Treatment of chronic hepatitis C genotype IV with interferon–ribavirin combination in Saudi Arabia: a multicentre study

Al-Faleh, Faleh Z.; Aljumah, Abdulrahman; Rezeig, Mohammed; Al-Kanawi,; Al-Otaibi, M; Al-Ahdal, Mohammed N.; Al‐Humayed, Suliman; Mayet, I. Y.; Aljuhani, Muhammad; Al-Karawi, Mohamed A.; George, Khalid; Sbeih, Fayiz

doi:10.1046/j.1365-2893.2000.00213.x

Cited by 24 publications

(36 citation statements)

References 13 publications

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“…Because NS5A exists as a quasispecies in vivo (13,16), it is possible that clinical isolates of NS5A may have different IL-8 transactivation activities which may lead to different levels of IL-8 in serum and different responses to IFN therapy. Although HCV genotype was not evaluated in the patients analyzed in this study, the prevalent genotypes in Saudi Arabia are types 4 and 1 (2,19), and similar to what has been observed in U.S. studies, types 1 and 4 tend to be quite resistant to IFN therapy (1,3). In future studies, it will be interesting to explore the relationship between levels of IL-8 in serum, NS5A amino acid sequence, HCV genotype, and virological response to therapy.…”

Section: Hcv Infection and Levels Of Il-8 And Tnf-␣ In Serumsupporting

confidence: 67%

Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy

Polyak

Khabar²,

Rezeiq

et al. 2001

J Virol

222

160

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Hepatitis C virus (HCV), a major cause of liver disease worldwide, is frequently resistant to the antiviral alpha interferon (IFN). We have recently found that the HCV NS5A protein induces expression of the proinflammatory chemokine IL-8 to partially inhibit the antiviral actions of IFN in vitro. To extend these observations, in the present study we examined the relationship between levels of IL-8 in serum, HCV infection, and biochemical response to IFN therapy. Levels of IL-8 were significantly elevated in 132 HCV-infected patients compared to levels in 32 normal healthy subjects and were also significantly higher in patients who did not respond to IFN therapy than in patients who did respond to therapy. This study suggests that HCV-induced changes in levels of chemokine and cytokine expression may be involved in HCV antiviral resistance, persistence, and pathogenesis.Chronic hepatitis C virus (HCV) infection is a significant clinical problem throughout the world. About 85% of people infected with HCV develop chronic infection, and approximately 70% of patients develop histological evidence of chronic liver disease (9).Interferon (IFN) and the guanosine analogue ribavirin are widely used treatments for chronic HCV infection (5,11,17). However, as many as 60% of patients with high-titer HCV genotype 1 infections remain nonresponsive to combination therapy.The HCV NS5A protein has been implicated in the resistance of HCV to antiviral therapy (reviewed in reference 14). We have recently found that NS5A induces the CXC chemokine interleukin 8 (IL-8) to inhibit the antiviral actions of IFN in vitro (15). To investigate the clinical significance of these results, in this study we investigated the relationship among levels of IL-8 and tumor necrosis factor alpha (TNF-␣) (a potent inducer of ) in serum, HCV infection, and response to IFN therapy.One hundred thirty-two patients from Saudi Arabia with hepatitis C disease were studied. Diagnosis was reached using appropriate serological, virological, biochemical, and histological criteria. All sera from patients diagnosed to have chronic hepatitis C showed elevated liver enzymes, tested positive for anti-HCV antibodies by a second-generation enzyme-linked immunosorbent assay (ELISA), and were confirmed to be reactive with HCV recombinant immunoblot assay-2. Patients with hepatitis B surface antigen positivity, autoimmune disease, alcohol-or drug-induced liver diseases, hepatic failure, decompensated cirrhosis, schistosoma mansoni, or hematological abnormalities were excluded from the study. Genotypes were not determined, although the predominant HCV genotypes in Saudi Arabia are genotype 4 and 1 (2, 19). IFN-␣2a was administered intramuscularly three times per week at 3 million U per dose. The study was performed with the approval of the King Faisal Specialist Hospital and Research Centre research advisory council. Response to therapy was assessed biochemically based on normalization of alanine aminotransferase values 6 months after termination of therapy.To measure IL-8 ...

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Section: Hcv Infection and Levels Of Il-8 And Tnf-␣ In Serumsupporting

confidence: 67%

Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy

Polyak

Khabar²,

Rezeiq

et al. 2001

J Virol

222

160

View full text Add to dashboard Cite

show abstract

“…Important differences in the HCV genotype exist among countries with genotype 1b being the most frequent both worldwide and in Spain. However, in some countries other genotypes are more prevalent as, for instance, genotype 4 in West Africa and Middle East [1][2][3][4][5][6][7][8] . HCV-4 infection in the West affects two groups: immigrants from endemic countries and natives infected in their own countries.…”

Section: Introductionmentioning

confidence: 99%

Clinical and Pathological Characteristics and Response to Combination Therapy of Genotype 4 Chronic Hepatitis C Patients: Experience from a Spanish Center

Trapero-Marugán¹,

Moreno-Monteagudo²,

Garcı́a-Buey³

et al. 2007

Journal of Chemotherapy

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This observational study evaluated the characteristics of genotype 4 chronic hepatitis C (CHC) patients and their response to combination therapy in Spain. 383 patients with CHC, 44 with genotype 4-HCV infection, were investigated. Nineteen genotype 4-HCV infected patients received IFNalpha-2b (3 MU three times weekly) plus ribavirin (1-1.2 g/day) and ten received Peg-IFNalpha-2b (1.5 microg/kg/week) plus ribavirin (1-1.2 g/day) for 12 months. A sustained virological response (SVR) was evaluated. Genotype 4-HCV was detected in 11.5% of patients, and was significantly associated with a higher proportion of infection through intravenous drug use (46% vs 11%; p<0.001), a higher alcohol intake (35% vs. 7%; p<0.001), higher proportion of anti-HBc positivity (41% vs. 22%; p<0.05), lower ALT (87+/-50 vs. 139+/-142 IU/L; p<0.001) and AST (53+/-30 vs. 85+/-126 IU/L; p<0.001) levels, lower viremia (4.1 +/- 7.7 (x 10(5)) vs . 7.3 +/- 9.8 IU(x 10(5) )/mL) p<0.05) and less fibrosis (stage 3-4 in 21% vs. 32%; p<0.06). Sixteen (55%) out of the 29 patients treated with combination therapy achieved a sustained virological response (SVR) while 10 (36%) were non-responders and 3 (9% relapsed. In conclusion, the lower stage of fibrosis, lower viremia and higher SVR rate than genotype 1 suggest a less aggressive pattern of diseased caused by this genotype.

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“…46,47,49 50 In a recent study, Al Faleh et al reported a disappointing response rate of only 5% among Saudi genotype 4 CAH patients. 51 Although preliminary, these results may emphasize the role of HCV genotypes even with combination therapy.…”

Section: Combination Therapy: Ifn Plus Ribavirinmentioning

confidence: 79%

“…[32][33][34] Although about 40% of patients achieve response at the end of treatment, patients relapse in almost 50% of cases. Viral genotypes lb and 4 infections seem to be poorly responsive to IFN treatment 16,35 compared to genotypes 1a, 2 and 3.…”

Section: Classification Of Interferons (Ifns)mentioning

confidence: 95%

Chronic Hepatitis C Treatment: A Review

2000

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Treatment of chronic hepatitis C genotype IV with interferon–ribavirin combination in Saudi Arabia: a multicentre study

Cited by 24 publications

References 13 publications

Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy

Elevated Levels of Interleukin-8 in Serum Are Associated with Hepatitis C Virus Infection and Resistance to Interferon Therapy

Clinical and Pathological Characteristics and Response to Combination Therapy of Genotype 4 Chronic Hepatitis C Patients: Experience from a Spanish Center

Chronic Hepatitis C Treatment: A Review

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