Subgenotyping and genetic variability of hepatitis C virus in Palestine

Abstract

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Genotyping of HCV is crucial for successful therapy. To determine the HCV subgenotypes circulating in Palestine and to study the genetic variability of their core, we collected 84 serum samples which had tested positive for anti-HCV antibodies. Thirty-seven of these samples came from hemodialysis patients. Serum samples were subjected to viral RNA isolation and amplification of the HCV core gene. Thirty-three of the samples (39%) tested positive for HCV RNA. The HCV subgenotypes circulating in Palestine included 1a, 3a, and 4a, detected in 38%, 25%, and 22% of the samples, respectively. Furthermore, subgenotype 1b was present in three samples (9%), while the rare subgenotype 4v was present in two samples (6%). We identified a number of substitutions in the retrieved HCV core sequences, such as HCV 1b substitutions R70Q and M91L, which some studies have associated with hepatocellular carcinoma risk and poor virological response. In contrast to two previous studies reporting that HCV genotype 4 was predominant in the Gaza strip (present in just over 70% of samples), genotype 4 was detected in only 31% of the samples in our current study, whereas genotype 1 and 3 were present in 69% of samples. These differences may relate to the fact that many of our samples came from the West Bank and East Jerusalem. The co-circulation of different HCV genotypes and subgenotypes in Palestine suggests that subgenotyping prior to treatment is crucial in Palestinian patients.

Fig 1. Distribution of HCV subgenotypes in the Palestinian study sample.

Total represents the overall distribution of subgenotypes in the 33 samples, HD represents the distribution of subgenotypes in the hemodialysis patients, and non-HD represents the subgenotypes in the non-hemodialysis group.

Fig 2. Distribution of HCV subgenotypes of study sample in Palestinian districts.

The number of the different subgenotypes detected in each district are indicated.

Fig 3. Neighbor-Joining phylogenetic analysis of Palestinian HCV 1a, 1b, 4a, and 3a isolates.

Palestinian 1a (red), 1b (purple), 3a (blue), and 4a (green) HCV isolates were compared with regional and international isolates. Origin of NCBI-archived subgenotypes is indicated in parentheses.

Fig 4. Neighbor-Joining phylogenetic analysis of Palestinian HCV 4v isolates.

Palestinian 4v isolates were compared with NCBI-archived 4a, 4b, 4c, 4d, 4f, 4g, 4k, 4l, 4m, 4n, 4o, 4p, 4q, 4r, 4t, 4v, and unknown type 4 subgenotypes. The Palestinian 4v isolates and the other two NCBI-archived 4v isolates are colored orange. Origin of NCBI-archived subgenotypes is indicated in parentheses.