Screening for maternal cytomegalovirus infection during pregnancy and pregnancy outcome in patients with liver disease: an observational study.

BACKGROUND: Cytomegalovirus (CMV) infection among pregnant females could induce CMV hepatitis with possible changes in liver stiffness measurement (LSM) which could be reversibly increased during normal pregnancies, particularly in the third trimester. This study aimed to detect the prevalence of CMV infection among pregnant females with and without chronic liver disease and to evaluate the effects of CMV infection on LSM and pregnancy outcomes in comparison to non-CMV-infected pregnant females. METHODS: This is an observational prospective study that included 201 pregnant ladies presented to the liver disease with pregnancy clinic, Cairo University from March 2018 to April 2019. We assessed the laboratory results, abdominal ultrasonography, LSM using ARFI elastography, and pregnancy outcomes. RESULTS: Two hundred and one pregnant ladies were divided into ; group 1: pregnant ladies with normal pregnancy (n = 128), group 2: pregnant ladies with chronic liver diseases not related to pregnancy (n = 35), and group 3: pregnant ladies with pregnancy-related liver diseases (n = 38). Positive CMV serology (either/or, +ve CMV-IgM, IgG) was detected in 106/201 patients (52.74%), and fifteen of them had an active infection (IgG +, IgM+, PCR+). Pregnant females with chronic liver diseases not related to pregnancy had significantly higher serum levels of CMV IgM, IgG, and PCR. Moreover, LSM had a significant correlation with CMV IgG and CM_PCR in normal pregnant ladies. Maternal mortality occurred only in pregnant females with chronic liver diseases in 5.7% (2/35). CONCLUSION: Maternal CMV infection carries a significant risk to pregnant females with chronic liver disease. Routine CMV screening for women planning to be pregnant, especially those with chronic liver disease could help to avoid bad maternal and fetal outcomes.

Evaluation of GALAD Score in Diagnosis and Follow-up of Hepatocellular Carcinoma after Local Ablative Therapy.

Background and Aims: Strategies for detection of early hepatocellular carcinoma (HCC) are still limited. The GALAD score is a serum biomarker-based model designed to predict the probability of having HCC. We aimed to assess the ability of GALAD score to diagnose early HCC and its validity to follow patients after local ablation therapy. Methods: This multicenter prospective study included 108 patients in two groups, 58 HCC patients (67 focal lesions) with local ablative therapy (study group), and a control group of 50 patients with liver cirrhosis. The GALAD scores of the study and control groups, and of the HCC patients before and after ablative therapy were compared. Results: Most patients were men (74.1% in study group and 76% in controls) with hepatitis C virus infection (98.30% in the study group, and 94% in controls). GALAD scores were significantly higher in HCC patients than in those with benign cirrhosis (2.65 vs. -0.37, p=0.001). Ablative therapy was successful in 94.4% of focal lesions <2 cm, and in 86.10% of 2-5 cm lesions. The GALAD score was also significantly lower at 1 month after ablation in patients with well-ablated tumors (2.19 vs. 0.98, p=0.001). The best cutoff values of GALAD score for diagnosis of early HCC, and for prediction of well ablation of HCC were 0.74 and ≤3.31 (areas under the curve of 0.92 and 0.75, sensitivities of 84.48% and 76.19%, specificities of 89.13% and 83.33%, positive predictive values of 90.74% and 94.1%, and negative predictive values of 82% and 35.7% respectively). Conclusion: The GALAD score was effective for the diagnosis of early HCC and for follow-up after ablative therapy.

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.

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.

HCV/HIV coinfected Egyptian patients: a cross-sectional study of their main characteristics and barriers to HCV treatment initiation.

BACKGROUND: This study investigates different barriers preventing a cohort of Egyptian HIV/HCV coinfected patients from accessing HCV treatment, despite being available and free of charge, aiming to improve the long-term outcomes of coinfected patients and decreasing their liver-related morbidity and mortality. METHODS: This study included HIV patients who were referred to Kasr Alainy Viral Hepatitis Center to receive HCV treatment and who had to continue pretreatment assessment in order to receive direct acting antiviral agents free of charge. Patients who did not attend within 90 d were questioned via a telephone interview. Questions addressed sociodemographic status, HIV status and the main barriers to accessing healthcare. RESULTS: Overall, 474 HIV/HCV coinfected patients were eligible for HCV treatment and 223 (47.1%) patients did not complete work-up for HCV treatment. Fear of community stigma concerning HIV/HCV was the most important barrier to compliance with treatment (73.3%), followed by lack of a supportive work environment and employment opportunities (51.5%), whereas 39.3% stopped follow-up due to the lack of integrated services in the healthcare facility. CONCLUSIONS: Managing HCV in HCV/HIV coinfected patients still represents a major challenge, not only for healthcare providers, but also at a community level, to improve community awareness and manage the major obstacle facing those patients regarding community stigma.

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.

Hepatitis C viral RNA in blood mononuclear cells of patients treated with directly acting antivirals.

BACKGROUND AND STUDY AIMS: Occult hepatitis C viral infection (OCI) may have serious complications, such as relapse, ongoing histological impairment, hepatic decompensation, hepatocellular carcinoma, and the possible risk of transmission. This study was conducted to assess the occurrence and prevalence of secondary OCI in patients with chronic hepatitis C viral infection (HCV) who received a complete course of directly acting antivirals (DAAs). PATIENTS AND METHODS: Antiviral therapy consisted of sofosbuvir + daclatasvir ± ribavirin for 12 weeks to 90 treatment-naive, compensated, chronic HCV patients. Plasma and peripheral blood mononuclear cells (PBMCs) were tested for HCV RNA viral load by quantitative, reverse transcription, real-time PCR at 8, 12 (Group I, n = 45), and 24 (Group II, n = 45) weeks after treatment initiation. RESULTS: By week 8, only 2 and 7 patients were positive for HCV RNA in plasma and PBMCs, respectively. No HCV RNA was detected by weeks 12 or 24 in the PBMCs of Groups I and II, respectively. Older age was significantly associated with HCV RNA positivity in plasma and PBMCs (n = 8) at week 8 compared with HCV RNA negativity (n = 82). No other significant differences were observed for any other variables. CONCLUSION: The development of secondary OCI among easy-to-treat patients following a full course of DAA treatment doesn't exist, hence, we do not recommend testing the HCV RNA in the PBMCs after complete course of treatment in this patient category. The detection of HCV RNA in PBMCs is recommended as a confirmatory test of cure following a shortened DAA treatment regimen.

The interrelation between lipid profile in chronic HCV patients and their response to antiviral agents.

OBJECTIVES: This study aims to assess the changes of lipid profile in chronic HCV patients; before, during, and after treatment with DAAs and their association with treatment response. METHODS: 301 chronic HCV patients who received SOF-based therapy were included. Serum lipid profile was assessed at different check points; baseline, 6 weeks on treatment, end of treatment (EOT) and 12 weeks after EOT; and compared between SVR and non-SVR groups. RESULTS: SVR group had significantly higher baseline lipid parameters compared to non-SVR group with significant increase in lipid parameters at different time points apart from HDL-C. Non-SVR group showed non-significant change in lipid parameters apart from LDL-C. On week6 on treatment, cholesterol level > 125 mg/dl was 92.8% sensitive, 97.3% specific with 95.5% NPV, and AUC of 0.989 in prediction of SVR. Similarly, LDL > 57 mg/dl was 83.7% sensitive, 100% specific with 93.3%, NPV and AUC of 0.952. Baseline cholesterol and LDL were significantly associated with SVR. CONCLUSION: Higher baseline lipid parameters and their further elevation starting from week 6 on treatment are good predictors of SVR in HCV patients. Successful HCV therapy with DAAs is associated with a significant increase in lipid parameters.

Fibro-indices versus liver stiffness for prediction of significant fibrosis in hepatitis B virus-infected Egyptian patients; a single-center experience.

Background: Liver fibrosis assessment is a key factor for disease management in hepatitis B virus (HBV). Several serum biomarkers have been introduced for noninvasive fibrosis assessment. This study aims to evaluate the validity of simple noninvasive indices, namely Fibrosis-4 score (FIB4), aspartate aminotransferase (AST) to Platelet Ratio Index (APRI), Goteborg University Cirrhosis Index (GUCI), and fibrosis index in evaluation of liver fibrosis in chronic HBV.Methods: 226 patients with chronic HBV genotype D were included. FIB4, APRI, GUCI, and fibrosis index were performed. Receiver operating characteristic (ROC) curves were used to predict ≥F2 fibrosis.Results: The mean age of patients was 39.00 years and 72.27% of patients were treatment naïve. Patients with ≥F2 hepatic fibrosis had significantly higher FIB-4 (1.58 ± 1.46 vs. 1.15 ± 1.09), APRI (0.68 ± 0.71 vs. 0.43 ± 0.37), GUCI score (0.75 ± 0.94 vs. 0.42 ± 0.29) and Fibrosis index (2.18 ± 0.84 vs. 1.84 ± 0.69). All studied indices were able to diagnose ≥F2 fibrosis. APRI had the highest area under the ROC (AUROC) of 0.67. Predictivity of all indices was higher in on-treatment vs naive patients.Conclusion: FIB4, APRI, and GUCI scores are acceptable, noninvasive, and cheap simple indices that can be helpful on treatment follow-up of fibrosis regression in the setting of low socioeconomic conditions compared to the relatively expensive fibroscan modality.

Sofosbuvir-containing regimens are safe and effective in the treatment of HCV patients with moderate to severe renal impairment.

BACKGROUND AND AIMS: This study aimed to assess the safety and efficacy of sofosbuvir (SOF)-based regimens in patients with moderate to severe renal impairment; a subject which has been questioned by many investigators with conflicting results. METHODS: This is a real-life multicentre retrospective cohort study on 4944 chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) (eGFR <60 mL/min/1.73 m2 ) who received SOF-based therapy in specialized treatment centres affiliated to the National Committee for the Control of Viral Hepatitis in Egypt. The efficacy and safety of SOF-based regimens was assessed. RESULTS: Week 12 virological response rates were 97.5%, 96.7%, 85.7% and 80% in the total cohort, patients with eGFR <30 mL/min/1.73 m2 , patients with associated hepatic decompensation and patients on dialysis respectively. Various treatment regimens did not statistically affect the response rates. Treatment experience, cirrhosis and diabetes were predictors of treatment failure on multivariate analysis. Serious adverse events occurred in 0.1% of cases. Forty patients (0.8%) discontinued treatment. CONCLUSION: Sofosbuvir-based regimens are effective and safe for treating patients with chronic HCV and moderate to severe CKD, and in those with associated hepatic decompensation.

Oral midodrine is comparable to albumin infusion in cirrhotic patients with refractory ascites undergoing large-volume paracentesis: results of a pilot study.

BACKGROUND AND AIMS: Albumin infusion reduces the incidence of postparacentesis circulatory dysfunction among patients with cirrhosis and tense ascites compared with no treatment. Less costly treatment alternatives such as vasoconstrictors have been investigated, but the results are controversial. Midodrine, an oral α1-adrenergic agonist, increases effective circulating blood volume and renal perfusion by increasing systemic and splanchnic blood pressure. Our aim is to assess whether or not morbidity in terms of renal dysfunction, hyponatremia, systemic, or portal hemodynamics derangement or mortality differed in patients receiving albumin versus midodrine. PATIENTS AND METHODS: Seventy-five patients with cirrhosis and refractory ascites were randomized to receive albumin infusion, oral midodrine for 2 days, or oral midodrine for 30 days after therapeutic large volume paracentesis (LVP). The primary endpoints were development of renal impairment or hyponatremia, change in systemic and portal hemodynamics, cost, and mortality in the short-term and long-term follow-up. RESULTS: No significant difference was found between groups in the development of renal impairment, hyponatremia, or mortality 6 and 30 days after LVP. A significant increase in 24-h urine sodium excretion was noted in the midodrine 30-day group. Renal perfusion improved significantly with the midodrine intake for 30 days only. The cost of midodrine therapy was significantly lower than albumin. CONCLUSION: Midodrine is as effective as albumin in reducing morbidity and mortality among patients with refractory ascites undergoing LVP at a significantly lower cost. Long-duration midodrine intake can be more useful than shorter duration intake in terms of improvement of renal perfusion and sodium excretion.

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 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.

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.

Planning and prioritizing direct-acting antivirals treatment for HCV patients in countries with limited resources: Lessons from the Egyptian experience.

BACKGROUND AND AIMS: The introduction of direct-acting antivirals for hepatitis C virus (HCV) in Egypt led to massive treatment uptake, with Egypt's national HCV treatment program becoming the largest in the world. The aim of this paper is to present the Egyptian experience in planning and prioritizing mass treatment for patients with HCV, highlighting the difficulties and limitations of the program, as a guide for other countries of similarly limited resources. METHODS: Baseline data of 337,042 patients, treated between October 2014 to March 2016 in specialized viral hepatitis treatment centers, were grouped into three equal time intervals of six months each. Patients were treated with different combinations of direct-acting antivirals, with or without ribavirin and pegylated interferon. Baseline data, percentage of patients with known outcome, and sustained virological response at week 12 (SVR12) were analyzed for the three cohorts. The outcomes of 94,258 patients treated in the subsequent two months are also included. RESULTS: For cohort-1, treatment was prioritized for patients with advanced fibrosis (F3-F4 fibrosis, liver stiffness ≥9.5 kPa, or Fibrosis-4 ≥3.25). Starting cohort-2, all stages of fibrosis were included (F0-F4). The prioritization strategy in the initial phase caused delays in enrollment and massive backlogs. Cohort-1 patients were significantly older, and more had advanced fibrosis compared to subsequent cohorts. The percentage of patients with known SVR12 results were low initially, and increased with each cohort, as several methods to capture patient results were adopted. Sofosbuvir-ribavirin therapy for 24 weeks had the lowest SVR12 rate (82.7%); while other therapies were associated with SVR12 rates between 94% and 98%. CONCLUSION: Prioritization based on fibrosis stage was not effective and enrollment increased greatly only after including all stages of fibrosis. The availability of generic drugs reduced costs, and helped massively increase uptake of the program. Post-treatment follow-up was initially very low, and although this has increased, further improvement is still needed. LAY SUMMARY: We are presenting the largest national program for HCV treatment in the world. We clearly demonstrate that hepatitis C can be cured efficiently in large scale real-life programs. This is a clear statement that global HCV eradication is foreseeable, providing a model for other countries with limited resources and prevalent HCV. Moreover, the availability of generic products has influenced the success of this program.

Impact of different sofosbuvir based treatment regimens on the biochemical profile of chronic hepatitis C genotype 4 patients.

BACKGROUND: Huge efforts have been made to control chronic HCV in Egypt with introduction of Direct-Acting Antivirals (DAAs). Current study aims at evaluating effect of various DAA regimens on liver biochemical profile and haematological indices during treatment. METHODS: 272 patients with chronic HCV genotype 4 treated by different DAA regimens (SOF/RBV, SOF/DAC ± RBV, SOF/SIM) for a duration of 12 or 24 weeks in Kasr Alainy Viral Hepatitis Center, Cairo University were followed up for serum bilirubin (BIL), albumin (ALB), alanine transaminase (ALT), aspartate aminotransferase (AST), prothrombin concentration, international normalized ratio (INR), and CBC at baseline, week-4 and end of treatment. RESULTS: Mean age was 54 years. Males comprised 64.7%, 72.4% were treatment-naïve, 39% were cirrhotic. Overall SVR12 rate was (93.4%). With all regimens, ALT and AST declined after treatment. In cirrhotics, there was a rise in BIL and INR; with no change in ALB and a decrease in White blood cells. Drop in Hemoglobin and platelets in cirrhotic patients were noted with SOF/RBV, while SOF/SIM showed rise in BIL. CONCLUSION: DAAs are safe and effective in genotype 4 chronic HCV patients. It improves liver necro-inflammatory markers in cirrhotics and non-cirrhotics. Cirrhotic patients require careful observation being more vulnerable for treatment related complications.

Methylene Tetrahydrofolate Reductase Gene Polymorphism is Associated with Severity of Liver Steatosis in Chronically Infected Patients with HCV Genotype 4.

BACKGROUND: Methylene tetrahydrofolate reductase (MTHFR) C677T polymorphism was reported as a genetic variant in liver steatosis and fibrosis. This is a study of the association between MTHFR C677T polymorphism and HCV core with severity of steatosis in HCV GT4 patients. METHODS: 111 HCV patients and 112 control subjects were recruited. Polymorphism was detected by RFLP analysis, core Ag was detected by ELISA. RESULTS: Combined HCV infection and MTHFR C677T polymorphism increases the risk to develop steatosis by 3.63- and 5.21-fold in subjects with single (CT) and double (TT) substitutions, respectively. Patients with chronic HCV infection had a 2.88- and 8.57-fold higher risk to develop steatosis in CT and TT genotypes, respectively, than patients with the (CC) genotype. No significant difference in core Ag titers were observed. CONCLUSIONS: MTHFR C677T polymorphism is a valuable genetic marker for steatosis, while HCV core Ag titer had no association with grades of steatosis in GT4 infections.

Real life Egyptian experience of efficacy and safety of Simeprevir/Sofosbuvir therapy in 6211 chronic HCV genotype IV infected patients.

BACKGROUND & AIMS: Major changes have emerged during the last few years in the therapy of chronic HCV. Several direct acting antiviral agents have been developed showing potent activity with higher rates of sustained virological response, even in difficult-to-treat patients. This study explores real life experience concerning efficacy, safety and possible predictors of response for the first cohort of Egyptian patients with chronic HCV genotype IV treated with Sofosbuvir/Simprevir combination therapy. METHODS: This real life study recruited the first (6211) chronic HCV genotype IV Egyptian patients, who received antiviral therapy in viral hepatitis specialized treatment centres affiliated to the National committee for control of viral hepatitis. All enrolled patients received 12 weeks course of daily combination of sofosbuvir (400 mg) and simeprevir (150 mg). Patients were closely monitored for treatment safety and efficacy. RESULTS: Overall sustained virological response 12 rate was 94.0% while the end of treatment response rate was 97.6%. sustained virological response 12 rates in easy and difficult-to-treat groups were 96% and 93% respectively. Univariate and multivariate logistic regression analysis revealed significant association of low albumin (<3.5), cirrhosis and Fib-4 score (>3.25) with treatment failure. Fatal adverse events occurred in 23/6211 cases (0.37%) due to liver cell failure adverse events or SAEs leading to treatment discontinuation occurred in 97 patients (1.6%). CONCLUSION: Sofosbuvir/Simeprevir combination is an effective and well tolerated regimen for patients with chronic HCV genotype IV.

Can Serum ICAM 1 distinguish pancreatic cancer from chronic pancreatitis?

Background and aim: Pancreatic cancer is the fourth leading cause of cancer-related death worldwide, with an overall 5-year survival of <5% mainly due to presence of advanced disease at time of diagnosis. Therefore development of valid biomarkers to diagnose pancreatic cancer in early stages is an urgent need. This study concerned the sensitivity and specificity of serum ICAM 1 versus CA 19-9 in differentiation between pancreatic cancer and healthy subjects and acohort of patients with chronic pancreatitis with a focus on assessing validity in diagnosis of early stages of pancreatic cancer. Methods: A cohort of 50 patients with histologically diagnosed pancreatic tumors, 27 patients with chronic pancreatitis, and 35 healthy controls were enrolled. Serum samples for measurement of CA19-9 and I-CAM 1 were obtained from all groups and analyzed for significance regarding diagnosis and disease stage. Results: At a cut off value of (878.5 u/ml) I-CAM 1 had 82% and 82.26% sensitivity and specificity for differentiation between cancer and non-cancer cases, with higher sensitivity and specificity than CA19-9 at different cut offs (CA19-9 sensitivity and specificity ranged from 64-80% and 56.4 ­ 61.2% respectively). The AUC was 0.851 for I-CAM and 0.754 for CA19-9. Neither of the markers demonstrated significance for distinguishing between early and late cancer stages. Conclusion: ICAM 1 is a useful marker in differentiation between malignant and benign pancreatic conditions, and superior to CA19-9 in this regard. However, neither of the markers can be recommended for use in differentiation between early and late stage pancreatic cancers.