Rate Of Liver Fibrosis Progression Research Articles

Fibrosis Progression in African Americans and Caucasian Americans With Chronic Hepatitis C

Prior studies suggest the rate of liver fibrosis progression is slower in African Americans (AAs) than Caucasian Americans (CAs) with chronic HCV infection. With a multi-state Markov model, fibrosis progression was evaluated in a well-characterized cohort of 143 AA and 157 CA adults with untreated chronic HCV genotype 1 infection. In subjects with a history of injection drug use, duration of infection was imputed from a fitted risk model rather than assumed to be the reported first year of use. The distribution of Ishak fibrosis stages was 0 (8.7%), 1/2 (55.7%), 3/4 (29.3%), and 5/6 (6.3%) and was similar in AAs and CAs (P = .22). After adjusting for biopsy adequacy, AAs had a 10% lower rate of fibrosis progression than did CAs, but the difference was not statistically significant (hazard ratio, 0.90; 95% confidence interval, 0.72-1.12). The overall 20-year estimates of probabilities of progression from stage 0 to stages 1/2, 3/4, and 5/6 were 59.3%, 28.8%, and 4.7%, respectively. The estimated median time from no fibrosis to cirrhosis was 79 years for the entire cohort and 74 and 83 years for CAs and AAs, respectively. In 3-variable models including race and biopsy adequacy, the factors significantly associated with fibrosis progression were age when infected, steatosis, ALT level, and necroinflammatory score. The rates of fibrosis progression were slow and did not appear to differ substantially between AAs and CAs.

Documented rapid course of hepatic fibrosis between two biopsies in patients coinfected by HIV and HCV despite high CD4 cell count

In HIV/hepatitis C virus (HCV)-coinfected patients, it is recommended to repeat liver biopsy every 3 years when anti-HCV treatment is not indicated. We studied fibrosis progression in HIV/HCV-coinfected patients, who were not receiving anti-HCV treatment, on the basis of two successive liver biopsies. Thirty-two patients were retrospectively included. Twenty-six patients (79%) were on antiretroviral treatment at the first biopsy. The mean CD4 cell count was 470 +/- 283/mm(3). Three patients were staged F2 and the remainder F0/F1. The median interval between the two biopsies was 49 (24-80) months. At the second biopsy, the stage distribution was F0 0%, F1 41% (n = 13), F2 34% (n = 11), F3 19% (n = 6) and F4 6% (n = 2). The mean fibrosis progression rate (FPR) was 0.25 points/year. Nine patients (28%) were considered as rapid fibrosis progressors (progression by more than two points) and their FPR was 0.5 point/year; comparison of these subjects with the other 23 patients showed no relation between FPR and age, alcohol consumption, CD4+ cell count, HIV viral load, HCV genotype, aspartate aminotransferase or alanine aminotransferase. Analysis of the treatment received between the two liver biopsies did not find any correlation between liver FPR and a specific compound. Fifteen patients started anti-HCV therapy based on the second biopsy. Liver fibrosis in HIV/HCV-coinfected patients should be evaluated at least every 3 years, as nine of 32 (28%) of our patients progressed by at least two fibrosis points despite a high CD4+ cell count. The second biopsy showed that 15 patients (45%) qualified for anti-HCV therapy. Development of noninvasive methods of fibrosis evaluation should permit more frequent monitoring.

Pathogenesis of HIV-HCV coinfection

Hepatitis C virus (HCV) and HIV-1 are often harbored in the same host, establishing chronic infections typically characterized by persistent viremia. HIV-1 has deleterious effects on the course of HCV infection by increasing the rate of HCV viral persistence, quantitative HCV RNA levels, and ultimately the liver fibrosis progression rate. Conversely, HCV may blunt the effectiveness of immune reconstitution following antiretroviral therapy in HIV-infected individuals. Better understanding of the pathogenic mechanisms underlying these clinical observations may facilitate novel and effective therapeutic interventions that tackle the clinical conundrums raised by HIV/HCV coinfection.

Efficacy and safety of peg-IFN alfa-2a with ribavirin for the treatment of HCV/HIV coinfected patients who failed previous IFN based therapy

Background Interferon (IFN) regimens for HCV treatment are less effective in HCV/HIV-coinfected patients. There are no effective treatments for patients who fail IFN therapies. We examined the safety and efficacy of peginterferon alfa-2a (peg-IFNα-2a) plus ribavirin (RBV) in 41 HCV/HIV-coinfected patients non-responsive to prior IFN treatment. Methods Patients received peg-IFNα-2a (180 mg/week) plus RBV (800 mg/day) for 24 weeks ( n = 41). At week 24, patients with non-detectable HCV RNA or ≥2-log decrease from baseline, received peg-IFNα-2a (180 mg/week) plus RBV (800 mg/day) for 24 weeks further. Patients not responding to treatment at week 24 were discontinued. Results Intent to treat (ITT) sustained viral response (SVR) was 21.9%. Patients who received at least 24 weeks of peg-IFNα-2a plus RBV treatment ( n = 35), SVR rates were 25.7%. SVR was associated with significant improvements in liver histology grade ( p = 0.02), stage ( p = 0.02), and fibrosis progression rate (FPR) ( p = 0.03). Patients that failed to achieve SVR had statistically significant decreases in grade ( p = 0.09) and FPR ( p = 0.01). Conclusion peg-IFNα-2a plus RBV is effective and safe to achieve SVR in HCV/HIV coinfected patients non-responsive to prior IFN treatment. Patients that achieve SVR have significant improvements in liver histology parameters. In patients that do not achieve SVR there are histological benefits beyond virological response that suggest that peg-IFNα-2a + RBV therapy may decrease risk of progression to end stage liver disease.

Does Cyclosporine Have a Beneficial Effect on the Course of Chronic Hepatitis C Infection After Renal Transplantation?

The aim of our study was to assess the long-term liver histology in renal transplant patients infected with hepatitis C virus (HCV) who were treated with a cyclosporine-based regimen. Among 55 anti-HCV(+)/RNA(+) patients, liver biopsies (LB) were requested every 3 to 4 years after transplantation: two LBs ( n = 55); three LBs ( n = 44); four LBs ( n = 10). Overall, the rate of liver fibrosis progression was 0.07 ± 0.03 Metavir U/y. Only three patients out of 55 (5.4%) developed cirrhosis. Liver fibrosis remained stable throughout follow-up in 21 patients; increased in 21 patients; and improved in the remaining 13 patients. The incidence of posttransplant diabetes mellitus was low (9%). We concluded that HCV infection is not harmful to liver histology in more than 50% of renal transplant patients with grafts functioning more than 6 years. Cyclosporine might have beneficial effects on the natural course of HCV infection after renal transplantation.

Interferon gamma‐secreting HCV‐specific CD8+ T cells in the liver of patients with chronic C hepatitis: relation to liver fibrosis – ANRS HC EP07 study*

Little is known about the role of specific hepatitis C virus (HCV) CD8+ T cells in liver damage, especially for the progression of fibrosis, during the highly variable course of chronic C hepatitis. The aim of this study was to investigate the presence of HCV-specific CD8+ T cells in the liver of patients with chronic C hepatitis and to examine their clinical significance by relating the response to liver fibrosis and progression rate, serum viral load, serum aminotransferase levels, inflammatory activity and in situ characteristics of the intrahepatic infiltrate. Fifteen patients were prospectively included in the study. Intrahepatic lymphocytes were tested for interferon gamma (IFNg) production in response to HCV class I-restricted epitopic peptides using enzyme-linked immunospot analysis. Liver biopsy samples were evaluated for fibrosis, fibrosis progression rate, activity, and in situ number of CD8+ cytotoxic lymphocytes and apoptotic cells. An IFNg-specific CD8+ T-cell response was detected in the liver samples of 47% of patients which was significantly related to a lower stage of fibrosis (P = 0.02) and a lower progression rate of fibrosis (P = 0.01). It was neither related to the number of cytotoxic lymphocytes infiltrating the liver nor to hepatocyte apoptosis. In conclusion, our results indicate that the presence of HCV-specific IFNg-secreting T cells in the liver of patients with chronic C hepatitis is associated with low liver fibrosis and fibrosis progression rate, suggesting that these IFNg-secreting T cells might limit the progression of liver damage.

Role of CYP2D6 polymorphism in predicting liver fibrosis progression rate in Caucasian patients with chronic hepatitis C

Previous studies have demonstrated that CYP2D6 polymorphism is associated with liver cirrhosis. The aim of the present study was to find out whether CYP2D6*4, the poor metabolizer allele can predict fibrosis progression rate. Seventy-five Caucasian patients with chronic hepatitis C infection were recruited. They were divided into two groups, 'fast fibrosers' and 'slow fibrosers', according to Poynard's fibrosis progression curves. Sixty-two patients underwent liver biopsy. Twenty healthy neonates were included as control population. DNA was extracted from peripheral blood and CYP2D6*4 was tested by polymer chain reaction using fluorescent hybridization probes in a lightCycler instrument. Forty-two patients were classified as 'fast fibrosers' and 33 patients as 'slow fibrosers'. The frequency of CYP2D6*4 allele in the 'fast fibrosers' (34.5%) was significantly higher compared with the 'slow fibrosers' (15%) (P-value=0.007). There was no significant difference between the frequency of CYP2D6*4 in the 'slow fibrosers' (15%) compared with the controls (12.5%). Carrier state of CYP2D6*4 was the only covariate that was significantly positively correlated with fast progression to cirrhosis (odds ratio=6.5, P=0.01). This study indicates for the first time that CYP2D6 genotype might be a significant predictor of liver fibrosis progression rate in chronic hepatitis C patients.

La diversification de la région hypervariable-1 du virus de l'hépatite C pourrait prédire l'évolution de la fibrose hépatique après transplantation rénale

The aim of our study was to assess hepatitis C virus (HCV) evolution and long term liver histology outcome in anti-HCV(+)/RNA(+) renal-transplant (RT) patients. Fifty-five anti-HCV(+)/RNA(+) RT patients underwent every 3–4 years after transplantation liver biopsies (LB) (2 LBs, N = 55; 3 LBs, N = 44; 4 LBs, N = 10). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.07 ± 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (group I, N = 21), those with progressing liver fibrosis (group II, N = 21), and those with a regression in liver fibrosis (group III, N = 13). Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between the transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in this study, after renal transplantation, HCV infection is not harmful upon liver histology in more than fifty percent of the patients. The diversification of the HVR-1 of the HCV genome might be used to predict liver fibrosis outcome.

Natural History of Hepatitis C Virus-Related Liver Fibrosis After Renal Transplantation

The aim of our study was to assess hepatitis C virus (HCV) evolution and long-term liver histology outcome in anti-HCV(+)/RNA(+) renal transplant (RT) patients. A total of 51 anti-HCV(+)/RNA(+) RT patients underwent liver biopsies (LB) every 3-4 years after transplantation (two LBs, n = 51; three LBs, n = 42; four LBs, n = 9). The hypervariable region (HVR)-1 of the HCV genome from all patients was characterized over time. Overall, the rate of liver fibrosis progression was 0.09 +/- 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (n = 21), those with progressing liver fibrosis (n = 21) and those with a regression in liver fibrosis (n = 10). In the last two groups, the progression and the regression of liver fibrosis were gradual during follow-up. Ferritin levels and hepatosiderosis were significantly higher in fibrosers. Initial fibrosis stage and high diversification of the HVR-1 of HCV genome between transplantation and the first liver biopsy were independent factors associated with liver fibrosis regression. In conclusion, in the current study, more than 10 years after renal transplantation, HCV infection was not harmful upon liver histology in more than 50% of patients. The diversification of the HVR-1 might be used to predict liver fibrosis outcome.

Lack of Evidence for Ribavirin Monotherapy Efficacy on Liver Fibrosis in Hepatitis C Virus Positive Renal Transplant Patients

To date there is still no efficient and safe treatment for chronic hepatitis C virus (HCV) infection after renal transplantation. Recently, Fontaine et al. (1) reported on the treatment of 13 renal transplant (RT) patients with ribavirin monotherapy. They found that ribavirin monotherapy was associated with a significant decrease in serum alanine aminotransferase levels without any effect upon either HCV RNA viremia or quantitative intrahepatic HCV RNA viral load. They also suggested that ribavirin monotherapy improved liver histopathology. We have previously observed similar findings with respect to liver enzyme levels and HCV RNA viremia in HCV-positive RT patients treated by ribavirin monotherapy (2). However, after 12 months of ribavirin therapy, our patients experienced a significant worsening in liver fibrosis; the mean time between the two liver biopsies (LB) was 17 (11–27) months. Conversely, in the study by Fontaine et al. (1), although they found a significant decrease in the mean activity score, there was no significant change in the grade of liver fibrosis (P= 0.1). The absence of a significant change in liver fibrosis grade might have been related to the fact that 5 of their 13 patients had already had cirrhosis before treatment and, consequently, had no potential to deteriorate their liver fibrosis grade further. The time between the two LBs was as long as 5.7 ± 9.3 years. Hence, the actual liver activity and fibrosis scores just before treatment are unknown and, consequently, we might wonder whether the modifications in liver histology observed in their patients were related to ribavirin therapy and/or to the natural history of HCV infection after renal transplantation. We, and others, have recently reported that liver fibrosis might regress in untreated HCV-positive RT patients despite the persistence of a high HCV RNA viral load (3, 4). Finally, in the study of Fontaine et al. (1), there was no control group; thus, the authors compared the yearly liver fibrosis progression rate of patients treated by ribavirin with the data obtained previously from a cohort of 28 RT patients who had undergone two consecutive LBs (5). In the study by Zylbergberg et al. (5), the yearly liver fibrosis progression rate was abnormally high (i.e., 0.26 ± 0.35) compared with the observations of Alric et al. (6) in HCV RNA-positive RT patients (i.e., 0.067 [−0.05–0.18]). In this prospective controlled study, we observed a slow progression of liver fibrosis in patients with early moderate liver disease. More recently, Fehr et al. (7) found no cases of cirrhosis amongst 23 RT patients infected with HCV for more than 15 years. The discrepancy between the results observed by Zylbergberg et al. (5) and the two other studies, which were not quoted in the paper of Fontaine et al. (1), might be related to the use of different immunosuppressive treatments because almost none of their patients were on cyclosporine-A-based immunosuppression. Conversely, in the studies of Alric et al. (6) and Fehr et al. (7), nearly all the patients were receiving cyclosporine A, which is known to inhibit HCV replication in vitro. Hence, to date, there is still no evidence for a beneficial effect of ribavirin monotherapy upon liver histology in RT patients. Further randomized studies in larger cohorts of renal transplant patients, including the analysis of intrahepatic cytokine profiles before and during ribavirin monotherapy, are required to evaluate the impact of ribavirin upon liver histology. Nassim Kamar Department of Nephrology, Dialysis and Multiorgan Transplantation CHU Rangueil Department of Virology CHU Purpan Toulouse, France Jacques Izopet Department of Virology CHU Purpan Toulouse, France Laurent Alric Department of Internal Medicine CHU Purpan Toulouse, France Lionel Rostaing Department of Nephrology, Dialysis and Multiorgan Transplantation CHU Rangueil Toulouse, France

Factors accelerating liver fibrosis progression in renal transplant patients receiving ribavirin monotherapy for chronic hepatitis C

In untreated hepatitis virus (HCV)-positive renal transplant patients, the rate of liver fibrosis progression is low. In contrast, in those treated by ribavirin monotherapy, liver fibrosis score increased significantly after only 1 year of ribavirin monotherapy. The aim of this study was to identify the factors that might contribute to accelerate liver fibrosis progression in this population. Eleven patients were included in the study. Intrahepatic transforming growth factor (TGF)-beta, interferon (IFN)-gamma, and interleukin (IL)-10 mRNA quantification determined by real-time reverse transcription-polymerase chain reaction (RT-PCR) were similar before and after ribavirin therapy. The number of amino acid substitutions observed in the hypervariable region (HVR)-1 of the HCV genome between baseline and 1 year after ribavirin monotherapy was low, i.e., 3 (1-11) amino acid substitutions, suggesting the absence of a high selection pressure induced by ribavirin. In contrast, due to ribavirin-induced hemolysis, there was a significant increase in serum ferritin levels (P = 0.02) and in intrahepatic iron deposition (P = 0.04). Transferrin level and total iron-binding capacity decreased significantly during ribavirin monotherapy (P = 0.004). The increased liver fibrosis observed in renal transplant patients receiving ribavirin monotherapy could be related to ribavirin-induced anemia. Severe chronic hemolysis is responsible for iron overload, liver iron deposition, and an acceleration in the progression of liver fibrosis.

Treatment of Chronic Hepatitis C in Human Immunodeficiency Virus/Hepatitis C Virus-Coinfected Patients in the Era of Pegylated Interferon and Ribavirin

A significant percentage of human immunodeficiency virus (HIV) -infected individuals are also infected with the hepatitis C virus (HCV). With the much-improved survival of HIV-infected patients through the use of highly active antiretroviral therapy, liver disease caused by coinfection with HCV has emerged as a significant threat to the health and survival of persons with HIV disease. HIV/HCV-coinfected patients with ongoing HIV viremia have a faster rate of HCV-related liver fibrosis progression and a more rapid progression to liver failure or hepatocellular carcinoma than HCV-monoinfected persons. In contrast to the deleterious effect of HIV on HCV-related liver disease, most studies have shown that HCV does not influence progression of HIV infection to AIDS or death. HCV therapy with peginterferon alfa (2a or 2b) plus ribavirin can achieve a sustained viral response in HIV/HCV-coinfected patients of up to 38% in HCV genotype 1 and up to 73% in genotypes 2 and 3. The safety profile is largely similar to therapy in HIV-monoinfected patients, but there is a higher incidence of mitochondrial toxicity in patients taking didanosine or stavudine and of anemia in patients taking zidovudine. There is no proven anti-HCV therapy for HIV/HCV-coinfected patients with end-stage liver disease (ESLD). Liver transplantation is being investigated as a potential therapeutic option for HIV-infected individuals with ESLD, and initial reports are encouraging. Given that pegylated interferon and ribavirin have been shown to be safe and effective for HIV/HCV coinfection as well as HCV monoinfection, all HIV/HCV-coinfected patients should be evaluated for therapy.

HIV and hepatitis C virus coinfection update

Sharing routes of transmission, hepatitis C virus (HCV) and human immunodeficiency virus type 1 (HIV-1) are often harbored in the same host, establishing chronic infections characterized by high serum viral loads. HIV-1 impacts the course of HCV infection by increasing the rate of HCV viral persistence, quantitative viral loads, and liver fibrosis progression rate. HCV in turn affects HIV management, particularly by increasing the risk of hepatotoxicity. Future studies will focus on understanding the pathogenesis of accelerated liver fibrosis in HIV-infected individuals, the natural history of HCV in the era of antiretroviral therapy, and the principles of managing these two infections within the same individual.

EVOLUTION OF THE HYPERVARIABLE REGION-1 OF HEPATITIS C VIRUS AND LIVER FIBROSIS PROGRESSION IN RENAL-TRANSPLANT RECIPIENTS

P793 Aim: The aim of our study was to assess hepatitis C virus (HCV) evolution and liver histology outcome in HCV(+)/RNA(+) renal-transplant (RT) patients. Methods: A total of 55 patients (34 men, 21 women, median age 38 years) underwent serial liver biopsies (LB) after transplantation (2 LB, n=11; 3 LB, n=35; 4 LB, n=9). The median times between transplantation and the first LB was 30 (9−145) months. The median time between two consecutive biopsies was 37 months. Results: Overall, the rate of liver fibrosis progression per year, defined as the ratio of the difference in fibrosis stage between two consecutive LBs and the time between these two biopsies, was 0.07 ± 0.03 Metavir units/year. We identified three groups of patients: those in whom liver fibrosis remained stable (group I, n=21), those with progressing liver fibrosis (group II, n=21, 0.34 ± 0.05 units/year), and those with a regression in liver fibrosis (group III, n=13, −0.25 ± 0.24 units/year). In the last two groups, the progression and the regression of liver fibrosis were progressive during follow-up. Demographic data, immunosuppressive treatment, the duration of HCV infection, HCV genotype, as well as liver enzyme (AST and ALT) levels, renal parameters, and HCV RNA concentrations before transplantation and at each LB, were similar in all groups. After transplantation, ALT only increased significantly in group II. In contrast, AST and HCV viremia increased significantly in all groups. At the third LB, ferritin levels and hepatosiderosis were significantly higher in group II compared with the other groups. Overall, liver activity scores were similar in the three groups. Sequence analysis of the hypervariable region-1 of the HCV genome revealed a significantly lower diversification between transplantation and the first biopsy in patients with stable or progressing liver fibrosis compared with those with regressing liver fibrosis. Conclusion: In conclusion, after renal transplantation, HCV infection is not harmful upon liver fibrosis in all patients. Sequencing of the hypervariable region-1 of HCV might predict the long-term liver histology outcome.

Progression of chronic hepatitis C to liver fibrosis and cirrhosis in patients coinfected with hepatitis C virus and human immunodeficiency virus.

To evaluate the factors associated with the evolution of chronic hepatitis C in human immunodeficiency virus (HIV)-infected patients, a cross-sectional analysis of 41 HIV-infected patients with chronic hepatitis C (known as "HIV-HCV [hepatitis C virus]-coinfected patients") and a control group of patients with chronic hepatitis C who did not have HIV infection (known as "non-HIV-infected patients") was performed. The association of histological variables with demographic parameters, HCV load and genotype, HIV load, CD4(+) T cell count, and response to highly active antiretroviral therapy (HAART) was evaluated. HIV-HCV-coinfected patients showed a significantly higher HCV load, more-advanced fibrosis, and a higher liver fibrosis progression rate (FPR) than did non-HIV-infected patients. A high HCV load and a low CD4(+) T cell count were associated with a higher FPR. The immune response induced by HAART did not influence this progression. In conclusion, HIV-HCV-infected patients, mainly such patients with a high HCV load and an immunodepressed state, have a higher FPR. An independent effect of the immune response to HAART was not evident.

Effect of host-related factors on the intensity of liver fibrosis in patients with chronic hepatitis C virus infection.

There is increasing interest in the identification of factors associated with liver disease progression in patients infected with hepatitis C virus (HCV). We assessed host-related factors associated with a histologically advanced stage of this disease and determined the rate of liver fibrosis progression in HCV-infected patients. We included patients submitted to liver biopsy, who were anti-HCV and HCV RNA positive, who showed a parenteral risk factor (blood transfusion or intravenous drug use), and who gave information about alcohol consumption. Patients were divided into two groups for analysis: group 1 - grades 0 to 2; group 2 - grades 3 to 4. The groups were compared in terms of sex, age at the time of infection, estimated duration of infection and alcoholism. The rate of fibrosis progression (index of fibrosis) was determined based on the relationship between disease stage and duration of infection (years). Logistic regression analysis revealed that age at the time of infection (P<0.01; 95% CI 1.06-1.22) and the duration of infection (P<0.01; 95% CI 1.06-1.32) were independently associated with a more advanced stage of hepatitis C. The median index of fibrosis was 0.14 for the group as a whole. A significant difference in the index of fibrosis was observed between patients aged < 40 years at infection (median = 0.11) and patients aged > or = 40 years (median = 0.47). The main factors associated with a more rapid fibrosis progression were age at the time of infection and the estimated duration of infection. Patients who acquired HCV after 40 years of age showed a higher rate of fibrosis progression.

Natural course of progression of liver fibrosis in Japanese patients with chronic liver disease type C--a study of 527 patients at one establishment.

Patients with chronic hepatitis C infection show a gradual progression of fibrosis to liver cirrhosis and hepatocellular carcinoma (HCC). We studied whether the progression of liver fibrosis differed among Japanese subjects who were infected with different hepatitis C virus (HCV) genotypes. In 527 patients we examined whether there was a relationship between gender, age, history of blood transfusion, interval between date of blood transfusion and date of liver biopsy or date of diagnosis of HCC, serum alanine aminotransferase level, platelet count or HCV genotype, with the extent of liver fibrosis, classified into four stages (F1-F4). Moreover, we compared the mean rate of liver fibrosis progression per year in patients with each HCV genotype. Patients who had a higher fibrosis score tended to be older, have a lower platelet count and a longer interval since blood transfusion than those who had a lower fibrosis score. The mean rate of liver fibrosis progression was 0.12 +/- 0.15 stages per year after the blood transfusion. However, the progression rate of liver fibrosis in patients who had received a blood transfusion when they were > or = 30 years of age was 0.19 +/- 0.22, while the progression rate of liver fibrosis in the patients who had received a blood transfusion when they were < 30 years was 0.09 +/- 0.09. In conclusion, chronic hepatitis C is a progressive disease, and patients with genotype 1b, 2a and 2b have a similar rate of progression of liver fibrosis. Particular attention should be paid to patients who are infected with HCV when > or = 30 years of age, because intrahepatic fibrosis rapidly progresses in these patients.