The value of the apparent diffusion coefficient value in the Liver Imaging Reporting and Data System (LI-RADS) version 2018.

PURPOSE: To assess role of the apparent diffusion coefficient (ADC) in the Liver Imaging Reporting and Data System (LI-RADS) version 2018 for the prediction of hepatocellular carcinoma (HCC). MATERIAL AND METHODS: Retrospective analysis of 137 hepatic focal lesions in 108 patients at risk of HCC, who underwent magnetic resonance imaging of the liver. Hepatic focal lesions were classified according to LI-RADS-v2018, and ADC of hepatic lesions was calculated by 2 independent blinded reviewers. RESULTS: The mean ADC of LR-1 and LR-2 were 2.11 ± 0.47 and 2.08 ± 0.47 × 10-3 mm2/s, LR-3 were 1.28 ± 0.12 and 1.36 ± 0.16 × 10-3 mm2/s, LR-4, LR-5 and LR-TIV were 1.07 ± 0.08 and 1.08 ± 0.12 × 10-3 mm2/s and LR-M were 1.02 ± 0.09 and 1.00 ± 0.09 × 10-3 mm2/s by both observers, respectively. There was excellent agreement of both readings for LR-1 and LR-2 (r = 0.988), LR-3 (r = 0.965), LR-4, LR-5 and LR-TIV (r = 0.889) and LR-M (r = 0.883). There was excellent correlation between ADC and LI-RADS-v2018 (r = -0.849 and -0.846). The cut-off ADC used to differentiate LR-3 from LR-4, LR-5, and LR-TIV were ≤ 1.21 and ≤ 1.23 × 10-3 mm2/s with AUC of 0.948 and 0.926. CONCLUSIONS: Inclusion of ADC to LI-RADS-v2018 improves differentiation variable LI-RADS categories and can helps in the prediction of HCC.

De Novo Hepatocellular Carcinoma in Hepatitis C-Related Cirrhosis: Are Advanced Glycation End Products a Key Driver?

Background and Purpose: The advanced glycation end products (AGEs) have been implicated in different diseases' pathogenesis, but their role in hepatocellular carcinoma (HCC) is still a matter of debate. This study aims to investigate the association of AGEs with HCC development in patients with hepatitis C-related cirrhosis. Methods: Only 153 of the 181 non-diabetic patients with cirrhosis were consecutively involved in this pilot cohort prospective study, along with 34 healthy control participants. Demographic characteristics, biochemical parameters, clinical data, and AGEs levels in all subjects at the starting point and every year after that for two years were assessed. Multivariable Cox regression analysis was used to settle variables that could predict HCC development within this period. Results: HCC developed in 13 (8.5%) patients. Univariate Cox regression analysis reported that body mass index (P=0.013), homeostatic model assessment-insulin resistance (P=0.006), alpha-fetoprotein (P <0.001), and AGEs levels (P <0.001) were related to HCC development. After adjusting multiple confounders, the multivariable Cox regression model has revealed that AFP and AGEs were the powerful parameters related to the HCC occurrence (all P<0.05). AGEs at a cutoff value of more than 79.6 ng/ml had 100% sensitivity, 96.4% specificity, and 0.999 area under the curve (all P<0.001), using the receiver operating characteristic curve, for prediction of HCC development. Conclusion: This work suggests that AGEs are associated with an increased incidence of HCC, particularly in cirrhosis, which is encouraging in decreasing the risk of HCC in these patients.

De novo Portal Vein Thrombosis in Non-Cirrhotic Non-Alcoholic Fatty Liver Disease: A 9-Year Prospective Cohort Study.

Background and Aims: Approximately 30-40% of portal vein thrombosis (PVT) remains of unknown origin. The association between non-alcoholic fatty liver disease (NAFLD) and PVT is a matter of debate. This study aimed to investigate the association between PVT and NAFLD. Methods: We included 94 out of 105 consecutive NAFLD patients in this prospective cohort study in addition to 94 from the healthy control group. We evaluated biochemical, clinical, immunological, and histopathological parameters; waist circumference (WC); leptin; adiponectin; and leptin/adiponectin ratio (LAR) for all participants at baseline and every 3 years thereafter. We described the characteristics of participants at baseline and showed individual WC, LAR, and PVT characteristics. Potential parameters to predict PVT development within 9 years were determined. Results: PVT developed in eight (8.5%) patients, mainly in the portal trunk. Univariate analysis showed three PVT-associated factors: diabetes mellitus (P = 0.013), WC (P < 0.001), and LAR (P = 0.002). After adjusting multiple confounding variables, the multivariate model showed that the only significant variables were WC and LAR. By applying the receiver operating characteristic curve, WC had 98.8% specificity, 87.5% sensitivity, and 0.894 area under the curve (AUC) for prediction of PVT (P < 0.001) at cutoff values of > 105 cm. In comparison, LAR had 60.5% specificity, 87.5% sensitivity, and 0.805 AUC for PVT prediction (P < 0.001) at cutoff values of >7.5. Conclusions: This study suggests that increased central obesity and LAR were independently associated with PVT development in non-cirrhotic NAFLD patients, and they should be considered risk factors that may participate in PVT multifactorial pathogenesis.

Prognostic value of vascular endothelial growth factor in both conventional and drug eluting beads transarterial chemoembolization for treatment of unresectable hepatocellular carcinoma in HCV patients.

OBJECTIVES: This work aimed to measure serum vascular endothelial growth factor (VEGF) levels before and after Conventional transarterial chemoembolization (cTACE) versus drug-eluting beads (DEB)-TACE and evaluate its efficacy in predicting response to therapy and tumor recurrence. METHODS: 114 patients with unresectable hepatocellular carcinoma complicating hepatitis C virus-related cirrhosis were included. They underwent cTACE (58) or DEB-TACE (56). VEGF serum levels were measured before and on days 1 and 30 after TACE. Patients with complete response (CR) after TACE were followed-up for one year. Statistical analysis was done. RESULTS: VEGF level was higher than baseline after cTACE (P < 0.001), and DEB-TACE (P = 0.004). It was also significantly higher in patients with progressive disease (P < 0.001). VEGF level at cut off values of 97.3, 149.8, and 104.1 pg/ml could discriminate disease progression from treatment success with area under ROC curves of 0.806, 0.775, and 0.771, respectively. The sensitivity was 88.9%, 88.9%, and 77.8% and specificity was 62.5%, 64.6 and 66.7%, respectively. However, no relation to tumor recurrence in CR group could be detected after one year. CONCLUSION: VEGF serum levels may predict response to therapy in patients treated by DEB-TACE or cTACE but it has no relation to tumor recurrence.

Liver Imaging Reporting and Data System Version 2018: What Radiologists Need to Know.

In this article, we aim to review Liver Imaging Reporting and Data System version 18 (LI-RADS v2018). Hepatocellular carcinoma (HCC) is the most common primary hepatic malignancy. Liver Imaging Reporting and Data System developed for standardizing interpreting, reporting, and data collection of HCC describes 5 major features for accurate HCC diagnosis and several ancillary features, some favoring HCC in particular or malignancy in general and others favoring benignity. Untreated hepatic lesions LI-RADS affords 8 unique categories based on imaging appearance on computed tomography and magnetic resonance imaging, which indicate the possibility of HCC or malignancy with or without tumor in vein. Furthermore, LI-RADS defines 4 treatment response categories for treated HCCs after different locoregional therapy. These continuous recent updates on LI-RADS improve the communication between the radiologists and the clinicians for better management and patient outcome.

Interobserver Agreement of Magnetic Resonance Imaging of Liver Imaging Reporting and Data System Version 2018.

AIM: This study aimed to assess the interobserver agreement of magnetic resonance (MR) imaging of Liver Imaging Reporting and Data System version 2018 (LI-RADS v2018). SUBJECTS AND METHODS: Retrospective analysis was done for 119 consecutive patients (77 male and 42 female) at risk of hepatocellular carcinoma who underwent dynamic contrast MR imaging. Image analysis was done by 2 independent and blinded readers for arterial phase hyperenhancement, washout appearance, enhancing capsule appearance, and size. Hepatic lesions were classified into 7 groups according to LI-RADS v2018. RESULTS: There was excellent interobserver agreement of both reviewers for LR version 4 (κ = 0.887, P = 0.001) with 90.76% agreement. There was excellent interobserver agreement for nonrim arterial phase hyperenhancement (κ = 0.948; 95% confidence interval [CI], 0.89-0.99; P = 0.001), washout appearance (κ = 0.949; 95% CI, 0.89-1.0; P = 0.001); and enhancing capsule (κ = 0.848; 95% CI, 0.73-0.97; P = 0.001) and excellent reliability of size (interclass correlation, 0.99; P = 0.001). There was excellent interobserver agreement for LR-1 (κ = 1.00, P = 0.001), LR-2 (κ = 0.94, P = 0.001), LR-5 (κ = 0.839, P = 0.001), LR-M (κ = 1.00, P = 0.001), and LR-TIV (κ = 1.00; 95% CI, 1.0-1.0; P = 0.001), and good agreement for LR-3 (κ = 0.61, P = 0.001) and LR-4 (κ = 0.61, P = 0.001). CONCLUSION: MR imaging of LI-RADS v2018 is a reliable imaging modality and reporting system that may be used for standard interpretation of hepatic focal lesions.

Mansoura simple scoring system for prediction of spontaneous bacterial peritonitis: lesson learnt.

BACKGROUND AND OBJECTIVE: Spontaneous bacterial peritonitis (SBP) is a common bacterial infection with life-threatening sequelae in cirrhotic ascites. The purpose of this retrospective cohort study was to recognize the predictors of SBP to build up a noninvasive system to exclude or establish an episode of SBP. PATIENTS AND METHODS: Of 1194 consecutive patients with cirrhotic ascites, only 966 patients were enrolled in this study. SBP was diagnosed once polymorphonuclear count was at least 250 cells/mm and/or there was a positive ascitic fluid culture result. Biochemical and clinical parameters were evaluated as predictors of SBP. A scoring system was established in the training group of 682 and validated in a second group of 284 participants. RESULTS: The incidence of SBP was 12.3 and 12% in the training and validation groups, respectively. Age of at least 55 years, mean platelet volume (MPV) of at least 8.5 fl, neutrophil-to-lymphocyte ratio (NLR) of at least 2.5, and C-reactive protein (CRP) of at least 40 mg/l were identified as independent predictors of SBP. A scoring system including these four variables (age, MPV, and NLR with 1 point each, whereas CRP with 2 points) achieves a specificity of 98.2% with a positive predictive value for the diagnosis of SBP of 88.1% (score≥4). At a threshold of 1 point, the negative predictive value is 97.5% with a sensitivity of 92.9%. SBP is not associated with a high Model for End-stage Liver Disease score (P=0.135). CONCLUSION: The combination of age, MPV, NLR, and CRP in a simple scoring system, Mansoura simple scoring system, supports quick and accurate exclusion or diagnosis of SBP.

Helicobacter pylori and non-alcoholic fatty liver disease: A new enigma?

BACKGROUND AND AIM: The relationship between Helicobacter pylori (H. pylori) and nonalcoholic fatty liver disease (NAFLD) is a matter of debate. We achieved this prospective work to study whether H. pylori infection is a risk factor for NAFLD. METHODS: A cohort multicenter pilot study of 369 adults without NAFLD at baseline was followed up for 2 years. Serum leptin, insulin, tumor necrosis factor-α, adiponectin, and interleukin-6 were measured using an enzyme-linked immunosorbent assay (ELISA). Homeostasis model assessment of insulin resistance (HOMA-IR) and leptin/adiponectin ratio (LAR) were calculated. Fecal H. pylori antigen was measured by ELISA. A total of 127 participants with H. pylori positive were treated and then followed up for 3 months. RESULTS: Helicobacter pylori-positive patients (46.3%) were associated with an increase in IR, proinflammatory cytokines, C-reactive protein (CRP), LAR, NAFLD-liver fat score (NAFLD-LFS), and hepatic steatosis index (HSI) (all P < 0.01). Multivariate analysis of NAFLD according to HSI and NAFLD-LFS reported that presence of H. pylori, LAR, CRP, IL-6, smoking, and age (all P < 0.01) were independent risk factors for the presence of NAFLD. Multiple models adjusted for potential mediators or confounders such as metabolic, inflammatory, and biochemical factors were constructed. After therapy of H. pylori infection, there was a significant reduction in lipogenic profile, IR, leptin, LAR, CRP, proinflammatory cytokines, HSI, and NAFLD-LFS, as well as, increasing HDL. CONCLUSION: Helicobacter pylori infection was related to an increased risk of NAFLD development, through increased markers of IR, inflammatory mediators, and lipid metabolism. Moreover, its eradication can recover these NAFLD risk factors.

Rifaximin in nonalcoholic fatty liver disease: hit multiple targets with a single shot.

BACKGROUND/AIMS: The pathogenesis of nonalcoholic fatty liver disease (NAFLD) may include increased insulin resistance, upregulation of proinflammatory cytokines, lipopolysaccharide, and BMI. Rifaximin is a minimally absorbable antibiotic that might act against a broad spectrum of gut bacteria. This study aimed to investigate the effects of rifaximin on NAFLD. PATIENTS AND METHODS: Fifty participants with biopsy-proven nonalcoholic steatohepatitis (NASH) were registered in this multicentric, double-blind, randomized, placebo-controlled study. BMI, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, lipid profile, serum endotoxin, homeostatic model assessment, toll-like receptor-4, interleukin-10 (IL-10), IL-6, tumor necrosis factor-α, and cytokeratin-18 (CK-18) levels were evaluated at baseline and at 1, 3, and 6 months of rifaximin therapy (1100 mg/day). RESULTS: Patients were randomized into two groups (rifaximin group; n=25 and placebo group; n=25). After 6 months of rifaximin therapy, patients with NASH showed a significant reduction in homeostatic model assessment, alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, endotoxin, toll-like receptor-4, IL-6, tumor necrosis factor-α, CK-18, and NAFLD-liver fat score (all P<0.05), but no changes in the lipid profile; moreover, there was a mild nonstatistically significant reduction of BMI. However, in the placebo group, there was no significant difference in these variables at baseline and after therapy. CONCLUSION: Rifaximin therapy appears to be effective and safe in modifying NASH through reduction of serum endotoxin and improvement of insulin resistance, proinflammatory cytokines, CK-18, and NAFLD-liver fat score.

Do we need to screen for de-novo diabetes mellitus in chronic hepatitis C patients after a sustained virological response?

BACKGROUND AND AIM: There are millions of chronic hepatitis C (CHC) virus-infected patients who have been treated with a combination therapy (interferon and ribavirin) and have achieved a virological response (SVR) worldwide. The aim of this study is to evaluate the risk factors for de-novo diabetes mellitus in CHC patients treated with combination therapy (interferon and ribavirin) and have achieved an SVR. PATIENTS AND METHODS: A total of 214 nondiabetic CHC patients with SVR and baseline homeostasis model assessment (HOMA) less than or equal to 2 were divided into group A, which included 108 patients with a BMI less than 25, and group B, which included 106 patients with a BMI of at least 25 and less than 30. HOMA insulin resistance (IR) and BMI were measured at the baseline, at achievement of an SVR, and 1 year after achievement of an SVR. Leptin levels were assessed at baseline and 1 year after achievement of an SVR in patients with increased BMI. RESULTS: One year after SVR, 36 (33.33%) patients from group A developed increasing BMI with no significant changes in HOMA versus that at SVR (P=0.53), but showed a significant reduction versus baseline HOMA (P=0.02). In group B, 68 (64.1%) patients showed increased BMI of at least 25, with a significant increase in HOMA versus that at SVR (P=0.02), and with no significant reduction versus baseline HOMA (P=0.44). In group B, serum leptin showed a significant reduction 12 months after achievement of an SVR versus baseline in patients with increased BMI. Six patients from group B with increased BMI after 1 year developed de-novo IR and type two diabetes mellitus. CONCLUSION: In nondiabetic CHC patients with SVR and baseline BMI of at least 25, the post-SVR increase in BMI predisposed to an increase in HOMA-IR and could be considered a predisposing factor for diabetes mellitus.

A novel model using mean platelet volume and neutrophil to lymphocyte ratio as a marker of nonalcoholic steatohepatitis in NAFLD patients: multicentric study.

BACKGROUND AND AIM: Nonalcoholic fatty liver disease (NAFLD) is a leading cause of progressive and chronic liver injury. Mean platelet volume (MPV) and the neutrophil-lymphocyte ratio (N/L ratio) may be considered cheap and simple markers of inflammation in many disorders. We aimed to investigate the clinical utility of MPV and the N/L ratio to predict fibrosis in NAFLD patients and the presence of nonalcoholic steatohepatitis (NASH). MATERIALS AND METHODS: A total of 873 patients with biopsy-proven NAFLD and 150 healthy controls were included. Patients were divided into two groups: non-NASH group (n=753) and NASH group (n=120). Liver biopsy, MPV, lymphocyte, and neutrophil counts were registered; the N/L ratio was calculated. Proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) were measured by an ELISA. RESULTS: NASH patients had higher MPV compared with non-NASH patients (10.9±1.8 and 9.5±1.6 fl, respectively, P<0.001). MPV correlated positively with the NAFLD activity score, proinflammatory cytokines, and C-reactive protein (CRP) (P<0.001). Patients with advanced fibrosis (F3-4) had increased MPV (11.3±0.9 fl) compared with patients with early fibrosis (F1-2) (10.2±0.8 fl, P<0.001). NASH patients had an increased N/L ratio compared with non-NASH cases (2.6±1.1 and 1.9±0.7 fl, respectively, P<0.001). The N/L ratio correlated positively with NAFLD activity score, proinflammatory cytokines, and CRP (P<0.001). In addition, patients with advanced fibrosis (F3-4) had an N/L ratio (2.5±1.1) comparable with that of patients with early fibrosis (F1-2) (1.8±0.9) (P<0.001). CONCLUSION: MPV and the N/L ratio were elevated in NASH patients versus non-NASH cases, and in patients with advanced fibrosis (F3-4) versus early fibrosis (F1-2). They can be used as noninvasive novel markers to predict advanced disease.