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.

Uniting the Global Gastroenterology Community to Meet the Challenge of Climate Change and Nonrecyclable Waste.

Climate change has been described as the greatest public health threat of the 21st century. It has significant implications for digestive health. A multinational team with representation from all continents, excluding Antarctica and covering 18 countries, has formulated a commentary which outlines both the implications for digestive health and ways in which this challenge can be faced.

Africa Guidelines for Hepatocellular Carcinoma Buildup Process.

PURPOSE: Hepatocellular carcinoma (HCC), the fourth most common cancer in Africa, has a dismal overall survival of only 3 months like in sub-Saharan Africa. This is affected by the low gross domestic product and human development index, absence of coherent guidelines, and other factors. METHODS: An open forum for HCC-experienced health care workers from Africa and the rest of the world was held in October 2021. Participants completed a survey to help assess the real-life access to screening, diagnoses, and treatment in the North and Southern Africa (NS), East and West Africa (EW), Central Africa (C), and the rest of the world. RESULTS: Of 461 participants from all relevant subspecialties, 372 were from Africa. Most African participants provided hepatitis B vaccination and treatment for hepatitis B and C. More than half of the participants use serum alpha-fetoprotein and ultrasound for surveillance. Only 20% reported using image-guided diagnostic liver biopsy. The Barcelona Clinic Liver Cancer is the most used staging system (52%). Liver transplant is available for only 28% of NS and 3% EW. C reported a significantly lower availability of resection. Availability of local therapy ranged from 94% in NS to 62% in C. Sorafenib is the most commonly used systemic therapy (66%). Only 12.9% reported access to other medications including immune checkpoint inhibitors. Besides 42% access to regorafenib in NS, second-line treatments were not provided. CONCLUSION: Similarities and differences in the care for patients with HCC in Africa are reported. This reconfirms the major gaps in access and availability especially in C and marginally less so in EW. This is a call for concerted multidisciplinary efforts to achieve and sustain a reduction in incidence and mortality from HCC in Africa.

Egyptian Society of Liver Cancer Recommendation Guidelines for the Management of Hepatocellular Carcinoma.

Globally, hepatocellular carcinoma (HCC) is the fourth most common cause of death from cancer. The prevalence of this pathology, which has been on the rise in the last 30 years, has been predicted to continue increasing. HCC is the most common cause of cancer-related morbidity and mortality in Egypt and is also the most common cancer in males. Chronic liver diseases, including chronic hepatitis C, which is a primary health concern in Egypt, are considered major risk factors for HCC. However, HCC surveillance is recommended for patients with chronic hepatitis B virus (HBV) and liver cirrhosis; those above 40 with HBV but without cirrhosis; individuals with hepatitis D co-infection or a family history of HCC; and Nonalcoholic fatty liver disease (NAFLD) patients exhibiting significant fibrosis or cirrhosis. Several international guidelines aid physicians in the management of HCC. However, the availability and cost of diagnostic modalities and treatment options vary from one country to another. Therefore, the current guidelines aim to standardize the management of HCC in Egypt. The recommendations presented in this report represent the current management strategy at HCC treatment centers in Egypt. Recommendations were developed by an expert panel consisting of hepatologists, oncologists, gastroenterologists, surgeons, pathologists, and radiologists working under the umbrella of the Egyptian Society of Liver Cancer. The recommendations, which are based on the currently available local diagnostic aids and treatments in the country, include recommendations for future prospects.

Tumor necrosis factor-alpha -308G/A polymorphism and risk of hepatocellular carcinoma in hepatitis C virus-infected patients.

Tumor necrosis factor-alpha (TNF-α) is an important cytokine in generating an immune response against infection with hepatitis C virus (HCV). The functions of TNF-α may be altered by single-nucleotide polymorphisms (SNPs) in its gene structure. We hypothesized that SNPs in TNF-α may be important in determining the outcome of an HCV infection. To test this hypothesis, we investigated the role of the polymorphism -308G/A, which is located in the promoter region of the TNF-α gene, in the progression of HCV infection in Egyptian patients using a quantitative real-time polymerase chain reaction (qRT-PCR). The distribution of this polymorphism and its impact on the serum level of TNF-α was compared between 90 HCV-infected patients [45 with HCV-induced cirrhosis and 45 with HCV-related hepatocellular carcinoma (HCC)] and 45 healthy Egyptian volunteers without any history of liver disease. Our results showed that at the TNF-α -308 position, the G/G allele was most common (78.5%) in the study population, with the G/A and A/A alleles occurring less frequently (13.3% and 8.1%, respectively). Frequencies of G/G, G/A, and A/A genotypes were 87%, 7%, and 6% in patients with liver cirrhosis and were 94%, 4%, and 2% in patients with HCC, respectively. Serum levels of TNF-α were significantly higher in HCV-infected patients than in healthy controls, indicating that the TNF-α -308 polymorphism does not influence the production of TNF-α. The serum level of TNF-α was positively correlated with HCV infection. Taken together, these findings suggest that the TNF-α -308 polymorphism may not be a host genetic factor associated with the severity of HCV infection, but may be an independent risk factor for HCC.

Role of Climate Change in Changing Hepatic Health Maps.

PURPOSE OF REVIEW: Climate change (CC) is currently responsible for global weather extremes. These weather extremes could contribute to changes in the pattern of health problems. The purpose of this review is to discuss the role of CC on remapping of hepatic diseases and the mechanisms of re-mapping. RECENT FINDINGS: CC was found to have a major influence on the distribution and severity of hepatic diseases, such as outbreaks of vector-borne, water or food-borne, parasitic diseases, re-emerging of disappeared diseases, or emerging of new forms of infectious agents. Migration of infected people from endemic areas due to the CC disasters results in rapid dissemination of infectious diseases that leads to outbreaks or endemicity of diseases in new areas. CC could cause increasing chemical emissions, or change in its biodegradability, or restriction in its dispersion, such as PM, PAHs, heavy metals, mycotoxins, and aquatic toxins. Increase in the concentrations of these chemicals may have significant impacts in changing the health map of hepatic toxicity and liver cancer. The current review confirms the role of CC in changing the pattern of several liver health problems and remapping of these problems in several regions of the world. This review could be of high importance to the health decision-makers as an early alarm and prediction of hepatic health problems with the projected CC.

The egyptian clinical practice guidelines for the diagnosis and management of metabolic associated fatty liver disease.

The landscape of chronic liver disease in Egypt has drastically changed over the past few decades. The prevalence of metabolic-associated fatty liver disease (MAFLD) has risen to alarming levels. Despite the magnitude of the problem, no regional guidelines have been developed to tackle this disease. This document provides the clinical practice guidelines of the key Egyptian opinion leaders on MAFLD screening, diagnosis, and management, and covers various aspects in the management of MAFLD. The document considers our local situations and the burden of clinical management for the healthcare sector and is proposed for daily clinical practical use. Particular reference to special groups was done whenever necessary.

Challenges During Review of COVID-19 Research Proposals: Experience of Faculty of Medicine, Ain Shams University Research Ethics Committee, Egypt.

The COVID-19 pandemic resulted in an overwhelming increase in research studies submitted to research ethics committees (RECs) presenting many ethical challenges. This article aims to report the challenges encountered during review of COVID-19 research and the experience of the Faculty of Medicine, Ain Shams University Research Ethics Committee (FMASU REC). From April 10, 2020, until October 13, 2020, the FMASU REC reviewed 98 COVID-19 research protocols. This article addressed the question of how to face an overwhelming amount of research submitted to the REC while applying the required ethical principles. Ethical challenges included a new accelerated mode of review, online meetings, balance of risks vs. benefits, measures to mitigate risks, co-enrolment in different studies, protection of a vulnerable COVID-19 population, accelerated decisions, online research, how to handle informed consent during the pandemic, and justification of placebo arm.

Diabetes Association with Liver Diseases: An Overview for Clinicians.

BACKGROUND: There is a strong association between liver diseases and diabetes (DM) which is higher than expected by a correlation between two very common diseases. Liver diseases may occur as a result of diabetes, and the reverse is true as well. AIM: To review the etiology of this association between liver diseases and diabetes and how to diagnose it. METHODS: Studies that identified this association between liver diseases and diabetes and how to diagnose it was reviewed. RESULTS: This association can be divided into the following categories: liver disease related to diabetes (Diabetic hepatopathy), hepatogenous diabetes (HD), and liver diseases that occur in conjunction with Diabetes mellitus. Two hours after glucose loading is the best screening test for HD. HbA1c may neither be suitable for diagnosis nor monitoring of diabetes that links liver disease. CONCLUSION: NAFLD, hepatogenous diabetes, glycogenic hepatopathy and diabetic hepatosclerosis are the most important association between liver diseases and diabetes. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is the best screening test for HD due to the fact that fasting glucose can be normal early in the disease. The tool used for diabetes monitoring depends on stage and severity of liver condition.

Managing diabetes and liver disease association.

There is strong association between liver diseases and diabetes (DM) which is higher than expected by a chance association of two very common disorders. It can be classified into three categories: Liver disease related to diabetes, hepatogenous diabetes (HD), and liver disease occurring coincidentally with DM. The criteria for the diagnosis of diabetes associating liver disease are the same for primary diabetes. Two hours post glucose load is a better screening test for HD. HbA1c may not be suitable for diagnosis or monitoring of diabetes associating advanced liver disease. Apart from the increased cardiovascular risk in patients with type 2 DM (T2 DM) and NAFLD, the cardiovascular and retinopathy risk is low in HD. Patients with metabolic derangement should be screened for NAFLD which in turn may predict T2 DM development. Similarly, patients with established T2 DM should also be screened for NAFLD which further contributes to diabetes worsening. Diabetes is a significant risk factor for progression of the chronic liver disease. It is associated with poor patient survival. Treatment of diabetes associating liver disease appears beneficial. Metformin, if tolerated and not contraindicated, is recommended as a first-line therapy for patients with diabetes and chronic liver disease (CLD). If the hepatic disease is severe, insulin secretagogues should be avoided because of the increased risk of hypoglycaemia. Pioglitazone may be useful in patients with fatty liver disease. DPP-4 inhibitors showed effectiveness and safety for the treatment of T2 DM in CLD patients up to those with child B stage. GLP-1 receptor agonists and SGLT-2 inhibitors exhibit positive effects on weight and are associated with minimal risk of hypoglycaemia. Insulin must be used with caution, as hypoglycaemia may be a problem. Insulin analogues are preferred in the context of hypoglycaemia Statins can be used to treat dyslipidaemia in NAFLD, also the use of angiotensin II receptor antagonist for hypertension is safe and beneficial Given the clear association between diabetes mellitus and hepatocellular carcinoma, the strict control of glycaemia with insulin sensitizers can be essential in its prevention. The addition of DM to the currently used scores (Child-Pugh and MELD scores) may enhance the sensitivity and the specificity for prediction of morbidity and mortality rates in cirrhotic patients. In the new era of directly acting antiviral agents (DAAs) for HCV treatment, it is recommended to follow up lipid profile and blood sugar levels following SVR in order to adjust doses of medications used in diabetic (SVR is associated with reduction in insulin requirements) and dyslipidaemic patients (rebound increase in the lipid profile after clearing the virus may increase risk of cardiovascular disease (CVD)). The issues of post liver transplant diabetes and relation between DM and chronic HBV are highlighted. This narrative review and Consensus-based practice guidance (under revision and criticism) are based on a formal review and analysis of the recently published world literature on the topic (Medline search up to September 2017); and the experience of the authors and independent reviewers.

Effect of endoscopic variceal obliteration by band ligation on portal hypertensive gastro-duodenopathy: endoscopic and pathological study.

INTRODUCTION AND AIM: A few studies have shown that the degree of portal hypertensive gastropathy (PHG) and duodenopathy (PHD) has been worsening after the introduction of therapeutic endoscopic interventions. This study aimed to determine the impact of esophageal variceal eradication by endoscopic variceal ligation (EVL) on PHG and PHD using endoscopic and histopathologic assessment. METHODS: Fifty patients with esophageal varices for which EVL was indicated were included. EVL was carried out until complete variceal eradication was achieved. The degree of severity of PHG and PHD were recorded before and 4 weeks after variceal eradication. Biopsies were taken from various parts of the stomach and duodenum before and 4 weeks after variceal eradication. RESULTS: The whole Baveno score (4 vs. 2.5) increased significantly after variceal eradication when compared to those before eradication (p < 0.05). After obliteration, only 19 (38 %) patients had mild PHG versus 37 (74 %) before EVL, while severe PHG was found in 31 (62 %) patients versus 11 (22 %) before EVL and the difference was highly statistically significant. No significant changes were found regarding endoscopic PHD lesions before and after variceal eradication. Pathological changes as average blood vessel count, angiogenesis, ectasia and blood extravasation in stomach and duodenum significantly increased after EVL. Large esophageal varices (III-IV) and Baveno score (>1) at baseline endoscopy were independent risk factors for development of severe PHG after variceal obliteration (p < 0.05). CONCLUSION: PHG increased significantly, endoscopically and pathologically, after variceal obliteration by EVL. Although PHD did not significantly change as documented by endoscopy, pathological examination documented statistically significant changes in the duodenum after EVL.

N-butyl-2-cyanoacrylate, iso-amyl-2-cyanoacrylate and hypertonic glucose with 72% chromated glycerin in gastric varices.

AIM: To compare n-butyl-2-cyanoacrylate, iso-amyl-2-cyanoacrylate and a mixture of 72% chromated glycerin with hypertonic glucose solution in management of gastric varices. METHODS: Ninety patients with gastric varices presented to Endoscopy Unit of Ain Shams University Hospital were included. They were randomly allocated into three groups; each group included 30 patients treated with intravariceal sclerosant injections in biweekly sessions till complete obturation of gastric varices; Group I (n-butyl-2-cyanoacrylate; Histoacryl(®)), Group II (iso-amyl-2-cyanoacrylate; Amcrylate(®)) and Group III (mixture of 72% chromated glycerin; Scleremo(®) with glucose solution 25%). All the procedures were performed electively without active bleeding. Recruited patients were followed up for 3 mo. RESULTS: 26% of Scleremo group had bleeding during puncture vs 3.3% in each of the other two groups with significant difference, (P < 0.05). None of Scleremo group had needle obstruction vs 13.3% in each of the other two groups with no significant difference, (P > 0.05). Rebleeding occurred in 13.3% of Histoacryl and Amcrylate groups vs 0% in Scleremo group with no significant difference. The in hospital mortality was 6.6% in both Histoacryl and Amcrylate groups, while it was 0% in Scleremo group with no significant difference. In the first and second sessions, the amount of Scleremo needed for obturation was significantly high, while the amount of Histoacryl was significantly low. Scleremo was the less costly of the two treatments. CONCLUSION: All used sclerosant substances showed efficacy and success in management of gastric varices with no significant differences except in total amount, cost and bleeding during puncture.

Causes and outcome of upper gastrointestinal bleeding in Emergency Endoscopy Unit of Ain Shams University Hospital.

This prospective follow-up study was designed to analyze the causes and outcome of upper gastrointestinal bleeding among patients presenting by hematemesis and/or melena to Emergency Endoscopy Unit, Ain Shams University Hospitals. One thousand patients presented by upper GIT bleeding were subjected to complete clinical evaluation, emergency upper gastrointestinal endoscopy and therapeutic interventions as indicated. Follow up was done for occurrence of re-bleeding or mortality. Variceal causes of bleeding were the most common, representing 70.1% followed by non-variceal causes (26.1%) and obscure causes (3.8%). Esophageal varices (EV) alone represented 17.8% of causes of variceal bleeding, while combined esophageal and gastric varices represented 39.5% and isolated gastric varices 12.8%. Gastric lesions were the most common causes of non variceal bleeding. Recurrence of bleeding occurred in 19.4% of variceal group in comparison to 6.1% of non variceal group, while mortality was found in 4.3% of variceal group in comparison to 1.5% of non variceal group with very highly significant difference (P <0.001). Hypertension, ascites, EV columns, EV grade IV, presence of gastric varices and associated respiratory disorder were independent factors associated with recurrence of bleeding in variceal group. In non variceal group, recurrence of bleeding was significantly related only to the presence of gastric ulcers (P=0.035). Independent factors associated with mortality in studied patients were age, associated diabetes, presence of esophageal varices and associated duodenal ulcer.

Liver fibrosis: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL).

Liver fibrosis is a common pathway leading to cirrhosis, which is the final result of injury to the liver. Accurate assessment of the degree of fibrosis is important clinically, especially when treatments aimed at reversing fibrosis are being evolved. Liver biopsy has been considered to be the "gold standard" to assess fibrosis. However, liver biopsy being invasive and, in many instances, not favored by patients or physicians, alternative approaches to assess liver fibrosis have assumed great importance. Moreover, therapies aimed at reversing the liver fibrosis have also been tried lately with variable results. Till now, there has been no consensus on various clinical, pathological, and radiological aspects of liver fibrosis. The Asian Pacific Association for the Study of the Liver set up a working party on liver fibrosis in 2007, with a mandate to develop consensus guidelines on various aspects of liver fibrosis relevant to disease patterns and clinical practice in the Asia-Pacific region. The process for the development of these consensus guidelines involved the following: review of all available published literature by a core group of experts; proposal of consensus statements by the experts; discussion of the contentious issues; and unanimous approval of the consensus statements after discussion. The Oxford System of evidence-based approach was adopted for developing the consensus statements using the level of evidence from 1 (highest) to 5 (lowest) and grade of recommendation from A (strongest) to D (weakest). The consensus statements are presented in this review.