SHAILESH PATIL DISSERTATION

 THESIS TOPIC

CLINICAL PROFILE AND THERAPEUTIC OUTCOMES IN PATIENTS WITH NON ALCOHOLIC FATTY LIVER DISEASE

NAME OF THE STUDENT : DR.SHAILESH SAMBHAJI PATIL ( PG 2020-2023)

DEPARTMENT OF GENERAL MEDICINE

KAMINENI INSTITUTE OF MEDICAL SCIENCES, NARKETPALLY

UNIVERSITY: KALOJI NARAYANA RAO UNIVERSITY OF MEDICAL SCIENCES,TELANGANA.

HEAD OF THE DEPARTMENT OF GENERAL MEDICINE : DR RAKESH BISWAS . MBBS , MD GENERAL MEDICINE ( PGIMER, CHANDIGARH )

GUIDE: DR A.PRAVEEN NAIK , MBBS , MD ( GENERAL MEDICINE )

   ASSOCIATE PROFESSOR , DEPARTMENT OF GENERAL MEDICINE

CO GUIDE : DR NAGESHWAR RAO , MEDICAL GASTRO ENTEROLOGIST

BACKGROUND –

It was the Roman anatomist Galen who made the liver the principal organ of the human body, arguing that it emerged first of all the organs in the formation of a fetus

It Is a tough job for the liver to keep the cleaning function of the body especially with the present-day unhealthy eating and drinking habits of people.

Non-alcoholic fatty liver disease (NAFLD) is a broad term which includes patients with simple steatosis as well as non-alcoholic steatohepatitis (NASH). NASH is a recently recognized entity, which histologically simulates alcoholic hepatitis in the absence of alcohol ingestion or intake of <20g/day and has the propensity to progress on to cirrhosis of the liver and hepatocellular carcinoma (HCC). NAFLD has emerged as a major hepatic problem in developed as well as developing countries

Although NAFLD is thought to be a relatively benign condition ranging from simple steatosis to steatohepatitis, it has now become clear that it may progress to cirrhosis, liver failure as well as to the catastrophic illness like hepatocellular carcinoma

Obesity, type 2 diabetes mellitus (T2DM) and hyperlipidaemia are coexisting conditions frequently associated with NAFLD. Because of the strong association with various metabolic abnormalities, NAFLD is now considered a part of spectrum of metabolic syndrome

Non-alcoholic fatty liver disease (NAFLD) was recognized by Zelman, and Westwater as early as five decades ago. For a longtime, ‘fatty liver’ was ignored, and was considered to be a fanciful appendage. All this changed approximately one-quarter of a century ago when Ludwig et al. at Mayo described the histological findings of fatty liver and coined the term ‘non-alcoholic steatohepatitis (NASH), and gave the entity a modicum of respectability.

AIM - To study the clinical and biochemical profile of non alcoholic fatty liver disease

OBJECTIVES - To study the clinical and biochemical profile of non alcoholic fatty liver disease

To study the relation of non alcoholic fatty liver disease with metabolic syndrome

INCLUSION CRITERIA - 1. Non-alcoholic individuals, with age >18 years defined as total abstainers.

2. Ultrasound showing hyperechoic liver suggestive of fatty liver

EXCLUSION CRITERIA

Patients with history of alcohol intake.

 Patients with history of jaundice or HBsAg positive.

Patients with history of following drug intake – steroids, synthetic estrogen, heparin, calcium channel blockers, amiodarone, valproic acid and antiviral agents ,Warfarin.

 Pregnancy

Total parenteral nutrition

 Autoimmune diseases

METHODOLOGY –

PLACE OF STUDY : KAMINENI INSTITUTE OF MEDICAL SCIENCES, NARKETPALLY.

TYPE OF STUDY : CROSS SECTIONAL STUDY

PERIOD OF STUDY: NOVEMBER 2020 TO OCTOBER 2022

SAMPLE SIZE: 60

All cases included into the study underwent a complete clinical, anthropometric and laboratory evaluation after a screening ultra-sound scan of liver. Brightness and posterior attenuation were considered indices of the extent of fatty infiltration and fibrosis and evaluated by a single radiologist

CRITERIA FOR DIABETES MELL1TUS • Symptoms of diabetes plus R.B.S. > 200 mg/dl. Or • Fasting plasma glucose > 126 mg/dl.

 CRITERIA FOR OBESITY

       B.M.I. ≥ 30.

ANTHROPOMETRIC DATA COLLECTION

Body weight was measured in light clothing and without shoes to the nearest half-kilogram.

• Height was measured without shoes to the nearest half-centimeter.

• Body mass index was calculated as weight (kg) divided by height (m2 )

• Waist circumference (at the nearest half centimeter) was measured at the mid-point between the lower border of rib cage and the iliac crest.

• Hip circumference (at the nearest half centimeter) was measured at the widest point between hip and buttock

GRADING OF HEPATIC ECHOGENICITY ON USG

GRADE 1- Normal echogenicity.

GRADE 2- Slight, diffuse increase in fine echoes in liver parenchyma with normal visualization of intra hepatic vessels and diaphragm.

GRADE 3- Moderate, diffuse increase in fine echoes in liver parenchyma with slight impaired visualization of intra hepatic vessels and diaphragm.

GRADE 4- Marked, diffuse increase in fine echoes in liver parenchyma with poor or no visualization of intra hepatic vessel borders, diaphragm & posterior right lobe of the liver.

INVESTIGATIONS

Complete blood picture

 SERUM BILIRUBIN

 Aspartate transaminase

Alanine transaminase

ALBUMIN

Fasting blood sugar

Fasting lipid profile

 ANTI-HCV

HBsAG

 Ultrasonography of abdomen

DISCUSSION –

Non alcoholic steatohepatitis was considered to be a medical curiosity for many years but now it is a well-established cause of chronic liver disease in the western world. There is dearth of literature about the magnitude of non alcoholic steatohepatitis in Indian subcontinent.

The available reports (Aggarwal et al. 2001 ; Amarapurkar et al. 2001. Francis j et aI. 2001; Satheesh K et al. 2001; Farooq et al; Sreenivasa Rao et al) confirms that non alcoholic steatohepatitis equally prevalent in Indian population.

The present study was conducted on 60 patients presented or referred to gastroenterology clinic and general medicine clinic and the admitted patients in the wards of KAMINENI INSTITUTE OF MEDICAL SCIENCES HOSPITAL,NARKETPALLY for persistently altered liver function test in the absence of common causes of liver diseases.

The patients In the study had a variety of complaints or symptoms. The commonest symptom was fatigability and malaise which was present in 40 (66.66%) patients. The second commonest symptom was right upper abdominal discomfort which was present in 28 (46.66%) patients. These findings were contrary to the findings of Patel T and Lee JG 2001; Aggarwal et al. 2001.

2The predominant population studied was females who might be having associated nutritional anemia which is a common coexisting problem in many females in India, which was not analyzed further

Most patients with non-alcoholic steatohepatitis have no symptoms or signs of liver disease at the time of diagnosis. 30 (50%) patients were asymptomatic at presentation whereas Aggarwal et al found asymptomatic cases in that series only 9%.

 The commonest clinical sign detected in this study was of hepatomegaly or palpable liver found in 54 (90%) subjects.

. This disease commonly progresses without much clinical symptoms and signs. These findings were similar to a study by Angulo et al5 were hepatomegaly was the only physical finding.

Truncal obesity seems to be an important risk factor for non-alcoholic steatohepatitis. Out of total 24 males, 8 (33.33%) patients were viscerally obese where as 28 (77.77%) out of total 36 females had visceral obesity. So a total of 52 (86.67%) patients were viscerally obese in our study.

The association between diabetes mellitus and non-alcoholic steatohepatitis is strong.

In this study, out of total 60 patients, 35(58.33%) patients were found diabetic. These were similar to the findings of Marchesini G et al. 18

In this study out of 60 patients, there were23 (38.33%) patients in whom the lipid profiles were in the normal range. Dyslipidemia was noted in 37 (61.67%) patients and this finding was consistent with the findings of James OFW, Day CP et al. 1998.

Hypoalbuminemia may be found in patient with cirrhotic stage of nonalcoholic steatohepatitis . In our study total serum protein and serum albumin values were with in normal range in many cases. The total serum proteins ranged from 5 – 8.2 gm/dl and the mean was 6.56±0.75 gm/dl. The serum albumin ranged from 1.9 – 5.2 gm/dl and the mean was 3.63±0.71 gm/dl.

Mildly to moderately elevated serum levels of SGOT, SGPT or both are the most common and often the only laboratory abnormality found in patients of non-alcoholic steatohepatitis.

In our study the mean serum glutamate pyruvate transferase (SGPT) was 47.47±23.39 IU/L and ranged from 11 – 110 IU/L

 The mean serum glutamate oxaloacetate transferase (SGOT) was 43.88±21.95 IU/L and ranged from 13 -100 IU/L.

 31 (51.67%) had SGOT elevation more than 40 IU/L and 37 (61.67%) had SGPT elevation more than 40 IU/L.

These findings different to the findings of Wanless IR, Lentz JS et al. 1990 and Viggiano TR 1980 et al. where the most common abnormality in liver Function test was two to five fold elevation of transaminases.

Surprisingly prevalance of transaminitis was found to be higher in person without MS as compared to those with MS. This observation is important as it depicts higher rate of liver damage in cases of NAFLD without MS hence more propensity towards progression of hepatic complication in later life. Hence a patient having fatty liver disease without MS should be closely monitored.

In this study, hepatomegaly was found in 54 (90%) of the patients on ultrasonography and cirrhosis was found in 6 (10%) patients.

2 (3.33%) patients had mild steatosis (grade 1), 34(56.67%) had moderate steatosis (grade 2) and 24(40%) patients had severe steatosis (grade 3).

 The sensitivity and specificity of detecting steatosis by ultrasonography is 89% and 93% respectively on ultrasonography examination and this finding is consistent with Angulo P et al 2000

This study demonstrates that features suggestive of the metabolic syndrome are observed more frequently in patients with non-alcoholic steatohepatitis and patients of non-alcoholic steatohepatitis share many of the systemic disorders that constitute insulin resistance syndrome, hyperlipidemia, hypertension, obesity, type 2 diabetes and hepatic steatosis.

In our study non-alcoholic steatohepatitis was found in 51.66% patients. The risk factors found were diabetes in 35% patients, hyperlipidemia in 6.66% patients, obesity in 51.66% patients and truncal obesity in 60% patients.

The findings In this study further supports the theory of preponderance of women in developing steatosis and consequently steatohepatitis more than males.

Observations in this study have corroborated the other reports of nonalcoholic steatohepatitis in Indians population that non-alcoholic steatohepatitis is often seen in men even in the absence of diabetes and hyperlipidemia.

LIMITATIONS - The present study is a pilot study and long term follow up has not been done. I have observed that there is a need for further epidemiological studies for long term follow up to evaluate the magnitude of non-alcoholic steatohepatitis in India and the role of invasive interventions to prevent the progression to chronic liver disease with the use of drugs like urso deoxycholic acid, diet therapy and strict regulation of diabetes

REFERENCES

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Musso G et al. (2010). “Meta-analysis: Natural history of non-alcoholic fatty liver disease (NAFLD) and diagnostic accuracy of non-invasive tests for liver disease severity”. Ann Med. 43(8): 1–33.

.Marchesini G, Brizi M, Bianchi G, et al. Nonalcoholic fatty liver disease. A feature of the metabolic syndrome. Diabetes 2001; 50: 1844–50

Ludwig J, Viggiano TR, McGill DB, Ott BJ: Nonalcoholic steatohepatitis: Mayo Clinic experiences with a hitherto unnamed disease. Mayo Clin Proc 1980, 55:434–438.

Sanyal AJ, Chalasani N, Kowdley KV, et al (2010).Pioglitazone, vitamin E or placebo for Non alcoholic steatohepatitis. N. Engl. J.

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 McCullough AJ. The epidemiology and risk factors of NASH. In: Farrell GC,George J, Hall P, Mc McCullough AJ,eds. Fatty Liver Disease: NASH and Related Disorders. Oxford: Blackwell Publishing, 2005: 23–37.