Host and Viral Determinants of the Outcome of Exposure to HCV Infection Genotype 4: A Large Longitudinal Study

Kamal, Sanaa M.; Kassim, Samar K.; Ahmed, Amany I.; Mahmoud, Sara; Bahnasy, Khaled; Hafez, Tamer; Aziz, Ibrahiem A; Fathelbab, Iman F; Mansour, Hoda

doi:10.1038/ajg.2013.427

Cited by 18 publications

(10 citation statements)

References 54 publications

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“…Further, Thomas et al44 showed that the SNP rs12979860 upstream of IL28B and the C/C genotype were associated with spontaneous clearance of HCV, and this finding was confirmed by recent studies in patients with acute HCV 37,41. Interestingly, jaundice during acute infection was more common in patients with the C/C genotype 24,46. The T/T genotype occurred more often in people of African descent, had an intermediate frequency among Europeans, and a lower frequency among Asians, a finding that partly explains the ethnic differences seen in spontaneous acute HCV recovery rates across different ethnic groups.…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 82%

“…In a recent study24 of a well characterized cohort of acute HCV patients, we showed that a decrease in alanine aminotransferase within 4 weeks (odds ratio [OR] 6.83; P <0.0001), jaundice (OR 3.54; P =0.001), female sex (OR 2.39; P =0.007), and a >2.5 log 10 decrease in HCV-RNA within 8 weeks (OR 2.48; P =0.016) were independently associated with spontaneous clearance. IL28B CC was also associated with a multispecific T-cell response ( r 2 =0.0.835; P <0.001).…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 94%

“…To date, there are no reliable criteria to predict patients in whom HCV infection will spontaneously resolve and those who will develop chronic infection. The acute phase of the infection is the period during which PEG-IFNα monotherapy is associated with high response rates of up to 80%–90% 17–24. It is generally acceptable to treat patients with acute HCV who fail to clear viremia 3 months after infection with 12–24-week courses of PEG-IFNα monotherapy 17–19.…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

“…Patients younger than 40 years of age, children, women, and patients with symptomatic disease, particularly jaundice, are more likely to undergo spontaneous resolution 10,17,24–28…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

“…IFNλ includes IFNλ 1, 2 and 3, also known as IL29, IL28A, and IL28B 43. Several studies24,44–48 have shown that single nucleotide polymorphisms (SNPs) in the IL28B region may play a critical role in determining the outcome of acute infection (clearance versus persistence). A strong association has been found between polymorphisms in or near IL28B , the pathogenesis of HCV, and outcome of acute HCV infection.…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

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Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Kamal¹

2014

HMER

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Hepatitis C virus (HCV) has emerged as a major viral pandemic over the past two decades, infecting 170 million individuals, which equates to approximately 3% of the world’s population. The prevalence of HCV varies according to geographic region, being highest in developing countries such as Egypt. HCV has a high tendency to induce chronic progressive liver damage in the form of hepatic fibrosis, cirrhosis, or liver cancer. To date, there is no vaccine against HCV infection. Combination therapy comprising PEGylated interferon-alpha and ribavirin has been the standard of care for patients with chronic hepatitis C for more than a decade. However, many patients still do not respond to therapy or develop adverse events. Recently, direct antiviral agents such as protease inhibitors, polymerase inhibitors, or NS5A inhibitors have been used to augment PEGylated interferon and ribavirin, resulting in better efficacy, better tolerance, and a shorter treatment duration. However, most clinical trials have focused on assessing the efficacy and safety of direct antiviral agents in patients with genotype 1, and the response of other HCV genotypes has not been elucidated. Moreover, the prohibitive costs of such triple therapies will limit their use in patients in developing countries where most of the HCV infection exists. Understanding the host and viral factors associated with viral clearance is necessary for individualizing therapy to maximize sustained virologic response rates, prevent progression to liver disease, and increase the overall benefits of therapy with respect to its costs. Genome wide studies have shown significant associations between a set of polymorphisms in the region of the interleukin-28B (IL28B) gene and natural clearance of HCV infection or after PEGylated interferon-alpha and ribavirin treatment with and without direct antiviral agents. This paper synthesizes the recent advances in the pharmacogenetics of HCV infection in the era of triple therapies.

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Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 82%

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 94%

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

“…Patients younger than 40 years of age, children, women, and patients with symptomatic disease, particularly jaundice, are more likely to undergo spontaneous resolution 10,17,24–28…”

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

Section: Acute Hepatitis C: An Emerging Field Of Pharmacogeneticsmentioning

confidence: 99%

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Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Kamal¹

2014

HMER

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Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response

Abdelwahab

Zakaria²,

Sobhy³

et al. 2015

Arch Virol

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The CC genotype of the interleukin (IL)-28B.rs12979860 gene has been associated with spontaneous hepatitis C virus (HCV) clearance and treatment response. The distribution and correlation of an IL28B.rs12979860 single-nucleotide polymorphism (SNP) with HCV-specific cell-mediated immune (CMI) responses among Egyptian healthcare workers (HCWs) is not known. We determined this relationship in 402 HCWs who serve a patient cohort with ~85% HCV prevalence. We enrolled 402 HCWs in four groups: group 1 (n = 258), seronegative aviremic subjects; group 2 (n = 25), seronegative viremic subjects; group 3 (n = 41), subjects with spontaneously resolved HCV infection; and group 4 (n = 78), chronic HCV patients. All subjects were tested for an HCV-specific CMI response using an ex-vivo interferon-gamma (IFNγ) ELISpot assay with nine HCV genotype-4a overlapping 15-mer peptide pools corresponding to all of the HCV proteins. All subjects were tested for IL28B.rs12979860 SNP by real-time PCR. An HCV-specific CMI was demonstrated in ~27% of the seronegative aviremic HCWs (group 1), suggesting clearance of infection after low-level exposure to HCV. The frequency of IL28B.rs12979860 C allele homozygosity in the four groups was 49%, 48%, 49%, and 23%, while that of the T allele was 14%, 16%, 12 and 19%, respectively, suggesting differential distributions among subjects with different HCV status. As reported, IL28B.rs12979860 predicted the outcome of HCV infection (p < 0.05), but we did not find any relationship between the IL28B genotypes and the outcome of HCV-specific CMI responses in the four groups (p > 0.05). The data show differential IL28B.rs12979860 genotype distribution among Egyptian HCWs with different HCV status and could not predict the outcome of HCV-specific CMI responses.

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Hepatitis C Treatment in the Era of Direct-Acting Antiviral Agents

Kamal

2018

Hepatitis C in Developing Countries

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Host and Viral Determinants of the Outcome of Exposure to HCV Infection Genotype 4: A Large Longitudinal Study

Cited by 18 publications

References 54 publications

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Pharmacogenetics of hepatitis C: transition from interferon-based therapies to direct-acting antiviral agents

Differential distribution of IL28B.rs12979860 single-nucleotide polymorphism among Egyptian healthcare workers with and without a hepatitis C virus-specific cellular immune response

Hepatitis C Treatment in the Era of Direct-Acting Antiviral Agents

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