Appraisal of a newly developed ALBI-sarcopenia score as a prognostic marker in patients with hepatocellular carcinoma.

OBJECTIVE: This study aimed to evaluate the impact of the combined Albumin-bilirubin (ALBI)/sarcopenia score as a newly developed prognostic model for hepatocellular carcinoma (HCC), with a focus on its utility in predicting mortality. METHODS: This prospective study was conducted on HCC patients who were followed for 1 year or until death. Sarcopenia was assessed radiologically by computed tomography at the level of L3. The study consisted of two sets: a development set in which the new ALBI-sarcopenia score was created, comprising 262 HCC patients, followed by an internal validation set with 100 patients. RESULTS: The development cohort primarily included males (69.5%), aged 59.6 ± 8.09 years. In patients with sarcopenia, the ALBI score was -2.03 ± 0.42 ( P < 0.006), the model for end-stage liver disease (MELD) score was 11.29 ± 2.43 ( P < 0.001*), and the MELD-sarcopenia score was 21.29 ± 2.43 ( P < 0.001*). The distribution of barcelona clinic liver cancer (BCLC) staging was as follows: BCLC A 18 (15.9%), BCLC B 63 (55.8%) and BCLC C 32 (28.3%) ( P < 0.001*), with a notable association with higher mortality ( P < 0.001). Multivariate analysis identified sarcopenia and ALBI scores as independent predictors of mortality in HCC ( P < 0.001*). In the development set, the ALBI-sarcopenia score successfully predicted mortality at a cutoff >-11 with an area under a curve of 0.837 (95% CI, 0.784-0.889), while in the validation set, it predicted mortality at a cutoff >-11.55 with an area under a curve of 0.842 (95% CI, 0.753-0.930). CONCLUSION: The newly introduced ALBI-sarcopenia score has demonstrated superior effectiveness in comparison to MELD-sarcopenia score, overcoming the shortcomings associated MELD score in forecasting outcomes for patients with HCC.

Evaluation of ABCA1 gene polymorphism as a prognostic index of fibrosis progression in NAFLD patients.

INTRODUCTION: It had been evident that non-alcoholic fatty liver disease (NAFLD) is the new era epidemic. Despite emergence of many drugs on the pipeline that considered candidates to cure NAFLD/NASH, the critical need for defining the cohort liable to fibrosis progression is yet unmet. AIM: Evaluate ABCA1 (rs1800977) genotyping as a noninvasive predictor of liver fibrosis severity. MATERIALS AND METHODS: This study included 118 liver biopsy-proven NAFLD-patients. According to Metavir-fibrosis-staging, cases were divided to early fibrosis (74 cases), and 44 cases with significant fibrosis (>F2), added to 49 healthy control subjects. All patients were subjected to liver function tests, lipids profile, triglyceride TG index, and hepatic steatosis index (HSI) and real-time PCR ABCA1 SNP (rs1800977). RESULTS: Significant differences in transaminases (p > .05), albumin (p < .009), cholesterol (p0.03), low density lipoproteins (LDL) (0.006), triglycerides (p < .001), HSI (p < .001), FIB4 (p < .001) and APRI (p < .001) were reported in those with significant than early fibrosis and control groups. CC was the most prevalent in significant (36.4%) than early fibrosis (13.5%) and control groups (8.2%), with prevalence of C allele in significant fibrosis (p ≤ .003). Univariate analysis revealed that DM (p ≤ .001), TG index (p ≤ .022), cholesterol (p ≤ .03), HSI (p ≤ .006), LDL (p ≤ .02), HDL (p ≤ .01), APRI (p ≤ .02) and CC genotype (p ≤ .005) were the main factors affecting fibrosis progression in NAFLD. However multivariate analysis proved only the role of HSI (p ≤ .005), LDL (p ≤ .02), HDL (p ≤ .003) and CC genotype (p ≤ .03) in predicting fibrosis severity. CONCLUSION: Dyslipidemias, hepatic steatosis index and ABCA1 (rs1800977) gene polymorphism CC genotype; were the only independent predictors of advanced fibrosis in NAFLD-patients.

The association between micro-RNA gene polymorphisms and the development of hepatocellular carcinoma in Egyptian patients.

INTRODUCTION: The development and progression of hepatocellular carcinoma (HCC) is a multistage process involving the deregulation of genes that are crucial to cellular processes. Multiple risk factors are correlated with HCC. MicroRNA is differentially expressed in the development of different types of malignancies, including hepatic malignancy. Single nucleotide polymorphisms (SNPs) are the most common sequence variation in the human genome. SNPs in miRNAs may affect transcription, processing, or target recognition and result in malignant disease. The aim of the study was to determine the association between microRNA gene polymorphisms and the development of HCC in Egyptian patients. MATERIAL AND METHODS: This study included 200 individuals who were matched in age and sex. Tumour staging was done using the BCLC staging system. Quantification and genotyping of microRNA were performed. RESULTS: Among the 200 patients, 2 groups were described: group I included 90 HCC patients with a male majority (72.2%), and group II comprised 110 controls. Three microRNA SNPs were assayed in both patients and controls. There was a significant association between rs10061133 miR-499b and the risk of HCC. The genotypes GG or G allele were significantly associated with an increased risk of HCC (GG: OR = 2.91, 95% CI: 1.23-4.22, p = 0.013; G allele: OR = 1.79, 95% CI: 1.12-2.15, p = 0.026) compared with the genotype of AA or AG or A allele. CONCLUSIONS: There is an association between the miRNA SNPs and the susceptibility to HCC, to explore some roles and mechanisms of SNPs within miRNAs in the occurrence and development of HCC.

Janus Kinase-2 Mutation Associated Portal Vein Thrombosis Complicating Liver Cirrhosis and Hepatocellular Carcinoma.

BACKGROUND: Portal vein thrombosis (PVT) might be a catastrophic event complicating liver cirrhosis and hepatocellular carcinoma (HCC). AIM: role of JAK2 RS V617F mutation as a risk factor for PVT development in liver cirrhosis and HCC. METHODS: A case control study conducted on 100 PVT patients (76 HCC and 24 liver cirrhosis) additionally, 100 healthy individuals used as a control group. PVT was diagnosed incidentally by Doppler ultrasound during routine follow-up HCC screening. Prothrombin G20210A mutation, MTHFR mutation, Factor V Leiden mutation (VFL), antithrombin III (ATIII), protein C, S, and antiphospholipid antibodies, along with JAK2 RS V617F  mutation by real-time polymerase chain reaction all were analyzed. RESULTS: Patients with PVT were significantly older (p <0.001), thrombocytopenic (p <0.001), with high alkaline phosphatase (p <0.001). JAK2 RS V617F mutation was found in 28/100 (28%) in idiopathic PVT complicating liver cirrhosis and hepatocellular carcinoma. Cases with positive JAK2 rs V617F mutation were significantly accompanied by protein S deficiency (P 0.03), LA absence (p 0.06), and high frequency of ascites (P 0.03). While, the MTHFR heterozygous mutation (p0.001), ATIII (P 0.02), and VFL (P 0.01) were more frequent with negative JAK2 rs V617F mutation. The comparison between demographic data and thrombophilic parameters in PVT cases revealed that no significant differences were recorded except for male gender, Diabetes Mellitus, splenomegaly significantly increased among HCC cases (p <0.05). CONCLUSIONS: JAK2 rs V617F mutation must be considered in any case of PVT with liver cirrhosis and hepatocellular carcinoma without identified thrombophilic risk factors, with potential considerations of evolving myeloproliferative disorders. New diagnostic and therapeutic implications are still awaited.

Value of IFNL3 genetic polymorphism in the prediction of HCV treatment response to direct-acting antiviral drugs versus interferon therapy.

Background: Despite the outstanding results of direct-acting antiviral therapies (DAAs) of Hepatitis C infection (HCV), non-responders had to be more defined. Aim: assess the outcome of DAAs in linkage with Interferon lambda 3 (IFNL3) in HCV patients. Methods: This case-control-study was conducted on 495 chronic-HCV (genotype-4a), previously treated Egyptians by either DAAs (responders 195, 120 relapsers) or interferon/ribavirin (IFN/RBV) (140 responders, 60 relapsers), and 98 healthy controls. IFNL3 distribution, clinical and laboratory data were assessed. Results: CT was the most predominant genotype in Egyptians (51%). All genotypes were sensitive to DAAs mainly CT genotype (60%), even TT genotype (resistant to IFN/RBV 40%) had 29.2% sensitivity. CT genotype was predominant in sofosbuvir/Daclatasvir responders (67.6%) (OR = 0.66), while non-CT prevailed in relapsers (56.7%). TT genotype may respond to SOF/Ledi better than other regimens (66.7%). In IFN/RBV relapsers; CT genotype was commoner (50%) than others, while CC genotype predominated in responders (54.3%). The c allele was the commonest in responders to IFN/RBV (71.4%), while the T allele was resistant to treatment (65% in relapsers). Addition of RBV to SOF/DCV reported higher resistance with CT genotype (42.2%-50%) and TT genotype (17.8%-27.8%). Conclusion: This study recommended IFNL3 genotyping to be a prerequisite before stratifying treatment for HCV-4a Egyptians.

On-treatment improvement of an emerging psychosomatic depressive disorder among salmonella carriers: a multicenter experience from Egypt.

BACKGROUND: As physicians in a referral hospital, we observed the association between history of enteric fever and somatic disorders associated with low mood. At the Al-Hussein University Hospital, Cairo and the National Liver Institute Hospital, Menoufia, we receive patients from all over Egypt, including rural areas where enteric fever is endemic. AIM: Here in, 60 Egyptian patients referred to us for evaluation of different somatic disorders are reported. METHODS: After extensive evaluations, the patients' symptoms were function-related. Also, their typhoid carrier states were documented, and the severity of depression using Hamilton-D (HAM-D) questionnaire was evaluated and recorded. All patients were treated with ceftriaxone, 2 gm, IV, daily for 15 days. The clinical evaluation and Hamilton score were reassessed at the end of the treatment and 6 weeks thereafter. The patients did not receive any anti-depressant nor anti-anxiety treatment during their course. Typhoid carrier was defined by documenting the history of typhoid fever that was diagnosed by culturing the Salmonella species, and not by serology, isolated from stool culture along with febrile condition, plus the absence of fever in the past 3 weeks. The Widal test was not accepted as a criterion for enrollment. RESULTS: Patients showed clinically significant improvement in the somatic complaints, and their HAM-D score immediately post-treatment that was consolidated for 6 weeks post-treatment completion. CONCLUSION: In this study, the typhoid carrier was associated with the psychosomatic depression that improved by antibiotic therapy.

High efficacy of generic and brand direct acting antivirals in treatment of chronic hepatitis C.

BACKGROUND: Direct acting antivirals (DAAs) are highly effective for treatment of hepatitis C (HCV) but brand products are priced beyond the means of most low and middle income countries (LMICs). Although a few DAAs are offered at reduced prices in access programs, they are still beyond affordability in limited resource settings with a large HCV infected population. Cheap generics might fill this economic need, but studies comparing their clinical efficacy to that of original products are limited. AIM: To compare efficacy of brand and generic DAAs used in the national treatment program in Egypt. METHODS: HCV treatment eligible patients (n=971) were enrolled. They were treated with 12 weeks of either sofosbuvir-daclatasvir (SOF-DCV) or SOF-ledipasvir (SOF-LDV). Ribavirin (RBV) was added to patients with cirrhosis and to SOF experienced patients. Patients with cirrhosis who were RBV intolerant were treated for 24 weeks without RBV. RESULTS: Most patients were males (61.4%), treatment naïve (88.6%), without cirrhosis (61.7%), and the mean age was 51.3±11.31 years. Baseline characteristics were not different in patients treated with brand or generic medications regarding age, liver tests, creatinine, platelets, MELD score, baseline HCV-RNA and transient elastography. Overall sustained virologic response (SVR) rate was 98.1%, which was similar for generic and brand drugs (98.2% vs. 98.1%; p=1), and similar with both regimens used (SOF-DCV±RBV: brand: 98.1%, generic 97.8%; p=0.729, SOF-LDV±RBV: brand 98.2%, generic 100%; p=0.729). AST and ALT decreased significantly with initiation of therapy with both generic and original drugs. CONCLUSION: Generic and brand DAAs are equally effective for achieving SVR and improving aminotransferases.