New genetic markers for diagnosis of hepatitis C related hepatocellular carcinoma in Egyptian patients.

BACKGROUND AND AIM: Early detection of hepatocellular carcinoma (HCC) enhances effective and curative management. New genetic markers with distinct diagnostic ability are required. AIM: determine the expression of GPC3, PEG10, SERPINI1, MK and QP-C in the peripheral blood of HCC patients. METHODS: 74 HCV patients were recruited and divided into three groups; chronic hepatitis (I), liver cirrhosis (II) and HCC (III). Demographics, laboratory and imaging data were collected. Child score and metastatic work up were completed. The expression of the five candidate genes in the peripheral blood was performed by qRT-PCR assay. RESULTS: Groups were gender matched, age in group I was significantly lower than in groups II and III (37.7 vs 50.4 and 55.6, p value <0.005). CHILD score; group II and III A/B/C = (7/5/6) and (20/6/3). AFP was significantly higher in group III than I and II (204 vs 3.9 and 6.9, p < 0.01). In HCC group 69% of the lesions were < 5 cm, and had 1-2 nodules; 14% had metastases. GPC3, PEG10, SERPINI1 and MK mRNA were significantly higher in the HCC group compared to the other groups while QP-C mRNA was higher in chronic hepatitis C group compared to other groups. The gene expression values in HCC patients were independent of the tumor size, AFP levels or extrahepatic metastasis. Combined measurement of the five gene markers showed 100% sensitivity and 33% specificity, 48% PPV and 100% NPV. CONCLUSION: GPC3, PEG10, SERPINI1 and MK are genetic markers that can represent a useful tool for detection of HCC.

Hepatic fibrosis and serum alpha-fetoprotein (AFP) as predictors of response to HCV treatment and factors associated with serum AFP normalisation after treatment.

BACKGROUND AND STUDY AIM: Elevated levels of alpha-fetoprotein (AFP) can be seen in patients with chronic hepatitis C (CHC) and liver cirrhosis without hepatocellular carcinoma and were negatively associated with treatment response. However, factors associated with its changes are not identified. We aimed in this study to verify a cut-off value for AFP as a predictor of response to standard of care (SOC) antiviral therapy in Egyptian chronic hepatitis C virus (HCV)-infected patients and identify factors associated with its changes post treatment. PATIENTS AND METHODS: A total of 175 chronic non-cirrhotic HCV-infected patients were evaluated for baseline serum AFP and liver biopsy were classified according to Ishak scoring system of hepatic fibrosis. All patients were scheduled to receive SOC antiviral therapy for 48weeks and had been followed up to week 72. Reassessment of AFP and repeated liver biopsy at week 72 were feasible only in 79 patients. RESULTS: High baseline AFP levels were observed in non-respondents (non-sustained virological respondents (non-SVRs)) (P<0.01); the AFP level decreased in all patients post treatment (P=0.01), especially in the SVRs (P<0.01). In multivariate analysis, hepatic fibrosis was a predictor of response to treatment (P=0.02), while body mass index (BMI) (25-30kgm(-2)), hepatic activity (A2), hepatic fibrosis stage (F2-F4) and fibrosis improvement were predictors of AFP difference (P=0.007, 0.01, 0.012, <0.001, 0.030, and 0.018), respectively. The diagnostic performance to predict the HCV treatment response was best by adding both AFP and hepatic fibrosis stage factors; the best cut-off value for AFP was 3.57ngdl(-1) with 50% sensitivity and 68% specificity with area under the curve (AUC) of 0.55 and for hepatic fibrosis stage was 3, with a sensitivity of 88%, a specificity of 30% with an AUC of 0.58. CONCLUSION: In chronic HCV-infected patients, serum AFP below 3.57ngdl(-1) and hepatic fibrosis ⩽stage 3 are expected to have good response to treatment; BMI (25-30kgm(-1)), A2, fibrosis >2 and fibrosis improvement predict AFP change post treatment.

The Effect of Peginterferon Alpha-2a vs. Peginterferon Alpha-2b in Treatment of Naive Chronic HCV Genotype-4 Patients: A Single Centre Egyptian Study.

BACKGROUND: Egypt has one of the highest (16-8%) prevalence rates of HCV infection in the world. Approximately 90% of Egyptian HCV isolates belong to a single subtype (4a), which responds less successfully to interferon therapy than other subtypes. Studies comparing the efficacy and safety of PEGIFN alfa-2a and PEGIFN alfa-2b in treatment-naive HCV-infected patients have shown conflicting results. OBJECTIVES: Assessing the effects of Peginterferon alpha-2a versus Peginterferon alpha-2b on the sustained virological response in naive chronic HCV genotype-4 Egyptian patients. PATIENTS AND METHODS: This retrospective study cohort consists of 3718 chronic HCV patients admitted to a large, Egyptian medical center. 1985 patients had been treated with PEG-IFN alfa-2a plus RBV and 1733 patients with PEG-IFN alfa-2b plus RBV between years 2007-2011. Efficacy outcomes were sustained virologic response (SVR) and treatment discontinuation rates due to serious adverse effects. RESULTS: The ETR & SVR in patients treated with PEGIFN alfa-2a was 64.1% and 59.6% as compared to treatment with PEGIFN alfa-2b where these parameters were 58.2% and 53.9% respectively (P < 0.05). Treatment discontinuation rates, were similar in the two types of PEGIFN [0.66 (0.37-1.16); P = 0.15]. Significant dose reduction was evident with peginterferon alfa-2b (35.3%) than peginterferon alpha-2a (27.3 %) (P < 0.01). Patients with lower base line AFP and ALT were most likely to achieve SVR using INF alpha 2-a. CONCLUSIONS: Peginterferon alpha-2a has a higher efficacy regarding ETR and SVR as compared to Peginterferon alfa-2b in treatment of naive chronic HCV genotype-4 patients.

Serum autoantibodies positivity prevalence in patients with chronic HCV and impact on pegylated interferon and ribavirin treatment response.

BACKGROUND & AIMS: Prevalence of serum autoantibodies in chronic hepatitis C (HCV) patients is higher than that in the general population. Interferon may induce autoimmune manifestations in patients treated with peg-interferon and ribavirin. Effect of autoantibody seropositivity and treatment response are limited and controversial. To detect the prevalence of serum autoantibodies in patients with chronic HCV and impact on histopathology and treatment response. METHODS: Retrospective study including 3673 Egyptian chronic HCV naïve patients enrolled in the Egyptian national programme for HCV treatment with pegylated interferon and ribavirin in the years 2007-2010. Antinuclear antibody (ANA) was determined by ELISA considered positive with a titre ≥ 1:40 by indirect immunofluorescence. ANA-positive patients pre treatment workup including serum aminotransferases, thyroid profile and liver biopsy, follow-up during treatment and sustained virological response (SVR) were assessed compared to ANA-negative patients. RESULTS: Serum ANA was positive in 1.6% of the studied patients. There were no statistically significant differences concerning the demographic, biochemical and histopathological data in ANA positive and negative patients. SVR was comparable between ANA-positive and ANA-negative patients (67.8% and 61.3% respectively). Follow-up treatment; ANA-positive patients' did not experience statistically significant haematological complications, flare-up of serum transaminases, thyroid dysfunction. No systemic autoimmune disorders developed during follow-up. CONCLUSIONS: ANA positivity is not a factor in chronic HCV disease progression and does not affect the treatment response. Pegylated interferon and ribavirin therapy is safe and effective in autoantibodies-positive chronic HCV patients with no need for further follow-up or worry during the treatment in absence of systemic autoimmune disorders.

Non-invasive prediction of hepatic fibrosis in patients with chronic HCV based on the routine pre-treatment workup.

BACKGROUND: Hepatic fibrosis is an inclusion indicator for treatment and a major independent predictor of treatment response in patients with chronic hepatitis C. Liver biopsy, considered as the "gold standard" for evaluating liver fibrosis, has carried some drawbacks. Currently used noninvasive predictors of fibrosis are considered less accurate than liver biopsy. OBJECTIVES: Our aim was to assess noninvasive predictors of fibrosis in patients with chronic hepatitis C using the routine laboratory pre-treatment workup. PATIENTS AND METHODS: Cross sectional study including 4289 Egyptian patients with chronic hepatitis C were assessed for the need to interferon and ribavirin therapy. Routine pre-treatment workup and reference needle liver biopsy were performed. FIB-4 index, APRI and modified APRI scores were validated. Patients were divided into two groups, first with no or minimal fibrosis, and second with moderate and marked fibrosis using the Metavir score. RESULTS: Multivariate logistic regression analysis showed that age, body mass index, aspartate aminotransferase, alpha fetoprotein, platelets count, FIB-4 index, APRI and modified APRI score were significant independent predictors of fibrosis. Age > 43 years, aspartate aminotransferase > 47U/L, platelets < 205×103/mm(3), and alpha fetoprotein > 2.6 ng/ml had the highest cutoff points in receiver operator characteristic curves. Taking into account the four variables together; the presence of ≥ 2 variables is associated with moderate and advanced fibrosis with a sensitivity of 0.81, specificity of 0.5, positive predictive value of 0.53 and negative predictive value of 0.79. FIB-4 index represented the best performing receiver operator characteristic curve for diagnosing moderate and marked fibrosis among other independent factors with a sensitivity of 0.74, specificity of 0.6, positive predictive value of 0.56 and negative predictive value of 0.76. CONCLUSIONS: Chronic HCV pre-treatment routine work up and composite fibrosis scores are good noninvasive predictor of liver fibrosis and can be used as an alternative method to invasive liver biopsy without adding more financial expenses to the treatment.

Incidence of Bcl-2 expression in bladder cancer: relation to schistosomiasis.

OBJECTIVES: Apoptosis (programmed cell death) and the genes regulating this process (e.g., Bcl-2) have recently become a focus of interest in the study of cancer development and progression. The bcl-2 gene product plays a role as an inhibitor of apoptosis; it contributes to oncogenesis by suppressing signals that induce apoptotic cell death. The aim of this study was to determine the expression of bcl-2 in schistosomal bladder cancer and to compare it with the established clinicopathological factors. METHODS: Tumor tissues from 118 patients with bladder cancer were examined [57 with squamous cell carcinoma (SCC) and the remaining 61 with transitional cell carcinoma (TCC)]. Of 118 patients, 60 had schistosomiasis associated with bladder cancer. Bcl-2 expression was determined by enzyme immunoassay and the results were confirmed by Western blot and immunodot blot techniques. RESULTS: Bcl-2 was significantly expressed in SCC compared to those with TCC type in the presence of schistosomiasis. Moreover, bcl-2 was associated with clinical stages and lymph node involvement but not with histological grades. CONCLUSIONS: These observations detect a potential role for bcl-2 expression in schistosomal carcinogenesis, and hence selecting patients for future anti-bcl-2 therapy.