Dalia Omran

INTRODUCTION: Scarce reports have commented on hepatocellular carcinoma (HCC) behavior after direct-acting antivirals (DAAs).

AIM: To analyze differences in tumor behavior between patients with hepatitis C virus (HCV)-induced HCC and were either treated or not using DAAs.

PATIENTS AND METHODS: This case-control study includes patients with HCV-related HCC who received generic DAAs (group I) and all non-DAA treated patients with HCC who presented to our clinic during the same period (group II). Patient and tumor characteristics, treatment types and outcome were compared between the two groups.

RESULTS: Group I included 89 patients and group II included 207 patients. No significant difference was detected between groups regarding HCC number or size. Group I showed a more infiltrative HCC pattern, whereas group II had more circumscribed and delineated lesions. The incidence of portal vein thrombosis and significant lymphadenopathy was significantly higher in group I (P=0.03 and 0.03, respectively). Serum levels of α-fetoprotein were significantly higher in group I (P=0.02). These factors significantly affected the response to HCC management (P=0.03). Incidence of complete responses were 47.2 and 49.8% for groups I and II, respectively, whereas incomplete responses were 12.4 and 25.1%, respectively. Supportive treatment was applied to 40.4% in group I and 25.1% in group II.

CONCLUSION: HCC behavior was more aggressive in DAA-treated patients regarding portal vein thrombosis, malignant lymphadenopathy, and HCC imaging characteristics, which affected the chance of ablation and the treatment response.

BACKGROUND: A large Egyptian treatment program for HCV was launched in2014 after the introduction of direct-acting antiviral agents (DAAs). This program depended mainly on establishing specialized independent centres for HCV treatment. These centres represent the major strengths in the Egyptian model of care, as they provide integrated care for HCV patients and have enabled Egypt to treat more than one million patients in 3 years. The New Cairo Viral Hepatitis Treatment Center (NCVHTC) is an example of these specialized centres.

METHODS: The Egyptian experience in the management of HCV was evaluated by analysing the data of real-life HCV management in the NCVHTC from 2014 to 2017. Results of different treatment regimens in addition to their strengths, limitations and areas for improvement are discussed in this report.

RESULTS: A total of 7042 HCV patients have been evaluated for treatment in the NCVHTC. Among them, 5517 patients received treatment by seven different DAA regimens with excellent results.

CONCLUSIONS: All regimens were highly effective at treating HCV in a real-life setting, apart from SOF/RBV, which was the least effective. A nationwide screening program and enhancing the follow-up of treated patients are the main missing pillars in the Egyptian model.

IL28B single nucleotide polymorphism (rs12979860) is an etiology-independent predictor of hepatitis C virus (HCV)-related hepatic fibrosis. Data mining is a method of predictive analysis which can explore tremendous volumes of information from health records to discover hidden patterns and relationships. The current study aims to evaluate and compare the prediction accuracy of scoring system like aspartate aminotransferase-to-platelet ratio index (APRI) and fibrosis-4 (FIB-4) index versus data mining for the prediction of HCV-related advanced fibrosis. This retrospective study included 427 patients with chronic hepatitis C. We used data mining analysis to construct a decision tree by reduced error (REP) technique, followed by Auto-WEKA tool to select the best classifier out of 39 algorithms to predict advanced fibrosis. APRI and FIB-4 had sensitivity-specificity parameters of 0.523-0.831 and 0.415-0.917, respectively. REPTree algorithm was able to predict advanced fibrosis with sensitivity of 0.749, specificity of 0.729, and receiver operating characteristic (ROC) area of 0.796. Out of the 16 attributes, IL28B genotype was selected by the REPTree as the best predictor for advanced fibrosis. Using Auto-WEKA, the multilayer perceptron (MLP) neural model was selected as the best predictive algorithm with sensitivity of 0.825, specificity of 0.811, and ROC area of 0.880. Thus, MLP is better than APRI, FIB-4, and REPTree for predicting advanced fibrosis for patients with chronic hepatitis C.

INTRODUCTION: A recent appearance of direct-acting antivirals (DAAs) led to a surge in hepatitis C virus (HCV) management. Nowadays, a large proportion of treated patients have cirrhosis with a retained possibility to develop hepatocellular carcinoma (HCC) even after complete cure. We aimed to study tumoral differences between patients who developed HCC after DAAs as either a recurrence or de-novo HCC.

METHODS: We retrospectively analyzed 89 patients who presented to our HCC multidisciplinary clinic with HCC lesions following DAA therapy. A total of 45 patients had complete response to HCC according to the modified Response Evaluation Criteria in Solid Tumors before DAAs intake. Another 44 patients developed de-novo lesions after DAA treatment. Both groups were compared regarding their baseline characteristics, tumor criteria, response to DAAs as well response to HCC treatment.

RESULTS: Both groups showed no significant difference regarding their baseline characteristics (age, sex, Child-Pugh score, and performance status) or response to DAAs (P=0.5). No significant difference was present between groups according to number, site, and size of lesions. However, time elapsed between the end of DAAs therapy and first diagnosis of HCC was significantly longer in de-novo group (15.22±16.39 months) versus recurrence group (6.76±5.1 months) (P=0.008). In addition, response to ablation was significantly better in de-novo lesions compared with recurrent HCC (P=0.03).

CONCLUSIONS: Although de-novo HCC lesions significantly developed later than recurrent lesions in DAAs-treated patients, their response rates were significantly better. No differences were detected between both groups in their response to DAAs and their tumoral characteristics.

Stage of liver fibrosis is critical for treatment decision and prediction of outcomes in chronic hepatitis C (CHC) patients. We evaluated the diagnostic accuracy of transient elastography (TE)-FibroScan and noninvasive serum markers tests in the assessment of liver fibrosis in CHC patients, in reference to liver biopsy. One-hundred treatment-naive CHC patients were subjected to liver biopsy, TE-FibroScan, and eight serum biomarkers tests; AST/ALT ratio (AAR), AST to platelet ratio index (APRI), age-platelet index (AP index), fibrosis quotient (FibroQ), fibrosis 4 index (FIB-4), cirrhosis discriminant score (CDS), King score, and Goteborg University Cirrhosis Index (GUCI). Receiver operating characteristic curves were constructed to compare the diagnostic accuracy of these noninvasive methods in predicting significant fibrosis in CHC patients. TE-FibroScan predicted significant fibrosis at cutoff value 8.5 kPa with area under the receiver operating characteristic (AUROC) 0.90, sensitivity 83%, specificity 91.5%, positive predictive value (PPV) 91.2%, and negative predictive value (NPV) 84.4%. Serum biomarkers tests showed that AP index and FibroQ had the highest diagnostic accuracy in predicting significant liver fibrosis at cutoff 4.5 and 2.7, AUROC was 0.8 and 0.8 with sensitivity 73.6% and 73.6%, specificity 70.2% and 68.1%, PPV 71.1% and 69.8%, and NPV 72.9% and 72.3%, respectively. Combined AP index and FibroQ had AUROC 0.83 with sensitivity 73.6%, specificity 80.9%, PPV 79.6%, and NPV 75.7% for predicting significant liver fibrosis. APRI, FIB-4, CDS, King score, and GUCI had intermediate accuracy in predicting significant liver fibrosis with AUROC 0.68, 0.78, 0.74, 0.74, and 0.67, respectively, while AAR had low accuracy in predicting significant liver fibrosis. TE-FibroScan is the most accurate noninvasive alternative to liver biopsy. AP index and FibroQ, either as individual tests or combined, have good accuracy in predicting significant liver fibrosis, and are better combined for higher specificity.

INTRODUCTION AND AIM: The correlation between interleukin-28B (IL-28B) polymorphisms and chronic hepatitis C (CHC) progression is debatable. Here, we aimed to evaluate the relation between IL-28B C/T genotypes and the development of cirrhotic liver. Extracellular matrix (ECM) proteins, FibroScan and model for end-stage liver disease (MELD) were used to substantiate the severity of liver disease.

MATERIAL AND METHODS: IL-28B rs12979860, liver stiffness and ECM proteins were assessed in 272 CHC patients.

RESULTS: Cirrhosis percentage increased to 10%, 52% and 96% with the increasing number of T alleles (CC, CT and TT, respectively). Also, elevated ECM proteins levels were correlated with the increasing number of T alleles. Interestingly, among cirrhotic patients, liver stiffness, MELD and ECM proteins were significantly (P < 0.0001) higher in patients with TT more than CT genotype. FibroScan, hyaluronic acid, Laminin, Collagen IV and the N-terminal pro-peptide of collagen type III have high accuracy to differentiate liver status in CC from TT genotype. Area under receiver-operating characteristic curve (95% CI) were 1.0 (1.0-1.0), 0.97 (0.96- 1.0), 0.93 (0.85-1.0), 0.98 (0.97-1.0) and 0.93 (0.91-0.97), respectively.

CONCLUSION: This study suggests that IL-28B T allele affects the natural course of CHC type 4 and also suggests that carriage of the IL-28B C allele protects from unfavorable clinical outcomes in CHC as coexistence of C allele with T allele reduced cirrhosis severity.

BACKGROUND: Fibrosis markers are useful for the prediction of cirrhosis but clinical scores such as King's score, AST-Platelet ratio index (APRI), Biotechnology research center (BRC), Fibrosis routine test (FRT), Fibro-α score and Fibro-quotient (FibroQ) have limited accuracy for diagnosing significant fibrosis. We hypothesised that new markers (reflecting the balance between hepatic fibrogenesis and fibrolysis) together with other indirect fibrosis markers would together construct a more sensitive and specific score capable of identifying fibrosis than existing scores.

METHODS: Collagen IV, hyaluronic acid, platelet-derived growth factor (PDGF) and tissue inhibitor of metalloproteinase-1 (TIMP-1) were measured by ELISA, and AST, ALT, platelet count, albumin, total bilirubin, INR and AFP by routine methods in 148 patients with hepatitis C induced liver disease. Stepwise linear discriminant analysis and area under receiver-operating characteristic curves (AUCs) were used to create a predictive score and compare it to others.

RESULTS: Patients with significant fibrosis (n = 100, F2-F4) showed 2.08, 2.14, 1.80 and 1.90-fold increase in collagen IV, hyaluronic acid, PDGF and TIMP-1, respectively, over patients with no or mild fibrosis (n = 48, F0/F1)(all p < 0.01). Significant independent predictors of F2-F4 were AFP (AUC 0.79), age (0.76), PDGF (0.74), collagen IV (0.78) and TIMP (0.75), which together formed a five-marker score 'Fibro-Mark' for predicting F2-F4. In comparison with other scores, AUC for Fibro-Mark was 0.89, BRC was 0.83, followed by FRT and King's score (both 0.82), APRI (0.80), Fibro-α (0.70) and finally Fibro Q (0.63).

CONCLUSIONS: The Fibro-Mark score provides better discrimination in hepatic-fibrosis staging in chronic hepatitis C patients than existing scores.

The aim of this study was to retrospectively analyze the outcome of an unscheduled change in national Egyptian policies for the treatment of hepatitis C virus (HCV), which was transpired as a result of a reduction in interferon supplies, and to manage patients who already started interferon-based therapy. After completing a priming 4-weeks course of sofosbuvir/pegylated interferon/ribavirin (SOF/PEG IFN/RBV), a 12-weeks course of sofosbuvir/daclatasvir (SOF/DCV) combination was initiated. We evaluated the sustained virologic response at 12 weeks posttreatment (SVR12) for 2 groups of patients; Group 1, which included patients who had the previous regimen with IFN priming, and group 2, which included the first consecutive group of patients who received SOF/DCV for 12 weeks from the start without IFN priming. All group 1 patients (1,214 patients) achieved SVR12 (100%) and this was statistically significant when compared with the overall SVR12 in group 2 [8,869 patients with sustained virologic response [SVR] of 98.9%] (P value <0.001). No serious adverse events were reported in both groups. In this real-life treatment experience, interferon-based directly acting antiviral treatment with SOF/PEG IFN/RBV as a priming for 4 weeks, followed by SOF/DCV combination for 12 weeks, led to HCV viral suppression in all treated patients.