Serum ammonia as a non-invasive marker for early prediction of esophageal varices.

INTRODUCTION: There is a growing need for identification of non-endoscopic, non-invasive methods that can accurately predict esophageal varices (EV). Previous studies found an inconclusive correlation between blood ammonia level and the presence and size of EV. AIM: We aimed at assessing the value of serum ammonia as a non-invasive method for early prediction of EV. PATIENT AND METHODS: The study included 204 patients with HCV-related cirrhosis. The selected patients were categorized into two groups: patients with EV and those without, also patients with no or small EV and with large EV group. All patients underwent a complete biochemical workup, ultrasound and upper GI endoscopy. Child-Pugh class, Model of End-Stage Liver Disease (MELD) score and platelet count/splenic diameter ratio, and serum ammonia level. RESULTS: There was a statistical difference between the two groups of patients regarding the following parameters: serum ammonia, international normalized ratio, portal vein diameter, spleen diameter, Child-Pugh class, MELD score, platelet count/splenic diameter ratio, aspartate aminotransferase-to-platelet ratio index, alanine aminotransferase-to-aspartate aminotransferase ratio, Forns index, FIB-4 and King's score. Serum ammonia could predict the presence of EV using a cutoff value of 82 (µmol/L) with a sensitivity of 92.3%, specificity 92%. In addition, a cutoff of 95.5 (µmol/L) could predict large EV with a sensitivity of 92.7% and a specificity of 92.3%. Serum Ammonia in cirrhosis with large EV was 143 ± 39 µmol/L and in cirrhosis with small/without EV was 80.7 ± 9.7 µmol/L (P < 0.0001). Platelet/spleen ratio was 555.9 ± 187.3 in cirrhosis with EV and 694.4 ± 74.2 in cirrhosis without EV (P < 0.0001). Platelet/spleen ratio was 407.7 ± 107.1 in cirrhosis with large EV and 690.4 ± 103.7 in cirrhosis with small/without EV (P < 0.0001). CONCLUSION: Serum ammonia can accurately predict the presence and the size of EV in patients with liver cirrhosis with high sensitivity and specificity.

Increased liver stiffness by transient elastography and acoustic radiation force impulse imaging in patients with extrahepatic cholestasis.

BACKGROUND: Transient elastography and acoustic radiation force impulse (ARFI) imaging are noninvasive tools for liver stiffness measurement (LSM), which may be influenced by cholestasis. AIM: The aim of the study was to evaluate the performance of transient elastography and ARFI in extrahepatic cholestasis and correlate changes in LSM with biochemical activity. MATERIALS AND METHODS: A total of 38 patients with extrahepatic cholestasis prospectively underwent transient elastography and ARFI. Changes in LSM by transient elastography/ARFI were evaluated after 1 week of ERCP and correlated with biochemical parameters. The optimal ARFI cutoffs according to stages of clinical interest were analyzed. RESULTS: Biliary obstruction was calcular in 21 (55.3%) and noncalcular in 17 (44.7%) (benign n = 15, malignant n = 2). After 1 week, adequate biliary drainage reduced total bilirubin from 7.7 to 2.2 mg/dL (P < 0.001) which significantly correlated with reduction of LSM by transient elastography from 12.38 ± 6.68 kPa to 8.08 ± 3.21 kPa (P < 0.001), and by ARFI from 1.73 ± 0.51 m/s to 1.56 ± 0.70 m/s (P = 0.014). The LSM percentage change showed a decrease (nonsignificant, P = 0.843) by 25.83% using transient elastography and a significant decrease (P < 0.001) by 18.42% using ARFI in the improved patients. At initial visit, transient elastography positively correlated with ARFI, bilirubin and platelets, also, transient elastography had a positive correlation with ARFI, bilirubin, alkaline phosphatase (ALP), γ-glutamyl transpeptidase (GGT) in follow-up visit. LSM by ARFI (visit 1) negatively correlated with ALT, while in (visit 2), ARFI positively correlated with bilirubin, ALP, GGT and negatively correlated with albumin. CONCLUSION: The increased LSM in patients with extrahepatic cholestasis is reduced after adequate biliary drainage, implying that increased values are not solely due to liver fibrosis, but due to biliary congestion leading temporarily to increased elasticity.

Acoustic radiation forced impulse-based splenic prediction model using data mining for the noninvasive prediction of esophageal varices in hepatitis C virus advanced fibrosis.

BACKGROUND: Esophageal varices (EV) are serious complications of hepatitis C virus (HCV) cirrhosis. Endoscopic screening is expensive, invasive, and uncomfortable. Accordingly, noninvasive methods are mandatory to avoid unnecessary endoscopy. Acoustic radiation forced impulse (ARFI) imaging using point shear wave elastography as demonstrated with virtual touch quantification is a possible noninvasive EV predictor. We aimed to validate the reliability of liver stiffness (LS) and spleen stiffness (SS) by an ARFI-based study together with other noninvasive parameters for EV prediction in HCV patients. Also, we aimed to evaluate the diagnostic performance of a new simple prediction model (incorporating SS) using data mining analysis. PATIENTS AND METHODS: This cross-sectional study included 200 HCV patients with advanced fibrosis. Labs, endoscopic, ultrasonographic, LS, and SS data were collected. Their accuracy in diagnosing EV was assessed and a data mining analysis was carried out. RESULTS: Ninety patients (22/46% of F3/F4 patients) had EV (39/30/18/3 patients had grade I/II/III/IV, respectively). LS and SS by ARFI showed high significance in differentiating not only patients with/without EV (P = 0.000 for both) but also correlated with the grading of varices (R = 0.31 and 0.45, respectively; P = 0.000 for both). Spleen longitudinal diameter (SD), splenic vein diameter (SVD), platelets to spleen diameter ratio, LOK index, and FIB-4 score were the best ultrasonographic and biochemical predictors for the prediction of EV [area under receiver operating characteristic (AUROC) 0.79, 0.76, 0.76, 0.74, and 0.71, respectively]. SS (using ARFI) had better diagnostic performance than LS for the prediction of EV (AUROC = 0.76 and 0.70, respectively). The diagnostic performance increased using data mining to construct a simple prediction model: high probability for EV if [(SD cm) × 0.17 + (SVD mm) × 0.06 + (SS) × 0.97] more than 6.35 with AUROC 0.85. CONCLUSION: SS by ARFI represents a reliable noninvasive tool for the prediction of EV in HCV patients, especially when incorporated into a new data mining-based prediction model.

High SVR rate following retreatment of non-sustained virological responders to sofosbuvir based anti-HCV therapies regardless of RAS testing: A real-life multicenter study.

Aim: Evaluation of the efficacy and safety of sofosbuvir/daclatasvir/ribavirin (SOF/DCV/RBV) in treating non-sustained virological responders (non-SVR12) to prior sofosbuvir-based therapy, in absence of RAS testing in mass treatment, and determination of the optimal timing to start re-treatment. Methods: Real-life prospective observational study included prior non-responders to 24-weeks SOF-RBV (n = 679, 67%) or 12-weeks SOF- RBV- PEG (n = 335, 33%). Patients were re-treated with daily SOF/DCV/RBV for 12 (n = 270) or 24 weeks (n = 744). The primary efficacy endpoint was SVR12. The primary safety endpoints were reported adverse events (AEs) from baseline to SVR12 time point. Results: We included 1,014 patients [age 52 ± 9 years, 58.48% men]. Cirrhosis was documented in 46.98% and 27.5% of SOF-RBV and SOF-RBV-PEG non-responders respectively. Overall, SVR12 was 90.6% [92.2% for 12 weeks therapy and 90.05% for 24 weeks therapy]. Mild AEs occurred in 5.13% (n=52) and 3.1% (n=32) discontinued treatment including eight on-treatment mortalities. Higher baseline FIB-4 and shorter interval before starting retreatment (<6 months) were independent predictors of non-SVR12 on multivariate regression analysis. Conclusion: SOF/DCV/RBV is an effective and safe treatment option for non-responders to prior sofosbuvir-based therapy. Six months interval before retreatment is optimal for achieving favorable SVR.

Percutaneous microwave ablation for HCV-related hepatocellular carcinoma: Efficacy, safety, and survival.

BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) has a poor prognosis if managed late. Percutaneous microwave ablation (MWA) emerged as one of the top therapeutic decisions for non-surgical patients. The aim of the present study aim was to evaluate the efficacy, side effects, and survival after MWA of hepatitis C virus (HCV)-related HCC tumors with spectrum sizes up to 5 cm. MATERIALS AND METHODS: Fifty-nine patients with early HCC were treated in the Hepatology Department using percutaneous MWA. Patients were assessed for side effects and efficacy that includes the rate of complete ablation, primary or de novo recurrence, and survival. RESULTS: Complete ablation was achieved in 57 (96.6%) patients treated by MWA, with a minor complication rate of 3.3% (n=2) including liver abscess formation and abdominal skin burn. The ablation rates in lesions <3 versus 3-5 cm were not different. Of the patients, 3 (5%) had primary recurrence in the treated HCC tumors, de novo lesions (secondary recurrence) developed in 8 (13.5%, 5 of them >3 cm), and 2 (3.3%) had malignant portal vein thrombosis. The survival rates were 95.4% and 69% at 1 and 2 years, respectively. CONCLUSION: Percutaneous MWA had achieved a safe and effective treatment with good overall survival in patients with HCV-related HCC.

Serum cytokeratin-18 and its relation to liver fibrosis and steatosis diagnosed by FibroScan and controlled attenuation parameter in nonalcoholic fatty liver disease and hepatitis C virus patients.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) has emerged as the most common cause of chronic liver disease worldwide. Multiple diagnostic noninvasive methods for NAFLD were studied (both serological and imaging), either single or combined. Attention has been focused on cytokeratin-18 (CK18) as a novel serological marker for the diagnosis of steatosis/fibrosis in NAFLD and hepatitis C virus (HCV) patients. AIM: The aim of this study was to evaluate serum CK18 in NAFLD and HCV fibrosis/steatosis and also to correlate its performance with the diagnostic accuracy of transient elastography (TE) and controlled attenuation parameter (CAP) in the diagnosis of fibrosis/steatosis in these patients. PATIENTS AND METHODS: Three equal groups of participants were enrolled (n=135): group I included patients with chronic HCV, group II included NAFLD patients, and group III included control participants. For all groups, TE/CAP and labs including serum CK18 were performed. Liver biopsy was performed for the NAFLD group. RESULTS: Serum CK18 was significantly higher in the NAFLD group (19.01±3.49 ng/ml) versus the HCV group (8.95±1.06 ng/ml) and the control group (4.83±1.6 ng/ml) (P<0.001). The CK18 levels in biopsy stages (steatosis, ballooning, inflammation, and fibrosis) and FibroScan/CAP degrees showed that CK18 increased significantly with steatosis and fibrosis stages (biopsy or FibroScan/CAP), but did not reach significance with ballooning or inflammation grades. CK18 was significantly different in nonalcoholic steatohepatitis versus non-nonalcoholic steatohepatitis patients (P=0.041). The best CK18 cutoff to detect steatosis (S≥2) in NAFLD and HCV was 11.65 and 6.84 ng/ml, respectively with an overall sensitivity and specificity over 97%. The CK18 cutoff for significant fibrosis (F≥2) by FibroScan in the NAFLD/HCV groups was 9.115 ng/ml, with 62.5%/69.2% sensitivity/specificity (P=0.031). However, inflammation had a cutoff with a marginal P value (P=0.080), and a reliable cutoff for ballooning was not attained (P=0.386). There was a positive correlation between CK18 and fibrosis (by FibroScan) in the NAFLD and HCV groups (P<0.05). The correlation between CK18 and steatosis in CAP and the nonalcoholic fatty liver disease activity score was very good (P<0.001). CONCLUSION: Serum CK18 is related strongly to the development/progression of NAFLD and HCV-related fibrosis/steatosis. TE was correlated highly with liver biopsy results. The combination of CK18 with other noninvasive modalities increases the diagnostic yield of these tests.

Entecavir and other nucleos(t)ide analogs prophylaxis in hepatitis B virus-related liver transplantation: long-term efficacy and safety.

BACKGROUND AND AIM: Although hepatitis B virus (HBV) recurrence after liver transplantation (LTx) has been reduced since the application of the combination of hepatitis B immunoglobulin (HBIG) and nucleos(t)ide analogs (NUCs), the optimum regimen to prevent HBV recurrence with LTx favorable outcome is still not clear. AIM: The aim was to evaluate the efficacy and safety of NUCs prophylaxis (±HBIG) against HBV recurrence after LTx. PATIENTS AND METHODS: This was a retrospective cohort-longitudinal study on 44 HBV-related post-LTx patients on anti-HBV prophylactic therapy. They included the entecavir (ETV)-based (n=34, 30 males) and the other NUC-based (n=10, 7 males) groups±HBIG. RESULTS: The median age was 63.5 (60-70) years in ETV and 62.5 (55-65) years in other NUCs groups. The mean follow-up duration was 6.09±1.83 years in ETV-based group and 6.3±1.89 years in other NUCs-based group. The mean ETV duration was 3.47±3.04 years. In ETV+HBIG patients, none of them developed HBV recurrence throughout the ±8 years. In the 14 patients on ETV+other NUC+HBIG, four developed HBsAg positive and then transformed to HbsAb positive at the end of ±8 years without hepatitis or detectable HBV-DNA. Liver graft function showed nonsignificant difference for ETV-based patients, in comparison with other NUC groups (P=0.09). With subdivision, the graft function was maintained significantly better in ETV+HBIG or other NUCs+HBIG (P=0.04) groups. None of our patients reported NUCs-related complications or adverse effects. CONCLUSION: ETV and other NUCs were effective and safe as a long-term prophylaxis of HBV recurrence after LTx, leading to a good graft function. HBsAg temporally reappeared in a minority of patients, where all showed HBsAb seroconversion without detectable HBV-DNA or clinical hepatitis.

Liver stiffness measurement by acoustic radiation forced impulse and transient elastography in patients with intrahepatic cholestasis.

BACKGROUND: Transient elastography (TE) and acoustic radiation force impulse (ARFI) imaging enable a noninvasive assessment of liver stiffness measurement (LSM) and liver fibrosis/cirrhosis staging. However, their use in cholestatic diseases is still scarce. AIM: The aim of this study was to evaluate the performance of TE and ARFI for the initial assessment of hepatic fibrosis in intrahepatic cholestatic (IHC) diseases and assess LSM changes after 3 months of specific therapy. PATIENTS AND METHODS: This prospective study was carried out on 50 IHC patients. Assessment at baseline and after 3 months of LSM by TE and ARFI was performed. RESULTS: Overall, 60% of the patients were women (36.5±9.2 years). IHC etiologies were 23 (46%) autoimmune hepatitis, eight (16%) primary sclerosing cholangitis, eight (16%) drug induced, and five (10%) primary biliary cirrhosis. TE could diagnose ≥F2, ≥F3, and F4 stages at cutoffs of at least 6.7, 9.4, and 14.0 kPa, sensitivity/specificity were 100/50% for ≥F2, 88.2/83% for ≥F3, and 90/100% for F4. Moreover, the sensitivity and specificity of ARFI were 93/50% for ≥F2 (cutoff: 1.53 m/s); 71/67% for ≥F3 (cutoff 1.77 m/s); and 90/100% for F4 (cutoff: 2.43 m/s).Follow-up showed a significant decrease in TE and ARFI values by 27 and 22.3% (P<0.001 and <0.001, respectively) and, accordingly, fibrosis stages decreased significantly by both TE and ARFI (P=0.002 and <0.001, respectively). CONCLUSION: TE and ARFI represent noninvasive methods with adequate diagnostic performance for the assessment of fibrosis, and monitoring disease progression and treatment response in intrahepatic cholestasis.

The clinical usefulness of elastography in the evaluation of nonalcoholic fatty liver disease patients: A biopsy-controlled study.

BACKGROUND: We aimed at determination of the usefulness of elastography [acoustic radiation force impulse (ARFI) and FibroScan] for evaluation of nonalcoholic fatty liver disease (NAFLD) patients. PATIENTS AND METHODS: A prospective cross-sectional study included 60 biopsy-proven NAFLD patients (mean age: 45 years) was carried out. All patients were subjected to lab works, liver biopsy, and measurement of liver stiffness by ARFI and FibroScan and steatosis by controlled attenuation parameter (CAP). CAP measurements were adjusted for the presence of NAFLD and presence or absence of diabetes and according to BMI. RESULTS: Linear regression analysis showed that CAP is an independent predictor for significant hepatic steatosis (P<0.001). No significant difference was found in diagnostic accuracy between adjusted and nonadjusted CAP values for diagnosis of mild (>S1) or significant (>S2) hepatic steatosis (P=0.17 and 0.29 respectively). The median ARFI velocities for F1, F2, F3, and F4 were 0.92, 1.08, 1.07, and 2.58 m/s, respectively. Although there was an overall significant increase in ARFI values across the fibrosis grades (P<0.04), the difference in ARFI values was only significant between fibrosis grades F1 and F4 (P=0.02). CONCLUSION: Elastography is a promising noninvasive tool for diagnosis and grading of hepatic steatosis and fibrosis in patients with NAFLD/nonalcoholic steatohepatitis with good sensitivity and specificity, especially in moderate to marked grades.

Genetic Variants in nicotinamide-N-methyltransferase (NNMT) gene are related to the stage of non-alcoholic fatty liver disease diagnosed by controlled attenuation parameter (CAP)-fibroscan.

BACKGROUND AND AIMS: Various genetic polymorphisms play a key-role in the pathogenesis of NAFLD and progression to NASH with fibrosis to cirrhosis. We aimed to study the association between single-nucleotide polymorphisms (SNPs) in NNMT gene, namely rs694539 and the development of different stages of NAFLD diagnosed by controlled attenuation parameter (CAP) of FibroScan Echosens®. METHODS: Transient elastography (FibroScan®) with controlled attenuation parameter (CAP) measurement was performed in 81 NAFLD patients (35 of them with liver biopsy) and 80 non-NAFLD controls. The accuracy of CAP and FibroScan for the detection and quantification of hepatic steatosis/fibrosis, respectively, was assessed based on liver biopsy aspect. Genetic variants of NNMT gene rs694539 were analyzed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: According to BMI (kg/m2), among the patients, 17 (21%) were overweight, 56 (69.1%) obese, and 8 (9.9%) morbidly obese. CAP and FibroScan diagnosed steatosis/fibrosis correlated significantly with liver biopsy. There was a significant association between polymorphisms of rs694539-NNMT gene and NAFLD presence and stages. The mutant type (AA-genotype) was found in 33% NAFLD patients versus 1.2% controls (P<0.001), whereas the wild type (GG-genotype) was present in 21% versus 63.8% controls (P<0.001). Moreover, the AA-genotype significantly correlated with the steatosis degree by CAP but not the fibrosis degree by FibroScan. Multivariate regression analysis of all the independent risk factors showed non-significant correlations with the degree of steatosis on CAP. However, by using a stepwise approach, waist circumference showed significance as an independent predictor of NAFLD. CONCLUSIONS: Polymorphisms in rs694539-NNMT gene (mutant AA-genotype) could be a genetic risk factor for developing NAFLD and NASH (indicating susceptibility for progression and complications). Individuals with wild type (GG-genotype) are at less risk of NAFLD development. CAP and FibroScan efficiently diagnosed steatosis and fibrosis.

Enhanced liver fibrosis test using ELISA assay accurately discriminates advanced stage of liver fibrosis as determined by transient elastography fibroscan in treatment naïve chronic HCV patients.

Evaluation of liver fibrosis stage is crucial in the assessment of chronic HCV patients, regarding decision to start treatment and during follow-up. Our aim was to assess the validity of the enhanced liver fibrosis (ELF) score in discrimination of advanced stage of liver fibrosis in naïve chronic HCV patients. We prospectively evaluated liver fibrosis stage in one hundred eighty-one naïve chronic HCV Egyptian patients by transient elastography (TE)-FibroScan. Patients were categorized into mild to moderate fibrosis (≤F2) group and advanced fibrosis (≥F3) group. The ELF score components, hyaluronic acid (HA), amino-terminal propeptide of type-III-procollagen (PIIINP) and tissue inhibitor of metalloproteinase type-1 (TIMP-1), were done using ELISA test. The mean values of ELF and its individual components significantly correlated with the hepatic fibrosis stage as measured by TE-FibroScan (P value 0.001). ELF cutoff value of 9.8 generated a sensitivity of 77.8%, specificity of 67.1%, area under the receiver operator characteristic curve (AUROC) of 0.76 with 95% confidence interval [CI] (0.68-0.83) for detecting advanced fibrosis (F ≥ 3). ELF panel is a good, reliable noninvasive test and showed comparable results to TE-FibroScan in detecting liver fibrosis stage in treatment naïve chronic HCV patients.

Effect of N-Acetylcysteine on Mortality and Liver Transplantation Rate in Non-Acetaminophen-Induced Acute Liver Failure: A Multicenter Study.

INTRODUCTION AND AIM: Previous studies and systematic reviews have not provided conclusive evidence on the effect of N-acetylcysteine (NAC) in non-acetaminophen-induced acute liver failure (NAI-ALF). We aimed to study the value of intravenous NAC in reducing liver transplantation and mortality in NAI-ALF. PATIENTS AND METHODS: In a prospective, multicenter, observational study, acute liver failure patients without clinical or historical evidence of acetaminophen overdose were enrolled. NAC infusion (in empirical dose) was given as 150 mg/kg in 100 ml dextrose 5% over half an hour, then 70 mg/kg in 500 ml dextrose 5% over 4 h, then 70 mg/kg in 500 ml dextrose 5% over 16 h. Thereafter continuous infusion was administered over 24 h of 150 mg/kg in 500 ml dextrose 5% until up to two consecutive normal international normalized ratios (INRs) were obtained. Our endpoints were recovery, transplantation, or death. The primary outcome of the study was to assess reduction in mortality or liver transplantation. The secondary outcome was the evaluation of other clinical outcomes (length of ICU and hospital stays, organ system failure, and hepatic encephalopathy). RESULTS: The study included a total of 155 adults; the NAC group (n = 85) were given NAC between January 2011 to December 2013 and the control group (n = 70) were not given NAC and were included from files dating between 2010 and 2011. Both groups (before NAC) were comparable with regard to etiology, age, sex, smoking, presence of co-morbidities, encephalopathy, liver profile, and INR. The success rate (transplant-free survival) in the NAC group was 96.4%. While in the control group, 17 patients (23.3%) recovered and 53 (76.6%) did not recover, of these 37 (53.3%) had liver transplantation and 16 (23.3%) died (p < 0.01). The NAC group had significantly shorter hospital stays (p < 0.001), less encephalopathy (p = 0.02), and less bleeding (p < 0.01) than the control group. The control group reported a higher ICU admission (p = 0.01) rate and abnormal creatinine and electrolytes (p = 0.002, p < 0.01, respectively). Liver profile and INR (after NAC infusion) differed significantly between the two groups with regard to bilirubin (increased in controls, p = 0.02), AST and INR (decreased in NAC group, p < 0.001 for both), but the ALT decrease showed no statistical significance between the two groups. CONCLUSIONS: When administered on admission, intravenous NAC caused a reduction in NAI-ALF mortality and need for transplantation. NAC decreased encephalopathy, hospital stay, ICU admission, and failure of other organs.

Regulatory and activated effector T cells in chronic hepatitis C virus: Relation to autoimmunity.

AIM: To investigate how Tregs are regulated in chronic hepatitis C virus (HCV) patients via assessment of Tregs markers (granzyme 2, CD69 and FoxP3), Teffs markers [TNFRSF4 (OX40), INFG] and CD4, CD25 genes. METHODS: A prospective study was conducted on 120 subjects divided into 4 groups: Group I (n = 30) treatment naïve chronic HCV patients; Group II (n = 30) chronic HCV treated with Peg/Riba; Group III (n = 30) chronic HCV associated with non-organ specific autoantibody and Group IV (n = 30) healthy persons as a control group. Tregs and Teffs markers were assessed in peripheral blood mononuclear cells by quantitative real time reverse transcriptase-polymerase chain reaction. RESULTS: Chronic HCV patients exhibited significant higher levels of both Teffs and Tregs in comparison to healthy control group. Tregs markers were significantly decreased in Peg/Riba treated HCV patients in comparison to treatment naïve HCV group. In HCV patients with antinuclear antibody (ANA) +ve, Tregs markers were significantly decreased in comparison to all other studied groups. Teffs markers were significantly elevated in all HCV groups in comparison to control and in HCV group with ANA +ve in comparison to treatment naïve HCV group. CONCLUSION: Elevated Tregs cells in chronic HCV patients dampen both CD4+ and CD8+ autologous T cell immune response. Interferon-α and ribavirin therapy suppress proliferation of Tregs. More significant suppression of Tregs was observed in HCV patients with autoantibodies favoring pathological autoimmune response.

Virologic response and breakthrough in chronic hepatitis B Egyptian patients receiving lamivudine therapy.

BACKGROUND: Lamivudine monotherapy is effective in suppressing hepatitis B virus (HBV) replication to undetectable levels by PCR, in ameliorating liver disease and to some extent in achieving HBsAg seroconversion. This study aimed at assessing the virological and biochemical responses as well as breakthrough in HBeAg-negative chronic HBV (CHB) Egyptian patients receiving lamivudine therapy. METHODS: This retrospective study included 140 CHB patients with positive serum HBV-DNA by quantitative PCR assays and negative HBeAg who had never received prior anti-viral therapy for HBV. According to duration of lamivudine therapy (100 mg/day) patients were grouped into: group I (n=59) who received lamivudine for 1 year, group II (n=50) who received lamivudine for 2 years, and group III (n=31) who received lamivudine for 3 years. RESULTS: In group I, 76.3% patients had virologic response but this was reduced in group II and group III to 72% and 67.7% respectively. None of the patients in group I developed virologic breakthrough, whereas 12% and 25.8% in groups II and III respectively developed breakthrough. In group I, 25% of patients having high pre-treatment viremia showed virologic response compared to 84.6% and 83.3% having mild and moderate viremia respectively (P<0.01). However, in groups II and III, there was no significant relationship between pre-treatment viremia and virologic response. No significant relationship was found between pre-treatment viral load and incidence of breakthrough within each group. CONCLUSION: Lamivudine remains one of the antiviral therapies for HBeAg negative CHB patients. The rates of maintained virologic and biochemical responses to lamivudine decrease in time due to selection of drug-resistant mutants and, hence, breakthrough.

Caspase recruitment domains. New potential markers for diagnosis of hepatocellular carcinoma associated with HCV in Egyptian patients.

UNLABELLED: BACKGROUND AND RATIONALE FOR THE STUDY: Chronic HCV is a major cause of HCC development. Caspase Recruitment Domains (CARD) is protein modules that regulate apoptosis and play an important role in various carcinogenesis processes, our aim is to assess the possible role of CARD9, CARD10 and Caspase only protein (COP) in progression of liver fibrosis and pathogenesis of HCC in Egyptian chronic HCV patients. MATERIAL AND METHODS: 130 patients were recruited and classified into 4 groups; I: chronic HCV, II: chronic active hepatitis, III: liver cirrhosis, IV: HCV related HCC. Biochemical, virological studies, abdominal ultrasonography and liver biopsy were performed. Quantitative estimation of mRNA of CARD9, CARD10 and COP gene expression was performed by RT- PCR in liver biopsy from all patients. RESULTS: In HCC patients; age, AFP and liver profile were significantly higher, HB and platelets were significantly lower (p value <0.01). The expression levels of mRNA of CARD9, CARD10 and COP in liver biopsies of HCC were significantly higher than other groups with direct correlation with age and no correlation with AFP, viral load, liver fibrosis or necroinflammatory activity. On differentiation between HCC and non HCC patients each CARD was assessed separately and combined, on combing the 3 CARDs, the sensitivity was 100%, specificity was 48%, positive predictive value 47% and negative predictive value 100%. CONCLUSIONS: CARD9, CARD10 and COP had no role in liver fibrosis but may be involved in hepatic carcinogenesis and they could be used as markers for HCC diagnosis and candid genes for molecular target therapy.

Hypertonic saline-enhanced radiofrequency versus chemoembolization sequential radiofrequency in the treatment of large hepatocellular carcinoma.

BACKGROUND AND STUDY AIM: Large hepatocellular carcinoma (HCC) appears to be a major obstacle for radiofrequency ablation (RFA); therefore, attempts to increase the volume of coagulation by injecting hypertonic saline before and/or during RFA have been made. Transarterial chemoembolization (TACE) combines the effect of targeted chemotherapy with ischemic necrosis and eliminates heat loss if combined with RFA. Our aim was to compare the efficacy of hypertonic saline-enhanced RFA versus TACE sequential RFA in the treatment of medium and large nodular HCC. PATIENTS AND METHODS: This prospective study was carried out on 40 patients with 40 HCCs between 2008 and 2010 in the Tropical Medicine and Hepatology Department, Faculty of Medicine, Cairo University. They were divided into two groups (20 patients each): the first group received hypertonic saline-enhanced RFA (RFA+HS) and the second group underwent transarterial chemoembolization, followed by RFA (TACE+RFA). RESULTS: Triphasic computed tomography 1 month after the procedure showed that 17 (85%) patients in each group achieved complete ablation, whereas three (15%) in each group achieved partial ablation. In the RFA+HS group, 12/13 (92%) of medium HCC and 5/7 (71%) of large HCC were successfully ablated. In the TACE+RFA group, 8/8 (100%) medium HCC and 9/12 (75%) of large lesions were successfully ablated. The relation between success rate and lesion diameter was statistically significant only in RFA+HS group. After 6 months, 73.7% of patients in the RFA+HS group and 83.3% of patients in the TACE+RFA group showed maintained ablation (P=0.86). CONCLUSION: RFA+HS and TACE+RFA are safe and equally effective treatments for medium to large HCC.

Genetic variability of antigen B among Echinococcus granulosus Egyptian isolates.

Genetic polymorphisms of encoding antigen B2 gene (AgB2) in Echinococcus granulosus were studied using PCR-RFLP and DNA sequencing among 20 Egyptian isolates. Five isolates from different host origins (humans, camels, pigs, and sheep) were collected and used. All examined isolates of each host group gave very similar patterns of PCR-RFLP after restriction enzyme digestion with AluI, with the gene size of approximately 140 bp and 240 bp for sheep and human isolates, and approximately 150 bp and 250 bp for pig and camel isolates. No digestion pattern was obtained after incubation of all studied isolates with EcoRI. These results reveal high intra-group homogeneity. DNA sequence analysis highlighted that human infecting strain showed 100% identity with respect to sheep infecting isolate, 96% and 99% with pig and camel infecting isolates, respectively.