jal/t04/i2/jalt04i2p55.pdf

42. PATHOLOGICAL FINDINGS
IN LIVER AUTOPSY
• An autopsy study of 100 cases of liver
specimens from Punjab in North India
• Fatty change was the predominant finding.
• Out of 100 livers of individuals above 40
years of age, 39 had fatty change.
• The authors attributed the increased cases
of fatty change to greater alcohol
consumption in this region (Patiala Peg!).

44. Fatty liver: Experience from
western India
• Retrospective autopsy study from Western India
• 1230 adult autopsies were screened
• Overall prevalence of steatosis was found to be
15.8%.
• The commonest risk factor for steatosis was
found to be chronic alcoholism (38.4%) followed
by tuberculosis (25.6%).
• A close look: perhaps only 30 of 195 cases of
fatty liver could be attributable to NAFLD,
• This brings the prevalence of NAFLD down to
2.44% !
Amarapurkar & Ghansar, 2007

45. That NAFLD is quite common in Orissa
is also highlighted by following study
• This study was performed to evaluate the
efficacy of ultrasonography for diagnosis of fatty
liver.
• The subjects in this study included 31
consecutive persons who underwent liver biopsy
for diagnostic evaluation of liver abnormalities.
• Fatty liver was confirmed by histology in 25
(80.65%) patients. [Fatty liver was diagnosed by
ultrasonography in 25 of the 31 patients who
underwent liver biopsy]
Singh SP, et al. Assessment of ultrasonography as a tool for
diagnosis of fatty liver. Orissa Medical Journal 2002;21:56-58.

46. • The study material included the liver histology of
103 consecutive victims of fatal traffic casualties
who underwent medico-legal autopsy in the
department of forensic medicine of S. C. Medical
College, Cuttack situated in the coastal region of
the state of Orissa in India.

47. • Fatty liver was found in 14.6 %, mild hepatocellular
cholestasis in 3 persons, alcoholic hepatitis in 2, and
passive venous congestion in 1.
• No cases of cirrhosis, chronic aggressive hepatitis,
changes compatible with chronic persistent hepatitis,
viral hepatitis, or other internationally accepted
morphological diagnoses were found.

50. NAFLD Epidemic in India:
If so – what? why bother?

52. TNFα
Insulin
resistance
Oxidative stress
Endotoxins
Normal ATP depletion
FFA
Fatty
liver
Steatohepatitis
Cirrhosis

53. CLINICAL OUTCOME OF NAFLD: Serial Biopsy Studies
STUDY n F/U[years] Cirrhosis Fibrosis No Improved
change
Lee 1989 12 3.5 2 3 7 -
Powell et al 13 4.5 3 3 6 1
1990
Bacon et al 2 5 1 - 1 -
1994
Ratzui et al 4 5 1 1 2 -
1995
‘n’ represents patients with baseline NASH without cirrhosis

54. HISTOLOGICAL PROGRESSION IN NASH
• 40% had worsening histology
• 20% developed worsening fibrosis
• Up to 20% progressed to Cirrhosis
Follow up period [Mean] = 5 to 7 years

55. Burden of NAFLD in India?
• NAFLD is quite common in India, and this is an
entity which we can only ignore at our own peril.
• Presuming an overall NAFLD prevalence rate of
20% translates to a staggering 244 million with
fatty liver in India.
• With increasing obesity and diabetes mellitus,
there is the gloomy possibility of fatty liver
prevalence increasing further.
• If the implications are any where near what is
suggested by data on natural history &
association with CAD, then its time to wake up
and assess the enormous burden this disease
can pose in Indians.

56. Current Population of India in 2012 1,220,200,000 (1.22 billion)
Total Male Population in India 628,800,000 (628.8 million)
Total Female Population in India 591,400,000 (591.4 million)

57. NAFLD Epidemic in India:
What should be done?

59. • My long-term goal is to understand the host of
factors that regulate the development of
NAFLD/NASH in Hispanics, and find interventions
that can alter its natural history and improve our
management strategies.
• The first step towards this goal is to determine
the magnitude of the NAFLD epidemic in
Hispanics with T2DM and its associated
metabolic/molecular abnormalities (Aim #1).

60. • Second, assess the long-term impact of
pioglitazone to reverse these defects (Aim
#2).
• This work will address a major public
health problem in South Texas and
nationally and yield key information for
longer-term, multi-center studies.

61. 3/19/2012 NAFLD - SP SINGH 61

62. Prevalence of fatty liver in different BMI
subgroups within normal range of BMI
BMI Category n Number of fatty Prevalence of
(normal range) liver patients fatty liver
<19 24 1 4.2%
19-19.9 11 1 9.1%
20-20.9 16 0 0%
21-21.9 17 2 11.8%
22-22.9 13 3 23.1%
23-23.9 17 7 41.2%
24-24.9 19 7 36.8%
p<0.001 SP Singh et al, 2004

63. Prevalence of Nonalcoholic Fatty
liver Disease in Coastal Eastern India
BMI Category n Number of fatty Prevalence of
(WHO criteria) liver patients fatty liver
<19 (subnormal) 24 1 53.8? 4.2%
19-24.9 (normal) 93 20 21.5%
25-29.9 (overweight) 35 13 37.1%
30 & above (obese) 7 5 71.4%
Overall 159 39 24.5%
Prevalence of fatty liver in different normal and abnormal BMI groups
SP Singh et al [Tropical Gastroenterology 2004]

64. BMI of Indian NAFLD patients
• Angulo et al: 31.2 • Uchil et al: 28.6* [21.7]
• Marceau et al: 47 • Singh et al: 25.9* [22.1]
• Garcia-Monson et al: • Duseja et al: 28.7*
50.5 • Das et al: 22.7 [19.6]
• Ratziu et al: 29.1 • Baba et al: 27.0*
• Dixon et al: 47.2 • Bajaj et al: 26.7* [22.7]
• Chitturi et al: 32 • Madan et al: 26.5*
• Harrison et al: 33.8
*Except Bengalis’ BMI, all values are in obese range !

65. 3/19/2012 NAFLD - SP SINGH 65

68. 3/19/2012 NAFLD - SP SINGH 68

69. WEIGHT
REDUCTION
IN NASH
3/19/2012 NAFLD - SP SINGH 69

70. PROF PRITHIKA CHARY
At THE TREADMILL
3/19/2012 NAFLD - SP SINGH 70

71. 3/19/2012 NAFLD - SP SINGH 71

72. 3/19/2012 NAFLD - SP SINGH 72

73. 3/19/2012 NAFLD - SP SINGH 73

74. 3/19/2012 NAFLD - SP SINGH 74

75. MANAGEMENT OF NAFLD –
THE UNFOLDING MONSTER!
• NAFLD is not merely a “Liver Disease.”
• It is a surrogate marker of Metabolic
Syndrome with its accompanying
dreaded appendages like coronary
artery disease.

76.  WE SHOULD NOT MERELY BE
CONCERNED WITH TREATMENT OF
NASH & ITS SEQUELAE
 WE SHOULD ALSO BE COMMITTED
ABOUT PREVENTION OF NASH

77. THANK YOU