• Non-alcoholic fatty liver disease is fast becoming one of the top concerns for clinicians due to the obesity epidemic and its 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.
• 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.
NAFLD Epidemic in India: What is an Epidemic? Is it not Endemic?
EPIDEMICThe “unusual” occurrence in a community or region ofdisease, specific health-related behaviour or otherhealth-related events clearly in excess of “expectedoccurrence”.ENDEMICIt refers to the constant presence of a disease orinfectious agent within a given geographic area orpopulation group, without importation from outside.HYPERENDEMICThe term expresses that the disease is constantlypresent at a high incidence and/or prevalence rate andaffects all age groups equally.
PANDEMIC n “An epidemic usually affecting a largeproportion of the population, occurringover a wide geographic area such as asection of the nation, the entire nation, a continent or the world”.
NAFLD Epidemic in India:Why should there be one?
NAFLDThe Metabolic Syndrome is synonymous to an iceberg with NAFLD abovethe surface but a group of other key cardiovascular disease risk factorslurking below.
The prevalence of insulin resistance is 2 - 3fold higher in Asian-Indians (59%) comparedwith 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.
The prevalence of insulin resistance was 2- to 3-fold higherin the Asian-Indians compared with all other ethnic groups.
Nearly 95% subjects had at least one abnormalparameter. The prevalence of MS was found to be 20%
India is home to thirty-five million people with diabetes - nearly 15percent of the global diabetes burden - and projections show thatthis will increase to seventy million by 2025.
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.
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.
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.
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.
• 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)
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.
• 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.
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.
• 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.
Available at: http://medind.nic.in/jal/t04/i2/jalt04i2p55.pdf
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!).
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
That NAFLD is quite common in Orissais 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 fordiagnosis of fatty liver. Orissa Medical Journal 2002;21:56-58.
• 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.
• 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.
NAFLD Epidemic in India:If so – what? why bother?
TNFα Insulinresistance Oxidative stress Endotoxins Normal ATP depletion FFA Fatty liver Steatohepatitis Cirrhosis
CLINICAL OUTCOME OF NAFLD: Serial Biopsy Studies STUDY n F/U[years] Cirrhosis Fibrosis No Improved changeLee 1989 12 3.5 2 3 7 -Powell et al 13 4.5 3 3 6 11990Bacon et al 2 5 1 - 1 -1994Ratzui et al 4 5 1 1 2 -1995 ‘n’ represents patients with baseline NASH without cirrhosis
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
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.
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)
• 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).
• 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.
Prevalence of fatty liver in different BMIsubgroups within normal range of BMIBMI 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
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]
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 !
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.
WE SHOULD NOT MERELY BE CONCERNED WITH TREATMENT OF NASH & ITS SEQUELAE WE SHOULD ALSO BE COMMITTED ABOUT PREVENTION OF NASH