Intrahepatic hepatitis C virus replication is increased in patients with regular alcohol consumption

AIMS: To assess clinical significance of liver hepatitis C virus RNA levels and their relationship with epidemiological, biochemical and histological factors. METHODS: A total of 50 patients (mean age 35.5+/-7 years) with biopsy-proven chronic hepatitis C infection were recruited. Risk factors were drug abuse (n=21), transfusion (n=16), other parental routes (n=8; surgery=3, tattooing=5), and idiopathic (n=5). Duration of infection was 16+/-9 years. All patients showed abnormal alanine aminotransferase levels and positive serum hepatitis C virus RNA. Hepatitis C virus genotype was assessed by Inno-Lipa. Liver biopsy was performed for histology and for hepatitis C virus RNA quantification by Amplicor-HCV-Monitor Daily alcohol consumption was recorded on two occasions by anamnesis. Inflammation grade was mild (n=31) or severe (n=19). Fibrosis was early stage (n=42) or advanced (n=8). RESULTS: Mean hepatitis C virus RNA levels were 9.4x10(5)+/-1.5x10(6) copies/microg of total RNA in liver tissue, and 9.1x10(5)+/-1.3x10(6) copies/ml in serum. Viral load in liver was positively correlated with that in serum (r=0.51, p<0.001) and there was a significant relationship between daily alcohol consumption and intrahepatic hepatitis C virus burden (r=0.53; p<0.001). Patients infected with genotype 3a showed lower intrahepatic hepatitis C virus load than patients infected with genotype 1b; albeit without reaching statistical significance (0.49x10(6)+/-0.89x10(6) vs 1.44x10(6)+/-1.9x10(6) copies/microg of total RNA; p=NS). No relationships were observed between liver viral burden and age, risk factor status, duration of infection, ferritin and alanine aminotransferase levels or with grading and staging. CONCLUSIONS: Hepatitis C virus load in serum is a mirror of intrahepatic hepatitis C virus levels. Chronic alcohol consumption enhances intrahepatic hepatitis C virus concentration.     

Hepatic Steatosis in Hepatitis C Virus Genotype 3 Infection: Does It Correlate with Body Mass Index, Fibrosis, and HCV Risk Factors?

Hepatic steatosis is a recognized feature of hepatitis C viral infection, particularly in genotype 3. The demographics and the associations contributing to moderate to severe steatosis in genotype 3 are not very well studied. The aim of this study is to determine the demographics and association of steatosis with fibrosis, obesity, diabetes, lipid levels, and risk factors among patients with hepatitis C virus (HCV) genotype 3. Two hundred ninety-three consecutive HCV patients (genotype 1, n = 218; genotype 2, n = 43; genotype 3, n = 32) at our institution were studied retrospectively. Demographic information such as height, weight, genotype, risk factors, serum cholesterol and triglyceride, and liver biopsy was collected. Steatosis was graded using the Brunt classification. HCV genotype 3-infected patients were younger (P < 0.04) and had lower serum cholesterol levels (P < 0.02) compared to nongenotype 3 patients. Moderate to severe steatosis was more prevalent in HCV genotype 3 patients (P < 0.001) with intravenous drug abuse as a risk factor (P = 0.04). Genotype 3 was the independent predictor of steatosis in all patients. There was no statistical association between grade of steatosis and body mass index, fibrosis, necroinflammation, or hyperlipidemia when only HCV genotype 3 patients were included in the multivariate logistic model. Hepatic steatosis is a feature of genotype 3. Patients with HCV genotype 3 are younger and have lower serum cholesterol levels. Genotype 3 is the independent predictor for steatosis in HCV patients. HCV genotype 3 patients with moderate to severe steatosis are more likely to have intravenous drug use as a risk factor.     

Effect of human immunodeficiency virus infection on hepatitis C virus infection in hemophiliacs

Chronic liver disease due to hepatitis C virus (HCV) infection is a major problem in hemophiliacs. Recent reports suggested that hemophiliacs coinfected with hepatitis C virus and human immunodeficiency virus (HIV) have an increased incidence of liver failure but the mechanism of accelerated liver injury is not clear. We tested plasma from 100 hemophiliacs for anti-HCV by second generation ELISA, anti-HIV by EIA, and HCV RNA and HIV RNA by branched DNA and polymerase chain reaction assays to determine if hemophiliacs coinfected with HCV and HIV have higher HCV RNA levels and more active liver disease. Seventy-nine (79%) patients were anti-HCV positive, of whom 85% were HCV RNA positive. None of the anti-HCV-negative patients had detectable HCV RNA in plasma. Forty-two (42%) patients were anti-HIV positive, of whom 47% had detectable HIV RNA. All the anti-HIV-positive patients were also anti-HCV positive. The prevalence of both anti-HCV and anti-HIV increased significantly with age. There was no difference in HCV RNA levels between anti-HIV-positive and anti-HIV-negative patients (mean: 21±4 vs 18±5 Meq/ml), although HCV RNA levels were significantly higher in anti-HIV-positive patients with CD4 counts<200/mm³ (P=0.008). There was an inverse correlation between HCV RNA levels and CD4 counts but no correlation was found between HCV RNA and serum aminotransferase levels. We found a high prevalence of HCV and HIV coinfection in our hemophiliacs. Hepatitis C virus replication appears to be increased in patients with severe immunodeficiency secondary to progressive HIV infection. However, there was no correlation between HCV RNA and serum ALT level, suggesting that HCV is not directly cytopathic.     

Clinical impact of genotype 1 TT virus infection in patients with chronic hepatitis C and response of TT virus to alpha-interferon

BACKGROUND: The relationship between genotype 1 TT virus (TTV) infection and the status of chronic hepatitis C was studied. METHODS: A total of 52 patients with chronic hepatitis C who were treated with interferon (IFN)-alpha were enrolled in the present study. Of those, 12 were infected with genotype 1 TTV and 40 were uninfected. RESULTS: Clinical backgrounds, including mean age, sex, blood transfusion history, serum alanine aminotransferase (ALT) level, and the results of liver biopsy did not differ between patients with and without genotype 1 TTV infection. The distribution of hepatitis C virus (HCV) genotypes did not differ between the two groups of patients, but TTV-infected patients tended to have a lower serum HCV-RNA level than uninfected patients (median (range) 26.0 (< 1-460) vs 135 (1.2-740) kilo copies/mL, respectively; P = 0.065). Patients with a sustained response of HCV to IFN-alpha were significantly more common in TTV-infected than -uninfected patients (58 vs 23%, respectively; P = 0.018). Multivariate logistic regression analysis revealed that patients with a sustained response of HCV correlated significantly with the serum HCV-RNA level (P = 0.006), but not with the presence or absence of genotype 1 TTV infection (P = 0.161). Serum TTV-DNA decreased with IFN-alpha therapy in all 12 patients and remained negative in six patients even after treatment. There was no correlation between patients with a sustained response of HCV and the same of TTV. Serum ALT levels correlated with changes in the status of HCV viremia, but not with changes in the status of TTV viremia. CONCLUSIONS: An opposing relationship between HCV and TTV proliferation was suggested, but coinfection with genotype 1 TTV did not affect the status of chronic hepatitis C.     

Clarification of interspousal hepatitis C virus infection in acute hepatitis C patients by molecular evolutionary analyses: Consideration on sexual and non‐sexual transmission between spouses

Aim: Previous studies evaluating the possibilities of interspousal sexual transmission of hepatitis C virus (HCV) have yielded many conflicting results. The aim of this study was to clarify the source of HCV infection in acute hepatitis C patients using phylogenetic analyses of nucleotide sequences of HCV E1 region. Methods: Four acute hepatitis C patients were hospitalized in 2002–2007. The diagnosis was based on medical records, laboratory tests including HCV markers, and ultrasonographic examination of the liver. In each spouse of four patients, serum HCV antibody was assayed. In the subjects whose serum HCV antibody was positive, additional tests on HCV viral load and genotype were carried out. Then phylogenetic analyses of nucleotide sequences of partial HCV E1 region (440 nucleotides) of the patients and their spouses were performed. Results: Hepatitis C virus antibody changed from negative to positive in the course of hospitalization and HCV RNA could be detected in every patient. Therefore they were diagnosed as acute hepatitis caused by HCV infection. In every spouse of four patients, HCV antibody and HCV RNA were positive. Three of four couples had the identical genotype and homogeneity of nucleotide sequences of HCV E1 region in three couples ranged from 97.9% to 100%. The results of phylogenic analyses suggested that interspousal HCV infection occurred in the three couples. Conclusion: In conclusion, interspousal infection might be one of the important sources of acute HCV infection in Japan. The usefulness of phylogenetic analysis of nucleotide sequences of HCV E1 region for clarifying interspousal HCV infection was validated.     

Liver Damage in Hemodialysis Patients with Hepatitis C Virus Viremia: A Prospective 10-Year Study

Hepatitis C virus (HCV) infection is a major problem associated with hemodialysis. The extent of liver damage in hemodialysis patients with chronic HCV infection has not been thoroughly documented. The aim of this study was to evaluate liver damage of hemodialysis patients infected with HCV. A total of 233 hemodialysis patients were categorized into two groups at entry: group X, 80 positive for serum HCV RNA, and group Y, 153 negative for serum HCV RNA. All were tested for serum alanine aminotransferase (ALT) serially from 1989 to 1998, and serum hyaluronic acid (HA), serum type-IV collagen (IV-C), platelet counts, and ultrasonographic examination of the liver was done in 1998. In group X, 61.3% had continuously abnormal ALT levels for over six months followed by normal ALT levels. Of the group X patients, 11.3% had abnormal ALT levels in 1998, and in three, hepatocellular carcinoma occurred. Mean HA and IV-C levels in group X (648.8 and 188.7 ng/ml, respectively) were significantly higher than in group Y (213.1 and 165.5 ng/ml, respectively) (P < 0.05). Ultrasonographic findings significantly correlated with serum HA level and platelet counts and showed significantly more abnormalities in group X than in group Y (P < 0.05). From these findings, a combined examination with ultrasonography and serum fibrogenesis markers is useful for detection of liver damage in hemodialysis patients with HCV viremia.     

Clinical study of cryoglobulinaemia in Chinese patients with chronic hepatitis C

Cryoglobulinaemia is the most common immunological disorders seen in patients with chronic hepatitis C virus (HCV) infection. We evaluated the incidence and clinical significance of cryoglobulinaemia in 122 Chinese patients with chronic hepatitis C. The pathogenic roles of HCV genotypes and viraemia in this phenomenon were also evaluated. Fifty-four (44%) of the 122 patients with chronic hepatitis C had cryoglobulinaemia. Eleven (20%) of the patients with cryoglobulinaemia had symptoms and signs of cutaneous vasculitis, arthralgia, neuropathy and renal involvement. The patients with cryoglobulinaemia were predominantly female and had a significantly higher mean serum level of rheumatoid factor and a lower mean serum C4 level compared with patients without cryoglobulinaemia (50 vs 29%, 23 vs 15 IU/mL, 25 vs 31 mg/dL, respectively, P < 0.05). The mean serum HCV RNA level, HCV genotype, the presence of serum auto-antibodies, and the rate of cirrhosis were not significantly different between the two groups. Univariate logistic regression analysis showed female serum levels of alanine aminotransferase (> 90 U/L), rheumatoid factor (> 15 IU/mL), C3c (< 100 mg/dL) and C4 (< 20 mg/dL) to be significant predictors of cryoglobulinaemia in chronic hepatitis C patients. However, multivariate analysis showed only serum C4 levels (< 20 mg/dL) as a significantly independent predictor. We concluded that 44% of Chinese patients with chronic hepatitis C had cryoglobulinaemia. Serum C4 levels were significantly lower in chronic hepatitis C patients with cryoglobulinaemia and the serum C4 level was the only clinical independent predictor associated with this phenomenon. Hepatitis C virus genotype and serum viral load were not clinical independent predictors.     

GB virus C infection among young,HIV‐negative injection drug users with and without hepatitis C virus infection

Summary. Our study examined the association between GB virus C (GBV‐C) and (i) hepatitis C virus (HCV) infection status, (ii) biomedical indicators of liver disease (alanine and aspartate aminotransferases) and (iii) HCV RNA level among young injection drug users (IDUs) recruited using street outreach and respondent‐driven methods. Cross‐sectional and longitudinal analyses were completed. GBV‐C (active or resolved) infection was significantly (P < 0.05) more prevalent among HCV antibody‐positive (anti‐HCV+) (65.1%) than antibody‐negative (anti‐HCV?) (32.3%) (OR = 3.9, 95% CI: 2.3–6.9) IDUs. The prevalence of resolved GBV‐C infection was highest among those with chronic HCV infection (41.9%), followed by those with resolved HCV infection (34.4%) and significantly lower (P < 0.05) among anti‐HCV participants (16.9%). Although not statistically significant (P = 0.13), a similar pattern was observed for active GBV‐C infection. No association between GBV‐C infection status and biomedical indicators of liver disease or HCV RNA level over time was observed. In conclusion, GBV‐C infection prevalence was higher among anti‐HCV+ compared to anti‐HCV? young IDUs, similar to prior studies among older populations. In particular, chronically HCV‐infected young IDUs had an increased rate of GBV‐C clearance.     

Serum lipids and their associations with viral levels and liver disease severity in a treatment-naïve chronic hepatitis C type 1-infected cohort

Summary. In patients with chronic hepatitis C virus (HCV) infection, steatosis and fibrosis have been shown to be inversely associated with total cholesterol (TC) and low‐density lipoprotein cholesterol. Steatosis and fibrosis have also been found to be associated with triglyceride (TG) levels; though, the direction of the relationship is inconsistent across studies. The objective of this study was to assess whether viral level and histological factors are associated with the serum lipid profile in a treatment‐naïve cohort with chronic HCV genotype 1 infection. Participants were from the prospective Study of Viral Resistance to Antiviral Therapy (Virahep‐C). Fasting lipid profiles were analysed for 160 African Americans and 170 Caucasian Americans. Linear regression was used to evaluate associations of each lipid with viral load and liver disease. TG levels were significantly and directly associated with HCV levels (P = 0.0034) and steatosis (P < 0.0001). Other lipid parameters were significantly lower in those with fibrosis [HDLc (P = 0.001) and TC levels (P = 0.004)] than in those without fibrosis. In patients with HCV genotype 1 infection, more severe liver disease was associated with lower lipid levels, with the exception of TG levels that were directly related to steatosis. The direct relationship between viral load and TG levels is consistent with proposed the mechanisms of very low density lipoprotein/HCV particle secretion. In contrast, the direct relationship between TG level and steatosis is inconsistent with posited mechanisms of HCV‐induced steatosis, a possible reflection of HCV genotype 1 infection and a metabolic aetiology of steatosis.