Genetic Variants Associated With the Risk of Gall Stones and Cirrhosis.

Genetic Variants Associated With the Risk of Gall Stones and Cirrhosis.

Gall stone disease is more common in patients with cirrhosis. This association has been well established in different studies. Among the various factors which predispose a patient with gall stone disease to have associated liver cirrhosis, genetics also plays an important role.

This study aims to do a genetic panel-based analysis of genes which are involved in cholestasis to find any association between liver cirrhosis and gall stone disease.

Patients with history of gall stone or history of cholecystectomy done for gall stone disease will be evaluated for the presence of liver cirrhosis by fibroscan and ultrasonography. Those patients with cirrhosis and without cirrhosis will undergo a panel based genetic test for the common cholestasis genes and multivariate analysis will be done for variants associated with lithogenesis and cirrhosis.

Study population:

• Patients > 18 years of age.
• Who have either gall stone disease or cirrhosis. Study design: All consecutive in-patients and out-patients requiring liver biopsy for evaluation of diffuse parenchymal liver disease will be evaluated for inclusion.

Study period: 1 year. Intervention: Blood sample from included patients will be subject to panel based NGS.

Monitoring and assessment: History of all patients including family history will be taken. Screening for cirrhosis will be done by fibroscan or ultrasound scanning. Gall stone diagnosis is made by USG. History about patients' parents, siblings, spouse, children will be taken with respect to gall stone and cirrhosis. NGS of cholecystitis will be send for the subject and the results will be collected as the fastQ file for analysis.

Statistical Analysis: MVA will be done to identify gene variants independently associated with lithogenesis and cirrhosis, along with demographic and environmental risk factors for these conditions. * From this data, overlapping risk-variants in common associated genes will be identified. A risk estimate (OR with 95% CI) will be calculated for each of the above identified genetic risk variant for the phenotype of cirrhosis with GS.

Adverse effects:

There are no adverse outcomes with respect to this study. Stopping rule of study: There are no stopping rules for the study.

Inclusion Criteria:

1. Patients > 18 years of age.
2. Who has a GSD diagnosed by USG or have history of cholecystectomy for gall stone disease.
3. Who is a diagnosed case of cirrhosis by Fibroscan or USG (Cirrhosis including alcohol related cirrhosis, Hepatitis B, Hepatitis C, Wilsons disease, Hemochromatosis are excluded.

Exclusion Criteria:

1. Patients who have haemolytic anaemia
2. Patients who do not consent for genetic study
3. Patients who has a diagnosed cause for liver disease, including alcohol related cirrhosis, Hepatitis B, Hepatitis C, Wilsons disease, Hemochromatosis.
4. Inability to provide informed consent.
5. Cannot understand Hindi or English should be excluded since they will not be able to reply objectively to questionnaire.