Steatosis regression assessed by cap after Vitamin 'D' supplementation in NAFLD patients with Vitamin 'D' deficiency.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease, and previous studies suggested a relationship between vitamin D deficiency and NAFLD. It is suggested that vitamin D supplementation may have significant beneficial effect on liver biochemistry and histology. OBJECTIVE: This study aims to assess the degree of possible steatosis regression using controlled attenuation parameter (CAP) in NAFLD patients with vitamin D deficiency after vitamin D supplementation and evaluating its effect on lipid profile and transaminases. PATIENTS AND METHODS: This study was conducted on 100 NAFLD patients with vitamin D deficiency. They received 10000 IU/week of vitamin D orally for 3 months. CAP was used to assess hepatic steatosis and fibrosis before/after intervention. Transaminases, lipid profile, and vitamin D levels were evaluated before/after treatment. RESULTS: Serum AST, ALT, cholesterol, TG, LDL and HDL showed a significant reduction posttreatment in patients with both normal and elevated baseline levels ( P < 0.001). The posttreatment mean CAP showed a significant reduction (300.44 ±â€…37.56 vs. 265 ±â€…36.19 dB/ml) ( P  < 0.001), and there was a significant improvement in the mean fibrosis values by LSM (5.32 ±â€…1.53 vs. 4.86 ±â€…1.28 KPa) ( P  = 0.001). After supplementation, serum vitamin D level was raised significantly in the majority of patients ( P  < 0.001); however, only 13% of them reached sufficient levels (>30 ng/ml), insufficient levels (20-29 ng/ml) was reached in 83% and 5% showed vitamin D deficiency (<20 ng/ml). CONCLUSION: A significant improvement was detected in hepatic steatosis (by CAP); mean values of LSM, transaminases and lipid profile after three months of oral vitamin D supplementation.

Apelin Association with Hepatic Fibrosis and Esophageal Varices in Patients with Chronic Hepatitis C Virus.

Portal hypertension and esophageal varices complicating hepatitis C virus (HCV)-related chronic liver diseases are some of the most devastating sequelae. Angiogenesis is the hallmark of their pathogenesis. Apelin is one of the recently identified angiogenic and fibrogenic peptides. We studied apelin gene expression, apelin (rs3761581) single-nucleotide polymorphism (SNP), and serum apelin level in patients with chronic HCV, and their association with liver fibrosis and esophageal varices in 112 patients with HCV-related chronic liver disease (40 with liver cirrhosis [LC]/low-grade varices, 33 with LC/high-grade varices, and 39 with fibrotic non-cirrhotic liver/no varices) and 80 healthy control subjects. Real-time polymerase chain reaction was used for apelin gene expression assay and apelin rs3761581 SNP analysis in peripheral blood samples. The serum apelin level was measured by ELISA. Apelin gene expression was undetectable in the studied samples. The SNP analysis revealed a greater frequency of the C (mutant) allele among patients compared with control subjects (P = 0.012; odds ratio, 3.67). The serum apelin level was significantly greater in patients with LC/varices (median, 31.6 ng/L) compared with patients without LC/varices (median, 2.9 ng/L; P < 0.001). A serum apelin level cutoff value of 16.55 ng/L predicted the presence of varices, with an area under the receiver operating characteristic curve value of 0.786. A positive correlation was found between serum apelin level and grade of liver fibrosis (r = 0.346, P < 0.001) and portal hypertension (r = 0.438, P < 0.001). In conclusion, the apelin rs3761581-C allele may be associated with the progression of HCV-related chronic liver disease and varices formation, and can be considered a potential therapeutic target to control fibrosis progression. The serum apelin level provided an accurate prediction of the presence of esophageal varices.

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.

Is Doppler/Dopplex ultrasonography reliable in the assessment of percutaneous ablative therapies of hepatocellular carcinoma: a prospective cross-sectional study.

INTRODUCTION: After hepatocellular carcinoma (HCC) interventional therapies, noninvasive vascular diagnostic imaging [duplex, Color/power Doppler ultrasonography, and triphasic computed tomography (CT)] determines the lesion complete/incomplete ablation. The aim was to analyze the usefulness of duplex, color/power Doppler ultrasonography in HCC ablation after percutaneous ablative therapies (PATs). METHODS: We included 30 patients with 33 HCCs subjected to duplex/Doppler ultrasonography, ultrasound-guided fine-needle aspiration cytology (FNAC), and triphasic CT, all these before and after PATs. RESULTS: One week after treatment ended, out of 21 lesions with pretreatment positive color-Doppler, signals disappeared in 19 (90.5%) lesions. Out of 29 lesions with pretreatment positive power-Doppler, signals disappeared in 24 (82.8%). Out of 13 lesions with pretreatment intralesional power/duplex arterial signals, signals disappeared in eight (61.5%). There was a significant correlation (P < 0.05) between power-Doppler arterial signals and FNAC. Before HCC ablation, power-Doppler demonstrated a sensitivity 40% and specificity 96% in HCC detection in relation to FNAC, it had a sensitivity 60% and specificity 85% in HCC detection compared to triphasic CT. After HCC ablation, power-Doppler had a sensitivity and specificity of 100% in viable malignancy detection in relation to FNAC. Power-Doppler had a sensitivity 89% and specificity 93% in residual malignancy detection in relation to triphasic CT. CONCLUSION: Power-Doppler is a good positive test as intralesional arterial signals in a cirrhotic liver lesion is highly suggestive of HCC. Power-Doppler was sensitive in HCC ablation assessment in pretreatment positive cases only. Both triphasic CT and duplex/Doppler are complementary and the use of different diagnostic modalities after ablation is mandatory.

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.

Secreted protein acidic and rich in cysteine gene variants: Impact on susceptibility and survival of hepatocellular carcinoma patients.

BACKGROUND AND AIM: Secreted protein acidic and rich in cysteine (SPARC) is a glycoprotein involved in extracellular matrix remodeling, which regulates cell growth. It could be involved in hepatic fibrogenesis related to chronic inflammations, hepatocellular carcinoma (HCC) angiogenesis, and tumor progression. We aimed to study the expressions of single nucleotide polymorphisms in the SPARC gene and their impact on susceptibility and survival of HCC patients. METHODS: We conducted a case-control study on 200 HCC patients and 50 matched healthy controls. All patients were subjected to laboratory investigations, ultrasound, and real-time polymerase chain reaction to detect the genetic polymorphisms (rs3210714, rs11950384, and rs7719521) in the SPARC gene in the blood. RESULTS: One hundred sixty (80%) patients were men with a mean age of 43 years. The SPARC gene showed a significant higher prevalence of rs3210714 mutation (i.e. AA or AG) and a significant lower prevalence of rs11950384 mutation (i.e. AA or AC) among HCC patients in comparison with controls (83% vs 22%, P ≤ 0.001) and (65.5 vs 86%, P = 0.005), respectively, while rs7719521 mutation did not reach significance. On univariate and multivariate analyses, elder age and having at least one copy of the mutant rs3210714 were associated with a significantly increased risk of HCC (P < 0.001 for both), whereas the presence of at least one copy of the mutant rs11950384 carried a significantly reduced risk of having HCC (P < 0.01). Overall survival did not differ significantly between any of the SPARC gene mutation groups. CONCLUSIONS: The SPARC gene polymorphisms had a diverse impact on the susceptibility of HCC due to its ability to inhibit or promote tumor progression. SPARC gene polymorphisms were not related to survival of our HCC patients, and probably, this needs further analysis of other SPARC gene nucleotides.

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.

Serum Zinc Deficiency and its Relation to Liver Fibrosis in Chronic HCV: a Real-Life Egyptian Study.

Zinc is essential for the activation of approximately 300 metallo-enzymes. Serum and hepatic zinc is decreased in chronic liver disease patients, and zinc depletion has been suggested to accelerate liver fibrosis. The study was designed to assess Zinc status in chronic HCV Egyptian patients and its relationship to fibrosis stage diagnosed by FibroScan. This was a cross-sectional study on 297 Egyptian patients with naïve chronic HCV. All patients underwent laboratory tests (including assessment of serum Zinc) and liver stiffness measurement (LSM) by Transient Elastography (FibroScan®). The study included 170 (57.2%) females and 127 (42.8%) males with a mean age 52.4 ± 10.2 years. Most of the patients had zinc deficiency as the mean zinc level was 55.5 ± 30.7 µg/dl. The FibroScan scores showed that 97 patients had mild to moderate fibrosis (≤F2), while 200 patients had advanced to severe fibrosis (˃F2). Zinc level was significantly lower in patients with ˃F2 than those with ≤F2 (52 ± 30.7 vs 62.5 ± 29.7, p value: 0.005), as the zinc values decreased with the progression of liver fibrosis. Serum zinc level had a negative significant correlation with INR and negative significant correlation with FibroScan score but no correlation to bilirubin, ALT, AST, or albumin. Most of Egyptian chronic liver disease patients had zinc deficiency. Zinc level gets significantly lower with progression of fibrosis. Zinc supplementation is essential before and during antiviral therapy for HCV.

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.

Ophthalmological side effects of interferon therapy of chronic hepatitis C.

BACKGROUND: Egypt has one of the highest prevalence of hepatitis C virus (HCV) worldwide. Ophthalmological side effects are recognized complications of interferon (IFN) therapy. This study aimed to evaluate IFN-induced ophthalmological manifestations in patients receiving PEGylated interferon (PEG IFN) and ribavirin (RBV) and to assess the effect of IFN duration, response and systemic risk factors on the severity. METHODS: We retrospectively analyzed 100 patients with chronic HCV who were candidates for PEG-IFN and RBV therapy. All patients were subjected to clinical and ophthalmological examination, laboratory investigations, abdominal ultrasound, colored fundus photography and fundus fluorescein angiography, follow up was made at weeks 12, 24, and 48 of treatment. RESULTS: IFN-induced retinopathy had been found in (9/100; 9%), 5 (5/9; 55.5%) of them had bilateral lesions, (3/9; 33.3%) were treatment responders and (6/9; 66.6%) non responders. The time of retinopathy appearance was mainly at W12. Retinopathy was asymptomatic in most of the affected patients (7/9; 77.77%) and reversible, cotton wool spots was the major associated sign. Patients with older age, DM and or HTN, and non-responders to antiviral therapy were associated with more severe retinopathy. CONCLUSIONS: Retinopathy is not a rare complication of IFN therapy for chronic HCV infection, but fortunately it's asymptomatic and reversible. Ophthalmological assessment at base-line and at follow up during IFN treatment is very important.