AIM: To identify the most common hepatitis B virus (HBV) genotype in Saudi Arabia, and correlate the prevailing genotypes with the clinical outcome of patients. METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral cen- ters. Patients were categorized into 4 different groups: group 1, patients with hepatitis B and normal liver en- zymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Ge- notyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides. RESULTS: Seventy patients were enrolled in this study. They were predominantly male (72.9%) in their mid- forty’s (mean age 47 years). Forty-nine (70%) patients were hepatitis B envelope antigen (HBeAg) negative. The majority of patients (64%) acquired HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient (1.4%) had geno- type C, and 4 patients (5.7%) had genotype E, while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender, aspartate transaminase, alanine transaminase, albumin,bilirubin, and alkaline phosphatase (all P < 0.001). In multivariate analysis decreased hemoglobin (r = -0.05; 95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease. In patients with HBV genotype D, HBeAg negativity was found to increase across advancing stages of liver dis- ease (P = 0.024). CONCLUSION: This study highlights that the vast ma- jority of Saudi patients with chronic hepatitis B have genotype D. No correlation could be observed between the different genotypes and epidemiological or clinical factors. The relationship between genotype D and HBeAg status in terms of disease severity needs to be further elucidated in larger longitudinal studies. METHODS: Patients were consecutively recruited from the hepatology clinics of two tertiary care referral cen- ters. Patients were categorized into 4 different groups: group 1, patients with hepatitis B and normal liver en-zymes; group 2, patients with hepatitis B and abnormal liver enzymes but without cirrhosis; group 3, patients with hepatitis B and liver cirrhosis; group 4, patients with hepatitis B and hepatocellular carcinoma. All patients had a positive hepatitis B surface antigen (HBsAg). Ge- notyping of HBV was performed by nested PCR-mediated amplification of the target sequence and hybridization with sequence-specific oligonucleotides. RESULTS: Seventy patients They were predominantly male (72.9%) in their mid-forty’s (mean age 47 years). Forty-nine (70%) patients were hepatitis B envel The majority of patients (64%) had HBV through unknown risk factors. Hepatitis B genotyping revealed that 57 patients (81.4%) were genotype D, 1 patient (1.4%) had genotype A, 1 patient ( 1.4%) had geno-type C, and 4 patients (5.7%) had genotype E while 7 patients (10%) had mixed genotype (4 patients ADG, 1 patient DE, 1 patient DF, and 1 patient ADFG). Based on univariate analysis of genotype D patients, significant predictors of advanced liver disease were age, gender, aspartate transaminase, alanine transaminase, albumin, bilirubin, and alkaline phosphatase (all P <0.001) 95% CI: -0.08 to -0.03; P = 0.001) and albumin levels (r = -0.004; 95% CI: -0.007 to -0.001; P = 0.002) were highly significant predictors of advanced liver disease. genotype D, HBeAg negativity was found to increase across advancing stages of liver dis- ease (P = 0.024). CONCLUSION: This study highli ghts that the vast ma- jority of Saudi patients with chronic hepatitis B have genotype D. No correlation could be observed between the different genotypes and epidemiological or clinical factors. The relationship between genotype D and HBeAg status in terms of disease severity needs to be further elucidated in larger longitudinal studies.