Role of Tumor Necrosis Factor Alpha in Patients with Liver Cirrhosis

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Illustration by The BMJ
Illustration by The BMJ

It is estimated that about 240 million people worldwide are infected with chronic hepatitis B and 600,000 people die each year due to complications from hepatitis B. Liver cirrhosis is a complication of hepatitis B that can develop into liver failure. Although it has not yet fully understood, the progression of hepatitis B to cirrhosis of the liver is influenced by several factors, including viral, environmental, and genetical factors.

In recent years, research on hepatitis B has focused a lot on the genetical factors of patients behind the differences in the progression of hepatitis B in each patient. Tumor Necrosis Factor-Alpha (TNF-α) is a cytokine that plays a role in the inflammatory process in the liver. In chronic hepatitis B conditions, excessive TNF-α production triggers inflammation and death of liver cells and increases the development of liver connective tissue. If this happens continuously, healthy liver cells will be damaged and replaced by connective tissue. This condition causes liver cirrhosis. Polymorphism or TNF-α gene variation is known to play a role in the course of liver disease, infection, and inflammation. Some research conducted abroad found that the existence of Single Nucleotide Polymorphism (SNP) or changes in one nucleotide base in the TNF-α gene at position -238 and -308 can affect the production of TNF-α itself.

This study is a preliminary study conducted to detect the SNP gene promoter TNF-α position -238 and -308 from samples of patients with liver cirrhosis with HBV infection in Endoscopic Clinic of Dr. Soetomo General Hospital Surabaya. We conducted this study because data on factors playing a role in the occurrence of liver cirrhosis in Indonesia is still limited. Our study took samples of patients with liver cirrhosis with chronic hepatitis B in Endoscopic Clinic of Dr. Soetomo General Hospital Surabaya from April-May 2017. SNP position -238 and -308 (rs361525 and rs1800629) TNF-α gene promoters were detected using molecular biology techniques Polymerase Chain Reaction-Restriction Fragment Length Polymorphism(PCR-RFLP) with specific primers for the TNF-α gene promoter region and NcoI and MspI endonuclease restriction enzymes. Furthermore, the determination of TNF-α gene promoter genotype was performed according to the length of the fragment produced in RFLP. Serum TNF-α levels were measured using the Enzyme Linked-Immunoassay (ELISA) method. All laboratory procedures in this study were carried out at Universitas Airlangga’s Hepatitis Laboratory, Institute of Tropical Disease (ITD).

In this study, 149 patients with hepatitis B, evidenced by positive HBsAg in Endoscopic Clinic of Dr. Soetomo General Hospital Surabaya. From this number of patients, 30 patients founded with cirrhosis. From the 30 serum samples of patients, as much as 6.67% showed the heterozygous SNP genotype GA for TNF-α gene promoters at position -238 and -308. No AA genotype was found in this study. TNF-α levels in female patients (38 ng / L) are higher compared to men (33 ng / L). TNF-α levels in patients with GA heterozygous SNP genotypes at positions -238 and -308 did not differ significantly compared with wild-type (GG genotype). In patients with liver cirrhosis with HBV infection in Endoscopic Clinic of Dr. Soetomo General Hospital Surabaya, heterozygous SNP GA (6, 67%) and no homozygous AA SNP gene promoter TNF-α (-238 and -308) were found. In contrast to similar studies abroad, the absence of AA genotype in the two SNP positions in our study could be a different thing found in Surabaya population. It is because gene polymorphisms differ in each ethnic and population. Further studies on various ethnicities and populations in Indonesia are needed to provide precise data on the diversity of SNP promoters TNF-α genes in liver cirrhosis from hepatitis B. The relationship between TNF-α gene polymorphisms on TNF-α protein expression produced also needs to be investigated further to better understand the effect of TNF-α on the course of liver disease.

Author: Citrawati Dyah Kencono Wungu, dr., M.Si

Details of this research available at:

https://e-journal.unair.ac.id/IJTID/article/view/7275

http://dx.doi.org/10.20473/ijtid.v7i5.7275

Citrawati Dyah Kencono Wungu, Mochamad Amin, S. Eriaty N. Ruslan, Priyo Budi Purwono, Ulfa Kholili, Poernomo Boedi Setiawan, Maria Inge Lusida, Soetjipto, Retno Handajani (2019). Detection of Tumor Necrosis Factor-α (TNF-α) Gene Promoters Polymorphism among Liver Cirrhosis Patients with Chronic Hepatitis B Virus (HBV) Infection in Surabaya, Indonesia. Indonesian Journal of Tropical and Infectious Disease, 7(5): 115-121

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