Therapeutic effectiveness of biosimilar standard interferon versus pegylated interferon for chronic hepatitis C genotypes 2 or 3

BackgroundPegylated interferon (Peg-IFN) and standard interferon (IFN) play a significant role in the treatment of hepatitis C virus (HCV) infection. Biosimilar standard IFN is widely available in Brazil for the treatment of HCV infection genotypes 2 or 3, but its efficacy compared to Peg-IFN is unknown.ObjectiveTo compare the sustained virological response (SVR) rates following treatment with biosimilar standard IFN plus ribavirin (RBV) versus Peg-IFN plus RBV in patients with HCV genotypes 2 or 3 infection.MethodsA retrospective cohort study was conducted in patients with HCV genotypes 2 or 3 infection treated with biosimilar standard IFN plus RBV or with Peg-IFN plus RBV. SVR rates of the two treatments were compared.ResultsFrom January 2005 to December 2010, 172 patients with a mean age of 44 +/? 9.3 years were included. There were eight (4.7%) patients with HCV genotype 2 infections. One hundred fourteen (66.3%) were treated with biosimilar standard IFN plus RBV, whist 58 (33.7%) patients were treated with Peg-IFN plus RBV. Between the two groups, there were no significant differences regarding age, gender, glucose level, platelet count, hepatic necroinflammatory grade, and hepatic fibrosis stage. Overall, 59.3% (102/172) patients had SVR. In patients treated with Peg-IFN plus RBV, 79.3% (46/58) had SVR compared to 49.1% (56/114) among those treated with biosimilar standard IFN plus RBV (p = 0.0001).ConclusionIn patients with HCV genotypes 2 or 3 infection, a higher SVR was observed in patients receiving Peg-IFN plus RBV related to patients treated with biosimilar standard IFN plus RBV.     

Thyroid disorders in patients with chronic hepatitis C using interferon-alpha and ribavirin therapy

ObjectiveTo investigate the frequency of thyroid disorders (TD) in patients with chronic hepatitis C before and during interferon-alpha (IFN-α) and ribavirin (RIB) treatment.Study designProspective study.Patients and MethodsWe prospectively studied 65 anti-HCV and viral RNA positive patients. Free thyroxine, thyroid-stimulating hormone, and thyroid peroxidase antibodies (TPO-Ab) were systematically tested at entry (m0), week 12 (m3) and week 24 (m6) of treatment.ResultsMean age of the 65 patients (38 females and 27 males) was 49.61 ± 11.83 years. Seven (10.76%) patients presented baseline thyroid disorders (m0), three had thyroid dysfunction, and four were TPO-Ab positive. Thyroid disorders occurred in the first 12 weeks of treatment in 11 (16.92%) patients, four with thyroid dysfunction, and seven with TPO-Ab positive (m3). A total of 18 patients (27.69%) developed TD after 24 weeks of treatment, 7 with thyroid dysfunction, and 11 with TPO-Ab positive (m6). The relative risk of developing hypothyroidism found in this study was 1.3 (95% CI: 1.1 to 1.6), hyperthyroidism 1.2 (95% CI: 1.1 to 1.4), and TPO-Ab positivity 7.6 (95% CI: 3.9 to 14.5). The study showed a significant association between female sex and thyroid disease (p = 0.009).ConclusionThyroid dysfunction and autoimmune TD were observed during IFN-α and RIB therapy.     

Successful treatment with peginterferon alfa-2b of HBeAg-positive HBV non-responders to standard interferon or lamivudine

OBJECTIVES: Antiviral therapy leads to HBeAg seroconversion in 10-40% of the patients with HBeAg-positive chronic hepatitis B. Nonresponse may result in progression of liver disease and increased risk of hepatocellular carcinoma. As part of a global randomized controlled trial we investigated the efficacy (i.e., loss of HBeAg at the end of follow-up) of peginterferon alfa-2b (Peg-IFN alpha2b) in patients who failed to respond to previous courses of standard interferon (IFN) or lamivudine. METHODS: We analyzed a total of 76 previous nonresponders: 37 were nonresponders to standard IFN, 17 were nonresponders to lamivudine, and 22 were nonresponders to both therapies. All patients received a 52-wks course of 100 microg Peg-IFN alpha2b weekly combined with either 100 mg lamivudine daily or a placebo. After therapy patients were followed for 26 wks. RESULTS: Thirteen (35%) nonresponders to previous IFN, five (29%) nonresponders to previous lamivudine, and four (22%) nonresponders to both IFN and lamivudine responded to treatment with Peg-IFN alpha2b. No difference in response was found for those treated with Peg-IFN alpha2b alone or in combination with lamivudine. Nonresponders to prior IFN therapy with baseline ALT (alanine aminotransferase) > 4 x ULN (upper limit of normal) responded better to Peg-IFN alpha2b than those with ALT levels 相似文献   

Sexual Dysfunction in Males with Hepatitis C Virus: Relevance to Histopathologic Changes and Peginterferon Treatment

Background/Aim:

The frequency of sexual dysfunction (SD) is not well known in patients with chronic hepatitis C virus (HCV). In spite of the fact that histological benefits of peginterferon (Peg-IFN)/ribavirin therapy are well established, the effects on sexual health are less certain. To assess the prevalence of the SD and explore its relevance to histopathologic changes and Peg-IFN treatment.

Materials and Methods:

The study included 100 HCV males; all the patients completed questionnaires to assess their sexual function before and during the treatment.

Results:

Before treatment, SD was reported only by 12 (19.4%) and 10 (29.4%) patients of early and advanced liver fibrosis, respectively. SD during HCV treatment (with Peg-IFN and ribavirin) for liver fibrosis was significant, as 24 (70.6%) out of 34 (100%) of HCV patients had advanced fibrosis but only 20 (32.3%) out of 62 (100%) patients had early fibrosis and were sexually affected (P = 0.01). SD before treatment was found in 22 (22%) patients; 16 (16%) were >40 years old and 6 (6%) patients were ≤40 years old. SD showed highly significant (P = 0.001) difference prior to and during treatment. Pre treatment, 78 (78%) patients denied any SD and only 22 (22%) were sexually affected, while during treatment, the number of patients who were sexually affected rose to 44 (44%). The rest of the group [56 (56%)] did not report any sexual impairment.

Conclusion:

SD was noticed during Peg-IFN and ribavirin treatment in patients with advanced liver fibrosis. Age and advanced liver fibrosis were important factors in inducing SD. This is of key importance for clinical practice as it modifies the management of HCV patients.     

The rate of fibrosis progression is an independent predictor of the response to antiviral therapy in chronic hepatitis C

summary . The response to antiviral therapy and the rate of fibrosis progression in chronic hepatitis C virus (HCV) infection are related to common factors, including age and gender. The aim of this study was to evaluate the relationship between the rate of fibrosis progression and the sustained virologic response (SVR) to interferon (IFN)-based treatment. A total of 332 patients treated for chronic HCV infection were evaluated. Using multivariate logistic regression analysis, the impact of the rate of fibrosis progression (defined as the stage of liver fibrosis according to the Metavir system/duration of infection) on the rate of SVR (negative HCV RNA at least 6 months following the end of treatment), was determined. The median age of the patients was 44 (range 25–77) years, 64% were male, and 66% were infected with genotypes 1, 4, 5 or 6. The median rate of fibrosis progression was 0.083 (range 0–2) Metavir units/year; 158 patients (48%) had F2–F4 fibrosis. After a median of 48 (range 2–126) weeks of therapy (IFN, n =190; IFN and ribavirin, n =96; pegylated IFN, n =20; pegylated IFN and ribavirin, n =26), 93 patients (28%) achieved an SVR. In univariate analysis, the rate of SVR was higher in slow [< 0.083 Metavir units/year ( n =162)] than rapid progressors [≥ 0.083 Metavir units/year ( n =170)] (35% vs 22%, P =0.01). After controlling for age, gender, genotype, viral load, and treatment regimen and duration, the rate of fibrosis progression remained an independent predictor of SVR (slow vs rapid progressors, OR 2.74; 95% CI 1.27–5.92; P =0.01). Hence the rate of fibrosis progression is an independent predictor of SVR to IFN-based therapy in patients with chronic hepatitis C. This additional factor should be considered in economic models evaluating this condition.     

Thyroid dysfunction in a UK hepatitis C population treated with interferon‐α and ribavirin combination therapy

Objective To assess the incidence of thyroid dysfunction (TD) in a UK cohort of patients with hepatitis C virus (HCV) infection treated with interferon‐α (IFNα) and ribavirin combination therapy (IFN/RBV). Design, patients and measurements A retrospective study of 288 patients who received IFN/RBV for HCV during a 2‐year period from January 2006 was performed. Thyroid function was assessed during a 24‐week or 48‐week course of IFN/RBV. If serum thyrotrophin (TSH) became undetectable (<0.01 mU/l) and serum free thyroxine (T4) was raised, a diagnostic thyroid isotope scan was performed. Results Full medical records were examined for 260 patients (172 men, 88 women) included in the study, of whom 22.3% (16.9% of men, 33.0% of women) developed TD during IFN/RBV. In total, 10.4% developed a suppressed serum TSH (0.8% Graves’ disease, 9.6% transient thyroiditis) while 11.9% developed an elevated serum TSH with 1.5% becoming permanently hypothyroid and requiring levothyroxine therapy. Women had a relative risk (RR) for developing TD of 1.96 (CI: 1.75–3.03, P = 0.004). A serum TSH ≥1.75 mU/l and a positive thyroid peroxidase (TPO) antibody titre pretherapy were associated with RRs for progression to TD of 6.02 (CI: 2.95–12.78, P < 0.0001) and 4.35 (CI: 2.58–6.52; P < 0.0001), respectively, while combination of baseline TSH and TPO antibody data predicted progression to TD with a sensitivity of 94.7%. Conclusions Although TD was common in this cohort, just 2.3% developed TD that required ongoing therapy. Pre‐IFN/RBV serum TSH and TPO antibody titre were found to predict progression to TD in this group of patients.     

Hepatitis C virus genotypes and hepatic fibrosis regulate 24-h decline of serum hepatitis C virus RNA during interferon therapy in patients with chronic hepatitis C

BACKGROUND AND AIMS: Recently, hepatitis C virus (HCV) dynamics during interferon (IFN) therapy have been studied in detail. We examined factors that regulate the viral kinetics and the relationship between the viral kinetics and clinical effect of IFN therapy. METHODS: Eighty-eight patients with chronic hepatitis C entered this study. All patients had been treated with 3 MU of IFN-beta twice a day for the first 2-4 weeks, then IFN-alpha for the next 20-22 weeks (three injections per week). The levels of serum HCV RNA were determined by Amplicor HCV Monitor version 1.0, before and 24 h after the first injection of IFN; then the decline of HCV was calculated. Liver inflammation and fibrosis were scored as 0 (none), 1 (mild), 2 (moderate) or 3 (severe) using biopsy specimens. RESULTS: The decline of serum HCV RNA was 1.42 +/- 0.65 log copies/mL in genotype 1b and 1.83 +/- 0.72 in genotype 2a or 2b (P < 0.01). By a logistic regression model, genotype (1b, 2a or 2b) and hepatic fibrosis (0 or 1, 2 or 3) associated with 24-h decline of serum HCV RNA, independently. As the predictor of IFN therapy, the decline of serum HCV RNA and serum HCV RNA levels before IFN therapy were the independent significant factors (P < 0.001). CONCLUSIONS: The decline of serum HCV RNA during the first 24 h of IFN therapy was regulated by genotypes and hepatic fibrosis. The decline of serum HCV RNA and initial HCV load were independent factors that can be the predictor of the subsequent sustained viral response to IFN therapy.     

Anti-Golgi complex antibodies during pegylated-interferon therapy for hepatitis C.

BACKGROUND/AIM: Pegylated interferon (Peg-IFN) plus ribavirin is the standard therapy for hepatitis C. Peg-IFN has several antiviral mechanisms, but its role in hepatitis C treatment seems to be related to its immunomodulatory effect. Ribavirin, an antiviral agent, potentiates IFN activity when added to it. Both drugs are associated with adverse reactions of different magnitudes. Autoimmune phenomena have been reported with this treatment. In this paper, we describe cases of ALT/GGT flares during Peg-IFN plus ribavirin treatment, which related to the appearance of anti-Golgi antibody and disease progress. METHODS: We investigated three patients with hepatitis C and severe ALT/GGT flares during Peg-IFN and ribavirin treatment coinciding with anti-Golgi complex antibody as the only marker of autoimmunity. We then reviewed the medical files and tested anti-Golgi antibody in stored sera from 25 patients treated with conventional IFN and in 14 patients treated with Peg-IFN. RESULTS: The three patients were male, over 45 years of age; all were relapsers and non-responders. Anti-Golgi antibody was positive during treatment coinciding with ALT/GGT flares but with hepatitis C virus (HCV)-RNA negativity, disappearing after stopping treatment, with normalization of ALT/AST levels. One patient had progression of fibrosis from F2 to F3 despite negativity of HCV-RNA. In the last group, only two patients treated with Peg-IFN experienced ALT/GGT flares but without anti-Golgi antibody CONCLUSIONS: The presence of anti-Golgi complex antibody could be a marker of a temporary autoimmune phenomenon and progressive disease.     

Long-term monitoring of platelet count, as a non-invasive marker of hepatic fibrosis progression and/or regression in patients with chronic hepatitis C after interferon therapy

Background: Platelet count has been shown to correlate with the hepatic fibrosis stage in chronic hepatitis C (CHC). The aim of the present study was to assess hepatic fibrosis progression or regression of CHC patients by long‐term monitoring of the platelet count. Methods: A total of 429 interferon (IFN)‐treated CHC patients were studied. Follow‐up data on the platelet count were collected every 6 months after IFN therapy. The IFN response was defined as follows: complete responders (CR, n = 121) demonstrating persistent clearance of serum hepatitis C virus (HCV) RNA; biochemical responders (BR, n = 94) demonstrating alanine aminotransferase (ALT) normalization for ≥6 months without eradication of HCV‐RNA; and non‐responder (NR, n = 214) demonstrating all other patterns. Results: In comparison with the baseline level, mean platelet count increased in the CR group from 0.5 years after IFN therapy (for each point, P < 0.01), but significantly decreased in the NR group from 1 year after IFN therapy (for each point, P < 0.01). In the BR group, an increase in mean platelet count was observed from 0.5 to 3.5 years following IFN therapy (for each point, P < 0.01), followed by a gradual decrease. Conclusion: An increase from baseline values in platelet count was observed, regardless of the presence of HCV‐RNA, in both the CR and BR groups, suggesting the importance of ALT normalization in preventing hepatic fibrosis progression in IFN‐treated CHC patients.     

Chemical shift magnetic resonance imaging is helpful in detecting hepatic steatosis but not fibrosis in patients with nonalcoholic fatty liver disease (NAFLD)

Background & Aim: Imaging modalities have a role in the diagnosis of patients with nonalcoholic fatty liver disease. Aim of the present study was to evaluate the role of chemical shift magnetic resonance imaging in assessing hepatic steatosis and fibrosis in patients with nonalcoholic fatty liver disease.Methods: Chemical shift magnetic resonance imaging was done in 10 biopsy proven patients (7 females, mean age 41 ± 9.2 years) with nonalcoholic fatty liver disease. Objective measurements of signal intensity (SI) were done and a ratio was calculated (SI out-of-phase liver/ SI out-of-phase kidney)/ (SI in-phase liver/ SI in-phase kidney). A lower ratio indicated a higher signal drop and hence higher fat content. The ratio was correlated with hepatic steatosis on histology (< 33% and > 33%). Patients were classified as having histological NASH or no NASH and MRI was assessed in diagnosing hepatic fi-brosis as seen on liver histology.Results: Six patients had > 33% hepatic steatosis on histology. Five patients (50%) had evidence of histological NASH. MRI was not helpful in differentiating patients with and without his-tological NASH. One patient amongst NASH patients did not have fibrosis, one had stage 1, 2 had stage 2 and one had stage 4 fibrosis. SI ratio ranged between 0.350.69 in 6 patients with steatosis > 33% and was in the range of 0.69-1.20 in four patients with steatosis < 33% on histology. Fibrotic changes seen in 4 patients on biopsy were not detected on MRI.Conclusion: Chemical shift MRI provides objective data on fat infiltration in patients with NAFLD without giving information about hepatic fibrosis.     

Comparison of the liver stiffness measurement by transient elastography with the liver biopsy

AIM： To compare the liver stiffness （LS） measurement by transient elastography （TE） to the liver biopsy （LB）considered the ＂gold standard＂ in the evaluation of patients with chronic hepatitis C. METHODS： During a period of 12 mo, we evaluated 199 consecutive patients with chronic hepatitis due to hepatitis C virus （HCV）, in which LB and LS assessments （by means of TE） were performed during the same session. RESULTS： Out of 199 patients, a valid measurement of the LS could not be obtained in 8. The mean value of LS in the cohort of 191 valid measurements was 8.45 ± 4.96 kPa, ranging from 2.3 to 38 kPa. The mean value of LS in patients with significant fibrosis at biopsy （161 patients with F ≥ 2 according to Metavir） was 9.02 ± 5.15 kPa, significantly higher than in patients with no or mild fibrosis （30 patients with F 〈 2 Metavir）： 5.39 ± 1.81 kPa （P 〈 0.0001）. For a cutoff value of 6.8 kPa, the LS had a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6% and a specificity of 93.3% for the presence of significant fibrosis （at least F2 Metavir）, with a diagnostic performance of 77.3% （AUROC 0.773）. Using this cut-off value, we reached the best discrimination between absence of fibrosis/ mild fibrosis （F 〈 2 Metavir） and the presence ofmoderate to severe fibrosis （F ≥ 2 Metavir）. CONCLUSION： In patients with chronic hepatitis due to HCV, a cut-off value of 6.8 kPa measured by TE can differentiate between significant fibrosis and absent or mild fibrosis, with a PPV of 98%, a NPV of 30.1%, a sensitivity of 59.6%, a specificity of 93.3%, and a diagnostic performance of 77.3%.     

Estimates of HCV-1 Patients Attaining RVR Following Dual Therapy with Peg-Interferon and Ribavirin

Background

Given the significant side-effects and healthcare costs associated with telaprevir- or boceprevir-combination therapy, identifying patients likely to respond to dual therapy peg-interferon (Peg-IFN)/ribavirin is highly desirable. Since the perception of how large the pool of patients who may achieve rapid virologic response (RVR) is vaguely ascertained, we searched the literature for this information.

Methods

Studies on patients treated with Peg-IFN/ribavirin were identified by searching MEDLINE and analyzed by meta-analysis. The primary end point was weighted estimates of RVR. The influence on race/ethnicity, baseline viremia, type of Peg-IFN, ribavirin dosage, and significant hepatic fibrosis on the results was evaluated.

Results

Across 38 studies on 13,219 patients, the fraction of RVR patients was 19.6 %. The only baseline factor influencing RVR was race/ethnicity, with higher rates in Asian (26.7 %) and Caucasian patients (22.5 %). Of the 1,735 RVR patients, 85.1 % attained sustained virologic response (SVR). In these, SVR was influenced by ribavirin dose (86.8 vs. 72.8 % for high or low), type of Peg-IFN (91.8 % for alpha-2b vs. 82.9 % for alpha-2a), and treatment duration (91.7 % for 48 weeks vs. 79.4 % for 24 weeks).

Conclusions

One fifth to one fourth of hepatitis C virus genotype 1 (HCV-1) patients can be safely treated with dual therapy of Peg-IFN/ribavirin, and may be spared from cost and inconvenience of regimens considering the addition of HCV protease inhibitors.     

Historical features are poor predictors of liver fibrosis in Canadian patients with chronic hepatitis C

The progression of fibrosis in chronic hepatitis C infection (HCV) is related to host factors including age, gender and alcohol consumption. Due to the morbidity and potential mortality of liver biopsy, a noninvasive method of assessing hepatic fibrosis is needed. The aim of this study was to assess the utility of historical features in predicting fibrosis using published rates of fibrosis progression. The charts of 239 untreated patients with HCV were reviewed; patients who had a liver biopsy and whose duration of infection could be estimated (n=106) were categorized according to gender, age at infection (≤ or > 40 years) and peak alcohol consumption (< or ≥ 50 g/day). Estimates of fibrosis were calculated using the product of the interval between infection and biopsy and published rates of fibrosis progression. Estimates were compared with liver biopsies staged according to the Metavir system (F0–F4; F0=no fibrosis; F4= cirrhosis). The mean age of patients was 42 ± 8 years, 61% were male and 36% consumed > 50 g of alcohol daily. The mean duration of infection was 19 ± 9 years (range, 1–40) and ALT was elevated > 1.5 times upper normal in 63%. When patients were classified into those with mild (F0–F2) and severe (F3–F4) fibrosis, the sensitivity, specificity, positive predictive value and negative predictive value of an estimate of mild fibrosis was 60%, 55%, 78% and 34%, respectively. An estimate of severe fibrosis had a sensitivity of 55%, specificity of 60%, positive predictive value of 34% and negative predictive value of 78%. Agreement between fibrosis estimates and actual histological stages was poor (kappa = 0.13, P=0.08). The prediction of hepatic fibrosis in HCV infection using historical features and published rates of fibrosis progression is poor in a Canadian clinical practice setting. Alternate noninvasive methods of predicting hepatic fibrosis are needed.     

Telaprevir- and boceprevir-based tritherapies in real practice for F3-F4 pretreated hepatitis C virus patients

AIM:To assess,in a routine practice setting,the sus-tained virologic response(SVR) to telaprevir(TPV) or boceprevir(BOC) in hepatitis C virus(HCV) nullresponders or relapsers with severe liver fibrosis.METHODS:One hundred twenty-five patients were treated prospectively for 48 wk with TPV or BOC + pegylated-interferon(peg-INF) α2a + ribavirin(PR) according to standard treatment schedules without randomization.These patients were treated in routine practice settings in 10 public or private health care centers,and the data were prospectively collected.Only patients with severe liver fibrosis(Metavir scores of F3 or F4 upon liver biopsy or liver stiffness assessed by elastography),genotype 1 HCV and who were null-responders or relapsers to prior PR combination therapy were included in this study.RESULTS:The Metavir fibrosis scores were F3 in 35(28%) and F4 in 90(72%) of the patients.In total,62.9% of the patients were null-responders and 37.1% relapsers to the previous PR therapy.The overall SVR rate at 24 wk post-treatment withdrawal was 59.8%.The SVR was 65.9% in the TPV group and 44.1% in the BOC group.Independent predictive factors of an SVR included a response to previous treatment,relapsers vs null-responders [OR = 3.9;(1.4,10.6),P = 0.0084],a rapid virological response(RVR) [OR 6.9(2.6,18.2),P = 0.001] and liver stiffness lower than 21.3 kPa [OR = 8.2(2.3,29.5),P = 0.001].During treatment,63 patients(50.8%) had at least one severe adverse event(SAE) of grade 3 or 4.A multivariate analysis identified two factors associated with SAEs:female gender [OR = 2.4(1.1,5.6),P = 0.037] and a platelet count below 150 × 103/ mm3 [OR = 5.3(2.3,12.4),P ≤ 0.001].CONCLUSION:More than half of these difficult-to-treat patients achieved an SVR and had SAEs in an actual practice setting.The SVR rate was influenced by the response to previous PR treatment,the RVR and liver stiffness.     

Validation of aspartate aminotransferase to platelet ratio for diagnosis of liver fibrosis and prediction of postoperative prognosis in infants with biliary atresia

AIM: To validate the value of aspartate aminotransferase to platelet ratio index(APRI) in assessment of liver fibrosis and prediction of postoperative prognosis of biliary atresia(BA) infants from Mainland China.METHODS: Medical records of 153 BA infants who were hospitalized from January 2010 to June 2013 were reviewed. The efficacy of APRI for diagnosis of liver fibrosis was assessed using the receiver operator characteristic(ROC) curve compared to thepathological Metavir fibrosis score of the liver wedge specimens of 91 BA infants. The prognostic value of preoperative APRI for jaundice persistence, liver injury,and occurrence of cholangitis within 6 mo after KP was studied based on the follow-up data of 48 BA infants.RESULTS: APRI was significantly correlated with Metavir scores(rs = 0.433; P 0.05). The mean APRI value was 0.76 in no/mild fibrosis group(Metavir score F0-F1), 1.29 in significant fibrosis group(F2-F3), and2.51 in cirrhosis group(F4)(P 0.001). The area under the ROC curve(AUC) of APRI for diagnosing significant fibrosis and cirrhosis was 0.75(P 0.001)and 0.81(P = 0.001), respectively. The APRI cut-off of 0.95 was 60.6% sensitive and 76.0% specific for significant fibrosis diagnosis, and a threshold of 1.66 was 70.6% sensitive and 82.7% specific for cirrhosis.The preoperative APRI in infants who maintained jaundice around 6 mo after KP was higher than that in those who did not(1.86 ± 2.13 vs 0.87 ± 0.48, P 0.05). The AUC of APRI for prediction of postoperative jaundice occurrence was 0.67. A cut-off value of0.60 showed a sensitivity of 66.7% and a specificity of 83.3% for the prediction of jaundice persistence.Preoperative APRI had no significant association with later liver injury or occurrence of cholangitis.CONCLUSION: Our study demonstrated that APRI could diagnose significant liver fibrosis, especially cirrhosis in BA infants, and the elevated preoperative APRI predicts jaundice persistence after KP.     

A case of intrahepatic cholangiocarcinoma detected after successful interferon therapy for chronic hepatitis C

A 65-year-old man presented at our hospital in 2006 because of a liver tumor. He had been treated for chronic hepatitis C with interferon-α2b for 6 months in 1998. A pathological examination showed that the hepatic tissue before interferon (IFN) therapy was classified as moderately active hepatitis with severe hepatic fibrosis. The IFN therapy induced the disappearance of the hepatitis C virus (HCV) RNA from his serum and normalized alanine aminotransferase activity. In 2005, a tumor (2 cm in diameter) was detected in the right lobe of the liver by ultrasonography and computed tomography, and the tumor was stained with contrast medium during abdominal angiography. A right lobectomy was performed under the diagnosis of hepatocellular carcinoma. The pathological examination revealed that the tumor was an intrahepatic cholangiocarcinoma (ICC). The noncancerous hepatic tissue was classified as having minimal activity with mild fibrosis. It is important to monitor closely for ICC as well as hepatocellular carcinoma even patients in whom the HCV RNA has disappeared after IFN therapy, because the outcome of treatment for small ICC is favorable.     

Noninvasive assessment of hepatic fibrosis using gadoxetate-disodium-enhanced 3T MRI

Introduction. Gadoxetate-disodium is a liver-specific MR contrast agent absorbed by hepatocytes via organic anion transporting polypeptide 1B3 and is excreted into the biliary system by multidrug resistance-associated protein 2. It has been suggested that relative parenchymal enhancement on hepatocyte phase image is associated with hepatic function. However, it is not clear whether gadoxetate-disodium-enhanced MRI can be used as a noninvasive fibrosis marker. Thus, the purpose of our study was to evaluate the diagnostic performance of gadoxetate-disodium-enhanced MRI in predicting the hepatic fibrosis stage.Materials and methods. A total of 113 patients who had fibrosis staged according to the Batts and Ludwig score were enrolled: F0 (n = 13), F1 (n = 18), F2 (n = 15), F3 (n = 32), and F4 (n = 35). All patients underwent gadoxetate-disodium-enhanced MRI before confirmation by biopsy (n = 67) or surgery (n = 46). For quantitative analysis, the contrast enhancement index (CEI) was calculated by measuring the signal intensity (SI) in liver and paraspinal muscle using a region of interest, as follows: CEI = (liver SI/paraspinal muscle SI) _{20 min hepatocyte phase image}/(liver SI/paraspinal muscle SI) _{pre-contrast T1–weighted image}. The diagnostic performance was evaluated by the ROC curve, adjusted for the prevalence of each fibrosis stage.Results. A significant negative correlation was observed between CEI and fibrosis stage (r = –0.545, P < 0.0001). The adjusted AUROC for CEI in the prediction of mild (≥ F1), moderate (≥ F2), or severe fibrosis (≥ F3) and liver cirrhosis (F4) was 0.668, 0.703, 0.73, and 0.84, respectively. In conclusion, our results demonstrate that quantitative analysis of relative hepatic enhancement using gadoxetate-disodium-enhanced MRI can predict the hepatic fibrosis stage.     

Assessment of hepatic fibrosis and necroinflammation among inactive HBsAg carriers in Egypt

Introduction. The inactive hepatitis B surface antigen (HBsAg) carrier state is usually characterized by minimal or absent liver pathology. However, in developing countries, owing to the very early age of infection with hepatitis B virus (HBV), this state is reached after a very prolonged immune tolerant and immune reactive phase, during which considerable liver damage may have occurred. The extent of liver damage in inactive HBsAg carriers has not been thoroughly assessed in developing countries. We thus sought to characterize liver pathology among Egyptian inactive HBsAg carriers.Material and methods. Liver biopsy was conducted on 30 inactive HBsAg carriers [positive for HBsAg; negative for HBeAg; positive for antibody to HBeAg (anti-HBe); HBV-DNA levels < 2,000 IU/mL; persistently normal serum alanine aminotransferase (ALT)]. Liver histopathology was assessed according to the Ishak scoring system.Results. Among the studied carriers, 6.7% had no hepatic fibrosis, 73.3% had stage 1 fibrosis, and 20% had stage 2 fibrosis. The majority (80%) of carriers had minimal hepatic necroinflammation (grades 2-4), while 20% had mild hepatic necroinflammation (grade 5). All patients with stage 2 fibrosis were males, while no gender predilection was observed for necroinflammation. Age, ALT and HBV-DNA levels did not differ significantly according to fibrosis or ne-croinflammatory scores. Conclusion. Our study findings do not support the presence of significant hepatic fibrosis or necroinflammation among Egyptian inactive HBsAg carriers. However, follow-up studies on these carriers may be required to monitor any further pathological progress of the disease.     

Histological response in patients treated by interferon plus ribavirin for hepatitis C virus-related severe fibrosis

BACKGROUND: Studies of viral hepatitis C have suggested that fibrosis can regress, at least in patients with sustained virological response. A recent study suggested that cirrhosis was reversible in sustained and non-virological responders. AIM: To study fibrosis progression rate and cirrhosis reversion in patients treated for severe fibrosis with interferon or interferon + ribavirin. PATIENTS AND METHODS: Ninety-nine patients were treated with interferon + ribavirin and 64 with interferon. The Metavir fibrosis score and the semiquantitative fibrosis score (SFS) were used to assess fibrosis. RESULTS: In sustained responders, fibrosis progression rate decreased from 0.26 Metavir unit (interquartile range: 0.19-0.34) to -0.67 (-0.67 to 0) (P < 0.0001) and from 0.81 SFS unit (0.48-1.13) to -1.33 (-3.67 to 0) (P < 0.0001). In non-responders, fibrosis progression rate decreased from 0.25 Metavir unit (0.17-0.33) before treatment to 0 (0-0) during treatment (P = 0.002) and from 0.63 SFS unit (0.49-1.12) to 0 (-2.67-1.33) (P = 0.18). Six out of 18 (33%) sustained virological responders and four of 43 (9%) non-responders regressed from cirrhosis (F4) to severe fibrosis (F3) (P = 0.058). No patient with cirrhosis had a decrease of Metavir fibrosis score of 2 points. CONCLUSION: Interferon can slow fibrosis progression in sustained virological responders with severe fibrosis. In patients with a non-virological response and treated for 12 months the fibrosis progression rate was nil, meaning that only fibrosis stabilization could be obtained in these patients. Then, longer treatment duration (3-4 years) could be evaluated in non-virological responders.