Current and future therapy for chronic hepatitis C virus liver disease

Therapy with recombinant human interferon alpha remains pivotal to the treatment for chronic hepatitis C virus liver disease. Semi-synthetic protein-polymer conjugates of interferon with polyethylene glycol have also been recently developed. These conjugates protect the protein from degradation; reduce the immunogenicity; and prolong exposure to drug by a sustained absorption, restricted volume of distribution and sustained high serum concentration. Therapy with pegylated interferons is associated with significantly greater sustained virological response rates (SVR) compared to the non-pegylated formulation. Ribavirin is a guanosine analog with minimal antiviral activity against HCV. It demonstrates significant clinical synergism when administered in combination with interferon. Amantadine blocks entry of influenza A virus into cells. Used in combination with ribavirin and interferon as triple therapy, it may have some benefit compared to dual or monotherapy. Current treatment with pegylated interferons combined with weight-based ribavirin, provides the highest sustained virological response rates. In the absence of suitable animal models, HCV dynamic studies in man have been helpful in defining the mechanisms of action of interferon in chronic HCV liver disease. Novel therapeutic agents are being developed as the replication cycle of HCV is being understood. However, their safety and efficacy remain to be established and availability for clinical use is unlikely within the next 3 to 5 years. This review describes current antiviral therapy in chronic HCV liver disease, addresses the potential role of viral dynamics in elucidating the mechanisms of action of the drugs and discusses future potential therapeutics agents.     

GB virus C/hepatitis G virus infection in chronic hepatitis C patients with and without interferon-alpha therapy.

GB virus C/hepatitis G virus (GBV-C/HGV) RNA, detected by polymerase chain reaction, and antibodies to the GBV-C/HGV envelope protein (anti-E2), detected by an enzyme-linked immunosorbent assay, were used to evaluate both the impact of GBV-C/HGV on the coexistent hepatitis C virus (HCV) infection and the course of GBV-C/HGV infection in chronic hepatitis C patients with and without interferon-alpha (IFN-alpha) treatment. Of the 162 chronic hepatitis C patients treated with INF-alpha, 17.9% were GBV-C/HGV RNA-positive and 18.5% anti-E2-positive (total exposure, 35.2%). Neither present nor past GBV-C/HGV infection had impact on the clinical features, HCV virological characteristics and response to IFN-alpha treatment in chronic hepatitis C patients. Among patients with ongoing HCV/GBV-C/HGV coinfection, 20.7% (6/29) in IFN-alpha-treated patients lost GBV-C/HGV RNA concomitant with anti-E2 seropositivity, which was significantly higher than 4.8% (2/42) in patients without INF-alpha treatment (P<0.05). Based on multivariate analyses, the significant factors associated with clearance of GBV-C/HGV viremia combined with anti-E2 seropositivity were baseline anti-E2 seropositivity and IFN-alpha treatment. In summary, GBV-C/HGV did not alter the course of coexistent HCV. IFN-alpha treatment was effective in some patients against GBV-C/HGV and might facilitate anti-E2 seroconversion in chronic hepatitis C patients with GBV-C/HGV viremia.     

13C-aminopyrine breath test to evaluate severity of disease in patients with chronic hepatitis C virus infection

BACKGROUND: There are few data on the use of the 13C-aminopyrine breath test to evaluate the severity of disease in patients with hepatitis C virus-related chronic liver disease, although these patients represent one of the most important problems in clinical hepatology. AIMS: To compare 13C-aminopyrine breath test results of patients with hepatitis C virus-related chronic hepatitis and Child-Pugh class A cirrhosis with those of normal subjects, and to evaluate different methods of expressing 13C-aminopyrine breath test results. METHODS: Twenty-four patients with hepatitis C virus-related chronic hepatitis and 17 patients with Child-Pugh class A cirrhosis underwent 13C-aminopyrine breath test. Breath samples were collected every 30 min up to 2 h after 13C-aminopyrine administration. 13C-Aminopyrine breath test results were expressed as a percentage of the administered dose of 13C recovered per hour (% dose/h) and the cumulative percentage of administered dose of 13C recovered over time (% dose cum). Nineteen healthy subjects served as controls. Patients with hepatitis C virus-related chronic hepatitis were divided into subgroups on the basis of histological staging and grading. RESULTS: The 13C-aminopyrine breath test result (% dose/h) at 30 min was significantly different among the three subgroups of subjects (normal subjects, 11.5 +/- 3.5; chronic hepatitis patients, 8.1 +/- 4.1; cirrhosis patients, 5.0 +/- 3.1; P < 0.0005). Moreover, the differences between chronic hepatitis and cirrhosis patients were statistically significant (P < 0.03). The fibrosis score showed a significant inverse correlation with the 13C-aminopyrine breath test result (% dose/h) at 30 min (rs=- 0.409, P=0.05). The 13C-aminopyrine breath test result (% dose/h) at 30 min also allowed normal subjects and chronic hepatitis patients with low (< or = 2) or high (> 2) fibrosis scores to be distinguished. The 13C-aminopyrine breath test results (% dose cum) at 30, 60 and 90 min allowed discrimination between normal subjects and chronic hepatitis and cirrhosis patients. The 13C-aminopyrine breath test result (% dose cum) was also able to distinguish between normal subjects and chronic hepatitis patients with high but not low fibrosis scores. Both 13C-aminopyrine breath test results (% dose/h and % dose cum) at 120 min allowed the differentiation between normal subjects and chronic hepatitis patients with high (> or = 6) necro-inflammatory activity. CONCLUSIONS: In patients with hepatitis C virus-related chronic liver disease, the 13C-aminopyrine breath test proved to be safe and easy to perform, and was able to evaluate different degrees of liver function impairment which were partly correlated to clinical and histological evaluation. In future studies, 13C-aminopyrine breath test results should be expressed in a standardized fashion to permit comparison.     

13C-methacetin breath test as liver function test in patients with chronic hepatitis C virus infection

BACKGROUND: The 13C-methacetin breath test enables the quantitative evaluation of the cytochrome P450-dependent liver function. AIM: To find out whether this breath test is sensitive in noncirrhotic patients also with chronic hepatitis C in early stages of fibrosis. METHODS: Sixty-one healthy controls and 81 patients with chronic hepatitis C underwent a 13C-methacetin breath test. In all patients, a liver biopsy was performed. The liver histology was classified according to the histology activity index-Knodell score. RESULTS: Delta over baseline values of the patients at 15 min significantly differed from controls (19.2 +/- 9.2 per thousand vs. 24.1 +/- 5.7 per thousand; P < 0.003). The cumulative recovery after 30 min in patients was 11.4 +/- 4.8% and in healthy controls 13.8 +/- 2.8% (P < 0.002). However, patients with early fibrosis (histology activity index IVB) did not differ in delta over baseline values of the patients at 15 min (23.2 +/- 7.9 per thousand vs. 22.6 +/- 7.2 per thousand; P = 0.61) or cumulative recovery (13.6 +/- 3.7% vs. 13.2 +/- 3.8%; P = 0.45) from patients with more advanced fibrosis (histology activity index IVC). Patients with clinically nonsymptomatic cirrhosis (histology activity index IVD; Child A) metabolized 13C-methacetin to a significantly lesser extent (delta over baseline values of the patients at 15 min: 8.3 +/- 4.9 per thousand; P < 0.005 and cumulative recovery after 30 min: 5.6 +/- 3.2%; P < 0.003). The 13C-methacetin breath test identified cirrhotic patients with 95.0% sensitivity and 96.7% specificity. CONCLUSION: The non-invasive 13C-methacetin breath test reliably distinguishes between early cirrhotic (Child A) and noncirrhotic patients, but fails to detect early stages of fibrosis in patients with chronic hepatitis C.     

The response of hepatitis C virus and TT virus to high dose and long duration interferon-alpha therapy in na?ve chronic hepatitis C patients.

To investigate responses of hepatitis C virus (HCV) and TT virus (TTV) to high dose and long duration interferon-alpha (IFN-alpha) therapy (540 million units in 36 weeks) and factors associated with the viral clearance, sera of 165 Taiwanese na?ve chronic hepatitis C patients were tested for alanine aminotransferase, HCV RNA levels, HCV genotypes and TTV DNA. With 41.8% of TTV DNA prevalence, TTV viremia was significantly associated with history of blood transfusion (P<0.01). After IFN therapy, HCV complete response was achieved in 60 (36.4%) patients and significantly associated with lower pretreatment levels of HCV RNA (P<0.01) and HCV genotype non-1b (P<0.05). Fifty-three patients with concurrent TTV infection were evaluated for TTV response. TTV sustained clearance was achieved in 24 (48%) patients and significantly associated with loss of TTV DNA at the end point of treatment. In conclusion, concurrent TTV infection is highly prevalent, related to blood transfusion and independent of HCV infection. After high dose and long duration IFN-alpha therapy, HCV and TTV clearance are achieved among more than one-third and around one-half patients. HCV RNA levels and HCV genotypes are predictors for HCV response and no clinical factors are observed to be associated with TTV clearance.     

慢性丙肝患者血清中自身抗体的检测与临床意义

目的：探讨慢性丙肝患者血清中自身抗体的检测与临床意义。方法：选取2008年12月～2010年10月我院收治的110例慢性丙肝患者,分为自抗阳和自抗阴两组,每组各55例。对其自身抗体RF、AMA、ASA、ANA及ACL阳性率进行检测。观察两组自抗体与其肝功、性别及年龄关系。结果：110例慢性丙肝患者血清中79例自身抗体至少有1种阳性。ACL阳性最多（59例）,然后依次为ANA（22例）、RF（18例）、ASA（9例）、AMA（2例）。自抗阳组比自抗阴组年龄大且女性患者多见,肝病及肝功能状态均差。结论：临床慢性丙肝血清中常出现自身抗体,其对肝功能状态造成严重影响,可进一步使病情恶化,为此在诊断治疗中应引起高度重视。     

Review article: hepatitis vaccination in patients with chronic liver disease

Evidence regarding the outcomes of viral super-infection in patients with chronic liver disease and practical strategies for hepatitis A and B vaccination of these individuals are reviewed. Patients with acute hepatitis A and chronic hepatitis B have a more severe clinical course and a higher death rate compared with otherwise healthy individuals with hepatitis A, and these differences are most pronounced in older patients and those with histological evidence of chronic hepatitis or cirrhosis, rather than in asymptomatic hepatitis B carriers. Patients with acute hepatitis A super-infection and chronic hepatitis C have an increased risk of fulminant hepatitis and death. In addition, patients with other chronic liver diseases also appear to be at increased risk for more severe disease with superimposed hepatitis A. Patients with chronic hepatitis B and hepatitis C virus co-infection have more severe laboratory abnormalities, more severe histological disease, a greater frequency of cirrhosis and complications of cirrhosis, and a higher incidence of hepatocellular carcinoma. Vaccines for both hepatitis A and B are safe and effective if used early in the course of chronic liver disease. Hepatitis A and B vaccination should be part of the routine management of patients with chronic liver disease, preferably as early as possible in the natural course of their disease.     

长期血液透析患者丙型肝炎病毒感染的研究

目的　调查长期血液透析患者丙型肝炎感染状况。方法　用酶联免疫吸附试验 ( EL ISA)法和RT- PCR法检测 13 7例长期血液透析患者血清中的抗丙型肝炎病毒 ( HCV)和丙型肝炎病毒核糖核酸( HCVRNA) ,并且同时检测丙氨酸转氨酶 ( AL T)和天冬氨酸转氨酶 ( AST) ,计算其变动率。结果　 13 7例长期血液透析患者中仅抗 HCV阳性 8例 ,仅 HCVRNA阳性 15例 ,抗 HCV与 HCVRNA同时阳性者 2 4例 ,感染率3 4 .3 %。且透析时间 <2 a的 HCV感染率为 15 % ,透析时间 >2 a以上的其感染率增至 3 7.6%。结论　血透患者中 HCV的感染应引起重视 ,透析的年限越长 ,被 HCV感染的机率就越大。酶学指征的变动率不能作为长期透析患者 HCV感染的敏感指标     

The prevalence of anemia in patients with chronic kidney disease

OBJECTIVE: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate. RESEARCH DESIGN AND METHODS: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2 years; 46.6% male); 237 physician practices. Eligible patients: > or = 18 years of age; serum creatinine: 1.5 mg/dL-6.0 mg/dL (females), 2.0 mg/dL-6.0 mg/dL (males). MAIN OUTCOME MEASURES: Primary study end point: prevalence and severity of anemia (hemoglobin < or = 12 g/dL). Data further stratified by hemoglobin (< or = 12 g/dL, < or = 10 g/dL). RESULTS: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60 mL/min/1.73 m2 for 97.7% of evaluable patients. Mean +/- SD serum creatinine level: 2.2 mg/dL +/- 0.9 mg/dL; 2.5 mg/dL +/- 1.0 mg/dL for males, 2.0 mg/dL +/- 0.8 mg/dL for females. Mean +/- SD hemoglobin: 12.2 g/dL +/- 1.6 g/dL (47.7% had hemoglobin < or = 12 g/dL; 8.9% had hemoglobin < or = 10 g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin < or = 12 g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. Prevalence of hemoglobin < or = 10 g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from > or = 60 mL/min/1.73 m2 to < 15 mL/min/1.73 m2. After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin < or = 10 g/dL was 0.54 (0.49-0.60) and for hemoglobin < or = 12 g/dL was 0.68 (0.65-0.72), with each 10-mL/min/1.73 m2 increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity. CONCLUSIONS: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.     

The prevalence of anemia in patients with chronic kidney disease

SUMMARY

Objective: Anemia is a complication of chronic kidney disease and may contribute to adverse clinical outcomes. Early identification and treatment of anemia may improve cardiovascular morbidity and mortality. No large-scale population data are available specifically for patients with chronic kidney disease regarding prevalence of anemia, subpopulations at risk, and relationships between anemia and kidney function. This study was undertaken to address these questions in patients with chronic kidney disease, and investigate the relationship between anemia and glomerular filtration rate.

Research design and methods: Large-scale, cross-sectional, US multicenter survey; 5222 patients (mean age, 68.2?years; 46.6% male); 237 physician practices. Eligible patients: ≥ 18?years of age; serum creatinine: 1.5?mg/dL–6.0?mg/dL (females), 2.0?mg/dL–6.0?mg/dL (males).

Main outcome measures: Primary study end point: prevalence and severity of anemia (hemoglobin ≤ 12?g/dL). Data further stratified by hemoglobin (≤ 12?g/dL, ≤ 10?g/dL).

Results: Primary etiologies of chronic kidney disease (5222 evaluable patients): diabetes (49.5%); hypertension (33.0%). Glomerular filtration rate: < 60?mL/min/1.73?m² for 97.7% of evaluable patients. Mean ± SD serum creatinine level: 2.2?mg/dL ± 0.9?mg/dL; 2.5?mg/dL ± 1.0?mg/dL for males, 2.0?mg/dL ± 0.8?mg/dL for females. Mean ± SD hemoglobin: 12.2?g/dL ± 1.6?g/dL (47.7% had hemoglobin ≤ 12?g/dL; 8.9% had hemoglobin ≤ 10?g/dL). Prevalence of anemia was strongly associated with declining glomerular filtration rate. Percentage of patients with hemoglobin ≤ 12?g/dL increased from 26.7% to 75.5% when glomerular filtration rate decreased from ≥ 60?mL/min/1.73?m² to < 15?mL/min/1.73?m². Prevalence of hemoglobin ≤ 10?g/dL increased substantially from 5.2% to 27.2% when glomerular filtration rate diminished from ≥ 60?mL/min/1.73?m² to < 15?mL/min/1.73?m². After controlling for other patient characteristics associated with increased prevalence of anemia, the prevalence odds ratio for hemoglobin ≤ 10?g/dL was 0.54 (0.49–0.60) and for hemoglobin ≤ 12?g/dL was 0.68 (0.65–0.72), with each 10-mL/min/1.73?m² increase in glomerular filtration rate. Predictors of anemia: diabetes, female sex, and race/ethnicity.

Conclusions: Anemia was present in 47.7% of 5222 predialysis patients with chronic kidney disease. Prevalence of anemia increased as kidney function decreased. Certain subgroups are at increased risk for anemia.     

Role of silent hepatitis B virus in chronic hepatitis B surface antigen(-) liver disease.

Despite a number of studies documenting hepatitis B virus (HBV) infection in the absence of hepatitis B surface antigen (HBsAg) a causal relationship between silent HBV infection and liver disease remain difficult to establish. In particular, both the prevalence and clinical significance of this observation are poorly understood. Why is HBV replication apparently so low in these patients? A number of studies have tried to elucidate the mechanism of HBsAg negative infections, and considerable data documenting HBV infectivity or reinfection in the absence of detectable HBsAg support the hypothesis that in some of these cases, HBV is undergoing low-level replication in the liver and this, in several situations including: (1) chronic liver disease, alcoholic liver disease, hepatocellular carcinoma; (2) viral reactivation following cancer chemotherapy or immunosuppression and (3) transmission via transfusion or from human serum to chimpanzees. In a recent study including 50 patients with chronic liver disease of unknown etiology we could detect serum HBV DNA by nested polymerase chain reaction (PCR) in 15/50 patients (50% at the cirrhosis stage) in the absence of HBsAg; in the liver of the 15 patients both HBcAg and/or HBsAg can be detected at very low-level. Viral host factors allowing HBV persistence in the absence of HBsAg can depend on several mechanisms. Coinfections with HCV can explain only a proportion of HBsAg(-) HBV infections. Secondly, HBV mutations in the core promotor region leading to a minimal viral replication, or mutations in the HBsAg-encoding region might explain the absence of serological recognition. Finally, it is possible that in some cases host immune mechanisms can maintain HBV infection in a latent state until transmission to another individual who subsequently develops a more active infection especially when immunosuppressive therapy is employed. Existence of HBsAg(-) HBV infections should be taken into account by the use of sensitive PCR tests for prevention of viral transmission in the settings of blood donations and organ transplants.     

Antipyrine clearance in comparison to conventional liver function tests in hepatitis C virus patients

In this study, 15 healthy volunteers and 96 patients with hepatitis C virus, classified according to Child-Pugh into 36 Child-A, 31 Child-B and 29 Child-C, were examined. All subjects ingested 600 mg antipyrine in the form of hard gelatinous capsules after overnight fasting. One milliliter of saliva was collected at 4 and 24 h after ingestion of antipyrine and analyzed using high-performance liquid chromatography. Blood samples were collected from all subjects for examination, using conventional liver function tests. The pharmacokinetic variables for antipyrine were determined using the two concentration time points selected. A cut-off value of 0.34 ml/min/kg was used to distinguish between cirrhotic and non-cirrhotic patients. Alanine aminotransferase, aspartate aminotransferase and gamma-glutamyl transferase values were significantly higher with significantly lower antipyrine clearance in Child-A, B, and C patients than in normal volunteers. The total protein concentration was significantly lower in Child-B and C patients. Moreover, AST was significantly higher in Child-C patients and antipyrine clearance was lower in Child-B and C patients than in Child-A patients. Antipyrine clearance showed a significant negative correlation with Child-Pugh scores, total protein, the international normalization ratio of prothrombin time and globulin, and a positive correlation with albumin and albumin-to-globulin ratio. Unlike most of the conventional liver function tests, antipyrine clearance, which represents the intrinsic clearance capacity of the liver, measured using saliva, proved to be a sensitive marker of liver function. It was significantly impaired in the Child-Pugh group A patients with the least hepatic impairment. The international normalization ratio of prothrombin time was just as informative as antipyrine clearance in identifying minimal hepatic impairment.     

The effect of cytokine profiles on the viral response to re-treatment in antiviral-experienced patients with chronic hepatitis C virus infection

Background

There have been few studies on the potential immunological factors associated with viral controls in antiviral-experienced patients on a second round of combination therapy. In this study, we evaluated the level of systemic cytokines and potential impact on combination therapy in both antiviral-naïve and -experienced patients chronically infected with hepatitis C virus.

Methods

Longitudinal analysis of 27 cytokines and chemokines was performed using the multiplex Biorad 27 plex assay in 37 antiviral-naïve and 24 experienced chronically HCV-1b-infected patients during combination therapy with peginterferon-alfa and ribavirin. A group of healthy donors was included as the control (n = 11).

Results

Fifty percent of antiviral-experienced chronically HCV-patients could achieve a delayed and slow virologic response after 48 weeks combination therapy, comparing with an early and fast virologic response in antiviral-naïve patients. A distinction of immune mediators profiling before and during antiviral therapy between antiviral-naïve and -experienced patients was identified, IL-4, IFN-γ and CCL-3 (MIP-1a) were significantly higher in naïve patients than those in experienced patients (P = 0.005, 0.047 and 0.017, respectively) while G-CSF in naïve was lower than in experienced patients (P < 0.05). Notably, higher Th1 type cytokine IFN-γ and lower Th2 type cytokine IL-4 at baseline and week 4 were associated with HCV clearance in naïve patients, and a similar trend appeared at week 12 in experienced patients.

Conclusions

We found a successful second round therapy in antiviral-experienced patients appears to be associated with the host immune response. Dominant Th1-polar cytokines, especially IFN-γ, is a potential predictor of viral responsiveness.     

Ultrasonographic and biochemical parameters in the non-invasive evaluation of liver fibrosis in hepatitis C virus chronic hepatitis

BACKGROUND: Prior studies suggest that platelet counts of <140 000/microL can discriminate patients with different stages of fibrosis. AIM: To determine the added value of abdominal ultrasound analysis of morphological liver features in increasing the diagnostic accuracy of platelet counts for the prediction of liver fibrosis at histology. METHODS: In a retrospective study, clinical records of 1143 chronic hepatitis C patients at their first presentation, naives to both liver biopsy and anti-viral treatment, were reviewed. Sensitivity, specificity, positive and negative predictive values, positive and negative likelihood ratios of following indices were evaluated singularly or in combination: platelet counts <140 000/microL; nodular liver surface, spleen and portal vein size. RESULTS: All indices had specificity rate of > or =90% in excluding bridging fibrosis/cirrhosis, whereas sensitivity was acceptable (51%) for only platelet counts <140 000/microL. None of the ultrasonographic parameters singularly evaluated and reached an acceptable sensitivity rate. For ruling cirrhosis in or out, specificity rate was > or =82% for all tests, with the highest value reported by portal vein size. Low platelet counts plus nodular liver surface had the best sensitivity. CONCLUSIONS: No additional significant predictive value was given by adding ultrasonographic parameters to low platelet counts, whereas only a mild non-significant improvement in sensitivity was obtained combining platelet counts <140 000/microL with the presence of nodular liver surface. The platelet counts <140 000/microL showed the best predictive value for including both significant fibrosis and cirrhosis.     

Platelet activation in patients with chronic hepatitis C

OBJECTIVE: To elucidate the mechanisms of thrombocytopenia in chronic hepatitis C (CHC), we investigated platelet activation in patients with chronic viral liver diseases. METHODS: Platelet activation was evaluated with flow cytometry in twenty-five patients with chronic viral hepatitis and 11 patients with liver cirrhosis of viral etiology. Liver biopsies were carried out in all patients. RESULTS: The platelet counts decreased significantly in patients with CHC and in patients with liver cirrhosis compared to controls, but not in patients with chronic hepatitis B (CHB). Patients with CHC had a significantly higher percentage of platelets positive for activation-dependent monoclonal antibodies (MoAbs), and also had a higher percentage of platelet microparticles (PMP), a marker of platelet activation, than patients with CHB. There was a significant correlation between the percentage of PMP and the levels of liver fibrosis markers, such as serum hyaluronate and N-terminal propeptide of type III procollagen (P-III-P), in CHC, suggesting the relationship between platelet activation and liver fibrosis. Platelet activation was markedly enhanced in CHC patients with high histological scores of liver fibrosis. CONCLUSION: Patients with CHC have increased platelet activation, which may contribute to the occurrence of thrombocytopenia in CHC. Liver fibrosis may play a role in activation of platelets in CHC.