Renal profile of chronic hepatitis C patients with sofosbuvir-based therapy.

PURPOSE: The impact of SOF-based therapy on renal functions is quite controversial in clinical practice. Therefore, we aimed to evaluate the serial changes of renal indices during SOF-based therapy in CHC patients with normal kidney function or mild renal impairment. METHODS: We retrospectively reviewed all CHC patients who received different SOF-based regimens from January 2015 until December 2017, and presented with a baseline eGFR ≥ 30 ml/min/1.73m2. Patients who didn't achieve SVR, with missing creatinine or eGFR data, and patients with eGFR less than 30 ml/min/1.73m2 at baseline were excluded. eGFR was calculated for each time of evaluation using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula. RESULTS: A total of 1004 patients were finally included. The mean serum creatinine and eGFR levels varied between 0.84 mg/dl and 106.53 ml/min/1.73m2 for baseline and 0.87 mg/dl and 104.24 ml/min/1.73m2 for SVR12, respectively. The maximum increase of creatinine was 3.69 mg/dl and the maximum decrease of eGFR level was 83.30 ml/min/1.73m2 during treatment. Moreover, 74.4% of treated patients stayed in the same eGFR category, 14.3% progressed to a higher eGFR category, and 11.3% had an improvement eGFR category at EOT and continued to SVR12. Age > 65 years, baseline eGFR, and ribavirin-containing regimens were independent risk factors of eGFR decline during and after SOF-based treatment. CONCLUSION: SOF-based therapies seem to be safe in CHC patients with baseline normal or slightly impaired renal function.

Improvement of liver stiffness measurement, acoustic radiation force impulse measurements, and noninvasive fibrosis markers after direct-acting antivirals for hepatitis C virus G4 recurrence post living donor liver transplantation: Egyptian cohort.

Progression of recurrent hepatitis C is accelerated in liver transplant (LT) recipients. Direct-acting antivirals (DAAs) have recently emerged as a promising therapeutic regimen for the treatment of hepatitis C virus infection. Rates of sustained virological response (SVR) have drastically improved since the introduction of DAAs. The aim is to elucidate the changes in liver stiffness measurement (LSM) by transient elastography (TE) as well as acoustic radiation force impulse (ARFI) elastography and fibrosis scores after DAA treatment in LT recipients with hepatitis C virus recurrence. A single-center, prospective study including 58 LT recipients with hepatitis C recurrence who received different sofosbuvir-based treatment regimens. Transient elastography and ARFI elastography values were recorded as well as fibrosis 4 score (FIB-4) and aspartate aminotransferase-to-platelet ratio index were calculated at baseline and SVR at week 24 (SVR24). The outcome was improvement in LSM and at least a 20% decrease in LSM at SVR24 compared with baseline. The sustained virological response was 98.1%. There was improvement of platelet counts, alanine aminotransferase, and aspartate aminotransferase, which in turn caused improvement in fibrosis scores at SVR24. LSM by TE and ARFI elastography decreased from the baseline median value of 6.3 kPa (interquartile range [IQR]; 4.6 to 8.8 kPa) and 1.28 m/s (IQR; 1.07 to 1.53 m/s) to an SVR24 median value of 6.2 kPa (IQR; 4.85 to 8.9 kPa) and 1.12 (IQR; 0.97 to 1.30 m/s), respectively. Logistic regression analysis showed that baseline viral load was the only significant predictor of improvement in LS after DAA therapy at SVR24. Sofosbuvir-based treatment resulted in an early improvement in parameters of liver fibrosis in post-LT patients with hepatitis C recurrence.

Longitudinal assessment of hepatic fibrosis in responders to direct-acting antivirals for recurrent hepatitis C after liver transplantation using noninvasive methods.

Successful eradication of recurrent hepatitis C virus (HCV) infection following liver transplantation (HCV) improves graft survival. This study aimed at evaluation of hepatic fibrosis changes among long-term responders to DAA therapy for recurrent HCV after liver transplantation using noninvasive methods. Patients with significant hepatic fibrosis (≥F2) who achieved SVR12 after treatment with DAAs for recurrent HCV were included (n = 52). Hepatic fibrosis status was assessed, noninvasively, by calculation of fibrosis-4 score (FIB-4) and Aspartate Aminotransferase Platelet Ratio Index (APRI) and by measurement of graft stiffness using FibroScan at baseline and 12 and 18 months post-treatment. Acoustic radiation force imaging (ARFI) was done for all patients 12 and 18 months post-treatment. Patients were classified into two groups based on baseline liver stiffness measurement (LSM) by FibroScan; significant fibrosis (F2; n = 28) and advanced fibrosis groups (≥F3). Over 18-month follow-up period, there was serial improvement of FIB-4, APRI, and LSM by FibroScan in both groups. Higher baseline LSM and delayed initiation of antiviral therapy were significant predictors of lack of fibrosis regression (P-value 0.01 and 0.04, respectively). Fibroindices and LSM improved over time in liver transplant recipients who responded to DAAs. Baseline LSM can predict post-treatment fibrosis regression.

Improvement of glycemic state among responders to Sofosbuvir-based treatment regimens: Single center experience.

Chronic HCV infection has emerged as a complex multifaceted disease with manifestations extending beyond the liver. HCV plays a direct role in glucose metabolism leading to both insulin resistance and type 2 diabetes. To evaluate the changes in the glycemic state following Sofosbuvir-based treatment regimens in diabetic HCV patients. Four hundred chronic hepatitis C patients who underwent Sofosbuvir-based treatment regimens were retrospectively screened. Sixty-five diabetic HCV patients only enrolled in our analysis. Baseline demographic and laboratory data were recorded. Pretreatment Transient elastography was performed. At 24-week post EOT (SVR24), Fasting Plasma glucose, and Hemoglobin A1c were re-evaluated and compared with baseline. All enrolled diabetic patients were responders. They showed statistically significant decline in Fasting Plasma glucose and Hemoglobin A1c values at SVR24. Whatever the degree of hepatic fibrosis, the level of Fasting Plasma glucose and Hemoglobin A1c decreased at SVR24 in comparison to baseline level. Fifty-one patients showed improvement in their Hemoglobin A1c values at SVR24 and this improvement was more likely to occur among patients with low Body mass index. The reduction in Fasting Plasma glucose >20 mg/dL (>1.1 mmol/L) and Hemoglobin A1c ≥0.5% was not associated with age, gender or hepatic fibrosis stage. Sofosbuvir-based regimens are a highly efficient antiviral therapy for diabetic chronic HCV patients resulted in improvement in Fasting Plasma glucose and Hemoglobin A1c.

Coronavirus disease 19 (Covid-19): A comparative study of pattern of liver injury in adult patients in different waves of Covid-19 infection.

BACKGROUND AND STUDY AIMS: Liver dysfunction is a common manifestation of the COVID-19 infection. We aimed to study transaminase abnormalities through different waves of COVID-19 and their relations to disease severity or mortality. PATIENTS AND METHODS: A retrospective study included 521 Egyptian patients diagnosed with COVID-19. Data was retrieved from the medical records of patients who were admitted from April 2020 to October 2021 in Kasr Al-Ainy Hospitals, Cairo University, with categorization according to disease severity in correspondence to the four waves. RESULTS: The median age was lower in the first wave compared to other waves, with male predominance across all waves. The most commonly encountered comorbidity overall was hypertension, followed by diabetes mellitus. White blood cells, ferritin, and interleukin-6 showed the highest median values in the second wave, with significantly higher median C-reactive protein on day 1 in the first wave. Forty percent of the patients showed elevated hepatic transaminases on admission in four waves, with no statistically significant difference between waves. On day 5, around half of the patients had elevated transaminases, with no significant difference between waves. Most CT findings were of moderate severity. Clinical severity was higher in the second wave. It was observed that the higher the disease severity, the greater the proportion of patients with elevated hepatic transaminases. The mortality rate was markedly high in cases who had elevated ALT or AST on day 5. The association between elevated enzymes on admission and mortality was seen in the first wave only, with a fatality rate of 22.5% in cases with increased baseline ALT and AST versus 5% in those with normal baseline enzymes. CONCLUSION: There was no significant difference in transaminases between the four waves. Elevated transaminases were positively associated with increased mortality and severity, reflecting their prognostic value.

Outcome and prognostic markers of cirrhotic and non-cirrhotic patients admitted to a hepatology ICU in a tertiary care university hospital.

Background and aim: Patients with decompensated liver cirrhosis are not given priority for ICU admission in the settings of limited place availability. Recently, advances in medical care led to improvement in their survival. Our aim is to study the outcome of patients admitted to our hepatology ICU. Methods: We retrieved the data of patients admitted to the Endemic Medicine Department ICU at Kasr Al-Ainy Hospital in the period from November 2014 to May 2018. We included 498 patients who had complete clinical and outcome data in this analysis. The primary outcome was ICU mortality and its predictors. Results: The overall mortality was 48.1% in the liver cirrhosis versus 52.9% in the non-cirrhosis group. The most common presentations of cirrhotic patients were hepatic encephalopathy and hypovolemic shock. The SOFA score and sepsis independently predicted mortality in the overall cohort. Conclusion: The mortality of cirrhotic patients admitted to ICU is not higher than non-cirrhotic patients. SOFA score is a good prognostic indicator in patients with cirrhosis.

Value of pancreatic cyst fluid SPINK1 and glucose in differentiating potentially malignant cysts from those of benign nature: A prospective cohort study.

Background: Diagnosis of malignant pancreatic cystic lesions (PCLs) is challenging as there is no investigation that offers both high diagnostic sensitivity and specificity for a definite diagnosis. Accurate diagnosis of cyst type is vital in order to not miss opportunities for early treatment of potentially malignant lesions and to avoid unnecessary surgeries. Serine protease inhibitor Kazal type I (SPINK1) and glucose are promising cyst fluid markers for differentiation of mucinous from non-mucinous cysts. We aim to validate the value of SPINK1 and glucose in detecting potentially malignant PCLs. Methods: A prospective study was conducted on 80 patients presenting with PCLs. Endoscopic ultrasound (EUS) evaluation of detailed cyst morphology and EUS with fine needle aspiration (FNA) were done. Fluid analysis for carcinoembryonic antigen (CEA), glucose and SPINK1 and cytopathology were done. We compared these data with the final diagnosis based on cytopathological and postoperative histopathological examination. Results: Cyst fluid SPINK1 was significantly higher in malignant or potentially malignant cysts compared to benign cysts (0.91 vs 0.47 ng/ml; P = 0.001). Also, glucose was significantly lower in malignant or potentially malignant cysts compared to benign cysts (21.5 vs 68.5 mg/dl; P = 0.0001). Glucose and SPINK1 had the best sensitivity and specificity for differentiating mucinous from non-mucinous cysts with 84.78% and 73.53% (AUC 0.76; 95% CI [0.65-0.88]; cutoff value = 42 mg/dl), and 70.59% and 65.22% (AUC 0.72; 95% CI [0.64-0.86]; cutoff value = 0.58 ug/L) respectively. CEA level >192 ng/ml, high SPINK1 level and lymph node enlargement were the independent predictors of malignant cysts. Conclusion: Cyst fluid SPINK1 and glucose are promising diagnostic markers for the diagnosis of potentially malignant PCLs.

Highly Sensitive Serum miRNA Panel for the Diagnosis of Hepatocellular Carcinoma in Egyptian Patients with HCV-Related HCC.

OBJECTIVE: This study aimed at exploring the potential role of a panel of serum micro-RNA (miRNA) markers in liver fibrosis and hepatocellular carcinoma (HCC) diagnosis in patients with chronic hepatitis C virus (HCV) infection. METHODS: The study included 157 chronic HCV patients and 62 HCC patients who presented to the Cairo University Center for Hepatic Fibrosis, Endemic Medicine Department, from 2015 to 2017. Relevant clinical and laboratory data were collected and sera were subjected to miRNA expression profiling. Eleven miRNA markers were studied and receiver operating characteristic curves were constructed to investigate the best cutoff values of the miRNAs that showed altered expression in HCC compared to HCV-associated advanced fibrosis. RESULTS: miRNA expression profiling revealed 5 miRNAs (miR-124, miR-141, miR-205, miR-208a, miR-499a) were significantly upregulated and 2 miRNAs were significantly downregulated (miR-103a, miR-15a) in HCC compared to advanced fibrosis patients. No significant difference was observed in miRNA expression between advanced fibrosis and early hepatic fibrosis apart from a significant downregulation of miR-155-5p in advanced fibrosis. CONCLUSION: Serum miRNAs could serve as potential diagnostic tools for the diagnosis of HCC.

Impact of sustained virological response on metabolic disorders in diabetic chronic hepatitis C virus patients after treatment with generic sofosbuvir and daclatasvir.

OBJECTIVES: To evaluate the effect of generic sofosbuvir and daclatasvir (SOF/DCV) treatment on the glycemic state and insulin resistance as well as lipid profiles of those who achieved sustained virological response (SVR) in diabetic chronic hepatitis C virus (CHC) patients. METHODS: We retrospectively reviewed 114 CHC patients with evidence of type 2 diabetes that were treated with generic SOF/DCV between May 2016 and August 2017. Baseline demographic and laboratory data were recorded. At 12-week post end of therapy (SVR12), glycemic state and insulin resistance as well as lipid profiles were re-evaluated and compared with baseline. RESULTS: A total of 98 diabetic CHC patients were finally included and were responders. A significant decline in the glycemic state as well as Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) values (P ≤ 0.0001) was observed, but HOMA-S showed a statistically significant increase (P ≤ 0.0001) at SVR12 in comparison to baseline values. Also, a significant increase in serum total cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels was observed at SVR12 compared to baseline, but serum triglycerides levels showed a significant decrease. Logistic regression showed that the higher baseline HOMA-IR was a significant predictive variable of a decrease ≥20% of HOMA-IR, while higher baseline HOMA-IR and baseline triglycerides emerged as the only significant predictors of the Δ increase LDL-C level at SVR12. CONCLUSION: SOF/DCV-based therapy led to an improvement of glycemic state associated with a global worsening of lipid profile. Further studies are strongly warranted to evaluate the cardiovascular balance between amelioration of insulin resistance and negative changes of the lipid profile.

Evaluation of red cell distribution width to platelet ratio as a novel non-invasive index for predicting hepatic fibrosis in patients with chronic hepatitis C.

BACKGROUND AND STUDY AIMS: Assessing the extent of fibrosis is an essential part of therapeutic decisions in patients with chronic hepatitis C (CHC). Liver biopsies are the "gold standard" for evaluating liver fibrosis but have many limitations. Thus, noninvasive predictors of fibrosis have been developed. This study aimed to determine the effectiveness of red cell distribution width (RDW) to platelet ratio as a simple noninvasive method for predicting the hepatic fibrosis stage in patients with CHC. PATIENTS AND METHODS: This cross-sectional study included 197 Egyptian patients with CHC. A routine pretreatment reference needle liver biopsy was performed. Fib-4, transient elastography (TE) by Fibroscan, AST to Platelet Ratio Index (APRI), and RDW to platelet ratio (RPR) were measured. Predictors of significant fibrosis (Metavir score ≥ F2) and advanced fibrosis (Metavir score ≥ F3) were identified. RESULTS: Fib-4, TE, APRI, and RPR values differed significantly when comparing different stages of fibrosis (p < 0.01). Fib-4, TE, APRI, and RPR were reliable diagnostic tools at cutoff values of 1.17, 7.75, 0.18, and 0.07, respectively, for predicting significant fibrosis and cutoff values of 1.99, 8, 1.77, and 0.08, respectively, for predicting advanced fibrosis. Using logistic regression analysis, TE was identified as an independent predictor associated with significant and advanced fibrosis. Fib-4 was significantly associated with advanced fibrosis only. CONCLUSION: The use of Fib-4, TE, APRI, and RPR measurements may decrease the need for liver biopsies for predicting significant and advanced fibrosis. RPR showed fair sensitivity, specificity, positive and negative predictive values, and overall accuracy for predicting significant fibrosis in patients with CHC.

Long-term clinical outcomes in sustained responders with chronic hepatitis C after treatment with direct-acting antivirals.

OBJECTIVE: Little is known about how the achievement of sustained virological response (SVR) after treatment with direct-antiviral agents (DAAs) affects fibrosis and clinical outcomes in the long term. Our study aimed to evaluate the impact of achieving SVR on long-term changes in fibrosis and clinical outcomes in CHC patients treated with different DAAs-based regimens. METHODS: a prospective, 3-year follow-up study of 113 CHC patients who had achieved SVR after treatment with different DAAs-based regimens between January and June 2015 was conducted. The clinical outcomes of SVR on the biochemical profile, changes in fibrosis, ALBI score and grade and occurrence of liver-related events were analyzed. RESULTS: Overall, liver function parameters and serum alpha-fetoprotein level showed improvement from baseline to SVR12 and remained steady thereafter. Moreover, the ALBI score showed nonsignificant change at baseline to SVR12 (P = 0.2) but it was significantly better at 3-years follow-up than at SVR12 (P = 0.001). Regarding liver stiffness (LS) by transient elastography, a significant decrease in TE values was observed between baseline to SVR12 (P ≤ 0.0001) as well as between SVR12 to 3-years follow-up (P = 0.0005). Stratified by fibrosis stage, patients with advanced fibrosis and cirrhosis showed a more pronounced and significant improvement of LS during follow-up after SVR compared to patients with less advanced fibrosis stage. During the follow-up period, 3 (5.2%) cirrhotic patients developed liver-related events, including 2 (3.4%) patients with de novo HCC and one (1.7%) patient experienced ascites for the first time. CONCLUSION: This 3-year follow-up study provides evidence for the durability of SVR, improvement of liver function parameters and ALBI score and grade in patients with an advanced stage of fibrosis, in particular, and reduction of the clinical events after successful treatment with DAAs.

Sustained virologic response and changes in liver fibrosis parameters following 12-wk administration of generic sofosbuvir and daclatasvir in HIV/HCV-coinfected patients with HCV genotype 4 infection.

BACKGROUND: Novel direct-acting antiviral agents have shown great efficacy and tolerability in HCV-monoinfected patients. However, data are lacking regarding their efficacy and safety in HIV/HCV-genotype (GT) 4-coinfected patients. METHODS: A single-centre, prospective study including HIV/HCV-GT 4-coinfected patients who were treated with sofosbuvir and daclatasvir (SOF/DCV) was conducted for 12 wk. Sustained virological response (SVR) at week 12 post-treatment (SVR12), adverse events (AEs) and changes in liver stiffness measurement (LSM) at SVR12 in comparison with baseline were evaluated. RESULTS: SVR12 was achieved in 46 of 50 patients (92%). No significant difference in SVR12 was noticed among patients who received antiretroviral therapy (ART) regimens compared with those who did not receive ART regimens or between those with insignificant fibrosis (

Acceleration of Gastric Emptying and Improvement of GERD Outcome After Laparoscopic Sleeve Gastrectomy in Non-diabetic Obese Patients.

PURPOSE: Obesity has become a pandemic nowadays. Bariatric surgery is increasingly performed to manage obesity. Currently, laparoscopic sleeve gastrectomy (LSG) is a widely accepted procedure given its feasibility and efficacy. Previous studies revealed conflicting results regarding the change of gastric emptying following sleeve gastrectomy. The primary aim of the present study is to assess gastric motor function by gastric emptying scintigraphy in a cohort of non-diabetic patients undergoing laparoscopic sleeve gastrectomy (LSG) for treatment of severe obesity. METHODS: This prospective observational study included 100 obese, non-diabetic patients attending the surgery clinic at Cairo University Hospitals and Al Azhar University Hospitals. LSG was performed following a standardized protocol, with no complications observed. All patients had gastric emptying scintigraphy done through a standard semisolid meal (250 kcal), marked with 0.5 mCiTc 99, pre-operatively and 3 months after LSG. RESULTS: The mean age was 38.71 years (9.2) and males comprised 57% of the cohort. The body mass index, low-density lipoproteins, and glycated hemoglobin declined significantly at 3-month postsurgery. The scintigraphy study revealed a significantly reduced percent retention at equivalent time points 3 months after LSG. In addition, the percent of patients suffering from GERD decreased significantly after LSG. CONCLUSION: Gastric emptying becomes faster after LSG in morbidly obese non-diabetic patients. GERD symptoms improve after surgery.

Diagnostic accuracy of acoustic radiation force impulse elastography (ARFI) in comparison to other non-invasive modalities in staging of liver fibrosis in chronic HCV patients: single-center experience.

PURPOSE: To evaluate the reliability of ARFI elastography for liver fibrosis staging and compare it to other non-invasive assessment of hepatic fibrosis (FIB-4 and APRI) in chronic HCV (CHC) patients. METHODS: A single-center, prospective study included 2103 CHC patients. Liver stiffness (LS) was evaluated by TE and ARFI elastography. FIB-4 and APRI were calculated. The area under the receiver-operating characteristic curve (AUROCs) was used to assess the diagnostic performance of ARFI elastography for staging of liver fibrosis using TE as a reference standard. RESULTS: The best cut off values of ARFI elastography for diagnosis of ≥ F2, ≥ F3and F4 were 1.36 m/s, 1.45 m/s, and 1.7 m/s with AUROCs of 0.89, 0.94 and 0.95, respectively. ARFI elastography cut offs are lower in patients with normal ALT level compared to those with ALT level (1.1-< 3 ULN) and those with ALT level ≥ 3ULN (1.35 m/s vs 1.39 m/s vs 1.54 for F ≥ 2, 1.44 m/s vs 1.58 m/s vs 1.6 m/s for F3, 1.69 m/s, 1.84 m/s, 1.86 m/s for F4). FIB-4 (0.82-0.86) and APRI (0.78-0.82) yielded lower AUC in prediction of significant fibrosis and cirrhosis than ARFI elastography (0.89-0.95). CONCLUSION: ARFI elastography is a reliable method for non-invasive staging of liver fibrosis in CHC patients when compared to TE with a good diagnostic performance comparable to FIB-4 and APRI scores for the prediction of significant fibrosis and cirrhosis.

Clinical impact of serum α-fetoprotein and its relation on changes in liver fibrosis in hepatitis C virus patients receiving direct-acting antivirals.

BACKGROUND: α-Fetoprotein (AFP) is used widely as a serological marker for hepatocellular carcinoma. However, the AFP value is elevated in chronic hepatitis C virus (HCV) patients without hepatocellular carcinoma. Yet, data on the impact of direct-acting antiviral agents (DAAs) therapy on AFP levels after viral eradication are still lacking. AIM: The aim of this study was to elucidate the changes in the serum AFP level in chronic hepatitis C patients treated with DAA-based therapy and their relation to response and liver fibrosis parameters. PATIENTS AND METHODS: A total of 456 chronic HCV patients who received different DAAs-based treatment regimens were enrolled. Laboratory data including serum AFP, transient elastography values, and fibrosis scores were recorded at baseline and sustained virological response at 24 weeks after treatment (SVR24). The outcome was the changes in the AFP level from baseline to SVR24 and its relation to changes in liver fibrosis parameters at SVR24 using Spearman's rank correlation test. RESULTS: Overall, 96.9% of enrolled patients were responders. A statistically significant improvement in serum transaminases, albumin, transient elastography values, and fibrosis scores at SVR24 was reported. The AFP level was significantly decreased from a median (interquartile range) of 6 (3.2-10.8) ng/ml before DAAs to 4 (2.3-6) ng/ml at SVR24 (P < 0.0001). Only 22.6% of patients showed an increase in the AFP level after treatment. On multivariate analysis, the only independent baseline variable associated with an increase in the AFP level after treatment was baseline AFP (odds ratio: 0.95, 95% confidence interval: 0.91-0.99, P = 0.02). There is a significant correlation between changes in AFP and liver fibrosis parameters at SVR24. CONCLUSION: DAAs-based regimens are a highly efficient antiviral therapy for chronic hepatitis C patients that resulted in improvements in the serum AFP level.

Evaluation of acoustic radiation force impulse (ARFI) elastography as non-invasive diagnostic tool in living donor liver transplantation.

BACKGROUND AND AIMS: Role of acoustic radiation force impulse (ARFI) elastography, in transplant setting, is not well established. We aimed to define the normal mean values of the liver stiffness by ARFI Elastography in healthy liver donors and to evaluate ARFI elastography as predictor of graft fibrosis post living donor liver transplant (LDLT) in comparison to other non-invasive methods (transient elastography [TE], APRI and FIB4). PATIENTS AND METHODS: A total of 100 subjects (70 recipients and 30 donors) were recruited. APRI and FIB4 scores were calculated for all recipients. TE and ARFI elastography (Siemens Acuson S2000 Ultrasound System, Germany) were performed to all subjects. All donors and only 30 recipients had liver biopsy. Significant fibrosis was defined as ≥ F2. RESULTS: The mean ARFI velocity among the donors was 1.05 ± 0.09 m/s. Regarding the recipients: mean age was 49.5 ± 8.49 years, 85.7% males, fibrosis stages < F2 were the most frequent stages by liver biopsy (86.7%) and TE (67.1%). ARFI median was significantly correlated with TE median, APRI and FIB-4 (r = 0.888, p = 0.000; r = 0.62, p = 0.000, and r = 0.585, p = 0.000, respectively). ARFI performed well in discriminating patients with ≥ F2 (AUROC = 0.93, 95% CI 0.86-0.99, p < 0.01) with best cutoff median value of 1.34 m/s (sensitivity 90%, specificity 82%). CONCLUSION: ARFI can be used as a reliable method in assessment of significant fibrosis post-LDLT.

High prevalence of HCV (GT4)-related TSH abnormality among 13402 Egyptian patients treated with direct acting antiviral therapy.

BACKGROUND: HCV is associated with several extra hepatic diseases including thyroid dysfunction. This study aims at evaluating prevalence of thyroid dysfunction and its possible predictors in a large cohort of HCV GT4-infected patients, and the role of thyroid dysfunction as a predictor of response in the setting of direct acting antivirals (DAAs). METHODS: Patients registered on the web-based registry system to receive therapy for chronic HCV in Beheira governorate viral hepatitis specialized treatment center affiliated to the National committee for control of viral hepatitis (NCCVH), Ministry of health, Egypt in the period from January 2015 to October 2016. Their data were exported and analyzed for the prevalence of thyroid dysfunction and its associated variables. RESULTS: Out of 13,402 patients, 2833 (21.1%) had elevated TSH level > 4.5 mIU/l (hypothyroidism). Female gender (62.7%), older age, higher FIB4, AST, and BMI and lower albumin were significantly associated with elevated TSH level on univariate analysis, while liver stiffness measured by fibroscan was not significantly associated. On the other hand, 466 patients (3.5%) showed low TSH level < 0.4 mIU/l (hyperthyroidism). Older age (median 52 years) and male gender (51.5%) were the only significantly associated variables. No association was found between SVR and baseline TSH level. Follow-up of 236 patients after SVR revealed improvement in TSH level in 80% of them. CONCLUSION: Hypothyroidism is prevalent in patients with chronic HCV GT4, and is influenced by patient gender and age. Pretreatment TSH does not affect SVR after DAAs. Despite limited data SVR achievement after DAAs improves thyroid dysfunction.

High sustained virologic response rate using generic directly acting antivirals in the treatment of chronic hepatitis C virus Egyptian patients: single-center experience.

BACKGROUND: Hepatitis C virus (HCV) is a major health problem in Egypt, with a high prevalence of genotype 4. AIM: This study aimed to evaluate the safety and efficacy of generic sofosbuvir (SOF) plus generic daclatasvir (DAC) with or without ribavirin in the treatment of Egyptian chronic HCV patients compared with the use of brand drugs. MATERIALS AND METHODS: An observational study that included 234 Egyptian chronic HCV patients was carried out. Patients were classified into two groups: group A (101 patients) received brand SOF 400 mg plus brand DAC 60 mg and group B (134 patients) received generic SOF 400 mg plus generic DAC 60 mg with or without ribavirin for 12 weeks. The end point was a sustained virological response at 12 weeks after treatment. RESULTS: Thirty-eight (37.2%) patients in group A were treatment experienced compared with 12 (9.02%) patients in group B; there were 39 (38%) cirrhotic patients in group A and 22 (16.5%) cirrhotic patients in group B. In group A, 50% of patients received ribavirin, while in group B, 42.1% of patients received ribavirin. All patients were followed up; all of them attended their week 12 post-treatment visit with negative HCV RNA, with achievement of sustained virological response at 12 in 100% of patients receiving generic drugs (group B) and 99% of patients receiving brand drugs (group A). Generic SOF and DAC were well tolerated, with mild adverse events including fatigue and headache. CONCLUSION: Use of generic SOF and DAC with or without ribavirin is an extremely effective and a well-tolerated treatment for Egyptian chronic HCV patients.

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.