Establishing ultrasound based transient elastography cutoffs for different stages of hepatic fibrosis and cirrhosis in Egyptian chronic hepatitis C patients

Background and study aim: transient elastography is widely used to assess fibrosis stage in chronic hepatitis C [CHC]. We aimed to establish and validate different transient elastography cut-off values for significant fibrosis and cirrhosis in CHC genotype 4 patients

Patients and Methods: the data of 100 treatment-naive CHC patients [training set] and 652 patients [validation set] were analysed. The patients were subjected to routine pretreatment laboratory investigations, liver biopsy and histopathological staging of hepatic fibrosis according to the METAVIR scoring system. Transient elastography was performed before and in the same week as liver biopsy using FibroScan [Echosens, Paris, France]. Transient elastography results were correlated to different stages of hepatic fibrosis in both the training and validation sets

Results: ROC curves were constructed. In the training set, the best transient elastography cut-off values for significant hepatic fibrosis [>/=F2 METAVIR], advanced hepatic fibrosis [>/=F3 METAVIR] and cirrhosis [F4 METAVIR] were 7.1, 9 and 12.2 kPa, with sensitivities of 87%, 87.5% and 90.9% and specificities of 100%, 99.9% and 99.9%, respectively. The application of these cut-offs in the validation set showed sensitivities of 85.5%, 82.8% and 92% and specificities of 86%, 89.4% and 99.01% for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, respectively

Conclusion: transient elastography performs well for significant hepatic fibrosis, advanced hepatic fibrosis and cirrhosis, with validated cut-offs of 7.1, 9 and 12.2 kPa, respectively, in genotype 4 CHC patients

FibroScan, APRI, FIB4, and GUCI: Role in prediction of fibrosis and response to therapy in Egyptian patients with HCV infection

Background and study aims: Multiple noninvasive methods have been used successfully in the prediction of fibrosis. However, their role in the prediction of response to hepatitis C virus [HCV] antiviral therapy is debatable. The aim of this study was to validate and compare the diagnostic performance of FibroScan, APRl [aspartate aminotransferase [AST]-to-platelet ratio index], FIB4, and GUCI [Goteborg University Cirrhosis Index] for the prediction of hepatic fibrosis and treatment outcome in HCV-infected patients receiving pegylated interferon and ribavirin [PEG-IFN/ribavirin]

Patients and methods: this study included 182 Egyptian patients with chronic HCV infection. They were classified into two groups based on the stages of fibrosis: mild to significant fibrosis [F1-F2] and advanved fibrosis [F3-F4]. The APRI, FIB4, and GUCI scores were calculated before the antiviral treatment. The FibroScan was performed for all patients before treatment

Results: stiffness and FIB4 have greater sensitivity and specificity in detecting advanced fibrosis of 80%, 77% and 88%, 84%, respectively. Based on multivariate regression analysis, FIB4, body mass index [BMI], and alpha-fetoprotein [AFP] level were found to be statistically significant predicators of advanced fibrosis [p-value: 0.000, 0.011, and 0.001, respectively] with odds ratio [OR: 3.184, 1.170, and 1.241, respectively]. With respect to virological response, the stiffness, APRI, FIB4, and GUCI were significantly lower in sustained virological responders. However, these are not good predictors of response to PEG-IFN/ribavirin therapy. AFP was the only statistically significant predictor of response [p = 0.002] with OR of 1.141 in multivariate regression analysis

Conclution: FibroScan and noninvasive scores such as APRI, FIB4, and GUCI can be used as good predictors of liver fibrosis in chronic hepatitis C. However, they are not good predictors of response to PEG-IFN/ribavirin therapy

Role of fibroscan and APRI in detection of liver fibrosis: a systematic review and meta-analysis

Fibroscan and APRI are promising noninvasive alternatives to liver biopsy for detecting hepatic fibrosis. However, their overall test performance in various settings remains questionable. The aim of our study was to perform a systematic review and meta-analysis of diagnostic accuracy studies comparing fibroscan and APRI with liver biopsy for hepatic fibrosis. Electronic and manual bibliographic searches to identify potential studies were performed. Selection of studies was based on reported accuracy of fibroscan and APRI compared with liver biopsy. Data extraction was performed independently by two reviewers. Meta-analysis combined the sensitivities, specificities, and likelihood ratios of individual studies. Extent and reasons for heterogeneity were assessed. 23 studies for fibroscan and 20 studies for APRI in full publication were identified. For patients with stage IV fibrosis [cirrhosis], the pooled estimates for sensitivity of fibroscan were 83.4% [95% confidence interval [CI], 71.7-95.0%] and specificity 92.4% [95% CI, 85.6-99.2%]. For patients with stage IV fibrosis [cirrhosis], the pooled estimates for sensitivity of APRI at cutoff point of 1.5 were 66.5% [95% CI, 25.0-100%] and specificity 71.7% [95% CI, 35.0-100%]. Diagnostic threshold bias was identified as an important cause of heterogeneity for pooled results in both patient groups. Fibroscan and APRI appear to be clinically useful tests for detecting cirrhosis however not useful tools in early stages of fibrosis

association of HLA class II DR B1 alleles with HCV infection in Egyptian children

Human leucocyte antigens [HLA] class II appear to play an important role in the individual's immune response to viral infection. The aim of this study is to assess the relationship between HLA class II antigens with the clinical, laboratory and histopathological state of the liver in Egyptian children and adolescents with chronic hepatitis C virus [HCV] infection. The study included 46 chronically infected HCV children and adolescents without - hepatitis B virus [HBV] nor human immunodeficiency virus - [HIV]. Their mean age was 10.4 +/- 4.23 years [3-17]. HLA-DRB typing was done by polymerase chain reaction [PCR] for the patients and 20 control subjects. Biochemical and haematological parameters were assessed as well as a liver biopsy was taken from the included patients. The most frequent alleles demonstrated among patients were DRB1*03, DRB1*04 and DRB1*13 [45.6%, 39.1% and 26.1%], respectively. Analysis of DRB1 frequencies between patients and control revealed that DRB1*15 is significantly reduced among patients when compared with the control group [p<0.01]. Patients possessing the allele DRB1*03 had significantly reduced platelet count [p=0.03], and this allele was presented to a greater extent in patients with minimal grade of inflammation. Patients with DRB1*04 had significantly low serum albumin [p=0.04] and patients with DRB1*13 had significantly high serum aspartate aminotransferase [AST] levels [p=0.05]. In Egyptian HCV-infected children, special HLA patterns were found; HLA DRB1*03 was present in nearly half of the patients, while the frequency of HLA DRB1*15 was significantly reduced among the cases in comparison to the control subjects

Clinical role of serum squamous cell carcinoma antigen in egyptian patients with hepatocellular carcinoma

Since major advances in our ability to treat hepatocellular carcinoma [HCC] are less likely to come from treating late stage disease it is therefore important to find early stage disease. Serum Alpha-fetoprotein [alpha - FP] is currently the most widely performed screening test, but this sensitivity poor. It has been reported, recently, that squamous cell carcinoma antigen [SCCA] could represent a useful screening marker in patients at risk. The aim of this study to investigate the diagnostic utility of serum SCCA as a non invasive marker in HCC patients compared to alpha-FP. We recruited for the study forty patients with HCC, 25 patients with liver cirrhosis and 15 healthy subjects. Serum levels of SCCA and alpha-FP together with clinical, laboratory, and imaging evaluation were done for all cases. Hepatic focal lesions with atypical CT pattern for HCC were confirmed histopathologically with ultrasound-guided biopsy. Mean values of serum SCCA in HCC group was significantly higher when compared with both the control and cirrhotic groups [p<0.001]. It was significantly elevated in HCC patients showing atypical enhancement pattern versus those with typical one [p<0.05]. At the value of the kit cutoff value [2 ug/l], the specificity and sensitivity of SCCA were 62% and 84% respectively. While when using the receiver operator curve [ROC] curve, to improve the specificity and sensitivity of SCCA, the cutoff value of 2.55 ug/l yielded a sensitivity and specificity of 52.5% and 96% respectively [best cutoff]. The diagnostic sensitivity of alpha-FP at a cutoff 200 ng/dl was 26% and the specificity 100%. The cutoff level of alpha-FP for diagnosis of HCC according to ROC was 91.5 ng/dl yielded a sensitivity and specificity of 62.5% and 92%, respectively [best cutoff]. Simultaneous measurement of alpha-FP and SCCA led to improve the sensitivity of serologic diagnosis of HCC up to 87.5%. SCCA represents a useful diagnostic biomarker for HCC detection, when combined with alpha-FP, it significantly increases the reliability of serologic diagnosis for this cancer. SCCA could specially diagnose those with atypical enhancement pattern in CT scan

Combined radiofrequency ablation [RFA] and percutaneous acetic acid injection [PAI] versus radiofrequency ablation alone for treatment of hepatocellular carcinoma [HCC]

Hepatocellular carcinoma [HCC] is one of the most commonly occurring solid tumors worldwide. Percutaneous acetic-acid injection [PAI] and radiofrequency ablation are options for treatment. The aim is to compare the efficacy and safety of combined radiofrequency and acetic acid injection versus radiofrequency alone for ablation of HCC. This study was conducted on 40 patients having HCC. Group 1 [20 patients] was subjected to radiofrequency ablation preceded by intra-tumoral acetic acid injection [RFA+AA]. Group 2 [20 patients was subjected to RFA alone. The procedure was successful in 18 [90%] patients of group 1 and in 15 [75%] of group 2. RFA+ AA are most effective than RFA alone as acetic acid injection may enhance the ablation induced by RFA

Impact of 10 years of hepatitis B vaccination on the frequency of acute symptomatic hepatitis B at a major urban referral center in Egypt

This study aimed to determine the impact of 10 years of universal hepatitis B immunization on the prevalence of acute symptomatic viral hepatitis B in Egypt compared with previous results reported by the same authors in 1983. Two hundred consecutive patients with acute symptomatic viral hepatitis, diagnosed clinically and biochemically, were enrolled from Embaba Fever Hospital [EFH], Giza Governorate, Egypt in the period from December 2001 to September 2002. Serological tests were done using ABBOTT AXSYM [Abbott laboratory, Abbott Park, III] for hepatitis A virus [anti-HAV IgM], hepatitis B virus [HBsAg, anti-HBc total and IgM, anti HBs], hepatitis C virus [anti-HCV IgM and total, in addition to PCR], hepatitis D virus [anti-HDV IgM] and hepatitis E [anti-HEV IgM]. In addition, the patients were screened for IgM Ab of cytomegalovirus [CMV], Ebstein barr virus [EBV] and PCR for HGV and transfusion transmitted virus [TTV]. In the present study, the overall acute HBV infection was accounted for 31.5% of the acute viral hepatitis cases, with a male predominance of 62.4% and a significant increased prevalence in adolescent and adults. Although the clinical presentation of HBV did not differ from those of the various causes of hepatitis, the mean ALT levels were significantly higher in acute HBV when compared with acute HAV infection. The frequency of acute hepatitis B was decreased from 43.4% in 1983 to 31.5% in 2002, which was particularly evident in children and there were no significant changes in the rate of acute hepatitis among HBsAg carriers [12.3% and 9%, respectively]. Despite the lower coverage rate of hepatitis vaccination in those <9 years [37.9%], there was virtual absence of acute hepatitis B. The use of multiple seromarkers decreased the prevalence of the undiagnosed cases in those suffering from acute hepatitis to 6.5%

community-based study of viral hepatitis infection in Giza Governorate, Egypt: Seroprevalence, risk factors and associated morbidity

Hepatitis viruses are major causes of acute and chronic liver diseases in Egypt. The aim of this study was to investigate the seroprevalence, risk factors and associated morbidity of viral hepatitis in Giza Governorate, Egypt. The study was conducted in 4 rural and 4 semiurban communities and included 2305 subjects selected by a cluster r and om method. They underwent complete clinical and abdominal ultrasonographic [US] assessment and laboratory tests including stool and urine examination, hemoglobin, ALT estimation and viral hepatitis markers by enzyme immunoassay. The latter included anti-HAV IgG, HBsAg, anti-HBc, anti-HBs, anti-HCV and anti-HEV IgG. Subsets of sera were tested for HBV DNA and HGV RNA by specific PCR. The overall prevalence of anti-HCV was 20.9% [age-adjusted prevalence = 24.5%; CI: 22.7-26.3%] and was significantly rising with age from 10% below age of 20 years to 40% among those above 50 years. The infection rate of hepatitis B virus [HBV] was 57.1% with HBsAg carrier rate of 3.6%. Seropositivity of anti-HBs and anti-HBc was very high [45.8% and 44.7%, respectively] and correlated positively with age with no sex-related difference. Combined HCV and HBV infection was evident in 13% of subjects. HBV DNA was detected in 86% of HBsAg-positive cases and in 20% of HBsAg-negative anti-HBc- and anti-HCV-positive cases. Seromarkers for hepatitis B and C were significantly commoner in semiurban than in rural communities. Dental manipulation and previous parenteral antischistosomal therapy were significant risk factors for hepatitis B and C infection. Anti-HAV was positive in 99.7% whereas anti-HEV was positive in HBV= Hepatitis B virus. CLD = Chronic liver disease. HCC = Hepatocellular carcinoma. US = Ultrasonography. ALT = Alanine transaminase. OR = Odds ratio. CI = Confidence interval. 9.2%. HGV RNA was detected in 16.5% of the studied samples. It was always associated with HBV and /or HCV infection. History of hematemesis was recorded in 1.2% of individuals. US examination revealed hepatomegaly in 19.2% of subjects, splenomegaly in 8.2%, bright liver in 31%, coarse liver texture in 10%, periportal fibrosis in 20% and ascites in 2%. These findings were significantly more common in anti-HCV- and HBsAg-positive subjects. ALT elevation was commonest and highest in individuals with positive HBsAg or with HBV-HCV coinfection. Hepatitis B and C infection and associated morbidity still constitute a great health problem in Egypt. Hepatitis A is holoendemic and hepatitis E is endemic. Hepatitis G is always associated with HBV or HCV infection. Occult hepatitis B should be considered in future studies