Hepatic Fibrosis In Chronic Hepatitis Research Articles

Value of α-smooth muscle actin and glial fibrillary acidic protein in predicting early hepatic fibrosis in chronic hepatitis C virus infection.

Introductionα-Smooth muscle actin (α-SMA)-positive hepatic stellate cells (HSCs) are pericytes responsible for fibrosis in chronic liver injury. The glial fibrillary acidic protein (GFAP), commonly expressed by astrocytes in the central nervous system, is expressed in vivo in the liver in a subpopulation of quiescent stellate cells. The reports concerning GFAP expression in human liver are still conflicting. The aim of the study is investigation the utility of GFAP compared to α-SMA as an indicator of early activated HSCs, in predicting fibrosis in chronic hepatitis C (CHC) patients.Material and methodsWith immunohistochemistry and a semi-quantitative scoring system, the expressions of α-SMA and GFAP on HSCs in liver biopsies from patients with pure CHC (n = 34), hepatitis C virus-induced cirrhosis (n = 24), mixed CHC/schistosomiasis (n = 11) and normal controls (n = 10) were analysed.ResultsThe immunoreactivity of α-SMA and GFAP in perisinusoidal, periportal and pericentral areas was assessed. α-Smooth muscle actin and GFAP-positive HSCs were significantly increased in all diseased groups compared with normal controls. In pure CHC with or without cirrhosis, perisinusoidal α-SMA-positive HSCs were predominant in relation to GFAP-positive cells. On the other hand, GFAP-positive cells were predominant in the group of schistosomiasis as compared with the other diseased groups. It was noticed that expression of GFAP on perisinusoidal HSCs in CHC patients sequentially decreased with the progression of fibrosis.ConclusionsGlial fibrillary acidic protein could represent a more useful marker than α-SMA of early activation of HSCs in CHC patients and seems to be an early indicator of hepatic fibrogenesis.

Liver fibrosis is induced by insulin resistance by enhancing the ductular reaction that undergo epithelial–mesenchymal transition in chronic hepatitis C

Background. The mechanisms for progression of liver injury towards hepatic fibrosis in chronic hepatitis C (HCV) are unknown. Insulin resistance (IR) is an independent predictor of HCV-related fibrosis. A ductular reaction (DR) occurs during chronic liver injury and represents a potential profibrogenic mechanism by the recruitment of myofibroblasts and by undergoing epithelial–mesenchymal transition (EMT).

Diabetes Mellitus Is Associated with Impaired Response to Antiviral Therapy in Chronic Hepatitis C Infection

Insulin resistance may promote hepatic fibrosis in chronic hepatitis C (HCV) and has emerged as a cofactor in failure to achieve sustained viral response (SVR). (1) To assess the association of diabetes mellitus (DM) in HCV patients to the severity of hepatic fibrosis and to the response to antiviral treatment. (2) To assess the safety of pegylated interferon and ribavirin combination therapy (Peg IFN/RBV) in diabetic HCV patients. Methods HCV diabetics (n=61) were identified. A 2:1 matching control group was used to identify independent factors of advanced fibrosis and treatment failure. Compared to HCV non-diabetics, HCV diabetics were more likely to have steatosis (P<0.0001) and advanced fibrosis (P=0.003). Patients' age, Caucasian ethnicity, obesity, and histologic activity index were independently associated with advanced fibrosis (P<0.05). Only 23% of HCV diabetics achieved SVR compared to 46% of HCV non-diabetics (P=0.003). DM, genotype 1, high baseline viral load, and African- American ethnicity were independently associated with less SVR (P<0.05). Significant adverse events were more common in HCV diabetics compared to HCV non-diabetics (P=0.001). Side effects did not increase in patients receiving PEG IFN/RBV and insulin sensitizers. Conclusion DM was associated with impaired virologic response to PEG IFN/RBV in HCV patients. Adverse events during therapy were more frequent in diabetic compared to non-diabetic HCV patients.

The presence of steatosis and elevation of alanine aminotransferase levels are associated with fibrosis progression in chronic hepatitis C with non-response to interferon therapy

Interferon (IFN) therapy leads to regression of hepatic fibrosis in chronic hepatitis C patients who achieve a sustained virologic response (SVR), while the beneficial effect is limited in those who fail to do so. The aim of the present study was to define factors associated with progression of fibrosis in patients who do not achieve a SVR. Fibrosis staging scores were compared between paired liver biopsies before and after IFN in 97 chronic hepatitis C patients who failed therapy. The mean interval between biopsies was 5.9 years. Factors associated with progression of fibrosis were analyzed. Fibrosis progressed in 23%, remained unchanged in 47% and regressed in 29%. Steatosis and a high average alanine aminotransferase (ALT) between biopsies were independent factors for progression of fibrosis with risk ratios of 5.53 and 4.48, respectively. Incidence and yearly rate of progression of fibrosis was 64% and 0.22+/-0.29 fibrosis units per year in those with both risk factors compared to 8% and -0.04+/-0.17 fibrosis units per year in those negative for both factors. Hepatic steatosis and elevated ALT levels are risk factors for progression of fibrosis in chronic hepatitis C patients who fail to achieve a SVR to IFN therapy and therefore may be therapeutic targets to halt the potentially progressive disease.

Serum hyaluronic acid as a noninvasive marker of hepatic fibrosis in chronic hepatitis B

Background/Aims:Chronic hepatitis B is a serious global health problem. Liver biopsy is currently recommended as the gold standard for the evaluation of the degree of fibrosis in patients with chronic hepatitis B. This procedure, however, is invasive and has potential complications. In this study, we attempted to validate the level of hyaluronic acid as a simple laboratory test to discriminate between patients with and without significant fibrosis in chronic hepatitis B.Methods:This study included 93 patients with chronic hepatitis B who had undergone percutaneous liver biopsy from 2003 to 2006. At the time of biopsy, a sample of serum was taken for the hyaluronic acid (HA) assay. Histological assessment consisted of the semiquantitative analysis of the degree of fibrosis according to the criteria proposed by the Ishak system. These findings were then compared by using statistical analysis.Results:HA levels and stage groups of fibrosis were well correlated (Spearman r = 0.945, P < 0.005). There was a significant increase in HA levels when considering S0 to S6. The mean values of HA concentrations were 59.7 ± 10.5 ng/mL for stages 0–2, 149.4 ± 15.9 ng/mL for stages 3–4 , and 284.5 ± 14.5 ng/mL for the last group (stages 5-6). There were significant differences between the three groups. Serum HA levels of cases with extensive fibrosis were significantly higher than in those with mild and moderate fibrosis (P = 0.0001, P = 0.0005, and P = 0.0001, respectively).Conclusion:Serum HA level is a precise predictor of extensive liver fibrosis in chronic hepatitis B. HA is well correlated with the stage of fibrosis and can reflect the severity of fibrosis. Thus, it can be used as a noninvasive test to monitor these patients.

Assessment of FIBRO Spect II to Detect Hepatic Fibrosis in Chronic Hepatitis C Patients

Assessment of FIBRO Spect II to Detect Hepatic Fibrosis in Chronic Hepatitis C Patients

The Accuracy of Sonography in Predicting Steatosis and Fibrosis in Chronic Hepatitis C

The accuracy and clinical significance of sonography (US) in demonstrating fatty liver and hepatic fibrosis in chronic hepatitis C (CHC) are rarely reported. US had sensitivity 71.1%, specificity 72.9%, 58.7% positive predictive value (PPV), and 82.3% negative predictive value (NPV) in demonstrating histological steatosis > or =5%. US had sensitivity 85.7%, specificity 60.4%, 13% PPV, and 98.4% NPV in demonstrating histological steatosis > or =30% with clinical significance in predicting prognosis and therapeutic response in CHC. Subjects with fatty liver on US had a greater prevalence of body mass index (BMI) > or =25 kg/m2, inflammation-necrosis grade >2, and total bilirubin <1.2 mg/dl in multivariate analyses. US had sensitivity 27.4%, specificity 62.5%, 71.9% PPV, and 19.7% NPV in demonstrating histological fibrosis of stage II or above, and sensitivity 13.6%, specificity 66.3%, 9.4% PPV, and 75.0% NPV in demonstrating fibrosis of stage III or above. There was no correlation between fibrotic sonographic patterns and histological stage of fibrosis (r = -0.167, P = 0.083). Besides hepatic steatosis, clinicians should be alert to the possibility of advanced necrosis-inflammation grade in interpreting a report of bright liver on gray-scale US. Gray-scale US cannot replace liver biopsy as the optimal diagnostic procedure for the prediction of hepatic steatosis and fibrosis prior to initiating therapy for CHC.

Abrogation of the Antifibrotic Effects of Natural Killer Cells/Interferon-γ Contributes to Alcohol Acceleration of Liver Fibrosis

Chronic alcohol drinking accelerates liver fibrosis in patients with viral hepatitis that cannot be fully explained by ethanol-enhanced liver damage. Here, we identified a novel mechanism by which alcohol accelerates liver fibrosis: inhibition of the antifibrotic effects of natural killer (NK) cells and interferon-gamma (IFN-gamma). Alcohol administration was achieved by feeding mice with a liquid diet containing 5% ethanol for 8 weeks. Liver fibrosis was induced by administration of carbon tetrachloride (CCl(4)) for 2 weeks. Hepatic stellate cells (HSCs) were also isolated and cultured for in vitro studies. CCl(4) treatment induced greater fibrosis and less apoptosis of HSCs in ethanol-fed mice compared with pair-fed mice. Polyinosinic-polycytidylic acid (Poly I:C) or IFN-gamma treatment inhibited liver fibrosis in pair-fed but not in ethanol-fed mice. Poly I:C activation of NK cell cytotoxicity against HSCs was attenuated in ethanol-fed mice compared with pair-fed mice, which was due to reduced natural killer group 2 member D (NKG2D), tumor necrosis factor-related apoptosis-inducing ligand, and IFN-gamma expression on NK cells from ethanol-fed mice. In vitro, HSCs from ethanol-fed mice were resistant to IFN-gamma-induced cell cycle arrest and apoptosis compared with pair-fed mice. Such resistance was due to diminished IFN-gamma activation of signal transducer and activator of transcription 1 (STAT1) in HSCs from ethanol-fed mice caused by the induction of suppressors of cytokine signaling proteins and the production of oxidative stress. Finally, HSCs from ethanol-fed mice were resistant to NK cell killing, which can be reversed by transforming growth factor-beta1 (TGF-beta1) neutralizing antibody. Chronic ethanol consumption attenuates the antifibrotic effects of NK/IFN-gamma/STAT1 in the liver, representing new and different therapeutic targets with which to treat alcoholic liver fibrosis.

Assessment of FIBRO Spect II to Detect Hepatic Fibrosis in Chronic Hepatitis C Patients

Background The degree of liver fibrosis in patients with Hepatitis C (HCV) provides important prognostic information; however, the only current method available to obtain this information is by performing a liver biopsy. Liver biopsies are invasive, associated with complications, and costly. There has been recent interest in developing a panel of serum markers that can reliably predict the presence of fibrosis and, thus, obviate the need for a liver biopsy. Our objective was to prospectively validate a panel of serum fibrosis markers (FIBRO Spect SM II) that has been recently developed. Methods Serum was obtained from 108 consecutive HCV (15% with HCV/ETOH) patients seen in a hepatology clinic at a single tertiary care center at the time of liver biopsy. The performance of FIBRO Spect II (consisting of 3 fibrosis markers: hyaluronic acid, tissue inhibitor of metalloproteinases 1, and alpha-2-macroglobulin) in differentiating mild (F0-F1) from significant (F2-F4) fibrosis was assessed by comparing the panel results with performed liver biopsy. Results The prevalence of significant fibrosis in the study group was 36.1%. The diagnostic value of the serum marker panel to detect significant fibrosis as assessed by area under the receiver operating characteristic (ROC) curve was 0.826. Performance characteristics are as follows: sensitivity 71.8%, specificity 73.9%, positive predictive value 60.9%, negative predictive value 82.3%, and overall accuracy of 73.1%. Conclusion This prospective study supports the clinical utility of serum markers in detecting fibrosis and validates the performance of FIBRO Spect II in a prospective cohort of patients. The high negative predictive value of the test provides a reliable alternative to rule out severe fibrosis.

Noninvasive diagnosis of hepatic fibrosis in chronic hepatitis C

Assessment of hepatic fibrosis is important for determining prognosis, guiding management decisions, and monitoring disease. Histological evaluation of liver biopsy specimens is currently considered the reference test for staging hepatic fibrosis. Since liver biopsy carries a small but significant risk, noninvasive tests to assess hepatic fibrosis are desirable. This editorial gives an overview on noninvasive methods currently available to determine hepatic fibrosis and their diagnostic accuracy for predicting significant fibrosis and cirrhosis in chronic hepatitis C. Based on available data, the performance of simple tests derived from routine laboratory parameters appears to be similar to that of more complex and expensive fibrosis panels. Transient elastography seems more accurate than blood tests for diagnosing cirrhosis.

Non-invasive markers of hepatic fibrosis in chronic Hepatitis B: A review

Assessment of fibrosis is important in chronic hepatitis B for a number of reasons including decision-making regarding treatment and predicting prognosis.Currently liver biopsy is considered the gold standard for assessing liver histology. However, since liver biopsy has significant limitations,the quest for a non-invasive alternative to assess hepatic fibrosis continues. A review of published literature reveals that extensive research has been carried out in this field, and several simple to complicated alternatives to liver biopsy for assessing hepatic fibrosis have been evaluated. A few have shown promise too, but we are still short of an ideal alternative to liver biopsy. Despite the fact that much has been done, we still have a long way to go before we can finally say farewell to liver biopsy.

APRI: An Easy and Validated Predictor of Hepatic Fibrosis in Chronic Hepatitis C

To evaluate the aspartate aminotransferase/platelet ratio index (APRI) as a predictor of the presence or absence of significant fibrosis on liver biopsy of patients with chronic hepatitis C (HCV). The decision to treat HCV is often made on the basis of the presence or absence of significant fibrosis on the liver biopsy. Because liver biopsy is expensive and invasive a noninvasive marker to evaluate hepatic fibrosis would be useful. The APRI is an easy to calculate index that is one of several markers that have been proposed. We retrospectively reviewed the charts of 339 patients with chronic HCV who had liver biopsies from January 2000 to March 2003. We subsequently evaluated 151 patients receiving pretreatment evaluation liver biopsies who had serum aspartate aminotransferase, platelets, routine liver function tests, and demographic data obtained. All liver biopsies were staged by the Batts Ludwig criteria. The area under the curve of the receiver operator characteristics of the calculated APRI compared with the liver biopsy demonstrated that the fibrosis score was 0.889 in the prospective group and 0.790 in the retrospective group. To achieve predictive values of approximately 90%, useful cutoffs were found at 0.40 and 1.5 in the retrospective study, and 0.42 and 1.2 in the prospective study leaving intermediate zones of 58.9% and 41.1%, respectively. In the prospective group, 34 of 36 patients with a value of <0.42 were accurately predicted as having mild fibrosis, whereas 50 of 54 patients with a value >1.2 were accurately predicted to have significant fibrosis. The APRI is a good estimator of hepatic fibrosis and was more accurate in a prospective group than a retrospective one. It potentially could be used to decrease the number of liver biopsies.

Severe hepatic fibrosis in chronic hepatitis C

Severe hepatic fibrosis in chronic hepatitis C

Progression of hepatic fibrosis in chronic hepatitis C and the need for treatment in mild disease

The natural history of fibrosis development in hepatitis C is highly variable. Host, hepatic and viral factors have all been reported to influence the rate of fibrosis progression. An understanding of these factors is particularly important in the management of patients with mild disease, where treatment should be tailored to their personal risk of progression to cirrhosis.

Assessment of biliary fibrosis by transient elastography in patients with PBC and PSC

Noninvasive measurement of liver stiffness with transient elastography has been recently validated for the evaluation of hepatic fibrosis in chronic hepatitis C. The current study assessed the diagnostic performance of liver stiffness measurement (LSM) for the determination of fibrosis stage in chronic cholestatic diseases. One hundred one patients with primary biliary cirrhosis (PBC, n=73) or primary sclerosing cholangitis (PSC, n=28) were prospectively enrolled in a multicenter study. All patients underwent liver biopsy (LB) and LSM. Histological and fibrosis stages were assessed on LB by two pathologists. LSM was performed by transient elastography. Efficiency of LSM for the determination of histological and fibrosis stages were determined by a receiver operating characteristics (ROC) curve analysis. Analysis failed in six patients (5.9%) because of unsuitable LB (n=4) or LSM (n=2). Stiffness values ranged from 2.8 to 69.1 kPa (median, 7.8 kPa). LSM was correlated to both fibrosis (Spearman's rho= 0.84, P < .0001) and histological (0.79, P < .0001) stages. These correlations were still found when PBC and PSC patients were analyzed separately. Areas under ROC curves were 0.92 for fibrosis stage (F) > or =2, 0.95 for F > or =3 and 0.96 for F=4. Optimal stiffness cutoff values of 7.3, 9.8, and 17.3 kPa showed F > or =2, F > or =3 and F=4, respectively. LSM and serum hyaluronic acid level were independent parameters associated with extensive fibrosis on LB. In conclusion, transient elastography is a simple and reliable noninvasive means for assessing biliary fibrosis. It should be a promising tool to assess antifibrotic therapies in PBC or PSC.

A simple non-invasive scoring system for prediction of severe hepatic fibrosis in chronic hepatitis C patients: Mohamed A Metwally, Claudia O Zein, Paul Angulo, Nizar N Zein, Mayo Clinic, Rochester, MN

A simple non-invasive scoring system for prediction of severe hepatic fibrosis in chronic hepatitis C patients: Mohamed A Metwally, Claudia O Zein, Paul Angulo, Nizar N Zein, Mayo Clinic, Rochester, MN

Effects of six months losartan administration on liver fibrosis in chronic hepatitis C patients: A pilot study

To evaluate the safety and efficacy of chronic administration of losartan on hepatic fibrosis in chronic hepatitis C patients. Fourteen patients with chronic hepatitis C non-responders (n = 10), with contraindications (n = 2) or lack of compliance (n = 2) to interferon plus ribavirin therapy and liver fibrosis were enrolled. Liver and renal function test, clinical evaluation, and liver biopsies were performed at baseline and after losartan administration at a dose of 50 mg/d during the 6 mo. The control group composed of nine patients with the same inclusion criteria and paired liver biopsies (interval 6-14 mo). Histological activity index (HAI) with fibrosis stage was assessed under blind conditions by means of Ishak's score. Subendothelial fibrosis was evaluated by digital image analyses. The changes in the fibrosis stage were significantly different between losartan group (decrease of 0.5+/-1.3) and controls (increase of 0.89+/-1.27; P<0.03). In the treated patients, a decrease in fibrosis stage was observed in 7/14 patients vs 1/9 control patients (P<0.04). A decrease in sub-endothelial fibrosis was observed in the losartan group. No differences were found in HAI after losartan administration. Acute and chronic decreases in systolic arterial pressures (P<0.05) were observed after the losartan administration, without changes in mean arterial pressure or renal function. Chronic AT-II type 1 receptor (AT1R) blockade may reduce liver fibrosis in patients with chronic hepatitis C.

Biomarkers as non‐invasive assessment of hepatic fibrosis in chronic hepatitis C

Abstract Liver biopsy has been considered as the gold standard for assessing the stage and the grade of chronic liver diseases. Biopsy has a high sampling error (33% for fibrosis staging and 24% for necrosis staging), and intra‐ and interpathologist variability greater than 10%. Biochemical markers, particularly recent panels of markers (FibroTest‐ActiTest) have good predictive values with a better benefit risk ratio and lower cost than liver biopsy. Discordances between biopsy and serological markers results can be either due to serological markers or to biopsy. Because of the improvement of biochemical markers, the limits and the risk of biopsy, liver biopsy should not be mandatory any longer in the management of patients with chronic liver hepatitis C.

968 Do cummulative serial alanine aminotransferase levels predict hepatic fibrosis in chronic hepatitis B over 3 years?

968 Do cummulative serial alanine aminotransferase levels predict hepatic fibrosis in chronic hepatitis B over 3 years?

545 Hepatic blood flow measurement with arterial and portal blood flow by xenon computed tomography: Quantitative analysis of correlation with hepatic fibrosis in chronic hepatitis C

545 Hepatic blood flow measurement with arterial and portal blood flow by xenon computed tomography: Quantitative analysis of correlation with hepatic fibrosis in chronic hepatitis C