Effect of branched-chain amino acid supplementation and exercise on quadriceps muscle quantity and quality in patients with cirrhosis as assessed by ultrasonography: A randomized controlled trial.

BACKGROUND/AIM: Sarcopenia and myosteatosis are common in patients with cirrhosis. The study aimed to evaluate efficacy of ultrasound to monitor muscle status during branched-chain amino acid (BCAA) supplementation and/or muscle exercise interventional approaches. PATIENTS AND METHODS: A randomized controlled study, included 220 liver cirrhosis patients with Child- Pugh B and C, randomized into a control group (55 patients) received only the standard care, and interventional groups (165 patients) equally distributed into three subgroups, in addition to standard care, they received BCAA, programmed exercise, or BCAA and programmed exercise. At baseline and after 28 days, all participants were subjected to ultrasound-measured quadriceps muscle thickness and echo-intensity, muscle strength using handgrip, performance using short physical performance battery (SPPB), Model for End-Stage Liver Disease (MELD) score and nutritional assessment using 7- point Subjective Global Assessment Score (SGA) and laboratory assessment. RESULTS: All interventional groups showed a significant improvement in the ultrasound detected quadriceps muscle thickness (p = 0.001) and echo intensity, in addition to muscle strength, muscle performance, and SGA. Hematological parameters (hemoglobin and platelet count), biochemical parameters (ALT, AST, bilirubin, creatinine, urea and INR) and MELD score were also improved in the interventional groups. In Child-Pugh B patients BCAA combined with exercise showed an add-on effect. CONCLUSION: BCAA supplements, programed muscle exercise and both are useful interventional methods in improving muscle quality and quantity in cirrhosis patients, which can be monitored by ultrasound. The best results can be achieved by combined intervention in Child-Pugh B, while in Child-Pugh C single intervention may lead to an acceptable improvement. The trial was registered retrospectively in the Clinical Trials Registry (registration number NCT06088550).

Efficacy and safety of ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with chronic kidney disease.

BACKGROUND AND STUDY AIMS: Hepatitis C virus (HCV) prevalence inchronic kidney disease (CKD) patients is significantly higher than in the general population. This study evaluated the efficacy and safety of combined ombitasvir/paritaprevir/ritonavir-based therapy in HCV patients with renal impairment. PATIENTS AND METHODS: Our study included 829 patients with normal kidney functions (group 1) and 829 patients with CKD (group 2),which were subdivided into patients not requiring dialysis (group 2a) and those on hemodialysis (group2b). Patients received regimens of ombitasvir/paritaprevir/ritonavir with or without ribavirin or sofosbuvir/ombitasvir/paritaprevir/ritonavir with or without ribavirin for 12 weeks. Clinical and laboratory assessment was done before treatment, and patients were followed up for12 weeks after treatment. RESULTS: The sustained virological response (SVR) at week 12 was significantly higher in group 1 than in the other three groups/subgroups, being 94.2% vs 90.2%, 90%, and 90.7%, respectively. The regimen with the highest SVR was ombitasvir/paritaprevir/ritonavir with ribavirin. The most common adverse event was anemia, which was more common in group 2. CONCLUSION: Ombitasvir/paritaprevir/ritonavir-based therapy in chronic HCV patients with CKD is highly effective, with minimal side effects despite ribavirin-induced anemia.

Nutrition in Cancer Patients Positive for COVID-19; Case Series and a Systematic Review of Literature.

Cancer is making patients vulnerable to diseases by impairing immunity directly or by anticancer therapy. In COVID-19 era, it is mandatory to face cancer with more organized & prompter response. Nutrition plays an important role in prevention & management of cancer patients. The objective of this study is to understand the role of nutrition in cancer patients during Corvid 19 era. We conducted literature searches till May 2020, electronic databases, evidence-based collections, relevant websites and trial registries about SARS-CoV2/COVID-19 and nutrition in cancer patients. Search generated 836 sources; 83/836 sources were relevant. This review summarized role of nutrition in predisposition, prevention and management of COVID-19 in cancer patient and role of vitamins, mineral supplements and microbiota in era of COVID-19. In this review, implementing appropriate nutritional care with vitamins or mineral supplementation & their effect on outcome remain largely unknown. COVID co-infection with cancer whether under chemotherapy or not have worse outcome especially in male adults. Findings may help in creating recommendations on nutritional protocol of management & prevention of complications during ongoing COVID-19 pandemic for all cancer patients.

Serum anandamide level as a potential indicator for nonalcoholic fatty liver disease severity.

INTRODUCTION AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a very common disease, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and is considered the hepatic expression of metabolic syndrome. Liver biopsy is currently considered the gold standard in diagnosis of NAFLD; however, it is an invasive technique and carries many risks. The serum anandamide level is recently discovered to play an important role as the potential indicator for NAFLD severity. The purpose of the study is to determine the association of endocannabinoid metabolite anandamide and NAFLD severity and to investigate its association with anthropometric and metabolic features in NAFLD patients. METHODOLOGY: A case-control study on 36 NAFLD biopsy-proven NAFLD patients and 15 healthy volunteers. They were subjected to full clinical history and examination, laboratory tests, abdominal ultrasound and serological testing of anadamide. RESULTS: The anadamide level was significantly higher among NAFLD subgroups (simple steatosis and NASH) vs. the normal group (1.1, 0.29 vs. 0.2 P value = 0.00085), with cutoff 0.58 in the NASH group (accuracy 89%; sensitivity 66% and specificity 100%) (P value < 0.01). CONCLUSION: Anandamide could be a specific serum marker for NASH and can be used to detect NAFLD severity.

De la medicina narrativa a los cuidados humanizados: El hospital El Cruce en pandemia

Este libro intenta compartir los aportes técnicos de los enfoques con las vivencias emocionales recogidas en múltiples relatos. Contiene descripciones rigurosas de las dos disciplinas que confluyen, la medicina narrativa y los cuidados humanizados, así como de las medidas adoptadas en la organización del hospital y la asistencia. Suma a esos contenidos el relato de la experiencia en todo el enfoque humanístico de la crisis, de la reflexión grupal en los talleres, las estrategias adoptadas para la resolución de problemas complejos como las visitas, el aislamiento y los cuidados del final de la vida. En cada tema, aporta textos comprometidos y personales de los actores y diversos profesionales de la salud que comparten sus emociones y conmociones en la circunstancia extrema de la pandemia. (AU)

Simple predictors of nonresponse to direct-acting antivirals in chronic hepatitis C patients.

OBJECTIVES: The introduction of direct acting antivirals (DAAs) has resulted in very high sustained virological response rates (SVR) in patients with chronic hepatitis-C (CHC). There are still a minority who fails to achieve SVR. This study aims to identify simple factors associated with nonresponse to DAAs using routine pretreatment workup. METHODS: A retrospective study included 10 655 CHC patients who were candidates for anti-viral therapy. Pretreatment demographics, laboratory results, ultrasonography and FIB-4were obtained. RESULTS: At post-treatment week 4, 10 495 patients (98.5%) were responders and 160 (1.5%) were non-responders. About 50.6% of non-responders were males and 61.3% were cirrhotic. Non-responders had significantly higher baseline BMI, liver enzymes, AFP and a significantly lower albumin, platelet count by univariate analysis ((P < 0.001). Sex, previous treatment, BMI, liver cirrhosis, AST, Albumin and platelet counts were the independent predictors of non-response. At post-treatment week 12, HCV-PCR results were available only for 7259 patients and 210 (2.9%) were non-responders. 54.8% of non-responders were cirrhotic and 51.4% were males. Non-responders had significantly higher AST, AFP and INR and a significantly lower albumin level, platelet count by univariate analysis (P < 0.05). Sex, previous treatment, AST, Albumin, WBC and platelet counts were the independent predictors of non-response. SVR-4 among treatment naive patients was 98.6% while among treatment experienced was 96.8%. SVR-12 among treatment naive patients was 97.9% while among treatment experienced was 87.9%.Cirrhotics had SVR-4 rate 97.7% and SVR-12 rate 96.21%. CONCLUSION: Routine pre-treatment work up for HCV G4 patients receiving DAAs can help in prediction of non-response.

Ritonavir-boosted paritaprevir, ombitasvir plus ribavirin could improve eGFR in patients with renal impairment and HCV: an Egyptian cohort.

BACKGROUND: The present study aimed at evaluation of changes in estimated glomerular filtration rate (eGFR) among chronic Hepatitis C virus (HCV) patients with chronic kidney disease (CKD) Stages 3-5 who were treated with 12 weeks of ritonavir-boosted paritaprevir, ombitasvir plus ribavirin. METHODS: Changes in renal functions were compared across follow up time points (baseline, SVR4, and SVR8). Data on on-treatment adverse events (AEs), serious AEs, laboratory abnormalities, treatment discontinuation were collected. RESULTS: 171 patients were included (females 35%, mean age 53 years). 29 patients had liver cirrhosis. The most common etiologies of CKD were diabetes and/or hypertension (n = 67). All included patient reached the end of treatment (EOT) with no treatment discontinuations. The overall EOT response was 100%. 122/122 (100%) patients who reached 4 weeks post-treatment have achieved SVR4, and 80/80 (100%) have achieved SVR12. No reported SAEs. Ribavirin therapy was interrupted in 25% (43/171) of patients due to anemia; 16 patients required blood transfusions. The median eGFR improved from 33.5 (15) mL/min/1.73 m2 at baseline to 35 (36) mL/min/1.73 m2 at SVR8 (p = 0.0003). CONCLUSIONS: The use of ombitasvir, paritaprevir, and ritonavir for treatment of HCV-infected patients with advanced renal disease was safe and effective, moreover, it was associated with significantly improved eGFR.

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.

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.

A new prognostic score can predict survival after hepatocellular carcinoma treatment in a cohort of 1302 Egyptian hepatocellular carcinoma patients.

INTRODUCTION: Survival of hepatocellular carcinoma (HCC) differs between regions and countries according to the different underlying factors and the degree of standard of care that enables early diagnosis and management. Our aim was to identify the most potent predictive factors of survival in Egyptian HCC patients receiving curative or palliative treatments. PATIENTS AND METHODS: This retrospective study included 1302 HCC patients attending the HCC multidisciplinary clinic, Cairo University, between February 2009 and December 2016. Clinical, laboratory, tumor characteristics, and treatment data were collected. Prognostic scores for each of the treatment categories, curative or palliative, were developed using routine laboratory tests. RESULTS: Patients were predominantly men, mean age 57.79±7.56 years. All cases developed HCC in addition to cirrhosis, mainly hepatitis C virus-related (88.2%). Most of the patients were Child-Pugh A (56.8%) or B (34.4%) and had single lesions. Transarterial chemoembolization was the most common line of treatment (42.08%). The overall median survival was 18.3 months from the date of diagnosis. Cigarette smoking, Child-Pugh score, performance status, number and size of the focal lesion, α-fetoprotein, and application of a specific treatment, particularly curative treatment, were the significant independent prognostic factors for survival. We found no impact of diabetes mellitus or hypertension on survival. Multidisciplinary HCC clinic predictive scores of survival after palliative and curative treatments were developed including independent prognostic factors, age, and portal vein status. CONCLUSION: A new Egyptian prognostic score of tumor and patients factors can predict the survival of patients with HCC after palliative and curative treatments.

Data mining of routine laboratory tests can predict liver disease progression in Egyptian diabetic patients with hepatitis C virus (G4) infection: a cohort study of 71 806 patients.

OBJECTIVES: Hepatitis C virus (HCV) and diabetes mellitus (DM) are prevalent diseases worldwide, associated with significant morbidity, mortality, and mutual association. The aims of this study were as follows: (i) find the prevalence of DM among 71 806 Egyptian patients with chronic HCV infection and its effect on liver disease progression and (ii) using data mining of routine tests to predict hepatic fibrosis in diabetic patients with HCV infection. PATIENTS AND METHODS: A retrospective multicentered study included laboratory and histopathological data of 71 806 patients with HCV infection collected by Egyptian National Committee for control of viral hepatitis. Using data mining analysis, we constructed decision tree algorithm to assess predictors of fibrosis progression in diabetic patients with HCV. RESULTS: Overall, 12 018 (16.8%) patients were diagnosed as having diabetes [6428: fasting blood glucose ≥126 mg/dl (9%) and 5590: fasting blood glucose ≥110-126 mg/dl (7.8%)]. DM was significantly associated with advanced age, high BMI and α-fetoprotein (AFP), and low platelets and serum albumin (P≤0.001). Advanced liver fibrosis (F3-F4) was significantly correlated with DM (P≤0.001) irrespective of age. Of 16 attributes, decision tree model for fibrosis showed AFP was most decisive with cutoff of 5.25 ng/ml as starting point of fibrosis. AFP level greater than cutoff in patients was the first important splitting attribute; age and platelet count were second important splitting attributes. CONCLUSION: (i) Chronic HCV is significantly associated with DM (16.8%). (ii) Advanced age, high BMI and AFP, low platelets count and albumin show significant association with DM in HCV. (iii) AFP cutoff of 5.25 is a starting point of fibrosis development and integrated into mathematical model to predict development of liver fibrosis in diabetics with HCV (G4) infection.

A polymorphism in the microsomal triglyceride transfer protein can predict the response to antiviral therapy in Egyptian patients with chronic hepatitis C virus genotype 4 infection.

BACKGROUND/AIMS: A polymorphism in the microsomal triglyceride transfer protein (MTP) is associated with hepatic fibrosis, and carriers showed higher levels of steatosis, higher levels of hepatitis C virus (HCV) RNA and advanced fibrosis. The aim of this study was to study MTP expression pattern in HCV patients and impact of the MTP polymorphism on the response to antiviral therapy. METHODS: One hundred consecutive naive HCV genotype 4 patients were recruited to receive antiviral therapy, and 40 control subjects were also recruited. Demographic, laboratory, and histopathology data were collected. DNA was isolated, and the samples were subjected to polymerase chain reaction analysis and genotyping for MTP by restriction fragment length polymorphism analysis. RESULTS: Patients and controls were age- and sex-matched (male/female, 56/44, age, 39.2±7.8 years for patients with HCV; male/female, 18/22, age, 38.1±8.1 years for controls). MTP single nucleotide polymorphisms (SNPs) (GG, GT, TT) and alleles (G, T) in the patients versus the controls were 70%, 21%, 9% & 80.5%, 19.5% versus 10%, 87.5%, 2.5% & 53.8%, 46.3%, respectively (p=0.0001). The sustained viral response (SVR) of the patients was 60%. SNPs in MTP genotypes (GG, GT, and TT) and alleles (G and T) in the responders and nonresponders were 71.7%, 25%, 3.3% & 84.2%, 15.8% versus 67.5%, 15%, 17.5% & 75%, 25% (p=0.038 and p=0.109, respectively). A multivariate analysis showed that the GT genotype was an independent predictor of SVR (area under the curve 90% and p=0.0001). CONCLUSIONS: MTP could be a new predictor for SVR to antiviral therapy in patients with HCV genotype 4 infection.

Promotor methylation: does it affect response to therapy in chronic hepatitis C (G4) or fibrosis?

BACKGROUND AND AIM: DNA methylation plays a critical role in the control of important cellular processes. The present study assessed the impact of promoter methylation (PM) of some genes on the antiviral response to antiviral therapy and it's relation to the presence of fibrosis in HCV-4 infected patients from Egypt. MATERIAL AND METHODS: Clinical, laboratory and histopathological data of 53 HCV-4 infected patients who were subjected to combined antiviral therapy were collected; patients were classified according to their response to treatment and the fibrosis status. The methylation profiles of the studied groups were determined using the following genes: APC, P14ARF, P73, DAPK, RASSF1A, and O6MGMT in patients' plasma. RESULTS: O6MGMT and P73 showed the highest methylation frequencies (64.2 and 50.9%) while P14 showed the lowest frequency (34%). Sustained virological response (SVR) was 54.7%with no significant difference in clinico-pathological or laboratory features between the studied groups. PM of O6MGM was significantly higher in non-responders (p value 0.045) while DAPK showed high methylation levels in responders with no significance (p value: 0.09) andPM of RASSF1A was significantly related to mild fibrosis (p value: 0.019). No significant relations were reported between PM of any of the studied genes and patients' features. CONCLUSION: PM of some Tumor Suppressor genes increases in chronic active HCV-4. However, only 06MGMT can be used as a predictor of antiviral response and RASSF1A as a marker of marked fibrosis in this small set of patients. An extended study, including more patients is required to validate the results of this preliminary study.

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.

Liver stiffness measurement by fibroscan predicts the presence and size of esophageal varices in egyptian patients with HCV related liver cirrhosis.

BACKGROUND AND AIM: Liver stiffness measured by transient elastgraphy correlates with Hepatic vein pressure gradient, liver Stiffness value of 21 kpa predicts significant portal hypertension. Aim is to predict esophageal varices presence by fibroscan and possible grading by degree of liver stiffness in HCV related cirrhotic patients. MATERIAL AND METHODS: Thirty two HCV related cirrhotic patients were recruited, age > 18 years, BMI< 35, no history of: upper GI bleeding, hepatocellular carcinoma, abdominal collaterals, ascites. Patients underwent clinical examination, laboratory investigations, abdominal ultrasonography, upper endoscopy and fibroscan. They divided into (Group I= no varices, Group II =small varices (Grade 1 & 2), Group III = large varices (Grade 3 & 4). RESULTS: Age is higher in Group III than I & II (55+6.6 vs 49.5+4.7 & 48.9+4.7, p-value 0.04) respectively, Groups were gender & BMI matched, fibroscan values in Group I vs II & III were 27 Vs 49.4, p value 0.01, cutoff 29.7 Kpa (sensitivity 95% & specificity 67%) while its value in Group II vs III were 38.4 vs 60.4, p value 0.002, cutoff 38.2 Kpa (sensitivity 100% & specificity77.3%). Platelet count, splenic size, platelet count/splenic size in Group I vs II & III were 107.166 vs 72.900, 13.8 vs 15.4, 803.6 vs 478, p value 0.01, 0.008, 0.005, cutoff 80.000, 14.5, 545, sensitivity & specificity (85%&75%, 75%&75%, 85%&84%) respectively. On multivariate analysis fibroscan (OR 1.113; p=0.005) & platelet count/splenic size (OR 0.995; p=0.012) were positive predictors of esophageal varices presence. CONCLUSION: Fibroscan is a good non-invasive method to predict esophageal varices presence & possible grading with high sensitivity.

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

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

Hepatitis C genotype 4 with normal transaminases: correlation with fibrosis and response to treatment, a cohort Egyptian study of 4277 patients.

BACKGROUND AND OBJECTIVE: Chronic hepatitis C virus (HCV) patients with persistently normal transaminases represent a subgroup of patients with mild, slowly progressive disease, natural history, and optimal management of these patients needs to be investigated in Egypt. Our aim is to assess the severity of hepatic fibrosis and response to therapy in a cohort of Egyptian HCV patients with normal transaminases. PATIENTS AND METHODS: Retrospective demographics, laboratory, histological features and treatment outcome of patients included in the national program for the control of viral hepatitis in Egypt since 2007 were collected. Combined pegylated IFN/ribavirin therapy was given for patients with fibrosis stage ≥ F1 and elevated transaminases while those with normal transaminase; therapy was initiated only in patients with fibrosis stage ≥ F2. RESULTS: Normal ALT and AST were detected in 1308/4277 (30.6%) and 1662/4277 (38.9%) patients, respectively, while both enzymes were normal in 943 patients (22%). Multivariate regression analysis showed that lower AFP and higher platelets count (compared with elevated transaminases group) were significantly correlated with normal transaminases (P<0.01), however, HCV-RNA levels did not show such significance. The number of patients with HAI score ≥ A1 was significantly lower in normal than elevated transaminases (36.5% vs 40.9%, respectively, P<0.01) and patients with fibrosis ≥ F2 was significantly lower in normal than elevated transaminases (36.4%) and (43%), respectively (P<0.01). There was no significant correlation between baseline transaminases levels and response to treatment. CONCLUSION: Normal transaminases are frequently encountered in chronic HCV Egyptian patients (22%). They show low AFP level, mild degree of activity and stage of fibrosis with no correlation with response to therapy.

Adipokines and insulin resistance, predictors of response to therapy in Egyptian patients with chronic hepatitis C virus genotype 4.

BACKGROUND: Hepatitis C virus (HCV) infection has major health impact worldwide and is a significant cause of chronic liver disease. In Egypt, HCV is highly endemic (up to 15% of the population); 91% of the patients are infected with genotype 4. Searching for new predictors of response to therapy is mandatory to decrease the cost and the adverse effects of current therapy. AIM: The aim of this study was to clarify the usefulness of serum leptin, adiponectin, and insulin resistance (IR) as predictors of response to treatment in hepatitis C virus genotype 4 (HCVG4). METHODS: One hundred patients with chronic HCVG4 who were candidates for treatment with pegylated interferon α and ribavirin were included in the study. Age, sex, and BMI were determined, and quantitative HCV PCR, assessment of serum leptin, adiponectin, IR, and pretreatment liver profile, and liver biopsy were performed. RESULTS: The male to female ratio was 68/32; the mean age of the patients was 40.9 ± 7.8 years and BMI was 28.3 ± 10 kg/m. Sustained virological response (SVR) was achieved by 56% of the patients. On performing logistic regression, BMI [odds ratio (OR) 6.5; P=0.004], serum leptin (OR 27.8; P ≤ 0.001), aspartate aminotransferase (OR 1.06; P ≤ 0.001), IR (OR 1.15; P ≤ 0.001), histological activity index (OR 1.77; P=0.006), and fibrosis (OR 2.93; P=0.001) were found to be independent negative predictors of SVR, whereas serum adiponectin (OR 0.74; P ≤ 0.001) was found to be an independent positive predictor of SVR. Pretreatment adiponectin (cutoff 13.75; sensitivity 92.86%; specificity 86.86%) shows area under the curve of 0.879 (95% confidence interval 0.802-0.956; P<0.001) and insignificant area under the curve for leptin or IR. CONCLUSION: BMI, pretreatment high leptin levels, and IR are negative predictors for SVR and pretreatment low adiponectin levels are an independent positive predictor for SVR in HCVG4.

HLA tissue typing has no effect on the outcome of patients undergoing a living-donor liver transplant: a single-center experience in Egypt.

OBJECTIVES: To analyze the effect of human leukocyte antigen tissue typing on outcome of live-donor liver transplant. MATERIALS AND METHODS: Fifty recipients underwent live-donor liver transplant in the Dar Al-Fouad Hospital in Egypt and were retrospectively evaluated. Patients were classified into 2 groups: those with human leukocyte antigen +ve, and those with human leukocyte antigen -ve and donors. Hepatitis C virus-related end-stage liver disease was the main indication for transplant. Demographic data, preoperative laboratory data, results of human leukocyte antigen tissue typing, Child score, model for end-stage liver disease score, graft/recipient weight-ratio, ischemia times, surgical complications, postoperative laboratory data, liver biopsy, immunosuppression, and pulse steroids were collected. Graft and patient survivals were studied using Kaplan-Meier curves. RESULTS: The mean model end-stage liver disease score was 18 ± 3.61 in group 1 and 17.73 ± 3.72 in group 2, with no significant difference. Graft/recipient weight ratio, ischemia times, and postoperative complications showed P = NS. Cyclosporine and tacrolimus were used in 5/9, 8/41, and 4/9 in group 1, and 32/41 in group 2 (P = NS). Rejection and pulse steroids were reported in 3/9 and 12/41 of group 1, and 3/12 and 11/41 of group 2 (P = NS). Hepatitis C virus-recurrence was diagnosed in 5/9 of patients (55%) and 8/41 of patients (29.5%) in groups 1 and 2 (P < .05). No statistical difference was found regarding mortality; 5-year patient and graft survival was 35/50 (70% in group 1 [human leukocyte antigen +ve]), 7/9 (77.8%), and 28/41 in group 2 (68.3%) (human leukocyte antigen -ve). CONCLUSIONS: Positive human leukocyte antigen typing before live-donor liver transplant has no effect on the incidence of postoperative complications, rejection episodes, and patient or graft survival. Recipients with positive human leukocyte antigen typing may have increased risk of hepatitis C virus-recurrence after live-donor liver transplant.