Association of single nucleotide polymorphisms in microRNAs with susceptibility to hepatitis B virus infection and HBV-related liver complications: A study in a Saudi Arabian population.

The aim of this study was to evaluate the association of 10 SNPs in different microRNAs (miRNAs) with susceptibility to hepatitis B virus (HBV) infection, HBV clearance, persistence of chronic HBV infection, and progression to liver cirrhosis and hepatocellular carcinoma (HCC). Patients were categorized into the following groups: inactive HBV carrier, active HBV carrier, HBV-cleared subject and cirrhosis+HCC. Samples were analysed for 10 SNPs in microRNAs using either PCR-based genotyping or the TaqMan assay. We found that rs1358379 was associated with susceptibility to HBV infection, HBV clearance, persistent chronic HBV infection and liver cirrhosis+HCC. In addition, we found that rs2292832 and rs11614913 were associated with risk of HBV infection, viral clearance and cirrhosis+HCC, whereas rs2910164 was associated with proneness to HBV infection, and ability to clear the virus. There was evidence of associations between rs6505162 and HBV clearance and the development of liver disease, whereas a single association was found between rs2289030 and HBV clearance. Similarly, rs7372209 and rs4919510 were specifically associated with the development of HBV-induced liver complications. SNPs in miRNAs affect the susceptibility, clearance and progression of HBV infection in Saudi Arabian patients. We found, using Gene Ontology or pathway analyses, that these genes may contribute to the pathophysiology of HBV infection and related liver complications. However, differences in the association of examined SNPs with various clinical stages indicate variations in the respective functional roles of these polymorphisms and their miRNAs, and thus, further investigation to fully explore their therapeutic potential is warranted.

Hepatitis C virus genotype 1: how genetic variability of the core protein affects the response to pegylated-interferon and ribavirin therapy.

Hepatitis C virus subgenotypes 1a and 1b are found worldwide and cause 60% of all hepatitis C cases. It has been reported recently that viral genetic variations have a critical impact on the patient treatment outcome. In particular, polymorphisms of the HCV core protein have been linked to poor treatment response. However, most of these studies were conducted on Asian populations, Japanese in particular who are infected with HCV subgenotype 1b. Hence, we aimed in this study to examine the core protein polymorphisms in Saudi patients who are infected with chronic HCV genotype 1 (1a and 1b subtypes) and its association with treatment outcome. Direct sequencing of full-length core protein and data mining analyses were utilized. Results have shown that the response to treatment is dependent on subgenotypes. Indeed, HCV-1b showed different point mutations that are associated with treatment outcome where the point mutations at positions 70 (Arg(70) Gln) and 75 (Thr(75) Ala) in HCV-1b are significantly associated with PEG-IFN/RBV treatment response. In contrast, HCV-1a showed no significant association between core protein mutations and response to treatment. In addition, analyses of HCV-1a core protein sequences revealed a highly conserved region especially in the responder group. This study provides a new insight in the genetic variability of full-length core protein in HCV genotype 1 in Saudi infected patients.

Discriminant value of serum HBV DNA levels as predictors of liver fibrosis in chronic hepatitis B.

Current guidelines recommend antiviral therapy in chronic hepatitis B (HBV) patients with significant histological disease. We aimed to compare histological fibrosis (METAVIR, ≥F2) in patients with HBV DNA ≥20,000 IU/mL vs. ≥2000 IU/mL and identify predictors of fibrosis. We performed prospective liver biopsies on 203 HBeAg-negative patients in four groups: Group I (n = 55): HBV DNA ≥20,000 IU/mL and persistently elevated alanine aminotransferase (ALT) levels (PEALT; >40 U/L); Group II (n = 34): HBV DNA ≥20,000 IU/mL and persistently normal ALT (PNALT); Group III (n = 40): HBV DNA <20,000 IU/mL and PEALT; and Group IV (n = 74): HBV DNA <20,000 IU/mL, and PNALT. We reanalysed all groups in relation to updated cut-off for treatable viremia (2000 IU/mL). Genotype D was detected in 86% of patients. Hepatic fibrosis ≥F2 was detected in 72.7%, 52.9%, 57.5% and 18.9% in Groups I-IV, respectively (P < 0.0001). Except in Group II with a trend for lower ≥F2 fibrosis (P = 0.067), there was no significant difference by using HBV DNA cut-off 20,000 vs. 2000 IU/mL. Multivariate logistic regression analysis identified study Group IV (OR, 0.0276; CI: 0.088-0.868; P = 0.0276) and milder (A0-1) necroinflammatory grade (OR, 0.135; CI: 0.063-0.287; P < 0.0001) as independent predictors of ≥F2 fibrosis. The specificity, positive and negative predictive values for PEALT in detection of ≥F2 fibrosis for viremia ≥2000 IU/mL (80%, 69% and 65%, respectively) or ≥20,000 IU/mL (86%, 73% and 63%, respectively) were similar, with a marginal gain in sensitivity (51% vs. 42%, respectively). Significant fibrosis is prevalent in a large proportion of HBeAg-negative patients with high viremia and persistently normal ALT. Lower HBV DNA cut-offs could be adopted with marginal gains in fibrosis detection and without loss of diagnostic accuracy.

Outcome of long-term ribavirin therapy for recurrent hepatitis C after liver transplantation.

Ribavirin therapy was initiated at a median of 181 days after liver transplantation in 18 patients with persistent elevation of alanine aminotransferase values and biopsy-proven hepatitis, and continued for 23 months (12-44 months). All patients had a prompt biochemical response, with alanine aminotransferase decreasing by 69%; complete normalization occurred in 5 (28%). Serum hepatitis C virus RNA levels did not change during therapy. Liver biopsies obtained after 17 months (9-38 months) of therapy showed no improvement in necroinflammation. However, worsening of fibrosis occurred in 12 patients; and cirrhosis developed in 5 patients (28%), with 3 patients progressing to graft failure. Biopsies from 27 untreated patients who did not fulfill treatment criteria (median follow-up, 38 months) and 4 patients who received 3 months of ribavirin (44 months) showed cirrhosis in 11 and 75%, respectively. Patient and graft survival rates for treated and untreated patients were similar. Although ribavirin improves alanine aminotransferase, it does not prevent the development or progression of fibrosis in patients with recurrent hepatitis C virus.

Kaposi's sarcoma in liver transplant recipients on FK506: two case reports.

We report two cases of Kaposi's sarcoma (KS) after orthotopic liver transplantation for cirrhosis of the liver related to hepatitis C virus. Both cases were Saudi-born Arabs who were negative for human immunodeficiency virus; one patient was receiving FK506 plus prednisolone, and the other patient was receiving FK506. One patient died of fulminant multicentric KS. The other patient, with lesions confined to the lower limbs, is still alive. These are the first case reports of KS in liver transplant recipients in the Kingdom of Saudi Arabia and, to our knowledge, these are the first case reports of KS in liver transplant recipients on FK506. All previous reports were related to either cyclosporine or conventional immunosuppressive therapy, i.e., azathioprine plus prednisolone.