The NAFLD-MAFLD debate: Eminence vs evidence.

Debates are inevitable in science and could be a powerful tool for addressing controversial topics as it promotes critical thinking and inspires individuals to consider alternate viewpoints. However, debates can help only to identify the issues that need to be clarified to address this question, but it can never help resolve the controversy itself. In the era of evidence-based medicine, the need for an evidence-based debate is mandatory. Polarising opinions and major debate have recently arisen in hepatology on the nomenclature and diagnostic criteria for fatty liver disease associated with metabolic dysfunction (non alcoholic fatty liver disease [NAFLD]-metabolic (dysfunction) associated fatty liver disease [MAFLD] debate). The aim of this viewpoint is to suggest a way to settle the debate through evidence. Descriptive review using PubMed to identify literature on the evidence and eminence-based medicine and studies comparing MAFLD and NAFLD criteria. The emerging studies comparing the performance of diagnostic criteria of NAFLD and MAFLD represent the dawn of a new era for reframing the ongoing debate by acquisition of the mandatory evidence that will both resolve the debate and lead to novel avenues of research. In conclusion, the time has come to hold debate and focus on gathering and building the evidence to settle it. It does not matter who wins the debate and once there is robust evidence, we should all follow it wherever it leads.

Ramadan fasting and liver diseases: A review with practice advices and recommendations.

Ramadan fasting is obligatory for Muslim healthy adults. However, there are many exemptions from fasting; including patients, whose diseases will be aggravated by fasting. Muslim patients with different liver diseases are frequently seen in the clinics discussing their intent to fast this month with their treating physicians. To answer our patients' inquiries about the expected benefits and/or risks of fasting and delivering them the best care, we carried out this review and we draw advices and recommendations based on the available evidence. A web-based search, combining multiple keywords representing different liver diseases with Ramadan fasting had been carried out. To answer the research question: Do adult Muslim patients with different liver diseases who fast the month of Ramadan have had a deleterious effect on their health in comparison to those who did not fast? Relevant publications were retrieved. No randomized controlled trials were focusing on Ramadan fasting and liver diseases in the filtered databases, eg Cochrane library. Consequently, non-filtered databases, eg PubMed, Google Scholar and Egyptian Knowledge Bank searched and full-text high-quality research articles were carefully analysed to draw recommendations. Other relevant publications with low quality of evidence like case studies and short communications were also reviewed to address practice advices. Although Ramadan fasting was found beneficial for patients with NAFLD, it was found deleterious to patients with Child B and C cirrhosis and patients with peptic ulcer. Patients with chronic hepatitis, Child A cirrhosis and those with non-complicated liver transplant can fast with prefasting assessment and strict follow up.

High success rates for the use of sofosbuvir/ombitasvir/paritaprevir/ritonavir + ribavirin and sofosbuvir/simeprevir/daclatasvir + ribavirin in retreatment of chronic hepatitis C infection after unsuccessful sofosbuvir/daclatasvir therapy: a real-life experience.

The aim of this work was assessment of the efficacy and tolerability of two different regimens for retreatment of hepatitis C virus (HCV) patients who failed to respond to SOF/DCV-based therapy. This prospective study included 104 HCV patients who failed to respond to SOF/DCV-based therapy. Patients were randomly allocated to two groups. Efficacy and tolerability were assessed. The 12-week sustained virological response (SVR12) rates were 96% and 94.4% in groups B and A, respectively, with no significant difference (p = 1.000). Most adverse events reported were mild to moderate, with no deaths during the study. Multi-target direct-acting antiviral (DAA) combinations are efficient for retreatment of HCV patients after failure of SOF/DCV-based therapy in real-world management.ClinicalTrials.gov identifier: NCT02992457.

Vibration Controlled Transient Elastography in Screening for Silent Liver Diseases.

OBJECTIVES: The objective of this study was to screen for significant hepatic fibrosis or steatosis in asymptomatic, apparently healthy subjects by using Vibration-controlled transient elastography and controlled attenuation parameter (CAP). METHODS: Prospectively, 433 asymptomatic apparently healthy adults were included. Fibroscan/CAP examination was performed for all of them. Subjects with liver stiffness measurement > 6 kPa or CAP >248 dB/m were further evaluated to assess underlying chronic liver disease. RESULTS: According to fibroscan/CAP examination, subjects were classified into four subgroups: normal (119) with CAP score of 215.85 ± 24.81 dB/m and fibrosis score of 4.47 ± 0.81 kPa, subjects with steatosis only 133 with CAP score of 309.41 ± 42.6 dB/m and fibrosis score of 4.74 ± 0.82 kPa, subjects with both steatosis and fibrosis 95 with CAP score of 318.20 ± 39.89 dB/m and fibrosis score of 7.92 ± 2.58 kPaand subjects with fibrosis only 86 with CAP score of 213.48 ± 22.62 dB/m and fibrosis score of 6.96 ± 1.11 kPa. S0 was present in 205 (47.3%), S1 in 48 (10.2%), S2 in 16 (3.7%) and S3 in 168 (38.8%) of studied subjects, whereas F0-1 was present in 371 (85.7%), F2 in 44 (10.16%), F3 in 16 (3.7%) subjects and F4 in only one (0.23%) subject. Subjects with both steatosis and fibrosis showed significantly higher transaminases, triglycerides and total cholesterol levels than other subgroups. CONCLUSIONS: Most asymptomatic, apparently healthy subjects (72%) have significant steatosis and fibrosis. Liver stiffness measurement and CAP might represent promising first-line noninvasive procedures to screen for silent liver diseases in the general population.

Hepatologists' awareness and knowledge toward NAFLD and the familiarity with renaming from NAFLD to MAFLD.

BACKGROUND & AIMS: Non-alcoholic fatty liver disease (NAFLD) is an emerging epidemic; it is a negative diagnosis that depends mainly on the presence of hepatic steatosis with or without inflammation after exclusion of other chronic liver diseases and excess alcohol intake. However, the new definition of MAFLD is a shift towards a diagnosis of inclusion based on the presence of metabolic dysfunction, regardless of alcohol consumption or other concomitant liver diseases. Given the growing relevance of the disease, data on hepatologists' views and understanding of NAFLD are limited, we aimed to determine hepatologists' awareness and expertise of NAFLD screening, diagnosis, and therapeutic options as well as the influence of changing the NAFLD name to MAFLD on awareness of the fatty liver disease (FLD). OBJECTIVE: Most of the hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, necessitating a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer a better awareness of FLD. METHODS: A multicenter online questionnaire of 655 hepatologists was carried out, giving a sample of 207 respondents. A survey composed of 36 questions was used to assess the level of hepatologists' awareness and practices in the screening, diagnosis, and management of NAFLD/MAFLD, as well as their familiarity with the nomenclature change from NAFLD to MAFLD. RESULTS: A total of 207 hepatologists were included, of which 107 (51.4%) were males, with a mean age was 36.4 years. 50.2% (n=104) of the hepatologists were oriented with NAFLD. Only 41 (19.8%) realized that NAFLD may frequently result in severe hepatic disease. NAFLD is rarely screened by the majority of the participating hepatologists (118, 57%), and (135, 65.2%) of them use liver biopsy for diagnosis of NAFLD. In (104, 50.2%) of hepatologists, changing the nomenclature of NAFLD was relatively familiar. Furthermore, 71.9% of hepatologists thought that the new nomenclature offers a better awareness of FLD. CONCLUSION: A small percentage of hepatologists agreed that NAFLD can cause serious hepatic illness and may be linked to metabolic risk factors, and around half of them realize that NAFLD necessitates a multidisciplinary approach to treatment. Hepatologists have a poor understanding of NAFLD care. The shift in terminology from NAFLD to MAFLD will be more known to hepatologists, and it may offer better awareness of FLD.

RECK gene polymorphisms in hepatitis B-related hepatocellular carcinoma: A case-control study.

BACKGROUND AND STUDY AIMS: Chronic hepatitis B (CHB) infection is a major risk factor for hepatocellular carcinoma (HCC). The RECK gene is a critical tumor suppressor gene. This study aimed to assess the association between RECK gene single nucleotide polymorphisms (SNPs) and the development of HCC in Egyptian patients with chronic hepatitis B. PATIENTS AND METHOD: In this case-control study, we enrolled patients with CHB from the Gastroenterology Department, Benha University, from June 2016 to February 2018. The RECK gene SNP rs10814325 was identified using real-time PCR allelic discrimination via TaqMan SNP genotyping assays (Applied Biosystems, USA). RESULTS: We enrolled 140 participants in this study. The participants were divided into Group I, which comprised 50 participants with CHB only, Group II, which comprised 50 participants with CHB and HCC, and Group III, which comprised 40 healthy participants. A significantly higher hepatitis B virus DNA viremia level was found in patients with HCC. The predominant RECK genotype was the T/T allele, followed by the T/C allele; however, no significant difference in the distribution of RECK gene SNPs was found between the study groups. No statistically significant difference in RECK gene SNPs was reported among patients with HCC of different Child classes or based on the number, site, size of HCC, and lymph node involvement. Receiver operating characteristic curves showed that a serum alpha-fetoprotein level of 92 ng/ml was 96 % sensitive and 100 % specific for the detection of HCC, with an area under the operating characteristic curve of 0.98. CONCLUSION: RECK gene SNPs have no significant association with the development and characteristics of hepatitis B-related HCC in Egyptian patients.

Serum Vitamin D Levels in Chronic Hepatitis B Patients Before and During Treatment.

BACKGROUND & AIMS: Hepatitis B is a potentially life-threatening liver infection and it is a major global health problem. Over the past decade, numerous studies have reported that patients with CLD, especially HCV-positive and HBV-positive patients, have decreased 25(OH) D levels. The current study was designed to assess the serum levels of vitamin D [25(OH) D3] in chronic hepatitis B patients, before and during treatment with antiviral therapy. METHODS: It was a prospective study in which 80 subjects were enrolled between December 2017 and June 2018. A total of 50 treatment-naïve chronic HBV patients and 30 healthy subjects were recruited. The studied cases received treatment in the form of Lamivudine 100 mg tablet, once daily. Full routine laboratory investigations, HBV DNA measurement by real-time PCR were conducted once before initiation of antiviral treatment and again at least 6 months later. Serum vitamin D level [25(OH)D3 was assessed twice, once before initiation of antiviral treatment and again at least 6 months later. This was done for all the patients enrolled in the study. RESULTS: The studied cases showed a significantly low mean serum Vitamin D level when assessed before treatment (21.6 ± 5.8 ng/ml), compared to the level after 6 ms of treatment (31.1 ± 7.3 ng/ml) which was comparable to that of the control group (33.4 ± 5 ng/ml). CONCLUSION: The present study highlights the impact of antiviral therapy on vitamin D deficiency in CHB patients, where effective therapy improves vitamin D levels. Meanwhile, it is recommended to study the impact of vitamin D replacement and correction on the disease progression or regression.

Hepatitis C Virus: Efficacy of New DAAs Regimens.

BACKGROUND: HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM: To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS: A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS: Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION: HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.

Evaluation of liver steatosis, measured by controlled attenuation parameter, in patients with hepatitis C-induced advanced liver fibrosis and hepatocellular carcinoma.

INTRODUCTION: Steatosis is a documented feature of chronic hepatitis C (CHC). There is an association between steatosis decrease and fibrosis progression. The association between steatosis and advanced fibrosis versus hepatocellular carcinoma (HCC) development has not been precisely evaluated. The controlled attenuation parameter (CAP) was applied as an immediate and efficient process to detect and quantify hepatic steatosis with adequate accuracy. AIMS: The aim of this study was to assess the difference in liver steatosis between patients with hepatitis C virus-related advanced hepatic fibrosis versus HCC. PATIENTS AND METHODS: This cross-sectional study included 130 patients with HCC, attending the multidisciplinary HCC clinic, Cairo University, and 54 patients with CHC between October 2015 and June 2016. Clinical and laboratory characteristics were recorded. Liver stiffness and CAP were obtained by using the FibroScan 502, touch. RESULTS: All included patients had genotype 4. The mean CAP value was significantly lower in HCC (209.5±57.1 dB/m) versus CHC (259.9±54.9 dB/m). Receiver operating characteristic curve revealed an area under the curve of 0.75 for the differentiation between groups. At a cutoff value of 237 dB/m, sensitivity was 72.3%, specificity was 70.7%, positive likelihood ratio was 2.5, and negative likelihood ratio was 0.4 in the differentiation between CHC versus HCC. Logistic regression analysis revealed an odds ratio of 6.4 for the diagnosis of HCC with CAP of less than 237 dB/m. Multivariate analysis, controlling for age, sex, BMI, triglycerides, and cholesterol levels, revealed a significantly increased odds for HCC diagnosis (odds ratio: 4.3, P=0.006). CONCLUSION: The progression of CHC is associated with a decrease in steatosis, particularly toward advanced fibrosis and HCC. Steatosis reduction less than 237 dB/m is likely to be associated with HCC.

Interleukin-18 and its gene single nucleotide polymorphisms (SNPs) influence chronic hepatitis C progression.

INTRODUCTION: Interleukin-18 (IL-18) is a pro-inflammatory cytokine that is induced by hepatitis C virus (HCV) infection. Inter-individual variations of IL-18 gene expression may alter HCV-associated liver injury. Variable single nucleotide polymorphisms (SNPs) have been detected within IL-18 gene sequence. Quantitative assessment of IL-18 plasma level and detection of genotype frequencies of 2 functional polymorphisms of its gene (-607 C/A and -137 G/C) were done to assess their impact on the severity of chronic hepatitis C (CHC). METHODOLOGY: Cases group (I) comprised 110 treatment naïve CHC Egyptian patients (78 Males and 32 Females, mean age = 40.7 ± 11.8 years) who underwent routine laboratory investigations. Assessment of plasma level of IL-18 was done by enzyme-linked immunosorbent assay (ELISA), detection of IL-18 gene polymorphisms at positions -607 C/A and -137 G/C by polymerase chain reaction sequence specific polymorphism (PCR-SSP) analysis and Liver biopsy with METAVIR scoring were done. The control group (II) comprised 90 healthy participants. RESULTS: Plasma levels of IL-18 were significantly higher in cases than the control group. We found a statistically highly significant (p < 0.001) positive correlation between IL-18 plasma level and both METAVIR necro-inflammatory grade and fibrosis stage. The A/A allele at -607 position was significantly more frequent (p < 0.05) in patients with F ≤ 1. CONCLUSIONS: Higher IL-18 plasma levels are found in CHC patients and positively correlate with the severity of liver disease. The presence of A/A allele at -607 position of IL-18 gene promoter is associated with milder liver disease.

Assessment of liver fibrosis in Egyptian chronic hepatitis B patients: A comparative study including 5 noninvasive indexes.

Fibrosis assessment in chronic hepatitis B (CHB) is essential for prediction of long-term prognosis and proper treatment decision. This study was conducted to assess predictability of 5 simple noninvasive fibrosis indexes in comparison to liver biopsy in CHB patients.A total of 200 CHB adult Egyptian patients were consecutively included in this study, all were subjected to liver biopsy with staging of fibrosis using METAVIR scoring system. Fibrosis indexes including S-index, red cell distribution width to platelets ratio index (RPR), fibrosis-4 index (Fib-4), AST to platelets ratio index (APRI), and AST/ALT ratio index (AAR) were compared to biopsy result and their predictabilities for the different fibrosis stages were assessed using area under receiver operating characteristic curve (AUROC) analysis.S-index showed the highest AUROCs for predicting fibrosis among the studied indexes. AUROCs of S-index, RPR, Fib-4, APRI, and AAR were: 0.81, 0.67, 0.70, 0.68, and 0.60 for prediction of significant fibrosis (F2-F4), 0.90, 0.66, 0.68, 0.67, and 0.57 for advanced fibrosis (F3-F4), and 0.96, 0.62, 0.61, 0.57, and 0.53 for cirrhosis (F4), respectively. The optimal S-index cutoff for ruling in significant fibrosis was ≥0.3 with 94% specificity, 87% PPV, and 68% accuracy, while that for ruling out significant fibrosis was <0.1 with 96% sensitivity, 91% NPV, and 67% accuracy. Accuracy of S-index was higher for predicting cirrhosis (91%) than that for predicting advanced fibrosis (79%) and significant fibrosis (68%).S-index has the highest predictability for all fibrosis stages among the studied fibrosis indexes in HBeAg-negative CHB patients, with higher accuracy in cirrhosis than in the earlier fibrosis stages.

Serum Vitamin D Levels in Treatment-naïve Chronic Hepatitis B Patients.

BACKGROUND AND OBJECTIVES: According to the demographic health survey conducted in 2015, Egypt had 10% documented prevalence of anti-HBc positive patients aged 1-59 and 1% viremic patients amongst the population in the same age group, with a domination of genotype D. Several studies claimed the possible role of vitamin D deficiency in hepatitis B virus (HBV) replication and disease progression. PATIENTS AND METHODS: Serum vitamin D levels [25(OH D3] were assessed in 96 HBeAg negative non-cirrhotic chronic HBV patients and 25 healthy subjects classified as following: Group I: 48 chronic HBV patients with persistently normal ALT levels and HBV DNA level < 2000 IU/mL for ≥ 6 months; Group II: 48 chronic HBV patients with CHB with persistently elevated ALT and HBV DNA level ≥ 2000 IU/mL for ≥ 6 months; and Group III: 25 apparently healthy subjects with normal liver enzymes and negative hepatitis viral markers were taken as the control group. RESULTS: Vitamin D was much more deficient in group II than in group I and group III being 11.55 ± 3.97 ng/mL, 15.03 ± 3.45, 27.00 ± 6.76 ng/mL (P < 0.001), respectively, and a strong negative correlation was observed between vitamin D levels and HBV DNA levels (P = 0.043) in groups I and II. CONCLUSION: The current study showed high HBV DNA replication in patients with vitamin D deficiency suggesting the antimicrobial immunomodulatory role of vitamin D.

Clinical significance of vascular endothelial growth factor in hepatitis C related hepatocellular carcinoma in Egyptian patients.

BACKGROUND AND AIMS: Several angiogenic factors are involved in the development and progression of hepatocellular carcinoma (HCC), a hypervascular tumor. Vascular endothelial growth factor (VEGF) is a primary driving force for angiogenesis, and its overexpression has been reported in HCC. However, the significance of plasma and tissue VEGF levels in HCC in Egyptian patients with chronic hepatitis C (CHC) infection is understudied. The aim of this study was to evaluate the role of VEGF (measured in plasma and liver tissue) in patients with hepatitis C virus-related HCC and to assess its significance in the diagnosis and prognosis of HCC. MATERIALS AND METHODS: A total of 90 subjects were studied. Among 90 subjects, 60 with CHC were examined and were subdivided into two groups: 30 patients with CHC-related HCC (HCC group) and 30 patients with CHC without HCC (non-HCC group). Thirty apparently healthy subjects served as the control group. VEGF was estimated in plasma by enzyme-linked immunosorbent assay and its expression in liver tissue was evaluated by real-time polymerase chain reaction. VEGF expression level and its relationship to tumor parameters, patients' liver function profile, and patients' clinical parameters were also investigated. RESULTS: Plasma VEGF levels in the HCC group were significantly higher than those of the non-HCC group, and both groups had significantly higher plasma VEGF levels than did the control group. Liver tissue VEGF expression was significantly higher in the HCC group than in the non-HCC group and positively correlated with plasma VEGF in the HCC group. The plasma VEGF levels were positively correlated with patients' age, aspartate aminotransferase levels, serum alpha-fetoprotein levels, the presence of portal vein thrombosis, and the number of hepatic focal lesions in the HCC group. However, plasma VEGF levels were not significantly correlated with the Child-Pugh score, alanine aminotransferase levels, the size of focal lesions, and Okuda stage. Using both the VEGF and alpha-fetoprotein levels to detect HCC maximizes the sensitivity and specificity. CONCLUSION: Plasma levels of VEGF may be a useful diagnostic and prognostic marker for HCC in patients who have been diagnosed with CHC.