Hep C - three studies
Data from India, the People's Republic of China and the United States advance knowledge in hepatitis C virus research
Genomics & Genetics Weekly - Jun. 09, 2006
Hepatitis c virus data are the focus of recent research from India, the People's Republic of China and the United States.
Study 1: According to recent research from India, hepatitis C virus (HCV) genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease.
"HCV genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied," wrote S.S. Hissar and colleagues, GB Pant Hospital.
They continued, "HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index & le;5 and/or fibrosis & le;2) or severe (histological activity index & ge;6 and/or fibrosis & ge;3) liver disease.
"Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33%>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and unsubtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and unsubtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%,4b:0.3%,4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients."
"The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade & ge;2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes," wrote the researchers.
The authors concluded, "Genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis."
Hissar and colleagues published their study in the Journal of Medical Virology (Hepatitis C virus genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease. J Med Virol, 2006;78(4):452-458).
For additional information, contact S.K. Sarin, GB Pant Hospital, Department of Gastroenterology, Room 201, Academy Block, New Delhi 110002, India.
Study 2: Research from the People's Republic of China has documented that combination therapy is influenced by fatty liver in chronic hepatitis C (CHC).
"Hepatic steatosis is a histological feature in patients with CHC and adversely affects the virologic response rates to anti-hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether the fatty liver and related factors have impact on the efficacy in CHC treated with peginterferon and ribavirin, and the associations between HCV genotyping and fatty liver," wrote J. Wu and colleagues, Harbin Medical College.
They continued, "Ninety-eight patients received subcutaneously 180 mcg peginterferon alpha-2a once a week plus ribavirin. HCV genotypes and the levels of plasma insulin of patients were measured. Fatty liver was detected by B ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated."
The researchers wrote, "Among 98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV genotype 1, 2, 3, respectively, which suggested that the distribution of fatty liver in different HCV genotypes was imbalanced (chi2=6.758, p=.034).
"In univariate analysis, the efficacy of combination therapy was significantly associated with BMI (p=.011), WHR (p=.024), the levels of plasma insulin (p=.001), genotype (p=.036), presence of fatty liver (p=.028), treatment dosage and duration (p=.012) and HOMA-IR (p=.002). With binary logistic regression analysis, the plasma insulin levels and HOMA-IR showed independent predictors to the efficacy of antiviral therapy."
"The prevalence of fatty liver in HCV genotype 3 was markedly higher than that of other genotypes. The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver, treatment dosage and duration and HOMA-IR were associated with the sustained virologic response," the authors reported.
They concluded, "The level of plasma insulin and HOMA-IR were independent factors for predicting effect of antiviral therapy."
Wu and colleagues published their study in Liver International (Effects of fatty liver and related factors on the efficacy of combination antiviral therapy in patients with chronic hepatitis C. Liver Int, 2006;26(2):166-172).
For additional information, contact S. Chen, Harbin Medical College, Affiliated Hospital 2, Department of Infectious Disease, Harbin 150086, People's Republic of China.
Study 3: According to researchers from the United States, intrahepatic cytokine expression is downregulated during hepatitis C virus HCV/HIV co-infection.
"HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown," wrote J.T. Blackard and colleagues, Massachusetts General Hospital.
"Total RNA was extracted from liver biopsies of 12 HCV monoinfected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta1, IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach."
The researchers wrote, "Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons."
"Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNF alpha, IL-8, and IL-10 were statistically significant."
"Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV monoinfected persons, with the exception of TGFbeta1," reported the authors.
They concluded, "These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver."
Blackard and colleagues published their study in the Journal of Medical Virology (Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection. J Med Virol, 2006;78(2):202-207).
For additional information, contact R.T. Chung, Massachusetts General Hospital, Gastrointestinal Unit, GRJ 825, Boston, MA 02114, USA.
Keywords: Boston, Massachusetts, United States, AIDS, Antiretroviral Therapy, Hepatitis C Virus, Human Immunodeficiency Virus, HIV, Cytokines, Downregulation, Co-Infections, RNA.
This article was prepared by Genomics & Genetics Weekly editors from staff and other reports. Copyright 2006, Genomics & Genetics Weekly via NewsRx.com.
Genomics & Genetics Weekly - Jun. 09, 2006
Hepatitis c virus data are the focus of recent research from India, the People's Republic of China and the United States.
Study 1: According to recent research from India, hepatitis C virus (HCV) genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease.
"HCV genotypes help to tailor the treatment response, but their influence on the disease severity and association with hepatic steatosis is not well understood. The prevalence of HCV genotypes and their correlation with the histopathological severity of liver disease and steatosis in Indian patients were studied," wrote S.S. Hissar and colleagues, GB Pant Hospital.
They continued, "HCV-RNA and genotyping was carried out in 398 patients with chronic hepatitis C. Liver biopsy was available in 292 (73.4%) patients. The severity of liver disease was graded on the basis of the histological activity index and the stage of hepatic fibrosis. The patients were categorized as having mild (histological activity index & le;5 and/or fibrosis & le;2) or severe (histological activity index & ge;6 and/or fibrosis & ge;3) liver disease.
"Steatosis was graded in 106 patients as 0 (no steatosis), 1 (<33%>66% of hepatocytes affected). HCV genotype 3 was detected in 80.2% patients (3a:24.4%, 3b:3.3%, 3c:0.5%, 3a/3b:36.7%, and unsubtypable 3:15.3%), genotype 1 in 13.1% (1a:3%, 1b:5.5%, 1a/1b:0.3%, and unsubtypable 1:4.3%), genotype 4 in 3% patients (4a:1.5%,4b:0.3%,4a/4c:0.5%, and un-subtypable 4:0.8%), 2 in 2.5% and mixed genotypes (more than one genotype) in 1.3% of patients."
"The median histological activity index and fibrosis scores were: 5 and 2 in genotype 1; 4 and 2 in genotype 2; 5 and 2 in genotype 3; 7 and 3 in genotype 4; and 5 and 2 in mixed genotypes, respectively. Severe liver disease was present in 17 of 38 (45%) with genotype 1; in 1 of 3 (33%) with genotype 2; in 128 of 236 (54%) with genotype 3; 7 of 10 (70%) with genotype 4; and in 1 of 4 (25%) with mixed genotype. Hepatic steatosis grade & ge;2 was found in 28.1% of genotype 3; 23.5% of genotype 1; 20% of genotype 4; and in none of genotype 2 and mixed genotypes," wrote the researchers.
The authors concluded, "Genotype 3 is the most prevalent genotype in patients with chronic hepatitis C in North and Central India and this is associated with significant hepatic steatosis and fibrosis."
Hissar and colleagues published their study in the Journal of Medical Virology (Hepatitis C virus genotype 3 predominates in north and central India and is associated with significant histopathologic liver disease. J Med Virol, 2006;78(4):452-458).
For additional information, contact S.K. Sarin, GB Pant Hospital, Department of Gastroenterology, Room 201, Academy Block, New Delhi 110002, India.
Study 2: Research from the People's Republic of China has documented that combination therapy is influenced by fatty liver in chronic hepatitis C (CHC).
"Hepatic steatosis is a histological feature in patients with CHC and adversely affects the virologic response rates to anti-hepatitis C virus (HCV) therapy. The aim of this study is to investigate whether the fatty liver and related factors have impact on the efficacy in CHC treated with peginterferon and ribavirin, and the associations between HCV genotyping and fatty liver," wrote J. Wu and colleagues, Harbin Medical College.
They continued, "Ninety-eight patients received subcutaneously 180 mcg peginterferon alpha-2a once a week plus ribavirin. HCV genotypes and the levels of plasma insulin of patients were measured. Fatty liver was detected by B ultrasound. The body mass index (BMI), waist-to-hip ratio (WHR) and homeostasis model assessment of insulin resistance (HOMA-IR) were calculated."
The researchers wrote, "Among 98 CHC patients, 38 (38.8%) were infected with genotype 1; 44 (44.9%) with genotype 2; 13 (13.3%) with genotype 3; 3 (3.0%) with indeterminate genotype. The prevalence of fatty liver was 10.5%, 11.4%, 38.5% in patients infected with HCV genotype 1, 2, 3, respectively, which suggested that the distribution of fatty liver in different HCV genotypes was imbalanced (chi2=6.758, p=.034).
"In univariate analysis, the efficacy of combination therapy was significantly associated with BMI (p=.011), WHR (p=.024), the levels of plasma insulin (p=.001), genotype (p=.036), presence of fatty liver (p=.028), treatment dosage and duration (p=.012) and HOMA-IR (p=.002). With binary logistic regression analysis, the plasma insulin levels and HOMA-IR showed independent predictors to the efficacy of antiviral therapy."
"The prevalence of fatty liver in HCV genotype 3 was markedly higher than that of other genotypes. The BMI, WHR, the levels of plasma insulin, genotype, presence of fatty liver, treatment dosage and duration and HOMA-IR were associated with the sustained virologic response," the authors reported.
They concluded, "The level of plasma insulin and HOMA-IR were independent factors for predicting effect of antiviral therapy."
Wu and colleagues published their study in Liver International (Effects of fatty liver and related factors on the efficacy of combination antiviral therapy in patients with chronic hepatitis C. Liver Int, 2006;26(2):166-172).
For additional information, contact S. Chen, Harbin Medical College, Affiliated Hospital 2, Department of Infectious Disease, Harbin 150086, People's Republic of China.
Study 3: According to researchers from the United States, intrahepatic cytokine expression is downregulated during hepatitis C virus HCV/HIV co-infection.
"HIV co-infection is associated with reduced HCV treatment response rates and accelerated HCV-related liver disease. Cytokines play an important role in regulating hepatic inflammation and fibrogenesis during chronic HCV infection, yet the roles of HIV and/or its therapies on cytokine expression are unknown," wrote J.T. Blackard and colleagues, Massachusetts General Hospital.
"Total RNA was extracted from liver biopsies of 12 HCV monoinfected and 14 HCV/HIV co-infected persons. We used real-time PCR to quantify cytokines that contribute to innate and adaptive immune responses, including IFNalpha, IFNgamma, TNFalpha, TGFbeta1, IL-2, IL-4, IL-8, IL-10, and IL-12p40. Positive- and negative-strand HCV RNA levels were quantified using a molecular beacon approach."
The researchers wrote, "Detection of positive-strand HCV RNA was 100% in both groups; negative-strand HCV RNA was detected in four (33%) HCV mono-infected persons and in nine (64%) HCV/HIV co-infected persons."
"Median strand-specific HCV RNA levels were not significantly different between the two groups. Detection rates of cytokine mRNAs were lower for the HCV/HIV co-infected group compared to the HCV mono-infected group; the detection rates for TNF alpha, IL-8, and IL-10 were statistically significant."
"Overall, cytokine mRNA quantities were lower for HCV/HIV co-infected compared to HCV monoinfected persons, with the exception of TGFbeta1," reported the authors.
They concluded, "These data suggest that a defect in cytokine activation may occur in HCV/HIV co-infected persons that limits efficient clearance of HCV from the liver."
Blackard and colleagues published their study in the Journal of Medical Virology (Intrahepatic cytokine expression is downregulated during HCV/HIV co-infection. J Med Virol, 2006;78(2):202-207).
For additional information, contact R.T. Chung, Massachusetts General Hospital, Gastrointestinal Unit, GRJ 825, Boston, MA 02114, USA.
Keywords: Boston, Massachusetts, United States, AIDS, Antiretroviral Therapy, Hepatitis C Virus, Human Immunodeficiency Virus, HIV, Cytokines, Downregulation, Co-Infections, RNA.
This article was prepared by Genomics & Genetics Weekly editors from staff and other reports. Copyright 2006, Genomics & Genetics Weekly via NewsRx.com.
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