Home  About us  Contact
 

Fibrosis Stage (fibrosis + stage)

Distribution by Scientific Domains
Medical Sciences100%
Distribution within Medical Sciences
Hepatology38%
Gastroenterology & Hepatology35%
Transplantation7%
4 Other Subdomains20%

Kinds of Fibrosis Stage

  • hepatic fibrosis stage
    		•

    Selected Abstracts

    Usefulness of non-invasive markers for predicting liver cirrhosis in patients with chronic hepatitis B

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 1 2010
    Kwang Gyun Lee
    Abstract Background and Aim:, Recently, various non-invasive blood markers and indices have been studied to overcome the limitations of liver biopsy, such as its invasiveness and sampling errors. However, the majority of these studies have focused on patients with chronic hepatitis C. Accordingly, this study was performed to evaluate the significances of various non-invasive serum markers in terms of predicting the presence of liver cirrhosis in chronic hepatitis B. Methods:, We included 125 chronic hepatitis B patients who had undergone liver biopsy. Fibrosis stage was assessed using the METAVIR scoring system (F0,F4), which defines liver cirrhosis as F4. In addition, we measured various blood markers at times of liver biopsy. Results:, Thirty four of the 125 patients (27.2%) were rated as F4 by liver biopsy. Age, platelet, white blood cells, aspartate aminotransferase (AST), alanine aminotransferase, haptoglobin, apolipoprotein-A1 (Apo-A1), collagen-IV, hyaluronic acid, ,2-macroglobulin, matrix metalloproteinase-2, and YKL-40 were significantly different between patients with chronic hepatitis and those with liver cirrhosis. However, multivariate analysis showed that only platelet, AST, haptoglobin, and Apo-A1 independently predicted the presence of liver cirrhosis. Having identified these four factors, we devised a system, which we refer to as platelet count, AST, haptoglobin, and Apo-A1 (PAHA). The area under the receiver-operating characteristics (AUROC) of PAHA indices for the presence of liver cirrhosis was 0.924 (95% confidence interval, 0.877,0.971), which was significantly greater than the AUROC of other indices of fibrosis. Conclusion:, The devised PAHA system was found to be useful for predicting the presence of liver cirrhosis in patients with chronic hepatitis B. [source]

    Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection,

    JOURNAL OF VIRAL HEPATITIS, Issue 1 2005
    J. D. Collier
    Summary., Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression. [source]

    Recurrent hepatitis C virus disease after liver transplantation and concurrent biliary tract complications: poor outcome

    CLINICAL TRANSPLANTATION, Issue 4 2006
    Lior H. Katz
    Abstract:, Recurrent hepatitis C virus (HCV) infection is particularly aggressive in the post-liver transplantation setting, with rapid progression of liver fibrosis. Biliary complications remain a significant cause of morbidity following liver transplantation. Post-cholecystectomy biliary strictures are associated with advanced hepatic fibrosis. The aim of this retrospective study was to determine whether the presence of biliary complications affects survival in liver transplant recipients with recurrent HCV disease. The files of liver transplant recipients (53.7% male; mean age 52.7 ± 10.3 yr) were reviewed for incidence, type and treatment of biliary complications, and findings were compared between those who developed recurrent HCV disease (n = 47, 83.9%) and those who did not (n = 9). Twenty-one biliary complications developed in 12 patients with recurrent HCV (25.5%). Treatment with endoscopic retrograde cholangiopancreatography or percutaneous transhepatic cholangiography with balloon dilatation and stent placement or surgical revision was successful in nine (75%). Three biliary complications developed in three patients with no recurrence (p = NS). There was no statistically significant association between recurrent HCV disease and biliary complications. However, among those with recurrent disease, the recurrence was severe in nine of 12 recipients with biliary complications (75%) but in only nine of 35 without biliary complications (26%) (p = 0.001). Death was documented in eight patients with severe recurrence (44.4%), including three (37.5%) with biliary complications and two (7%) with non-severe recurrence, neither of whom had biliary complications (p = 0.003). Antiviral treatment was successful in nine of 25 patients (36%) who received it. On multivariate analysis, biliary complications were a significant predictor of severe recurrence (OR 27.0, 95% confidence interval 2.07,351.4) (p = 0.012). Fibrosis stage in the second biopsy was significantly correlated with serum alanine aminotransferase (p = 0.01) and with duration of biliary obstruction (p = 0.07). In conclusion, biliary complications of liver transplantation strongly affect outcome in patients with recurrent HCV disease despite attempts to relieve the biliary obstruction and to treat the recurrent HCV disease. [source]

    Prospective risk assessment for hepatocellular carcinoma development in patients with chronic hepatitis C by transient elastography,

    HEPATOLOGY, Issue 6 2009
    Ryota Masuzaki
    Liver stiffness, noninvasively measured by transient elastography, correlates well with liver fibrosis stage. The aim of this prospective study was to evaluate the liver stiffness measurement (LSM) as a predictor of hepatocellular carcinoma (HCC) development among patients with chronic hepatitis C. Between December 2004 and June 2005, a total of 984 HCV-RNA positive patients, without HCC or a past history of it, visited the University of Tokyo Hospital. LSM was performed successfully in 866 patients, who gave informed consent. During the follow-up period (mean, 3.0 years), HCC developed in 77 patients (2.9% per 1 person-year). The cumulative incidence rates of HCC at 1, 2, and 3 years were 2.4%, 6.0%, and 8.9%, respectively. Adjusting for other significant factors for HCC development, patients with higher LSM were revealed to be at a significantly higher risk, with a hazard ratio, as compared to LSM ,10 kPa, of 16.7 (95% confidence interval [CI], 3.71-75.2; P < 0.001) when LSM 10.1-15 kPa, 20.9 (95% CI, 4.43-98.8; P < 0.001) when LSM 15.1-20 kPa, 25.6 (95%CI, 5.21-126.1; P < 0.001) when LSM 20.1-25 kPa, and 45.5 (95% CI, 9.75-212.3; P < 0.001) when LSM >25 kPa. Conclusions: This prospective study has shown the association between LSM and the risk of HCC development in patients with hepatitis C. The utility of LSM is not limited to a surrogate for liver biopsy but can be applied as an indicator of the wide range of the risk of HCC development. (HEPATOLOGY 2009.) [source]

    Relationship of serum fibrosis markers with liver fibrosis stage and collagen content in patients with advanced chronic hepatitis C,

    HEPATOLOGY, Issue 3 2008
    Robert J. Fontana
    This study determined the utility of a panel of serum fibrosis markers along with routine laboratory tests in estimating the likelihood of histological cirrhosis in a cohort of prior nonresponders with chronic hepatitis C. The relationship between serum markers and quantitative hepatic collagen content was also determined. Liver biopsy samples from 513 subjects enrolled in the HALT-C trial were assigned Ishak fibrosis scores. The collagen content of 386 sirius-red stained, nonfragmented biopsy samples was quantified using computerized morphometry. Serum tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), amino-terminal peptide of type III procollagen (PIIINP), hyaluronic acid (HA), and YKL-40 levels were determined using commercially available assays. Sixty-two percent of patients had noncirrhotic fibrosis (Ishak stage 2-4) whereas 38% had cirrhosis (Ishak stage 5,6). Multivariate analysis identified a 3-variable model (HA, TIMP-1, and platelet count) that had an area under the receiver operating curve (AUROC) of 0.81 for estimating the presence of cirrhosis. This model was significantly better than that derived from the cirrhosis discriminant score (AUROC 0.70), the AST-to-platelet ratio (AUROC 0.73), and a prior model developed in HALT-C patients (AUROC 0.79). Multivariate analysis demonstrated that the serum fibrosis markers correlated substantially better with Ishak fibrosis scores than with the log hepatic collagen content (AUROC 0.84 versus 0.72). Conclusion: A 3-variable model consisting of serum HA, TIMP-1, and platelet count was better than other published models in identifying cirrhosis in HALT-C Trial subjects. The stronger correlation of the serum markers with Ishak scores suggests that serum fibrosis markers reflect the pattern of fibrosis more closely than the quantity of hepatic collagen. (HEPATOLOGY 2008.) [source]

    Amino acid substitutions in the hepatitis C virus core region are the important predictor of hepatocarcinogenesis,

    HEPATOLOGY, Issue 5 2007
    Norio Akuta
    We showed previously that amino acid (aa) substitutions in hepatitis C virus core region (HCV-CR) are negative predictors of virologic response to pegylated interferon (IFN) plus ribavirin therapy. HCV-CR induces hepatocellular carcinoma in transgenic mice, but the clinical impact is still unclear. To evaluate the impact of aa substitutions in HCV-CR on hepatocarcinogenesis, we performed a follow-up study on 313 noncirrhotic consecutive naïve patients infected with HCV genotype 1b who received IFN monotherapy. The median follow-up was 14.7 years. A sustained virologic response (SVR) after the first IFN was achieved by 65 patients (20.8%) (group A). Of 248 patients (79.2%) of non-SVR after first IFN, 112 (35.8%) did not receive additional IFN (group B), and the remaining 136 (43.5%) received multicourse IFN monotherapy (group C). As a whole, cumulative hepatocarcinogenesis rates in double wild-type (arginine at aa 70/leucine at aa 91) of HCV-CR were significantly lower than those in nondouble wild-type. Multivariate analyses identified 3 parameters (fibrosis stage 3, nondouble wild-type of HCV-CR, and group B) that tended to or significantly influenced hepatocarcinogenesis independently. With regard to hepatocarcinogenesis rates in group C according to HCV-CR and the mean alanine aminotransferase (ALT) during IFN-free period, significantly higher rates were noted in patients of nondouble wild-type with ALT levels of more than 1.5 times the upper limit of normal (25.7%) compared with the others (2.4%). Conclusion: Amino acid substitutions in the HCV-CR are the important predictor of hepatocarcinogenesis. In multicourse IFN therapy to nondouble wild-type, we emphasize the importance of reducing the risk of hepatocarcinogenesis by mean ALT during an IFN-free period below 1.5 times the upper limit of normal. (HEPATOLOGY 2007.) [source]

    Insulin resistance and liver injury in hepatitis C is not associated with virus-specific changes in adipocytokines,

    HEPATOLOGY, Issue 1 2007
    Ian Homer Y. Cua
    The role of tumor necrosis factor ,, interleukin 6, leptin, and adiponectin in the pathogenesis of hepatitis C virus (HCV)-associated insulin resistance (IR) remains controversial. We tested the hypothesis that these adipocytokines contribute to chronic HCV-associated IR and liver injury by first comparing their serum levels and homeostasis model assessment of insulin resistance (HOMA-IR) in 154 untreated, non-diabetic, HCV-infected male subjects with fibrosis stage 0-2, to that in 75 healthy volunteers matched for age, body mass index (BMI), and waist-hip ratio (WHR). We next examined whether the adipocytokine levels were associated with the extent of hepatic steatosis, portal/periportal inflammation and fibrosis in our total cohort of 240 HCV-infected male subjects. Significantly higher levels of HOMA-IR (2.12 versus 1.63, P = 0.01), TNF, (1.28 versus 0.60 pg/ml, P < 0.001) and IL6 (2.42 versus 1.15 pg/ml, P = 0.001) were noted in the HCV cohort compared with healthy controls respectively, but there were no significant differences in leptin and adiponectin concentrations. By multiple linear regression, independent predictors of HOMA-IR included the body mass index, and the serum levels of leptin (positive correlation) and adiponectin (negative correlation), but not that of TNF, and IL6. Only TNF, levels were correlated with the extent of histological injury (portal/periportal inflammation, P = 0.02). Conclusion: Whereas leptin and adiponectin contribute to IR, none of the adipocytokines accounted for the elevated IR in HCV-infected subjects. The adipocytokines were not associated with histological features of chronic HCV infection except for TNF, which correlated with portal/periportal inflammation. HCV-associated IR is most likely an adipocytokine-independent effect of the virus to modulate insulin sensitivity. (HEPATOLOGY 2007;46:66,73.) [source]

    Reversibility of hepatic fibrosis in treated genetic hemochromatosis: A study of 36 cases,

    HEPATOLOGY, Issue 2 2006
    Ludivine Falize
    The current study was undertaken to assess whether fibrosis could regress under venesection therapy in patients with C282Y homozygous genetic hemochromatosis. The 36 patients studied were recruited from a subfile of our database consisting of 125 C282Y homozygotes with either severe fibrosis or cirrhosis (F3 or F4 fibrosis stage, respectively, according to the METAVIR grading system). The second liver biopsy was performed for management of liver cancer, extrahepatic surgery, or assessment of liver fibrosis. All paired biopsies were reviewed by two pathologists without knowledge of clinical data. Among the 13 patients who had F3 fibrosis on their initial liver biopsy, 3 had F0, 6 had F1, and 2 had F2 on their second liver biopsy. Among the 23 patients with cirrhosis on their initial liver biopsy, 1 had F0, 4 had F1, 3 had F2, and 2 had F3 on their second liver biopsy. When defining regression of fibrosis as a decrease of at least 2 METAVIR units, fibrosis regressed in 9 of 13 (69%) F3 and in 8 of 23 (35%) F4. When the ratio of gammaglobulins (g/L) to (platelets [n/mm3] × prothrombin activity [%]) was greater than 7.5, fibrosis never regressed. In conclusion, these data extend the concept of regression of fibrosis to patients with treated genetic hemochromatosis and suggest that some simple biochemical tests would be predictive of further regression of fibrosis as a result of venesection therapy. If confirmed on larger series, this could modify the ultrasound screening policy of hepatocellular carcinoma in genetic hemochromatosis. (HEPATOLOGY 2006;44:472,477.) [source]

    Endogenous ursodeoxycholic acid and cholic acid in liver disease due to cystic fibrosis

    HEPATOLOGY, Issue 6 2004
    Jeffery L. Smith
    Focal biliary cirrhosis causes significant morbidity and mortality in cystic fibrosis (CF). Although the mechanisms of pathogenesis remain unclear, bile acids have been proposed as potential mediators of liver injury. This study examined bile acid composition in CF and assessed altered bile acid profiles to determine if they are associated with incidence and progression of liver injury in CF-associated liver disease (CFLD). Bile acid composition was determined by gas,liquid chromatography/mass spectrometry in bile, urine, and serum samples from 30 children with CFLD, 15 children with CF but without liver disease (CFnoLD), and 43 controls. Liver biopsies from 29 CFLD subjects were assessed histologically by grading for fibrosis stage, inflammation, and disruption of the limiting plate. A significantly greater proportion of endogenous biliary ursodeoxycholic acid (UDCA) was demonstrated in CFnoLD subjects vs. both CFLD subjects and controls (2.4- and 2.2-fold, respectively; ANOVA, P = .04), and a 3-4 fold elevation in endogenous serum UDCA concentration was observed in both CFLD subjects and CFnoLD subjects vs. controls (ANOVA, P < .05). In CFLD, there were significant correlations between serum cholic acid and hepatic fibrosis, inflammation, and limiting plate disruption as well as the ratio of serum cholic acid/chenodeoxycholic acid to hepatic fibrosis, inflammation, and limiting plate disruption. In conclusion, elevated endogenous UDCA in CFnoLD suggests a possible protective role against liver injury in these patients. The correlation between both cholic acid and cholic acid/chenodeoxycholic acid levels with histological liver injury and fibrosis progression suggests a potential monitoring role for these bile acids in CFLD. (HEPATOLOGY 2004;39:1673,1682.) [source]

    Early identification of recipients with progressive histologic recurrence of hepatitis C after liver transplantation

    HEPATOLOGY, Issue 5 2000
    Raghavakaimal Sreekumar
    Approximately half of patients undergoing liver transplantation (LT) for hepatitis C virus (HCV) develop histologic evidence of recurrence within the first postoperative year. Early identification of recipients at risk for more severe recurrence of HCV may be useful in selecting patients for antiviral therapy. We determined whether recipients at greatest risk for more severe recurrence of HCV can be identified by pre- and/or early post-LT HCV-RNA levels in serum or tissue. Serum and tissue samples were prospectively collected pre-LT and at 7 days, 4 months, 1 year, and at 3 years posttransplantation from patients undergoing LT for HCV. Hepatitis activity index (HAI) and fibrosis stage (FS) were assessed in all liver biopsies. Forty-seven patients (32 men) were studied. Higher HCV-RNA levels at 4 months post-LT (,109 copies/mL, n = 29) were associated with higher HAI at 1 year and at 3 years post-LT. The HAI seen on protocol biopsies at 4 months correlated significantly with fibrosis stage (FS) at 1 year (r = .56, P , .001) and 3 years (r = .53, P = .002). Higher HCV-RNA levels at 7 days and 4 months post-LT were sensitive (66% and 84%, respectively) and specific (92% and 63%, respectively) in identifying recipients with an HAI greater than 3 at 3 years. Higher pre- and early post-LT HCV-RNA levels are associated with more severe recurrence of HCV. The correlation of early HAI with subsequent FS suggests that higher mean HAI will eventually translate into more advanced stages of fibrosis. Patients at risk for more severe post-LT recurrence of HCV can be identified by early posttransplant HCV-RNA levels. [source]

    Usefulness of transient elastography for assessment of liver fibrosis in chronic hepatitis B: Regression of liver stiffness during entecavir therapy

    HEPATOLOGY RESEARCH, Issue 9 2010
    Masaru Enomoto
    Aim:, The usefulness of transient elastography remains to be validated in chronic hepatitis B, particularly as a tool for monitoring the degree of liver fibrosis during treatment. Methods:, The subjects were 50 patients with chronic hepatitis B virus infection. Liver biopsy was performed in 38 patients, and in 12 patients with platelet counts of 50 × 109/L or less, cirrhosis was clinically diagnosed on the basis of specific signs of portal hypertension. Liver stiffness was measured by transient elastography at baseline and after 12 months of treatment in 20 nucleos(t)ide-naïve patients who started entecavir within 3 months after study entry. Results:, Twenty (40%) patients were classified as F1, 10 (20%) as F2, 5 (10%) as F3, and 15 (30%) as F4 (cirrhosis). Median liver stiffness (interquartile range) was 7.0 kPa (5.6,9.4), 9.8 kPa (5.6,14.7), 9.8 kPa (7.6,12.9), and 17.3 kPa (8.2,27.6) in fibrosis stages F1 to F4, respectively. Liver stiffness significantly correlated with fibrosis stage (r = 0.46; P = 0.0014). Of the patients who started entecavir, median liver stiffness significantly decreased from 11.2 kPa (7.0,15.2) to 7.8 kPa (5.1,11.9; P = 0.0090) during 12 months of treatment. Median levels of amino-terminal peptide of type III procollagen and type IV collagen 7S domain in serum significantly decreased from 0.9 (0.6,1.3) to 0.6 (0.5,0.7) U/mL (P = 0.0010) and from 5.0 (4.4,6.7) to 3.9 (3.2,4.4) ng/mL (P = 0.015), respectively. Conclusion:, Liver stiffness measurement can be useful for monitoring regression of liver fibrosis during entecavir treatment in patients with chronic hepatitis B virus infection. [source]

    Efficacy of ezetimibe for the treatment of non-alcoholic steatohepatitis: An open-label, pilot study

    HEPATOLOGY RESEARCH, Issue 6 2010
    Masato Yoneda
    Aim:, Non-alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations. Methods:, We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50,60%, fat 20,30%, protein 15,20%) and exercise counseling from 3 months before the ezetimibe treatment. Results:, The serum aspartate aminotransferase, alanine aminotransferase, ,-glutamyl transpeptidase, low-density lipoprotein cholesterol, high-sensitivity C-reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow-up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage. Conclusion:, Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large-scale clinical trial in the future. [source]

    Transient elastography: Applications and limitations

    HEPATOLOGY RESEARCH, Issue 11 2008
    Kentaro Yoshioka
    Transient elastgraphy with use of FibroScan is one of most accurate methods for assessment of liver fibrosis. FibroScan can be readily used with an operator with a short training. In many different studies, liver stiffness measured by transient elastgraphy correlates well with fibrosis stages, and cutoff values of liver stiffness for fibrosis staging are similar even among different diseases. However there is wide variation of stiffness values in the same fibrosis stage, and some overlap between the adjacent stages. In addition, inflammatory activity and size of nodule of cirrhosis affect the liver stiffness values. The reproducibility may be reduced by age, obesity, steatosis, narrow intercostal space and lower degrees of hepatic fibrosis in patients. Thus the estimation of fibrosis stages from liver stiffness should be cautiously done. To improve the accuracy of liver fibrosis staging, the combination of transient elastography with other noninvasive methods such as FibroTest should be required. [source]

    Guidelines for the antiviral therapy of hepatitis C virus carriers with normal serum aminotransferase based on platelet counts

    HEPATOLOGY RESEARCH, Issue 1 2008
    Takeshi Okanoue
    Aim:, We aimed to identify the candidates for antiviral therapy, among patients who are hepatitis C virus (HCV) carriers with normal serum aminotransferase (ALT), focused on the inhibition of hepatocellular carcinoma (HCC). Methods:, Four hundred and sixty-four HCV carriers with normal serum ALT and 129 HCV carriers with persistently normal ALT (PNALT) and platelet (PLT) counts ,150 000/,L who received liver biopsies were enrolled. HCV carriers with normal serum ALT were divided into four groups according to their ALT levels (,30 U/L or 31,40 U/L) and PLT counts (,150 000/,L or <150 000/,L). Results:, In 129 HCV carriers with PNALT, the rate of progression of fibrosis stage was 0.05/year and no HCC was detected during the follow up for 10 years. Approximately 20% of patients with ALT ,40 U/L and PLT counts ,150 000/,Lwere at stage F2,3; however, approximately 50% of patients with ALT , 40 U/L and PLT counts <150 000/,L were at stage F2,4. An algorithm for the management of HCV carriers with normal serum ALT was advocated based on ALT and PLT counts. Conclusion:, The combination of ALT and PLT counts is useful for evaluating the fibrosis stage in HCV carriers with normal serum ALT. Most patients with PLT counts <150 000/,L are candidates for antiviral therapy, especially those with ALT levels ,31 U/L when we focus on the inhibition of the development of HCC. [source]

    Validity of FibroScan values for predicting hepatic fibrosis stage in patients with chronic HCV infection

    JOURNAL OF DIGESTIVE DISEASES, Issue 2 2009
    Ryosuke TAKEMOTO
    OBJECTIVE: The aim of this study was to validate the FibroScan system compared with liver histology and serum markers for the diagnosis of hepatic fibrosis. We also tried to determine the cut-off levels and assess the feasibility of using FibroScan values to predict the fibrosis stage. METHODS: In 44 patients with HCV infection, liver stiffness was evaluated by FibroScan, serum fibrosis markers and a liver biopsy. Associations between these indices were also analyzed. RESULTS: FibroScan values showed a good correlation with serum levels of type IV collagen, hyaluronic acid and procollagen-III-peptide, and with the platelet count. Compared with liver histology, the FibroScan values increased proportionally with the progression of the histological fibrosis stage. Advanced fibrosis (F3 or F4) could be efficiently predicted by a FibroScan cut-off value of 15 kPa. The FibroScan sensitivity, specificity, positive predictive value, negative predictive value and accuracy were 100%, 73.9%, 77.8%, 100%, and 86.4%, respectively. CONCLUSION: FibroScan values gave a good correlation with various markers of fibrosis and increased proportionally with the progression of the hepatic fibrosis stage. A FibroScan value of 15 kPa was found to be a significant separation limit for differentiating advanced fibrosis stages (F3 and F4) from the milder stages (F0,F2). FibroScan values are clinically useful for predicting the fibrosis stages and helpful in managing interferon therapy in patients with chronic hepatitis C. [source]

    Prevalence and risk factors of hepatic steatosis and its impact on liver injury in Chinese patients with chronic hepatitis B infection

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 9 2008
    Jun-ping Shi
    Abstract Background and Aims:, The clinical significance of hepatic steatosis in chronic hepatitis B infection (CHB) is unclear. The aims of this study were thus to investigate the prevalence and risk factors for hepatic steatosis in patients with CHB and its relationship with liver injury. Methods:, Consecutive patients with biopsy-proven CHB at Hangzhou Sixth People's Hospital between January 2005 and June 2007 were included. Patients co-infected with other viruses or suffering from liver disease of any other cause were excluded. Liver steatosis, necroinflammation and fibrosis were assessed by both Brunt and Scheuer classifications. Results:, A total of 1915 patients (1497 men) with a mean age of 31 ± 9.5 years were analyzed. Hepatic steatosis was present in 260 (14%) patients. The steatosis involved < 33% of hepatocytes in 90% of cases, and was more frequent among men than women (15% vs 8%, P < 0.001). Two-thirds (178 of 260) of patients with steatosis were hepatitis B e antigen (HBeAg)-positive, but there was no correlation with either serum HBeAg status or hepatitis B virus DNA titer. Degree of inflammation and fibrosis were more mild among those with steatosis than those without. Multivariate analysis showed that steatosis was independently associated with body mass index, serum triglyceride, apolipoprotein B, uric acid, and fasting blood glucose. However, fibrosis was only independently associated with age and inflammatory grade, and the latter associated with viral load and fibrosis stage. Conclusions:, Hepatic steatosis is common in CHB, it is associated with metabolic factors not viral ones, and does not appear to affect the severity of liver disease. [source]

    Model consisting of ultrasonographic and simple blood indexes accurately identify compensated hepatitis B cirrhosis

    JOURNAL OF GASTROENTEROLOGY AND HEPATOLOGY, Issue 8pt1 2008
    Yong-Peng Chen
    Abstract Background and Aim:, Several models for significant fibrosis or cirrhosis have been introduced for hepatitis C, but are seldom for hepatitis B. The present study retrospectively evaluates the relationship between ultrasonography, blood tests, and fibrosis stage, and constructs a model for predicting compensated cirrhosis. Methods:, A total of 653 patients with chronic hepatitis B who underwent liver biopsies, ultrasonographic scanning, and routine blood tests were retrospectively analyzed. The patients were divided into the model set and validation set. Blood tests and ultrasonographic indexes were analyzed statistically. An ultrasonographic scoring system consisting of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly was introduced. Results:, There were significant differences between cirrhosis and other fibrosis stages in ultrasonographic indexes of liver parenchyma, gallbladder, hepatic vessel, and splenomegaly. Ultrasonographic scores were significantly different between F4 and other fibrosis, and significantly correlated with fibrosis stage. Apart from alanine aminotransferase and alkaline phosphatase, blood tests and patients' age were correlated with fibrosis, and were significantly different between patients with and without cirrhosis. The model for cirrhosis indexes consisting of ultrasonographic score, patient's age, and variables, including platelet, albumin, and bilirubin predicted cirrhosis with area under receiver,operator curve of 0.907 in the model set and 0.849 in the validation set. Using proper cut-off values, nearly 81% patients could be accurately assessed for the absence or presence of cirrhosis. Conclusion:, The model consisting of ultrasonographic score, patients' age, blood variables of platelet, albumin, and bilirubin can identify hepatitis B cirrhosis with a high degree of accuracy. The application of this model would greatly reduce the number of biopsies. [source]

    Chronic hepatitis: Role of diffusion-weighted imaging and diffusion tensor imaging for the diagnosis of liver fibrosis and inflammation

    JOURNAL OF MAGNETIC RESONANCE IMAGING, Issue 1 2008
    Bachir Taouli MD
    Abstract Purpose To determine the diagnostic performance of liver apparent diffusion coefficient (ADC) measured with conventional diffusion-weighted imaging (CDI) and diffusion tensor imaging (DTI) for the diagnosis of liver fibrosis and inflammation. Materials and Methods Breathhold single-shot echo-planar imaging CDI and DTI with b-values of 0 and 500 second/mm2 was performed in 31 patients with chronic liver disease and 13 normal volunteers. Liver biopsy was performed in all patients with liver disease with a median delay of two days from MRI. Fibrosis and inflammation were scored on a 5-point scale (0,4). Liver ADCs obtained with CDI and DTI were compared between patients stratified by fibrosis stage and inflammation grade. Receiver operating characteristic (ROC) curve analyses were conducted to evaluate the utility of the ADC measures for prediction of fibrosis and inflammation. Results Patients with liver fibrosis and inflammation had significantly lower liver ADC than subjects without fibrosis or inflammation with CDI and DTI. For prediction of fibrosis stage , 1 and stage , 2, area under the ROC curve (AUC) of 0.848 and 0.783, sensitivity of 88.5% to 73.7%, and specificity of 73.3% to 72.7% were obtained, for ADC ,1.40 × 10,3 mm2/second and ,1.30 × 10,3 mm2/second (using CDI), respectively. For prediction of inflammation grade , 1, AUC of 0.825, sensitivity of 75.0%, and specificity of 78.6% were obtained using ADC , 1.30 × 10,3 mm2/second (using CDI). CDI performed better than DTI for diagnosis of fibrosis and inflammation. Conclusion Liver ADC can be used to predict liver fibrosis and inflammation with acceptable sensitivity and specificity. J. Magn. Reson. Imaging 2008;28:89,95. © 2008 Wiley-Liss, Inc. [source]

    Optimal combinations of ultrasound-based and serum markers of disease severity in patients with chronic hepatitis C

    JOURNAL OF VIRAL HEPATITIS, Issue 8 2010
    J. F. L. Cobbold
    Summary., Combinations of noninvasive markers may improve discrimination of chronic liver disease severity. The aims of this study were to compare four validated serum and ultrasound-based markers of hepatic disease severity head-to-head with liver biopsy and to assess optimal combinations with consideration of cost. A total of 67 patients with biopsy-proven chronic hepatitis C underwent all four techniques on the same visit [aspartate aminotransferase (AST) to platelet ratio index (APRI); Enhanced Liver Fibrosis (ELF) panel; transient elastography (TE) and ultrasound microbubble hepatic transit times (HTT)]. Markers were combined according to increasing financial cost and ordinal regression used to determine contributions. APRI, ELF, TE and HTT predicted cirrhosis with diagnostic accuracy of 86%, 91%, 90% and 83% respectively. ELF and TE were the most reliable tests with an intra-class correlation of 0.94 each. Either ELF or TE significantly enhanced the prediction of fibrosis stage when combined with APRI, but when combined together, did not improve the model further. Addition of third or fourth markers did not significantly improve prediction of fibrosis. Combination of APRI with either ELF or TE effectively predicts fibrosis stage, but combinations of three or more tests lead to redundancy of information and increased cost. [source]

    Adiponectin changes in HCV-Genotype 4: relation to liver histology and response to treatment

    JOURNAL OF VIRAL HEPATITIS, Issue 10 2009
    M. Derbala
    Summary., Recently, attention has been focussed on adiponectin and its changes in different types of chronic liver disease. Its relation to hepatic fibrosis and insulin resistance in post-hepatitis liver disease is not clear. The aim of this study was to clarify the adiponectin changes in genotype 4 hepatitis C virus (HCV)-infected patient in relation to liver histology and insulin resistance, and its usefulness as a predictor of hepatic fibrosis and response to treatment. Total adiponectin and its high molecular weight (HMW) form as well as insulin levels were studied in 92 chronic HCV, genotype 4 and 66 healthy control volunteers. Neither total adiponectin (r = 0.101, P = 0.220) nor HMW adiponectin (r = 0.081, P = 0.328) correlated with viral load. Total and not HMW adiponectin was significantly correlated with hepatic fibrosis and inflammation (r = 0.267, P = 0.002, r = 0.278, P < 0.001, respectively). In addition, total adiponectin (r = 0.224, P = 0.002) and HMW adiponectin (r = 0.266, P < 0.0006) significantly correlated with insulin resistance. As fibrosis did not correlate with insulin resistance (r = 0.081, P = 0.204), the correlation between total adiponectin and fibrosis was not mediated by insulin resistance. Multivariable regression analysis, (including pretreatment cases and controls) revealed that total adiponectin was significantly associated with gender, being lower among male subjects (X2 = 13.04, P = 0.0001). The multivariable regression model supported the lack of association between insulin resistance and total adiponectin levels (X2 = 1.88, P = 0.171), while non cirrhotics had significantly lower total adiponectin levels than cirrhotics (X2 = 10.90, P = 0.004) and lower level of inflammation significantly lower total adiponectin levels than more severe inflammation (X2 = 8.95, P = 0.003). Total or HMW adiponectin did not yield receiver operating characteristic (ROC) curves with area under the curve (AUC) >75%, thus the cutoff points have poor sensitivity/specificity as predictors of fibrosis. However, as a predictor of end-of-treatment response, the ROC curve of adiponectin index gave yield an AUC = 81.4%. We can conclude that total adiponectin level, in HCV genotype 4 patients, increases with progression of hepatic fibrosis regardless of insulin resistance. Its high molecular form does not have such correlation. The adiponectin changes are not related to viral load, insulin resistance or other demographic data suggesting that this change is histologically related. In spite of this, no adiponectin cutoff level had reasonable sensitivity/specificity for predicting hepatic fibrosis stage, while this may be used as a predictor for antiviral response possibly reflecting improvement in hepatic inflammation post treatment. [source]

    Monitoring SCCA-IgM complexes in serum predicts liver disease progression in patients with chronic hepatitis

    JOURNAL OF VIRAL HEPATITIS, Issue 4 2008
    A. Biasiolo
    Summary., About 30% of the patients with chronic hepatitis develop a progressive liver disease and one of the most intriguing issues is the detection of noninvasive markers for fibrosis stage and disease progression. High levels of squamous cell carcinoma antigen (SCCA)-immunoglobulin M (IgM) are detectable in hepatocellular carcinoma and their increase in cirrhotic patients can predict tumour development. As SCCA-IgM can also be detectable at low percentages in patients with chronic hepatitis, the aim of this study was to assess SCCA-IgM complexes in relation to disease outcome in this group of patients. An ELISA assay was used to determine the presence of SCCA-IgM in 188 patients with chronic hepatitis and in 100 controls. An additional serum sample was available after a median period of 6 years in 57 untreated patients: these patients were subdivided in group A, including eight patients with a fibrosis score increase ,2 in a second liver biopsy and group B, including 49 patients without fibrosis progression during a similar follow up. SCCA-IgM complexes were detectable in 63 of 188 (33%) patients but in none of the controls. A significant increase of SCCA-IgM levels over time was observed in patients with fibrosis progression (mean ± SD: 117 ± 200 U/mL/year), but not in those without histologic deterioration (mean ± SD: ,8.8 ± 31 U/mL/year, P < 0.0001). In conclusion, monitoring SCCA-IgM levels over time appears a useful approach to identify patients with chronic hepatitis at higher risk for cirrhosis development. [source]

    Predicting progressive hepatic fibrosis stage on subsequent liver biopsy in chronic hepatitis C virus infection,

    JOURNAL OF VIRAL HEPATITIS, Issue 1 2005
    J. D. Collier
    Summary., Retrospective cross-sectional studies indicate that 20% with chronic hepatitis C virus (HCV) infection become cirrhotic within 20 years. Known risk factors for advanced hepatic fibrosis include age at time of infection, male sex, excess alcohol consumption and cytokine polymorphisms. Prospective study to assess and identify factors predictive of change in hepatic fibrosis stage in chronic HCV infection by interval protocol liver biopsy was performed. One hundred and five patients with paired liver biopsy specimens separated by a mean 41 months were recruited from a cohort of 823 HCV carriers. Five per cent developed worsening hepatic fibrosis by more than two stages. In 43% there was no change in fibrosis stage. Excessive alcohol intake currently (P = 0.037) or previously (P = 0.07) predicted progression. In contrast, always having a normal alanine transaminase (P = 0.038) and always being negative in serum for HCV RNA (P =0.067) predicted no progression. Three models were developed to predict outcome. Progressive fibrosis was predicted by baseline fibrosis (P = 0.018), steatosis (P = 0.02) and age (P = 0.017). The rate of progressive fibrosis was predicted by baseline fibrosis (P = 0.0002), steatosis (P =0.039) and lobular inflammation (P = 0.09). Fibrosis stage on the second biopsy was predicted by baseline fibrosis alone (P = 0.01). The rate of progression varies widely. Alcohol misuse is an important co-factor. Progressive fibrosis can be predicted at first liver biopsy, where baseline fibrosis is most critical, allowing targeted therapy for those with early disease and a significant risk of progression. [source]

    Reconstructing and predicting the hepatitis C virus epidemic in Greece: increasing trends of cirrhosis and hepatocellular carcinoma despite the decline in incidence of HCV infection

    JOURNAL OF VIRAL HEPATITIS, Issue 4 2004
    V. Sypsa
    Summary., In this study, a comprehensive methodology for modelling the hepatitis C virus (HCV) epidemic is proposed to predict the future disease burden and assess whether the recent decline in the incidence of HCV may affect the future occurrence of cirrhosis and hepatocellular carcinoma (HCC) cases. Using the prevalence of HCV, the distribution of chronic hepatitis C (CHC) patients within the various transmission groups and their infection-onset times, it was possible to reconstruct the incident infections per year in the past that progressed to CHC in Greece. The natural history of the disease was simulated in subcohorts of newly infected subjects using transition probabilities derived either empirically between fibrosis stages 0,4 or from literature review. Annual estimates of the incidence and prevalence of CHC by fibrosis stage, HCC and mortality in Greece were obtained up to 2030. HCV incidence peaked in the late 1980s at five new infections/10 000 person-years. Under the assumption of 20,100% decline in HCV incidence after 1990, the cumulative number of incident cirrhosis and HCC cases from 2002,2030 was projected to be lower by 9.6,48.2% and 5.9,29.5%, respectively, than that estimated under the assumption of no decline. However, the prevalent cirrhotic/HCC cases and HCV-related deaths are predicted to decline in the next 30 years only under the assumption of complete elimination of new HCV infections after 1990. Despite the progress in the reduction of HCV transmission, primary prevention does not seem adequate to reverse the rise in the incidence of cirrhosis and HCC. [source]

    A multicentre study of the usefulness of liver biopsy in hepatitis C

    JOURNAL OF VIRAL HEPATITIS, Issue 4 2004
    V. G. Bain
    Summary., The role of liver biopsy in the assessment of chronic hepatitis C is generally accepted yet there is no prospective data available to quantify its contribution. A previous single centre pilot study suggested that the clinician could predict the amount of fibrosis and to a lesser extent, inflammation with moderate accuracy. The 2002 National Institute of Health Hepatitis C Consensus Conference recommended further study of the role of liver biopsy. Our objective was to compare a prediction of biopsy findings by expert clinicians using usually available clinical and laboratory data to actual biopsy results in order to determine whether biopsy is required routinely. This was a prospective observational study conducted at seven university centres in which the accuracy of clinician's predictions of the degree of inflammation and fibrosis were compared with the actual liver biopsy using an adaptation of a standard histological scoring system. We studied 81 adults with previously untreated chronic hepatitis C, raised serum transaminases and positive HCV-RNA in serum. Clinicians predicted the inflammatory grade in 44 of 80 cases (55%) and the fibrosis stage in 46 of 81 cases (57%). Nine of 17 cirrhotic cases were predicted (sensitivity 53%, specificity 56%). No unexpected additional diagnoses were made on the biopsies. Thus despite knowledge of the clinical and laboratory investigations of patients with hepatitis C, clinicians are unable to accurately predict the hepatic inflammatory grade and fibrotic stage. Liver biopsy is an essential investigation to accurately evaluate the grade and stage of liver disease patients with hepatitis C. [source]

    Open-label pilot study of folic acid in patients with nonalcoholic steatohepatitis

    LIVER INTERNATIONAL, Issue 2 2007
    Phunchai Charatcharoenwitthaya
    Abstract: Background/Aims: Folate deficiency disturbs hepatic methionine metabolism and promotes the development of steatohepatitis in animal models. Our aims were (1) to determine the safety and efficacy of folic acid treatment in patients with nonalcoholic steatohepatitis (NASH) on changes in liver biochemistries, and (2) to investigate the presence of subclinical folate deficiency in this population. Methods: Patients with biopsy-proven NASH were treated with folic acid 1 mg/day for 6 months. Liver enzymes and adverse events were monitored every 3 months until completion. Results: Ten patients (one male and nine females) with a median age of 54 years were enrolled in this study. At baseline, the median steatosis grade was 2 (range 1,3), the median necroinflammatory grade was 1 (1,3), and the median fibrosis stage was 2 (0,4). The median level of red cell folate was 526 ng/ml (range 99,708); the normal level was 268,616 ng/ml. One compensated cirrhotic patient had folate deficiency. No serious adverse events occurred. After 6 months of therapy, no significant reductions in serum aspartate and alanine aminotransferase levels (60±25 vs. 54±29, P=0.5 and 86±29 vs. 83±42, P=0.6, respectively), were observed. Serum levels of bilirubin, alkaline phosphatase, albumin, and prothrombin time remained in the normal range during treatment in all patients. Conclusion: Six months of therapy with folic acid at a dose of 1 mg/day, although safe and well tolerated, does not lead to a significant biochemical improvement in patients with NASH. In a small number of patients, folate deficiency was present in only a cirrhotic patient. [source]

    Intrahepatic expression of the hepatic stellate cell marker fibroblast activation protein correlates with the degree of fibrosis in hepatitis C virus infection

    LIVER INTERNATIONAL, Issue 2 2002
    MT Levy
    Abstract: Background: Activated hepatic stellate cells (HSCs), recognised by their , smooth muscle actin immunoreactivity, are primarily responsible for liver fibrosis. However, the presence of , smooth muscle actin positive HSCs is not always associated with the development of liver fibrosis. Recently, other markers of human HSCs including the gelatinase fibroblast activation protein (FAP) and glial fibrillary acidic protein have been identified. Aims: We examined the relationship between the expression of these HSC markers and the severity of liver injury in patients with chronic hepatitis C virus infection. Methods: Liver tissue from 27 patients was examined using immunohistochemistry. Linear correlation analysis was used to compare staining scores with the stage and grade of liver injury. Results,Conclusions: FAP expression, seen at the tissue-remodelling interface, was strongly and significantly correlated with the severity of liver fibrosis. A weaker correlation was seen between glial fibrillary acidic protein expression and fibrosis stage. This contrasted with the absence of a relationship between , smooth muscle actin and the fibrotic score. A correlation was also observed between FAP expression and necroinflammatory score. In summary, FAP expression identifies a HSC subpopulation at the tissue-remodelling interface that is related to the severity of liver fibrosis. [source]

    Natural history of unexplained chronic hepatitis after liver transplantation

    LIVER TRANSPLANTATION, Issue 7 2007
    Wing-Kin Syn
    Unexplained chronic hepatitis (CH) in the adult liver allograft recipient is not uncommon, but its natural history and clinical significance is unknown. A retrospective study was undertaken of adult liver allograft recipients to determine the frequency and natural history of unexplained CH. We evaluated only those patients who had undergone ,2 liver biopsies after 6 months and were grafted for indications where recurrent disease could be confidently excluded (alcoholic liver disease [ALD] in those who remained abstinent and fulminant hepatic failure [FHF] from drug reactions). Of 288 patients who were transplanted for ALD or FHF, 30 fulfilled the above criteria. CH was first diagnosed at a median of 15.25 months after transplantation. A total of 24 patients showed mild necroinflammatory changes, and 12 had mild or moderate fibrosis. Liver tests did not reflect the presence or degree of inflammation or fibrosis. After a median of 4 years, necroinflammatory scores were increased in 5; new or progressive fibrosis was noted in 13%; 3 had developed cirrhosis; and 5 developed clinical evidence of portal hypertension. Progressive fibrosis was associated with a high titer of anti-nuclear antibodies (>1:1600) and a portal tract plasma cell infiltrate. There was a trend for correlation between necroinflammatory activity and fibrosis stage, but this did not reach statistical significance (P = 0.06). Serum alkaline phosphatase (P = 0.012) and female gender of the donor (P = 0.033) were associated with progressive fibrosis. Unexplained CH is not uncommon in the liver allograft and may progress to established cirrhosis in a subgroup of patients transplanted for ALD or FHF. Standard liver tests do not reflect the extent of these changes, so protocol liver biopsies may be required to detect these changes. We recommend careful history and follow-up in these patients. Liver Transpl, 2007. © 2007 AASLD. [source]

    Transient elastography in the assessment of liver fibrosis in adult thalassemia patients,

    AMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2010
    Mirella Fraquelli
    Transient elastography (TE) is a valuable noninvasive technique of measuring liver stiffness and a reliable tool for predicting hepatic fibrosis in patients with chronic liver disease. The role of TE in patients with ,-thalassemia has not been extensively investigated. The present study aimed to evaluate the role of TE in the assessment of hepatic fibrosis in 115 adult patients with ,-thalassemia major (TM) (#59) or intermedia (TI) (#56). TE was performed according to current practice. Histologic data were obtained in 14 cases. Liver iron concentration was assessed by atomic absorption spectrometry and T2* magnetic resonance. In patients with TM, the proportion of anti-HCV positive viremic patients, median serum ferritin levels, and TE values were significantly higher than in TI. In the group of 14 patients who underwent liver biopsy, a significant positive correlation was observed between liver stiffness and fibrosis stage (r = 0.73, P = 0.003). Severe fibrosis is diagnosed with a sensitivity of 60% and a specificity of 89%, whereas cirrhosis is detected with a sensitivity of 100% and a specificity of 92%. At multivariate analysis, the variables independently associated with TE were ALT, GGT, and bilirubin levels in both groups and, in patients with TM, HCV RNA positivity. In ,-thalassemia patients, TE is a reliable tool for assessing liver fibrosis even if the influence of iron overload has to be clarified. Am. J. Hematol. 85:564,568, 2010. © 2010 Wiley-Liss, Inc. [source]

    Insulin Resistance, Serum Adipokines and Risk of Fibrosis Progression in Patients Transplanted for Hepatitis C

    AMERICAN JOURNAL OF TRANSPLANTATION, Issue 6 2009
    B. J. Veldt
    In the nontransplant setting diabetes mellitus is a risk factor for disease progression in patients with chronic hepatitis C virus (HCV) infection. The impact of early insulin resistance on the development of advanced fibrosis, even in the absence of clinically apparent diabetes mellitus, is not known. Our aim was to determine whether the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) can be used to identify insulin-resistant patients at risk for rapid fibrosis progression. Cohort study including patients transplanted for chronic HCV between January 1, 1995 and January 1, 2005. One hundred sixty patients were included; 25 patients (16%) were treated for diabetes mellitus and 36 patients (23%) were prediabetic, defined as HOMA-IR >2.5. Multivariate Cox regression analysis showed that insulin resistance (hazard ratio (HR) 2.07; confidence interval (CI) 1.10,3.91, p = 0.024), donor age (HR 1.33;CI 1.08,1.63, p = 0.007) and aspartate aminotransferase (HR 1.03;CI 1.01,1.05, p < 0.001) were significantly associated with a higher probability of developing advanced fibrosis, i.e. Knodell fibrosis stage 3 or 4, whereas steatosis (HR 0.94;CI 0.46,1.92, p = 0.87) and acute cellular rejection (HR 1.72;CI 0.88,3.36, p = 0.111) were not. In conclusion, posttransplant insulin resistance is strongly associated with more severe recurrence of HCV infection. HOMA-IR is an important tool for the identification of insulin resistance among patients at risk for rapid fibrosis progression after liver transplantation for HCV. [source]

    An inhibitor of interleukin-6 trans-signalling, sgp130, contributes to impaired acute phase response in human chronic liver disease

    CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 3 2009
    A. Lemmers
    Summary In chronic liver disease, high circulating interleukin (IL)-6 contrasts with a poor acute phase response. We evaluated the impact of liver and circulating IL-6-receptor (IL-6R) forms on IL-6 bioactivity in chronic liver disease. IL-6, soluble IL-6-receptor and sgp130 levels were assayed in plasma from 45 patients with alcoholic liver disease, 84 with hepatitis C virus (HCV) infection undergoing transjugular liver biopsies and 15 healthy subjects. IL-6R mRNA was quantified on liver extracts from 54 patients with alcoholic liver disease with or without cirrhosis and 18 HCV-infected patients. The effect of gp130,Fc on fibrinogen secretion induced by IL-6 trans-signalling was evaluated on hepatocyte cultures. Levels of plasma IL-6 and sgp130, but not soluble IL-6R, increased with the stage of chronic liver disease, and correlated significantly with disease severity. Alcoholic liver disease patients had higher plasma IL-6 levels than hepatitis C, but lower liver IL-6R expression. In alcoholic and HCV-related liver diseases, liver IL-6R expression decreased with advanced fibrosis stage. In vitro, on hepatocytes, gp130,Fc blunted the acute phase response while soluble IL-6R enhanced IL-6 stimulation. In advanced chronic liver disease, high plasma IL-6 is associated with low liver IL-6R expression. This situation enables high plasma sgp130 to act as a major negative regulator of liver IL-6 trans-signalling, as demonstrated functionally here on hepatocytes. This might explain the poor acute phase response induced by IL-6 in chronic liver disease. [source]