Two or more synchronous combination of noninvasive tests to increase accuracy of liver fibrosis assessement in chronic hepatitis C; results from a cohort of 446 patients

Background

The prediction of fibrosis is an essential part of the assessment and management of patients with chronic liver disease. Non-invasive tests (NITs) have a number of advantages over the traditional standard of fibrosis assessment by liver biopsy, including safety, cost-effectiveness, and widespread accessibility.

Objectives

The aim of this study was to determine the accuracy of certain biomarkers and transient elastography (TE) alone or in combination to predict the stage of liver fibrosis in chronic hepatitis C (CHC). Also, we examined whether the combination of certain biomarkers and TE could increase the diagnostic accuracy of liver fibrosis assessment.

Patients and Method

A total of 446 patients who were previously diagnosed with CHC were included in the study. In the study group, 6 blood-based scores (APRI, Forns, Fib-4, Hepascore, FibroTest, and Fibrometer) were calculated, and TE was performed to validate the stage of fibrosis, compared with liver biopsy (LB) as the standard.

Results

Significant fibrosis (F ≥ 2) was predicted with an AUROC of 0.727, 0.680, 0.714, 0.778, 0.688, 0.797, and 0.751 for the APRI, Forns, Fib-4, FibroTest, Hepascore, and Fibrometer scores and TE (Fibroscan), respectively. Severe fibrosis (F ≥ 3) was predicted, with AUROCs ranging between 0.705 and 0.811 for Hepascore and Fibrometer, respectively. Of the biomarkers, Fibrometer had the highest AUROC value in predicting both significant and severe fibrosis. The combination of APRI or FIB-4 with Fibrometer increased the diagnostic accuracy for significant fibrosis (from 69.07 to 82.27 for APRI, P = 0.001 and from 57.74 to 81.33, P = 0.001 for Fib-4). Combining APRI or Fib-4 with TE also increased the diagnostic accuracy (from 69.07 to 80.70%, P = 0.001 for APRI and from 57.74 to 81.33%, P = 0.001 for Fib-4) for significant fibrosis. The association that included Fibrotest was also reliable for the improvement of diagnostic accuracy. These combinations were more accurate or the assessment of severe fibrosis.

Conclusions

The synchronous association between a simple, inexpensive score and a complex but expensive score or TE increases the diagnostic accuracy of non-invasive methods for the assessment of liver fibrosis stage.     

Insulin Resistance, Steatosis, and Fibrosis in Egyptian Patients with Chronic Hepatitis C Virus Infection

Background/Aim:

Both nonalcoholic fatty liver disease (NAFLD) and chronic hepatitis C virus (HCV) infection are common in Egypt, and their coexistence is expected. There is controversy regarding the influence of NAFLD on chronic HCV disease progression. This study evaluates the effect of NAFLD on the severity of chronic hepatitis C (CHC) (necroinflammation and fibrosis) and assesses the relative contribution of insulin resistance syndrome to the occurrence of NAFLD in patients with chronic HCV infection.

Patients and Methods:

Untreated consecutive adults with chronic HCV infection admitted for liver biopsy were included in this study. Before liver biopsy, a questionnaire for risk factors was completed prospectively, and a blood sample was obtained for laboratory analysis.

Results:

Our study included 92 male patients. Their mean ± SD age and aspartate aminotransferase (AST) level were 42 ± 7.7 years (range 20-56) and 68 ± 41.7 U/L (range 16-214), respectively. The mean insulin level and insulin resistance index were 15.6 ± 18.3 mIU/mL (range 5.1-137.4) and 5.9 ± 15.2 (range 0.9-136.2), respectively. Fifty four percent of patients had steatosis and 65% had fibrosis. In multivariate analyses, steatosis was associated with insulin resistance and fibrosis was associated with high AST level, age ≥40 years, and steatosis.

Conclusions:

Steatosis is a histopathologic feature in >50% of patients with chronic HCV infection. Insulin resistance has an important role in the pathogenesis of steatosis, which represents a significant determinant of fibrosis together with high serum AST level and older age.     

The effect of antiviral therapy on serum cholesterol levels in chronic hepatitis C

Background/Aims

The aims of this study were to evaluate the effect of antiviral therapy on serum total cholesterol (TC) levels and to investigate the factors related to serum TC changes in chronic hepatitis C (CHC) patients.

Methods

A total of 94 CHC patients, the majority of whom were infected with genotype 1 or 2 and were receiving antiviral therapy, were consecutively enrolled. TC levels before treatment, at week 4, at the end of treatment (EOT), and at 24 weeks after the EOT were analyzed, along with factors related to pre- and post-treatment TC levels.

Results

Pretreatment TC levels in the sustained virologic response (SVR) group (167±3.6 mg/dL) and the non-SVR group (158±8.3 mg/dL) were similar, and both decreased during antiviral therapy. The TC levels at 24 weeks after the EOT significantly increased in the SVR group (183±4.7 mg/dL), but not in the non-SVR group (160±7.1 mg/dL, p=0.044) after adjusting for the pretreatment TC levels. The grade of hepatic fibrosis, as measured by the METAVIR score or the aspartate aminotransferase-platelet ratio index (APRI), but not viral load (p=0.119), was an independent variable associated with the pretreatment TC levels (METAVIR score, p=0.011; APRI, p=0.033). After adjusting for the presence of a SVR by longitudinal data analysis using generalized estimating equations, the independent variable APRI was associated with the serum TC level after antiviral therapy (p=0.014), whereas a SVR was associated with the serum TC level only with marginal statistical significance (p=0.084).

Conclusions

Serum TC levels increased in the SVR group after antiviral therapy for CHC; however, this was probably due to an improvement in liver fibrosis rather than the eradication of virus.     

Non-Invasive Histologic Markers of Liver Disease in Patients With Chronic Hepatitis B

Background:

An exact histologic staging of liver fibrosis is essential for identifying the best therapeutic strategy and determining the disease prognosis in patients with chronic hepatitis B (CHB). While liver biopsy has a vital role in the management of liver diseases, it also sustains some limitations hampering its widespread use.

Objectives:

In this study, we evaluated and compared several available indices of the severity of liver diseases in patients with hepatitis.

Patients and Methods:

Exclusion criteria were as follows: decompensated liver disease, alcoholic liver disease or alcohol intake of 40 g or more per week; co-infection with human immunodeficiency virus, hepatitis C virus, or hepatitis D virus.

Results:

Results showed that AST to platelet ratio index (APRI) (odds ratio = 2.35, P = 0.01) and age (odds ratio = 1.04, P = 0.007) were independently predictive of the presence of significant liver necrosis and inflammation. On the other hand, AARPRI (odds ratio = 3.8, P = 0.07), age (odds ratio = 1.04, P = 0.02), and ALT levels (odds ratio = 1.01, P = 0.007) were predictive of a significant liver fibrosis. Further analysis with receiver-operating curve showed that none of these predictors had a fair diagnostic value (area under the curve < 70).

Conclusions:

The APRI had the highest sensitivity and specificity (64% and 71%, respectively) for prediction of the presence of liver disease. We suggest that APRI may be applicable for the detection of a severe liver disease.     

AST to platelet ratio index (APRI) for the noninvasive evaluation of liver fibrosis: Original Article

Liver biopsy is the recognized gold standard for liver fibrosis staging. The aspartate aminotransferase to platelet ratio index (APRI) has been proposed as a noninvasive and readily available tool for the assessment of liver fibrosis in chronic hepatitis C (CHC). This study aimed to validate, in a Mexican tertiary health care setting, the diagnostic usefulness of APRI in CHC, nonalcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH). In an observational, cross-sectional, comparative and retrolective fashion, consecutive patients with CHC, NAFLD or AIH were evaluated. Fibrosis was staged using the METAVIR scale. Receiver operating characteristic ROC curves were constructed for significant fibrosis, advanced fibrosis and cirrhosis. One-hundred-sixty-four CHC, 30 NAFLD and 42 AIH patients were evaluated. For the diagnosis of significant fibrosis, APRI values delimited an area under de ROC curve (AUC) of 0.776 in CHC, 0.564 in NAFLD, and 0.602 in AIH patients. For advanced fibrosis, the AUCs were 0.803, 0.568 and 0.532 in CHC, NAFLD and AIH patients, respectively. For cirrhosis, AUCs were 0.830 and 0.599 in CHC and AIH patients. In conclusion, APRI can be a useful noninvasive alternative for the diagnosis of significant fibrosis and cirrhosis in our CHC patients. APRI values of ≤ 0.3 and ≤ 0.5 rule out significant fibrosis and cirrhosis, and a value of ≥ 1.5 rules in significant fibrosis. In patients with NAFLD, APRI values tend to increase with the degree of fibrosis, suggesting that it could be useful in this disease. APRI appears to be of no value in patients with AIH.     

Effects of Metabolic Syndrome on Fibrosis in Chronic Viral Hepatitis

Background/Aims

Metabolic syndrome, comprising diabetes, hypertension, central obesity, and dyslipidemia, is increasingly prevalent worldwide. We aimed to study the relationship between metabolic syndrome and the risk of liver fibrosis in patients with chronic hepatitis B (CHB) and chronic hepatitis C (CHC).

Methods

In total, 954 patients (CHB, 850; CHC, 104 patients) with liver biopsy were included in the retrospective analysis. Extensive clinical and histological data were available. Metabolic syndrome was defined using the International Diabetes Federation definition of metabolic syndrome, 2006 criteria. Histological lesions were evaluated according to the histology activity index system.

Results

Metabolic syndrome was present in 6% of patients and significantly more prevalent in patients with CHC than in patients with CHB (5% vs 13%, p<0.001). Patients with metabolic syndrome were older among patients with CHB and patients with CHC, and, as expected, were mainly overweight or obese. Fibrosis was significantly more severe in patients with metabolic syndrome than in those without, regardless of whether they had CHB and CHC (CHB, 3.3±2.1 vs 2.4±1.3, p=0.025; CHC, 2.6±1.5 vs 1.3±0.7, p=0.006). Liver fibrosis (stages 3 to 4) was independently associated with increased age, higher transaminase level and metabolic syndrome (odds ratio, 2.421; p=0.017).

Conclusions

Metabolic syndrome is associated independently with severe fibrosis in patients with chronic viral hepatitis B and C.     

Serum markers for predicting advanced fibrosis in patients with chronic hepatitis B and nonalcoholic fatty liver disease

To compare the diagnostic utility of serum markers in nonalcoholic fatty liver disease (NAFLD) patients with chronic hepatitis B (CHB).This study enrolled 118 consecutive biopsy-proven NAFLD patients with or without CHB. Fibrosis scores of each marker were compared against histological fibrosis staging. Receiver operating characteristic curve (ROC) analysis helped assess the accuracy of each marker.In patients with both diseases, 12.96% (7/54) had advanced fibrosis on biopsy and aspartate aminotransferase (AST) to platelet ratio index was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC (95% confidence interval) for AST to platelet ratio index (APRI) were 0%, 93.62%, 0%, 86.27%, and 0.676 (0.524–0.828), respectively. The markers ranked as follows from highest to lowest with respect to their accuracy: APRI; BARD; fibrosis-4; and AST to ALT ratio. In patients without CHB, fibrosis-4 was the best performing marker for predicting advanced fibrosis. The sensitivity, specificity, PPV, NPV, and area under the ROC (95% confidence interval) for fibrosis-4 were 77.78%, 85.45%, 46.67%, 95.92%, and 0.862 (0.745–0.978), respectively.Serum markers are less reliable in predicting advanced fibrosis in NAFLD patients with CHB; APRI is the most accurate predictor of the absence of advanced fibrosis.     

A new scoring system for prediction of fibrosis in chronic hepatitis C

Background

Liver biopsy (LB) is still considered to be the gold standard for assessment of liver fibrosis.

Objectives

To evaluate the effectiveness of various non-invasive methods for predicting liver fibrosis, including transient elastography (TE), APRI score, Lok score, Forns score, FIB-4 score, Fibrosis Index, King score, and Bonacini score, in comparison with the effectiveness of LB and to create a new scoring system for fibrosis prediction.

Patients and Methods

This study included 212 patients with chronic HCV hepatitis. LB, TE, and various biological tests were performed during a single hospital visit. Using established formulae, data from these tests were used to create scores for assessment of liver fibrosis.

Results

The results of all the tests showed significant correlation with histological fibrosis. TE results (r = 0.62), King score (r = 0.57), and APRI score (r = 0.56) showed the closest correlation with severity of fibrosis. The following formula was derived from our data by multiple regression: Predicted liver fibrosis score (PLF score) = 0.956 + 0.084 × TE - 0.004 × King score + 0.124 × Forns score + 0.202 × APRI score. A direct correlation (r = 0.68) was found between the PLF score and liver fibrosis. The cut-off values of the PLF score for various stages of fibrosis were: F ≥ 1, 1.77 (Area under ROC curve (AUROC) = 0.76); F ≥ 2, 2.18 (AUROC = 0.78); F ≥ 3, 2.47 (AUROC = 0.86); and F = 4, 2.98 (AUROC = 0.97).

Conclusions

We found that our newly developed PLF score, which is derived from the scores of multiple tests, is more strongly correlated with fibrosis than each component score used individually. The PLF score is more effective than TE for predicting severe fibrosis, but they have similar effectiveness in predicting liver cirrhosis.     

FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎合并非酒精性脂肪性肝病进展期肝纤维化的诊断价值比较

目的评价FibroScan、GPR、APRI、NFS、FIB-4单独应用及FibroScan分别与GPR、APRI、NFS、FIB-4联合应用对慢性乙型肝炎(CHB)合并非酒精性脂肪性肝病(NAFLD)患者进展期肝纤维化的诊断价值。方法选取2014年11月-2018年8月在四川省人民医院行肝穿刺病理检查并确诊为CHB合并NAFLD的患者92例。根据肝穿刺病理SAF分级诊断标准,分为轻中度肝纤维化(F1+F2)组(n=69)和进展期肝纤维化(F3)组(n=23)。同时应用FibroScan测得肝脏硬度值,根据临床指标分别计算GPR、APRI、NFS、FIB-4。计量资料两组间比较采用Mann-Whitney U检验;相关性分析采用Spearman秩相关;多因素二元logistic回归构建联合预测因子(向前逐步回归法),绘制受试者工作特征曲线(ROC曲线),计算ROC曲线下面积(AUC),并采用Delong方法进行比较,评价各种无创诊断方法单独及联合应用对CHB合并NAFLD进展期肝纤维化的诊断价值。结果轻中度肝纤维化组的FibroScan、GPR、APRI、NFS及FIB-4水平明显低于进展期肝纤维化组(Z值分别为-4.910、-3.425、-3.837、-3.873、-3.990,P值均<0.05)。相关性分析结果显示,FibroScan、GPR、APRI、NFS、FIB-4与肝纤维化病理分期均呈正相关(r值分别为0.518、0.361、0.405、0.407、0.418,P值均<0.001)。FibroScan、GPR、APRI、NFS及FIB-4单独应用对诊断进展期肝纤维化均有一定价值(AUC分别为0.844、0.740、0.770、0.771、0.779,P值均<0.001),但FibroScan诊断价值并不优于GPR、APRI、NFS、FIB-4(P值均>0.05)。将FibroScan分别与GPR、APRI、NFS、FIB-4联合,诊断进展期肝纤维化的AUC均较单独应用时明显提高(Z值分别为1.977、2.076、2.361、2.206,P值均<0.05);将FibroScan与GPR+APRI+NFS+FIB-4同时联合诊断进展期肝纤维化的AUC及95%可信区间为0.896(0.813~0.950)。结论FibroScan、GPR、APRI、NFS及FIB-4诊断进展期肝纤维化均有一定的临床价值,FibroScan分别与GPR、APRI、NFS、FIB-4联合诊断进展期肝纤维化的效能优于单项血清学模型,其中FibroScan联合NFS或FIB-4的临床价值可能最佳。     

Transient elastography for measurement of liver stiffness measurement can detect early significant hepatic fibrosis in Japanese patients with viral and nonviral liver diseases

BACKGROUND: Many studies have reported the efficiency of transient elastography, a noninvasive, reproducible, and reliable method for predicting liver fibrosis, in patients with chronic hepatitis C (CHC) and B (CHB), but there are few reports about nonviral chronic liver disease (CLD) such as primary biliary cirrhosis (PBC), nonalcoholic steatohepatitis (NAFLD), and autoimmune hepatitis (AIH). We therefore compared the efficiency of transient elastography between CHC and nonviral CLD. METHODS: We assessed the accuracy of liver stiffness measurement (LSM) using Fibroscan, and compared these values with those of hyaluronic acid, type 4 collagen, platelet count, prothrombin index, and AST/platelet ratio index (APRI) as indices for the diagnosis of liver fibrosis in 114 patients with a variety of chronic liver diseases: CHC (n = 51), CHB (n = 11), NAFLD (n = 17), PBC (n = 20), and AIH (n = 15). The histology was assessed according to the METAVIR score by two pathologists. RESULTS: The number of fibrosis stage (F0/1/2/3/4) with CHC was 9/15/12/6/10, and that with nonviral CLD was 10/21/11/4/6, respectively. The ability, assessed by area under receiver operating characteristic (AUROC) curve, to predict liver fibrosis F >or= 2 for LSM, HA, type 4 collagen, platelet count, prothrombin index, and APRI, was 0.92, 0.81, 0.87, 0.85, 0.85, and 0.92 in CHC patients, respectively; and 0.88, 0.72, 0.81, 0.67, 0.81, and 0.77 in nonviral CLD patients, respectively. CONCLUSIONS: In patients with nonviral CLD, LSM was most helpful in predicting significant fibrosis (F >or= 2). Transient elastography is a reliable method for predicting significant liver fibrosis, not only in CHC patients but also in nonviral CLD patients.     

Routine indexes for cirrhosis and significant fibrosis detection in patients with compensated chronic hepatitis B

Background and aim

Fibrosis index based on the four factors (FIB-4) and aspartate aminotransferase to platelet ratio index (APRI) were not well validated in patients with chronic hepatitis B (CHB). The aim of this study was to validate the performances of these indexes and construct novel indexes for liver fibrosis assessment.

Non-alcoholic fatty liver disease and correlation of serum alanin aminotransferase level with histopathologic findings

Background

Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most common cause of chronic liver disease worldwide. It occurs in patients who do not consume alcohol in large amounts. Alanine aminotranferase (ALT) and aspartate aminotransferase (AST) are indicators of hepatocellular injury.

Objectives

To determine correlation between histopathologic specifications of NAFLD in patients with little or no history of alcohol consumption and the serum level of ALT.

Patients and Methods

In a cross-sectional study carried out in two gastroenterology and hepatology clinics in Tehran, Iran, the medical records of those who had undergone liver biopsies between years 2005 and 2009 were reviewed. Clinical and laboratory information of biopsy-proven cases of NAFLD were obtained from 147 eligible medical records. The histopathologic, demographic, and laboratory data of the participants were also collected. Two groups of patients according to their serum ALT level (cut-point of 35 U/L) were defined. The quantitative pathologic grade of the biopsy specimens was determined based on Brunt scoring system.

Results

We studied 147 NAFLD patients including 127 men (86.4%) and 20 women (13.6%) with a mean ± SD age of 41.4 ± 11.2 years. Considering serum ALT, the mean ± SD quantitative grade of hepatosteatosis was 1.50 ± 0.67 and 1.74 ± 0.73 (p=0.136); advanced fibrosis (consisted of grade III and cirrhosis) was found in 4.5% (1/22) and 5.6% (7/125) of patients (p=0.327).

Conclusions

We found that using the cut-off value of 35 U/L for serum ALT level, it has little contribution to predict NAFLD severity.     

A comparative study of non-invasive methods for fibrosis assessment in chronic HCV infection

Background and Aims

To compare several non-invasive methods of fibrosis assessment in chronic hepatitis C virus (HCV) infection (platelet count, the APRI score, the Forns score, the Lok score, FIB-4, Transient Elastography [TE]), versus percutaneous liver biopsy (LB).

Methods

Our study included 150 patients with chronic HCV infection in which LB, liver stiffness measurement (LSM) by means of TE and biological tests needed for calculating the scores (according to the classic formulas) were performed in the same session.

Results

The best test for predicting significant fibrosis (F = 2 Metavir) was LSM with AUROC-0.773, followed by APRI (AUROC-0.763), Forns (AUROC-0.744), platelet count (AUROC-0.732), Lok (AUROC-0.701) and FIB-4 (AUROC-0.669), but the differences were not statistically significant (P > 0.05). For excluding cirrhosis, all the tests had excellent NPV (>97%). The best test for predicting cirrhosis was LSM (AUROC-0.979), significantly better than platelet count (AUROC- 0.899, P = 0.022) and than FIB-4 (AUROC-0.839, P = 0.042), otherwise the differences were not statistically significant (P > 0.05). All of the non-invasive tests were statistically significantly correlated (P < 0.0001) to the severity of fibrosis: APRI r=0.570; Forns r=0.540; Lok r=0.4843; FIB-4 r=0.4171; platelet count r=-0.4842.

Conclusions

LSM by means of TE seems to be more sensitive than APRI, Forns, Lok and FIB-4 scores and than platelet count for the prediction of significant fibrosis, but the differences are not statistically significant. The APRI score and Forns scores correctly identified most (71%) of the patients having, or not having, significant fibrosis. LSM was the best method for predicting cirrhosis, but all the evaluated tests had excellent predictive value (AUROCs 0.839-0.979).     

Correlation between HBsAg quantitative assay results and HBV DNA levels in chronic HBV

Background

Viral load has been used to diagnose and monitor patients who are being treated for chronic hepatitis B (CHB). The Diagnosis methods are molecular-based and expensive. Quantitation of hepatitis B surface antigen (HBsAg) by automated chemiluminescent micro-particle immunoassay has been proposed to be a surrogate marker. Quantitating HBV DNA levels molecularly is expensive; thus, a cheaper laboratory test as a surrogate diagnostic marker might simplify our management.

Objectives

We determined whether quantitative HBsAg levels correlate with HBV DNA levels in CHB.

Patients and Methods

In this cross-sectional study, all CHB patients who were referred by a gastroenterologist to undergo quantitative HBV DNA assay in a qualified laboratory in Mashhad, Iran in 2009 were enrolled, and blood samples was obtained. Patients who were positive for antibodies to HCV and HDV were excluded. HBV DNA was measured by real-time polymerase chain reaction, and serum HBsAg was quantified byelectrochemiluminescence assay (Roche Diagnostic).

Results

Of 97 patients, 70 were male (72%) and 27 were female (28%); the mean age was 39 ± 11 years. Eighty-seven percent wasHBeAg-negative. By Mann-Whitney test,HBSAg titer differed significantly between HBeAg-positive and -negative patients (P = 0.001), as did HBV DNA levels (P = 0.009). By Spearman test, there was no significant correlation between HBsAg and HBV DNA levels (P= 0.606 and r = 0.53).

Conclusions

HBeAg-negative patients have higher levels of HBsAg and lower levels of HBV DNA. By electrochemiluminescence assay,HBsAg has no significant correlation with HBV DNA levels in CHB with predominant genotype D and HBeAg negativity in Iran.     

Meta-analyses of FibroTest diagnostic value in chronic liver disease

Background

FibroTest (FT) is a biomarker of liver fibrosis initially validated in patients with chronic hepatitis C (CHC). The aim was to test two hypotheses, one, that the FT diagnostic value was similar in the three other frequent fibrotic diseases: chronic hepatitis B (CHB), alcoholic liver disease (ALD) and non-alcoholic fatty liver disease (NAFLD); and the other, that the FT diagnostic value was similar for intermediate and extreme fibrosis stages.

Methods

The main end points were the FT area under the ROC curves (AUROCs) for the diagnosis of bridging fibrosis (F2F3F4 vs. F0F1), standardized for the spectrum of fibrosis stages, and the comparison of FT AUROCs between adjacent stages. Two meta-analyses were performed: one combining all the published studies (random model), and one of an integrated data base combining individual data. Sensitivity analysis integrated the independency of authors, lenght of biopsy, prospective design, respect of procedures, comorbidities, and duration between biopsy and serum sampling.

Results

A total of 30 studies were included which pooled 6,378 subjects with both FT and biopsy (3,501 HCV, 1,457 HBV, 267 NAFLD, 429 ALD, and 724 mixed). Individual data were analyzed in 3,282 patients. The mean standardized AUROC was 0.84 (95% CI, 0.83–0.86), without differences between causes of liver disease: HCV 0.85 (0.82–0.87), HBV 0.80 (0.77–0.84), NAFLD 0.84 (0.76–0.92), ALD 0.86 (0.80–0.92), mixed 0.85 (0.80–0.93). The AUROC for the diagnosis of the intermediate adjacent stages F2 vs. F1 (0.66; 0.63–0.68, n = 2,055) did not differ from that of the extreme stages F3 vs. F4 (0.69; 0.65–0.72, n = 817) or F1 vs. F0 (0.62; 0.59–0.65, n = 1788).

Conclusion

FibroTest is an effective alternative to biopsy in patients with chronic hepatitis C and B, ALD and NAFLD. The FT diagnostic value is similar for the diagnosis of intermediate and extreme fibrosis stages.     

Ischemia-modified albumin levels in children with chronic liver disease

Background/Aims

Ischemia-modified albumin (IMA) levels have been shown to correlate with the severity of liver failure in adults. However, the role of IMA levels has not been evaluated in children with chronic liver disease (CLD). We analyzed the clinical significance of IMA levels in children with CLD.

Methods

Thirty-three children with CLD and 33 healthy children were included in the study. Blood was collected to analyze biochemical parameters, oxidant status, and IMA. Liver biopsies were re-evaluated for liver fibrosis; severe fibrosis (SF) was defined as fibrosis stage ≥4.

Results

The IMA and and IMA to albumin ratios (IMARs) were significantly higher in children with CLD than in those without (IMA: 0.545±0.095 vs 0.481±0.062, p=0.003; IMAR: 0.152±0.046 vs 0.126±0.018, p=0.04). The IMAR was positively correlated with the pediatric end-stage liver disease score (p=0.03, r=0.503) and fibrosis score (p=0.021, r=0.400). Patients with SF had higher IMARs compared to patients with mild fibrosis (0.181±0.056 vs 0.134±0.025, p=0.003). The area under the receiver operation curve (AUROC) for predicting SF was 0.78 (p=0.006). Using a cutoff ratio value of 0.140, the sensitivity and specificity were 84% and 70%, respectively. The AUROC for predicting the need for liver transplantation and/or death was 0.82 (p=0.013). With a cutoff value of 0.156, the sensitivity and specificity was 83% and 82%, respectively. Kaplan-Meier analysis revealed increased morbidity and/or mortality in the group with an IMAR>0.156 (50% vs 4.3%, p=0.005).

Conclusions

IMARs have been shown to provide important clues in predicting the fibrosis stage of the disease and determining the outcome in children with CLD.     

Determination of the relationship of serum hyaluronic Acid levels to the degree of liver fibrosis in biopsies of patients with chronic viral hepatitis B and C

Background and Aims

Determining the stage of liver fibrosis and the grade of necroinflammation is important in predicting the prognosis and treatment response of patients with chronic viral hepatitis. Liver biopsy is associated with several technical problems and complications; therefore, its repetitive performance as a procedure in evaluating treatment response and in following up patients is not recommended. This study was performed to determine the correlation of serum hyaluronic acid (HA) levels with the stage and grade of histopathologic liver changes in patients with chronic hepatitis B and C.

Methods

This analytical cross-sectional study was performed on 69 patients with chronic hepatitis B or C in Mashhad, Iran, who were referred to our clinic and underwent liver biopsy and blood sampling simultaneously in 2006-2007. None of the patients were on medication that would affect the serum levels of (HA) and patients with signs of arthropathy were excluded from the study.

Results

Out of the 69 patients i this study, 48 (69.6%) were male and 21 (30.4%) were female. The causative virus in 29 patients (42%) was hepatitis C and in the rest (n = 40, 58%) hepatitis B. The severity of liver fibrosis (stage) had a direct correlation (r = 0.25, P = 0.042) with the levels of (HA) and an inverse correlation with the platelet level (r = 0.37, P = 0.002). The degree of liver necroinflammation (grade) did not have a significant correlation with the levels of (HA) and alanine transaminase (r = -0.01, P = 0.9; r = 0.21, P = 0.09 respectively); instead, there was an inverse correlation with platelet levels (r = 0.36, P = 0.003).

Conclusions

Our study results correspond with those of other international studies; thus suggesting that the (HA) serum level is a useful marker in determining the severity of fibrosis in patients with chronic viral hepatitis. To form a definite conclusion, further studies on large groups should be performed.     

Efficacy and safety of a novel pegylated interferon alpha-2a in Egyptian patients with genotype 4 chronic hepatitis C

BACKGROUND:

Hepatitis C virus (HCV) genotype 4 is a common infection in Egypt and is the leading cause of liver disease.

OBJECTIVE:

To study the efficacy and safety of a novel 20 kD pegylated interferon alpha-2a derived from Hansenula polymorpha in combination with ribavirin for the treatment of Egyptian patients with genotype 4 chronic hepatitis C (CHC).

METHODS:

One hundred seven patients with genotype 4 CHC were involved in the present study. Liver biopsy was performed in all patients. All patients received a fixed weekly dose of 160 μg of a novel pegylated interferon in combination with ribavirin in standard and adjusted doses. Serum HCV RNA levels were assessed by a real-time sensitive polymerase chain reaction assay at four, 12, 48 and 72 weeks after the start of therapy. Patients demonstrating an early virological response (EVR) completed a 48-week course of treatment.

RESULTS:

The overall sustained virological response (SVR) was 60.7%. The SVR in patients with a rapid virological response was significantly higher (91.7%) than in patients with complete EVR (67.74%) (P=0.033) and partial EVR (56.14%) (P=0.003). SVR was also significantly higher in patients with a low degree of liver fibrosis according to Metavir score (F1 and F2) (67.57%) compared with those with a high degree of liver fibrosis (F3 and F4) (45.45%) (P=0.017). The baseline viral load had no impact on SVR in the present series nor were any serious adverse events reported.

CONCLUSION:

The novel pegylated interferon alpha-2a assessed in the present study was effective for the treatment of patients with genotype 4 CHC, and was safe and well tolerated.     

Disease burden of chronic hepatitis B among immigrants in Canada

BACKGROUND:

The prevalence of chronic hepatitis B (CHB) infection among immigrants to North America ranges from 2% to 15%, 40% of whom develop advanced liver disease. Screening for hepatitis B surface antigen is not recommended for immigrants.

OBJECTIVE:

To estimate the disease burden of CHB among immigrants in Canada using Markov cohort models comparing a cohort of immigrants with CHB versus a control cohort of immigrants without CHB.

METHODS:

Markov cohort models were used to estimate life years, quality-adjusted life years and lifetime direct medical costs (adjusted to 2008 Canadian dollars) for a cohort of immigrants with CHB living in Canada in 2006, and an age-matched control cohort of immigrants without CHB living in Canada in 2006. Parameter values were derived from the published literature.

RESULTS:

At the baseline estimate, the model suggested that the cohort of immigrants with CHB lost an average of 4.6 life years (corresponding to 1.5 quality-adjusted life years), had an increased average of $24,249 for lifetime direct medical costs, and had a higher lifetime risk for decompensated cirrhosis (12%), hepatocellular carcinoma (16%) and need for liver transplant (5%) when compared with the control cohort.

DISCUSSION:

Results of the present study showed that the socio-economic burden of CHB among immigrants living in Canada is sub-stantial. Governments and health systems need to develop policies that promote early recognition of CHB and raise public awareness regarding hepatitis B to extend the lives of infected immigrants.     

Evaluation of the Relation Between Hepatic Fibrosis and Basic Laboratory Parameters in Patients With Chronic Hepatitis B Fibrosis and Basic Laboratory Parameters

Background:

The hepatitis B virus is an important healthcare problem. According to current clinical practice, a liver biopsy is required for the diagnosis and treatment of chronic liver disease. However, a liver biopsy is an invasive, inconvenient procedure, which requires an expert pathologist opinion. Therefore requirement of biochemical tests, which are considered to indicate hepatic fibrosis and may be repeated easily, increases gradually today.

Objectives:

This study evaluated the correlation between hepatic fibrosis and routine laboratory values in patients with chronic hepatitis B.

Patients and Methods:

The files of 456 patients with CHB (chronic hepatitis B) who were referred to the infectious diseases and clinical microbiology clinic between January 2009 and March 2012 were screened retrospectively. Liver biopsy samples were examined according to Ishak scoring. Laboratory parameters and histopathology reports were recorded, and correlations between the fibrosis grade and laboratory parameters were analyzed.

Results:

There were 320 male and 136 female patients, with a mean age 36.7 ± 12.1 years. According to liver biopsy results, a low fibrosis score (stage 0-2) was detected in 281 patients (61.6%), and a high fibrosis score (stage 3-5) was detected in 175 patients (38.4%). Patients with a high fibrosis score had significantly higher ALT (alanine amino transferase), AST (aspartate aminotransferase), and HBV-DNA values and a significantly lower platelet count compared with those with a low fibrosis score (P = 0.001, 0.001, 0.025, and 0.001, respectively). A positive correlation was detected between the fibrosis score and age, BMI, HAI, ALT, and AST values, and a negative correlation was detected between the fibrosis score and albumin and platelet counts. In the regression analysis performed to evaluate the factors associated with high-stage fibrosis, fibrosis was determined to be associated with thrombosis, ALT, and gender. The results of the regression analysis demonstrated that the risk of fibrosis was 4.6 fold higher in men.

Conclusions:

According to the results obtained in our study, advanced age, higher BMI, AST, ALT, and HBV-DNA levels, and low albumin and platelet levels are correlated with advanced fibrosis in patients with CHB.