Comparison of transient elastography and shear wave elastography in patients with MAFLD: A single-center experience.

BACKGROUND: Metabolic-associated fatty liver disease and liver fibrosis are intimately linked to insulin resistance, type 2 diabetes, obesity, and metabolic syndrome. Transient elastography (TE) and point shear wave elastography (pSWE) were used to measure liver stiffness in patients who met the ultrasound criteria for steatotic liver diseases (SLD). This study compared two methods for estimating liver stiffness in patients with SLD, which in turn correlated with liver fibrosis. METHOD: Ultrasound B-mode imaging was used to identify SLD. In total, 250 MAFLD patients were recruited. Patient characteristics, laboratory investigations, and liver stiffness measurements using TE and pSWE were assessed on the same day. RESULTS: In the study, 56.0% of the patients were male, with a mean age of 41.5 ± 10.7 years. The correlation between TE and pSWE was significant (Spearman's r = 0.867*, p < .001). The Bland-Altman Plot analysis confirmed this, with 97.5% of variations in LSM falling within 95% agreement ranges. Cohen's κ was used to assess the agreement between TE and pSWE fibrosis stages, showing almost perfect agreement (83.5% kappa agreement) and a strong association between pSWE and TE in the assessment fibrosis stages. CONCLUSION: In patients with MAFLD, TE, and SWE are reliable methods for measuring liver stiffness and can be used as non-invasive screening tools for the assessment of fibrosis in SLD.

Forgettable in the care of liver cirrhosis: the unseen culprits of progression from bad to worse.

Patients with liver cirrhosis constitute a critically ill and unique population, and their stability relies on a well-coordinated multidisciplinary team with a carefully structured plan. Overlooking any aspect of this plan can expedite disease progression, leading to severe complications. The lack of disease-specific nutritional guidance, the prevalent sedentary lifestyle among patients, and insufficient screening for hepatocellular carcinoma, oesophageal varices, sarcopaenia, minimal hepatic encephalopathy, and diabetes mellitus, along with fibrosis progression and cirrhosis decompensation, can add further complexities. Additionally, devaluing the impact of obesity in triggering liver cirrhosis can be disadvantageous. Prolonged and inappropriate use of proton pump inhibitors also poses a significant challenge with a wide range of complications. These often-unheeded aspects in the care of liver cirrhosis patients represents the unseen culprits of progression from bad to worse and warrant serious consideration.

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.

Role of liver biopsy in management of liver diseases without hepatic nodules following end of the interferon era: experience of a tertiary referral center.

Liver biopsy (LB) is the cornerstone in the management of patients with liver diseases. However, a lot of queries had emerged about its role following the end of the interferon era. The aim of this study was to re-evaluate the current role of LB in the diagnosis of liver diseases. All patients who had underwent LB at the Department of Hepatology, National Liver Institute, from January 2015 through December 2018 were recruited. Indications for LB, pathology reports and medical records of all cases were retrieved, reviewed and statistically analyzed. A total of 275 liver biopsies were collected, 191 males and 84 females with mean age 41.22 ± 13.36 years. Etiological diagnosis made by histopathological evaluation was 48 drug-induced liver injury (DILI), 42 nonalcoholic fatty liver disease (NAFLD), 34 chronic hepatitis B, or C with cholestasis, 29 autoimmune hepatitis, 34 primary sclerosing cholangitis, 13 primary biliary cholangitis, 7 autoimmune overlap syndrome, 13 active bilharziasis and 10 Wilson's disease. Minor number of cases was diagnosed by different other etiologies. Initial diagnosis was made by liver biopsy and confirmed by clinical response and laboratory findings. Liver biopsy is still considered as the gold standard diagnostic measure of different liver diseases representing an integral component of management decisions in hepatology.

Impact of intermittent fasting on laboratory, radiological, and anthropometric parameters in NAFLD patients.

Aim of the study: Despite the ample flow of non-alcoholic fatty liver disease (NAFLD) drugs in the pipeline, lifestyle modifications are still the optimal solution of NAFLD. The aim of the study was to assess short term effects of Ramadan fasting (RF) as a sort of intermittent fasting (IF) on biochemical, radiological, and anthropometric parameters of NAFLD patients. Material and methods: Ninety-eight NAFLD patients were recruited and voluntarily subjected to 16 hours daily fasting for an average of 22-29 days, without special dietary recommendations. Anthropometric, laboratory and radiological parameters were measured before, at 30 days, and one month after fasting (fasting and non-fasting phases). Results: Patients were mostly rural (76%), hypertensive (34.7%), diabetic (43.9%), and female (76.8%), with overt criteria of metabolic syndrome (67.3%). Liver transaminases (ALT and AST) were ameliorated significantly after fasting (p ≤ 0.01), which continued in the following month (p ≤ 0.01) especially in those with elevated ALT before fasting (46%). Eleven patients (24.4%) experienced ALT normalization after one month of fasting, which was further increased to 15 (33.3%) one month later. Lipid profiles (cholesterol, triglycerides, HDL, LDL, cholesterol/HDL risk ratio) were significantly corrected following IF (p ≤ 0.01) and continuing in the next phase (p ≤ 0.010). Body mass index (BMI) lessened following the fasting (p ≤ 0.01), while no remarkable changes were noted regarding waist, hip, and triceps skin fold thickness (p ≤ 0.01). Glycemic indices (HbA1c, postprandial, HOMA-IR) and fibrosis markers (FIB-4 and APRI) were significantly ameliorated (p ≤ 0.01), while reduction in inflammatory markers was not long lasting (p ≤ 0.01). Conclusions: Intermittent fasting led to momentous improvements in ultrasonographic, biochemical, and anthropometric parameters of NAFLD especially in early phases and prediabetics.

A case report of COVID-19 evoked cholangitic liver abscess.

BACKGROUND: Lately, the humanity has been being threatened by the coronavirus disease (COVID-19). The virus-related destructive motives can damage not only the lungs but also the brain, blood vessels, kidneys, and the heart. CASE PRESENTATION: A middle-aged female presented with jaundice post-COVID-19 pneumonia. The patient had past history of cholecystectomy 20 years ago. Both laboratory and imaging data revealed a picture of cholestasis with right lobe liver abscess. Despite drainage and culture-based antibiotics, no improvement ensued. Endoscopic retrograde cholangiopancreatography was done revealing mildly dilated common bile duct (CBD), multiple large stones, mildly dilated central biliary radicals, and an old overlooked stent inside the dilated CBD. Papillotomy and papilloplasty were undertaken followed by stones' extraction with insertion of 2 plastic stents (10 cm× 10 f), and a flow of thick dark bile was inspected. The patient was finally improved and safely discharged. CONCLUSION: Herein, we present the first case of long-retained quiescent biliary stent which was over-headed by a cholangitic abscess in the vicinity of COVID pneumonia.

Survival of a case of pre-eclampsia complicated with acute fatty liver of pregnancy and acute pancreatitis.

Acute fatty liver of pregnancy (AFLP) and acute pancreatitis are peculiar complications of pregnancy. When acute pancreatitis occurs co-incidentally with acute fatty liver of pregnancy, mortality is high. Here, we report a case of a 22-year-old lady in her 36th week of gestation, who presented with pre-eclampsia, acute fatty liver of pregnancy and acute pancreatitis. She fulfilled six Swansea criteria for diagnosis of AFLP, and the diagnosis of acute pancreatitis was based on clinical suspicion, elevated pancreatic enzymes and the sonographic appearance of a swollen pancreatic head.

Prevalence and predictors of post-liver transplantation metabolic bone diseases.

INTRODUCTION: Post-liver transplantation (LTx) bone diseases have been poorly investigated. The frequency of bone diseases (osteopenia and osteoporosis) after LTx is unknown. AIM OF THE STUDY: To define prevalence and risk factors of bone disorders following LTx. MATERIAL AND METHODS: This prospective study was conducted on 100 consecutive adult patients who underwent living donor liver transplantation (LDLT) at the National Liver Institute (NLI) and survived longer than a year. Bone mineral density (BMD) was evaluated by dual-energy X-ray absorption (DEXA), as well as other pre- and postoperative risk factors. RESULTS: The frequencies of osteopenia and osteoporosis were found to be 14% and 8% among post-LTx patients. Seven recipients of the osteoporotic group were males, with mean age, and body mass index (BMI) before and after LTx 49.5 ±7.4 years, 24.1 ±4.7 kg/m2 and 22.8 ±1.5 kg/m2, respectively. A significant association between hepatitis C virus (HCV)-related cirrhosis, liver disease severity according to Child-Turcotte-Pugh (CTP) score, and alcoholism with decreased post-LTx BMD was substantiated (p < 0.05, 0.006). Post-LTx development of diabetes mellitus (DM), weight gain, use of corticosteroids and basiliximab all significantly affected decreased post-LTx BMD (p < 0.05). However, binary regression revealed that post-LTx occurrence of DM (p = 0.012, odds ratio [OR] = 0.099), the severity of liver disease (p = 0.023, OR = 0.217), and HCV (p = 0.011, OR = 0.173) are the main independent predictors of metabolic bone disease (MBD) occurrence one year after LTx. CONCLUSIONS: Post-LTx bone disorders are not infrequent complications and should be more considered in those with HCV-related severe liver disease or developed DM after LTx.

Evaluation of different diagnostic modalities of minimal hepatic encephalopathy in cirrhotic patients: case-control study.

INTRODUCTION: Minimal hepatic encephalopathy (MHE) represents one of the most overlooked complications of liver cirrhosis. AIM OF THE STUDY: To compare the utility and efficacy of different MHE diagnostic modalities. MATERIAL AND METHODS: This case-control study was conducted on hepatitis C virus (HCV)-related compensated cirrhotic patients. The Psychometric Hepatic Encephalopathy Score (PHES) was used to assign patients to MHE and controls. All patients were subjected to plasma ammonia, serum 3-nitrotyrosine (3-NT), critical flicker frequency (CFF), and the modified inhibitory control test (ICT). RESULTS: CFF was significantly lower in the control group (38.5, 40 Hz, p = 0.003). The unweighted lures on ICT were 8.7, 4.9 in MHE and controls (p < 0.001). Moreover, ammonia was higher in the MHE group (89, 61.5 µmol/l, p < 0.001). 3-NT was also higher in the MHE group (31.5, 13.7 nmol/l, p < 0.001) respectively. CFF at cutoff < 39 Hz had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 57.5%, 77.5%, 71.9% and 64.6%, respectively; in modified ICT, at cutoff > 5 unweighted lures the values were 87.5%, 80%, 81.4% and 86.5%, respectively; in ammonia, at cutoff ≥ 76.45 µmol/l the values were 65%, 72.5%, 70.3% and 67.4%, respectively; for 3-NT at cutoff ≥ 14.15 nmol/l the values were 85%, 82.5%, 82.9% and 84.6%, respectively. The accuracy for MHE diagnosis was 67.5%, 83.3%, 68.8%, 83.8% relying on CFF, 3-NT, ammonia, and ICT respectively. On multivariate analysis, CFF < 39 Hz (OR = 10.2, p = 0.04), modified ICT > 5 unweighted lures (OR = 43.2, p = 0.002), and serum 3-NT levels ≥ 14.15 nmol/l (OR = 50.4, p < 0.001) were independent predictors of MHE. CONCLUSIONS: 3-NT and ICT are advantageous to reveal MHE in compensated liver cirrhosis, while CFF can be only used as adjuncts, with humble merits of ammonia.

CD62P (P-selectin) expression as a platelet activation marker in patients with liver cirrhosis with and without cholestasis.

AIM OF THE STUDY: P-selectin (CD62P) is a platelet activation marker that was claimed to mediate the accumulation of platelets induced by cholestasis. The nature of platelet dysfunction and hemostasis abnormalities in cholestatic liver disease needs to be more explored. The aim of this study was to assess platelet CD62P expression in cirrhotic patients with and without cholestasis, and to evaluate its relationship with a bleeding tendency. MATERIAL AND METHODS: 150 patients were included in this case-control study. Participants were divided into 84 patients with liver cirrhosis (group I), 44 of whom had cholestasis (Group Ia) and 40 patients were without cholestasis (group Ib); 36 patients who were cholestatic without liver cirrhosis (group II); and 30 healthy subjects who formed the control group (group III). Platelet CD62P expression was assessed by a flow cytometer. RESULTS: Platelets expressing CD62P were significantly increased in all patient groups compared to controls (p < 0.001). Platelets expressing CD62P were significantly increased in gastrointestinal (GIT) bleeders compared to non-bleeders in cirrhotic and cholestatic groups (p < 0.001 each). Among group I patients at cut-off > 12.4, up-regulation of platelet CD62P yielded 72% sensitivity and 44.1% specificity to discriminate bleeders from non-bleeders (p = 0.01), while among group II at cut-off > 12.9, it yielded 90% sensitivity and 80.8% specificity (p < 0.001). In cirrhotic patients, platelet CD62P expression was significantly increased in patients with an advanced Child-Pugh class (p < 0.001). Platelet expressing CD62P was shown as an independent risk factor for bleeding among cirrhotic cases with an odds ratio of 1.07 and CI 0.99-1.15. CONCLUSIONS: Up-regulation of platelet CD62P expression can serve as a GIT bleeding predictor in liver cirrhosis.

MELD-Sarcopenia is Better than ALBI and MELD Score in Patients with Hepatocellular Carcinoma Awaiting Liver Transplantation.

BACKGROUND: The albumin bilirubin (ALBI) score and model of end stage liver disease (MELD) are prognostic in patients with hepatocellular carcinoma (HCC). Aim was to compare MELD-sarcopenia to MELD and ALBI scores in patients with HCC awaiting liver transplantation. METHODS: patients with HCC (n=262) were included and followed up for 12 months. Baseline MELD, ALBI and MELD-sarcopenia models were calculated. RESULTS: The average age was 59.61 ±8.09 years. Most patients were males (69.5%), CTP class A (55.7%) and BCLC stage B (54.2%). Hepatitis C virus was the main cause of liver cirrhosis in most patients (88.9%). The average MELD, MELD-sarcopenia and median ALBI score were 10.65 ±2.54, 15.11 ±6.22 and -2.12 (0.74) respectively. Sarcopenia patients had higher MELD, ALBI and MELD-sarcopenia values. Patients with sarcopenia had lower survival (10.09 months) than those without (11.72 months). The ALBI, MELD and MELD-sarcopenia were associated with mortality. ALBI had AUROC of 0.717 (95% CI: 0.659 - 0.771), MELD had AUROC of 0.656 (95% CI: 0.595 - 0.713) and MELD-sarcopenia had AUROC of 0.798 (95% CI: 0.744 - 0.845). The ALBI and MELD scores had comparable AUROC (p=0.081). The MELD-sarcopenia had superior AUROC than MELD (p=0.001) and ALBI (p=0.05). CONCLUSION: MELD-sarcopenia is better prognostic model than the ALBI and MELD scores in HCC patients awaiting liver transplantation.
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Altered Protein and Gene Expression of Beclin-1 Correlates with Poor Prognosis of Hcv-Associated Hepatocellular Carcinoma in Egyptian Patients.

Autophagy modulation has recently been addressed as a novel target for overcoming therapeutic resistance in hepatocellular carcinoma (HCC) to currently available anti-HCC therapy. The aim of this study was to investigate the protein and gene expression of Beclin-1 and its correlation with prognosis in HCV-associated HCC in Egyptian patients. This prospective study included 50 patients with HCV-associated-HCC, treated with surgical resection. Immunohistochemistry of antibody and quantitative real-time PCR of Beclin-1 gene were assessed in liver tissues of HCC. A normal-like expression pattern of Beclin-1 was found in 100% of adjacent liver tissues, while in HCC three various patterns were recognized: negative expression [18 (36%)], over expression [16 (32%)] and normal pattern [16 (32%)] (p=0.001). Beclin-1 mRNA in HCC tissues correlated with protein expression with correlation coefficient of 0.774 (p <0.001). Patients with negative expression of Beclin-1 had a significantly poor overall survival rates compared with patients with normal-like expression pattern (p <0.007), which was confirmed by multivariate analysis (p=0.01). Over-expression of Beclin-1 was significantly associated with vascular invasion (p <0.003). However, high tumor histological grade, focal lesion multiplicity, presence of involved margin or cirrhosis were insignificantly related to Becin-1. Beclin-1 altered expression has an important role in development and prognosis of HCC.

Portal vein thrombosis in hepatitis C virus-related cirrhotic patients: Prevalence and clinical characteristics in an Egyptian cohort.

Portal vein thrombosis is a catastrophe not uncommonly complicating hepatitis C virus-related liver cirrhosis. To estimate its prevalence and clinical characteristics, we investigated 1000 cirrhotic patients by abdominal ultrasound or Doppler study at least. Portal vein thrombosis was found in 21.6%, of whom 157 (72.7%) had malignancy. Complete portal vein thrombosis was found in 70.4%. Half of all these patients had at least one episode of portal hypertensive bleeding, a third had abdominal pain and a quarter presented with jaundice. Portal bilopathy was diagnosed in two cases (0.9%). There was significant association between severity of liver disease, ascites, male gender and site of segmental focal lesion and portal vein thrombosis.

Serum ammonia as a non-invasive marker for early prediction of esophageal varices.

INTRODUCTION: There is a growing need for identification of non-endoscopic, non-invasive methods that can accurately predict esophageal varices (EV). Previous studies found an inconclusive correlation between blood ammonia level and the presence and size of EV. AIM: We aimed at assessing the value of serum ammonia as a non-invasive method for early prediction of EV. PATIENT AND METHODS: The study included 204 patients with HCV-related cirrhosis. The selected patients were categorized into two groups: patients with EV and those without, also patients with no or small EV and with large EV group. All patients underwent a complete biochemical workup, ultrasound and upper GI endoscopy. Child-Pugh class, Model of End-Stage Liver Disease (MELD) score and platelet count/splenic diameter ratio, and serum ammonia level. RESULTS: There was a statistical difference between the two groups of patients regarding the following parameters: serum ammonia, international normalized ratio, portal vein diameter, spleen diameter, Child-Pugh class, MELD score, platelet count/splenic diameter ratio, aspartate aminotransferase-to-platelet ratio index, alanine aminotransferase-to-aspartate aminotransferase ratio, Forns index, FIB-4 and King's score. Serum ammonia could predict the presence of EV using a cutoff value of 82 (µmol/L) with a sensitivity of 92.3%, specificity 92%. In addition, a cutoff of 95.5 (µmol/L) could predict large EV with a sensitivity of 92.7% and a specificity of 92.3%. Serum Ammonia in cirrhosis with large EV was 143 ± 39 µmol/L and in cirrhosis with small/without EV was 80.7 ± 9.7 µmol/L (P < 0.0001). Platelet/spleen ratio was 555.9 ± 187.3 in cirrhosis with EV and 694.4 ± 74.2 in cirrhosis without EV (P < 0.0001). Platelet/spleen ratio was 407.7 ± 107.1 in cirrhosis with large EV and 690.4 ± 103.7 in cirrhosis with small/without EV (P < 0.0001). CONCLUSION: Serum ammonia can accurately predict the presence and the size of EV in patients with liver cirrhosis with high sensitivity and specificity.

Baseline Sarcopenia is Associated with Lack of Response to Therapy, Liver Decompensation and High Mortality in Hepatocellular Carcinoma Patients.

OBJECTIVE: hepatocellular carcinoma (HCC) is a dreadful complication of liver cirrhosis. Aim was to study the effect of sarcopenia on the survival in patients with HCC. METHODS: we included 262 patients and were followed up for 12 months. Sarcopenia was calculated by skeletal muscle index (SMI). Sarcopenia was defined by SMI ≤39 cm2/m2 for women and ≤50 cm2/m2 for men. RESULTS: patients with sarcopenia (n= 113, 43.1%) were older, mainly males, Child-Pugh class B and smokers. Patients with sarcopenia had lower survival than those without (10.09 vs. 11.72 months). Survival was also lower in Barcelona clinic liver cancer stage C than B and A (9.02 vs. 11.21 vs. 11.89 months). Age and sarcopenia were hazardous of mortality (p <0.05). There was statistically significant difference of serial SMI in patients without baseline sarcopenia unlike patients with baseline sarcopenia. On follow up patients with sarcopenia had higher incidence of ascites (45% vs. 20.4%), spontaneous bacterial peritonitis (21.7% vs. 11.6%), hepatic encephalopathy (28% vs. 11.5%) and bleeding (22.9% vs. 12.7%). Totally patients with sarcopenia had higher incidence of progressive HCC (39% vs. 25.5%). CONCLUSION: Sarcopenia is associated with lack of response to therapy, liver decompensation and higher mortality in hepatocellular carcinoma patients.
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Urine Neutrophil Gelatinase-Associated Lipocalin a Possible Diagnostic Marker for Egyptian Hepatocellular Carcinoma Patients.

BACKGROUND: Most effective method for reducing mortality from hepatocellular carcinoma (HCC) is early diagnosis. Despite its lack of adequate sensitivity, ultrasound is considered fundamental for HCC screening. AIM: to evaluate urinary neutrophil gelatinase-associated lipocalin (NGAL) as non-invasive marker for HCC diagnosis in Egyptian patients. METHODS: One hundred and twenty patients were divided into three groups (40 patients each): patients with chronic viral hepatitis (HCV or HBV), cirrhotic patients and HCC patients and 40 healthy age and gender matched subjects were enrolled as control group. After clinical assessments, urinary NGAL was measured by enzyme-linked immunosorbent assay. RESULTS: Our results revealed that median level of urinary NGAL was 290, 834, 1090 and 1925 pg/ml in control, chronic hepatitis, cirrhotic and HCC groups respectively among studied groups (p<0.001). Receiver operating characteristics (ROC) analysis showed that urinary NGAL cutoff value of 1255 ng/ml could discriminate between HCC and cirrhosis. The area under curve (AUC) was 0.95 with 90% sensitivity, 87.5% specificity (p-value <0.001). In HCC group, urine NGAL level didn`t show significant correlation with Child Pugh score, MELD score or Barcelona Clinic Liver Cancer (BCLC) stage. CONCLUSION: Urinary NGAL could be a simple, non-invasive test for diagnosis of HCC in chronic liver disease patients.
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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.

Role of Ribavirin in the Era of Direct-Acting Antiviral Therapies of Chronic Hepatitis C.

BACKGROUND: The efficacy of adding ribavirin (RBV) to direct antivirals (DAAs) in HCV treatment is still debatable, with allegations of insecure profiles. OBJECTIVES: To evaluate safety and efficacy of RBV in the era of DAAs in chronic HCV Egyptian patients. METHODS: In this cohort retrospective study, data of 847 HCV patients treated with different regimens of DAAs with or without RBV were recruited between June 2017 and September 2018. Cases were categorized into five groups: non-cirrhotic (318), compensated (196), decompensated liver cirrhosis (53), post liver transplantation (30), and 250 treatment experienced patients. All patients' demographics and laboratory characteristics were evaluated at baseline, week4, 12, 24 of treatment. Ribavirin was prescribed or banned outside international guideline recommendations of HCV treatment in cases assembled from the private sector.Results: No statistically significant difference between RBV and non-RBV treated patients was documented regarding SVR12 (97.2%, 97.8%) respectively in the whole cohort (p 0.509). On grouping, adding RBV was only significant in the treatment experienced patients (96.8%, 85% in RBV and non-RBV regimens respectively) (p 0.001). Adding RBV to DAA regimens was generally associated with modest adverse events particularly anemia (8.5%), and hepatic decompensation (jaundice and ascites) (0.3%). Bilirubin, INR, and platelet counts all were found to be the most independent predictors of SVR achievement by multivariate analysis (p ≤ 0.05).Conclusion: RBV may still have an augmenting role in treatment experienced patients; permitting effectual shortening of therapy particularly in patients with cirrhosis, with modest side and adverse consequences.

Presentations, Causes and Outcomes of Drug-Induced Liver Injury in Egypt.

Drug-induced liver injury (DILI) is a frequent cause of liver injury and acute liver failure. We aimed to review all hospitalized DILI cases in a tertiary Egyptian center from January 2015 through January 2016. Cases with elevated alanine aminotransferase more than 3-fold and/or alkaline phosphatase more than 2-fold the upper limit of normal value were prospectively recruited and followed for one year. Drug history, liver biopsy whenever feasible and application of Roussel Uclaf Causality Assessment Method (RUCAM) were the diagnostic prerequisites after exclusion of other etiologies of acute liver injury. In order of frequency, the incriminated drugs were: Diclofenac (31 cases, 41.3%), amoxicillin-clavulanate (14 cases, 18.7%), halothane toxicity (8 cases, 10.7%), ibuprofen (4 cases, 5.3%), Khat (3 cases, 4%), tramadol (3 cases, 4%), Sofosbuvir with ribavirin (2 cases, 2.7%), and acetylsalicylic acid (2 cases, 2.7%) with one offending drug in 93.3% of cases. Forty-four cases (58.7%) were males; while 56 cases (74.7%) had HCV related chronic liver disease. Thirty-two cases (42.7%) presented with pattern of hepatocellular injury, while 23 cases (30.7%) were with cholestasis, and 20 cases (20.7%) with a mixed hepatocellular/cholestatic injury. One case received a transplant (0.75%), 7 cases died (9.3%), 23 cases (30.6%) developed liver decompensation (hepatic encephalopathy and ascites), and 44 cases completely resolved (58.7%). In conclusion, Diclofenac is the commonest offender in DILI occurrence in an Egyptian cohort. Age and prothrombin concentration were the only predictors of unfavorable outcomes of DILI.