The study aim to identify the risk factors of liver fibrosis among first degree relatives. This study consists of 2 parts (Cross Sectional and Case Control Study).

Part 1: The first primary objective will be achieved by following study design. Study population: First degree relatives of NRC. Study design: A Cross Sectional Study

Part 2 The second Primary objective will be achieved by following study design. Study design: A Case Control Study

Study population:

Case: NASH related Cirrhosis patients Control-1: Healthy Control. Control-2: HBV Disease Control Study period: 3 Years

All the patients diagnosed with NASH cirrhosis attending Institute of Liver and Biliary Sciences OPD/IPD will be enrolled. An informed consent will be taken. Complete details of the subject will be taken. The data will be collected on socio-demographic by (socio-demographic questionnaire), alcohol by AUDIT-C (Alcohol Use Disorders Identification Test), Tobacco by FTND (Fagerstrom Test Nicotine Dependence), physical activity by IPAQ (International Physical Activity Questionnaire), Diet by FFQ (Food Frequency Questionnaire), physical measurement & all the comorbidities.

Blood will be collected and analyzed for Platelets, PT/INR, Serum Creatinine, LFT, FBS, HOMA-IR, Lipid Profile, HBsAg, AntiHBs, Anti HBc, Anti HCV, Anti HAV, IgM anti HAV, IgM anti HEV, auto-Immune markers, Ceruloplasmin, Transferrin, S.Ferritin, Alpha1antitrpsin and genetic markers.

The stool will be collected and analyzed for gut microbiota profiling.

The data will be collected on socio-demographic by (socio-demographic questionnaire), alcohol by AUDIT-C (Alcohol Use Disorders Identification Test), Tobacco by FTND (Fagerstrom Test Nicotine Dependence), physical activity by IPAQ (International Physical Activity Questionnaire), Diet by FFQ (Food Frequency Questionnaire), 24-hour dietary recall method, physical measurement & all the comorbidities.

Blood will be collected and analyzed for CBC, LFT, KFT, PT/INR, FBS, HOMA-IR, Lipid Profile, HBsAg, AntiHBs, Anti HBc, Anti HCV, Anti HAV, IgM anti HAV, IgM anti HEV, auto-Immune markers, Ceruloplasmin, Transferrin, S.Ferritin, Alpha1antitrpsin and genetic markers.

The stool will be collected and analyzed for gut microbiota profiling. Controlled Attenuation Parameter and liver stiffness will be measured by using transient elastography. Ultrasound abdomen will be done First degree relatives of indexed patients will be enrolled. First degree relatives who will not accompanying the indexed subject will be contacted telephonically and will be requested to participate in the study.

The data on first degree relative will be collected on similar parameter as of the indexed patient. This will be a cross sectional study.

For each case, 1 healthy controls will be taken. Healthy Control will be identified from the OPD/IPD of ILBS. Liver transplant donors, hospital volunteers, Blood Donors, healthy attendants who are accompanying other patients of different specialties will be enrolled. An informed consent will be taken. The data will be collected on similar parameter as of the indexed patient. This will be case control study.

We will also have disease control (HBV control) for each case enrolled. Subject suffering from Hepatitis B virus related liver cirrhosis will be included as disease control. For each case, 1 disease control will be included. Disease Control will be identified from the OPD/IPD of ILBS. An informed consent will be taken. The data will be collected on similar parameter as of the indexed patient.

Genetic markers and stool microbiota profiling will be done in 30% of the subsets of sample i.e NASH related Cirrhosis, First Degree Relatives, Healthy Control and HBV Disease control.

Inclusion Criteria for NASH related Cirrhosis (Group 1-Index Case)

1. Age ≥18 yrs
2. Diagnosed cases of NASH with Cirrhosis.

Exclusion Criteria for NASH related Cirrhosis (Group 1)

1. Acute on Chronic Liver Failure
2. Patients with HBV, HCV, Wilson's, Hemochromatosis, alpha 1 antitrypsin deficiency, primary biliary cirrhosis).
3. Patient on treatment with amiodarone or methotrexate.
4. Patient with any malignancies
5. Patient on chemotherapy

Inclusion Criteria for First Degree Relatives (Group 2)

1. Age ≥8 yrs
2. All the first degree relatives of index case.

Exclusion Criteria for First Degree Relatives (Group 2)

1. Alcohol intake

Inclusion Criteria for Healthy Control (Group 3)

1. Age ≥18 yrs
2. Subjects with no history of any known liver disease
3. Non-Alcoholic
4. Matched with Age (+/- 5 yrs.) and Gender

Exclusion Criteria for Healthy Control (Group 3)

1. None

Inclusion Criteria for HBV Disease Control (Group 4)

1. Age ≥18 yrs
2. HBV Cirrhosis
3. Matched with Age (+/- 5 yrs.) and Gender

Exclusion Criteria for HBV Disease Control (Group 4)

1. Patient with any malignancies
2. HBV related Liver Fibrosis (≤ F3).

NASH related Cirrhosis ( Group 1-Index Cases), First Degree Relatives of index case (Group 2), Healthy Controls (Group 3) HBV Disease Controls (Group 4)