RESUMO
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.
Assuntos
Carcinoma Hepatocelular/genética , Predisposição Genética para Doença , Hepatite B/genética , Cirrose Hepática/genética , Neoplasias Hepáticas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Estudos de Associação Genética , Técnicas de Genotipagem , Hepatite B/complicações , Humanos , Cirrose Hepática/complicações , Arábia SauditaRESUMO
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.
Assuntos
Antivirais/uso terapêutico , Variação Genética , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/tratamento farmacológico , Interferons/uso terapêutico , Ribavirina/uso terapêutico , Proteínas do Core Viral/genética , Adulto , Biologia Computacional , Feminino , Genótipo , Hepacivirus/genética , Hepatite C Crônica/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Mutação Puntual , Arábia Saudita , Análise de Sequência de DNA , Resultado do TratamentoRESUMO
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.
