Evaluation of PNPLA3 genetic variants in Egyptian HBV-infected patients concomitant with metabolic-associated steatotic liver disease (MASLD)

Hepatitis B virus (HBV) infection and metabolic-associated steatotic liver disease (MASLD) increasingly coexist, creating complex diagnostic and therapeutic challenges. This study examined the association between the PNPLA3 rs738409 genetic variants and the progression of hepatic steatosis and fibrosis in HBV patients who have and do not have MASLD. A total of 170 Egyptian HBV patients were enrolled and categorized into two groups: non-MASLD (n=99) and MASLD (n=71). The assessment of liver stiffness and hepatic steatosis was conducted using transient elastography (FibroScan®) and controlled attenuation parameter (CAP). Genotyping for PNPLA3 was performed via real-time PCR. The PNPLA3 GG genotype and G allele were significantly linked to the progression of hepatic steatosis in HBV-MASLD patients. Moreover, the frequency of CG+GG genotypes was higher in HBV-MASLD patients during both early (53.1% vs. 34.2%, p=0.035) and late fibrosis stages (73.7% vs. 33.3%, p=0.014) compared to non-MASLD patients. No association was found between PNPLA3 genotypes and HBV DNA levels. HBV viral load was notably associated with different fibrosis stages but was not linked to steatosis. HBV patients carrying the PNPLA3 GG genotype or G allele are more susceptible to developing MASLD and severe steatosis. Additionally, PNPLA3 variants may be implicated in the progression of fibrosis within the context of metabolic dysfunction; this association is not apparent in non-MASLD cases. Furthermore, viral dynamics appear to influence the progression of hepatic fibrosis but not steatosis. The concomitant MASLD in HBV patients was not associated with the severity of hepatic fibrosis.