New Scanographic Index for the Detection of Frailty in Patients with Cirrhosis with a Prognostic Impact.

Background: Frailty is linked to an increased incidence of hepatic decompensation and mortality in cirrhosis. The aim of our study was to identify a novel scanographic score that predicts frailty and its impact in cirrhosis. Methods: This study included 51 patients with cirrhosis. We used the frailty scale risk assessment score to identify frail patients. The density and area of different muscles at L3 level were analyzed on computed tomography (CT) sections. The L3 skeletal muscle area adjusted to height and density ratio (L3-SMDHR) was defined as L3 muscle wall*height/density. Results: The L3-SMHDR is significantly higher in frail patients and in patients with Child B/C scores. Frailty was correlated with L3-SMHDR. Frailty and L3- SMHDR were correlated with liver-related events (LRE). We set the most appropriate cut-offs of L3-SMHDR for both sensitivity and specificity by using the ROC: 5.4 for males and 4.7 for females. The AUROC score was 0.784 for male and 0.975 for female patients. The Kappa score between frailty and L3-SMHDR was 0.752, with a percentage of agreement of 87.5%, showing a substantial agreement. This ratio with the divided categories has a sensitivity of 100%, a specificity of 76%, a positive predictive value of 79.3% and a negative predictive value of 100%. Patients with high L3-SMHDR have significantly lower survival time and a higher incidence of LRE. Conclusion: The L3-SMHDR is a new index for identifying frailty in cirrhosis by using measurable and reproducible variables. It can be used as a prognostic factor for frailty in patients with cirrhosis.

Impact of Diabetes, Drug-Induced Liver Injury, and Sepsis on Outcomes in MAFLD-Related Acute-on-Chronic Liver Failure.

BACKGROUND: The prevalence of Metabolic dysfunction associated fatty liver disease (MAFLD) and its complication, MAFLD-related acute on chronic liver failure (MAFLD-ACLF), is rising. Yet, factors determining patient outcomes in MAFLD-ACLF remain understudied. METHODS: Patients with MAFLD-ACLF were recruited from the AARC registry. The diagnosis of MAFLD-ACLF was made when the treating unit had identified the etiology of chronic liver disease (CLD) as MAFLD (or previous nomenclature such as NAFLD, NASH, or NASH-cirrhosis). Patients with coexisting other etiologies of CLD (such as alcohol, HBV, HCV, etc.) were excluded. Data was randomly split into derivation (n=258) and validation (n=111) cohorts at a 70:30 ratio. The primary outcome was 90-day mortality. Only the baseline clinical, laboratory features and severity scores were considered. RESULTS: The derivation group had 258 patients; 60% were male, with a mean age of 53. Diabetes was noted in 27%, and hypertension in 29%. The dominant precipitants included viral hepatitis (HAV and HEV, 32%), drug-induced injury (DILI, 29%) and sepsis (23%). MELD-Na and AARC scores upon admission averaged 32±6 and 10.4±1.9. At 90 days, 51% survived. Non-viral precipitant, diabetes, bilirubin, INR, and encephalopathy were independent factors influencing mortality. Adding diabetes and precipitant to MELD-Na and AARC scores, the novel MAFLD-MELD-Na score (+12 for diabetes, +12 for non-viral precipitant) and MAFLD-AARC score (+5 for each) were formed. These outperformed the standard scores in both cohorts. CONCLUSION: Almost half of MAFLD-ACLF patients die within 90 days. Diabetes and non-viral precipitants such as DILI and sepsis lead to adverse outcomes. The new MAFLD-MELD-Na and MAFLD-AARC scores provide reliable 90-day mortality predictions for MAFLD-ACLF patients.

Effect of Mediterranean Dietary Pattern on Cognitive Status in Community-Dwelling Older Adults.

Modifiable factors associated with cognitive decline (CD) require more attention, particularly dietary patterns. This study aimed to investigate the link between cognitive decline and associated factors, particularly dietary patterns (DPs), in community-dwelling older Lebanese of modest economic status. Our cross-sectional national study included 352 participants above 60 years old, from the medico-social centers of the ministry of social affairs all over the country. CD was screened based on literacy. Nutritional and dietary data were collected through a validated food frequency questionnaire. DPs were extracted by the K-mean cluster analysis. CD was found in 32.7% and 61.5% of literate and illiterate groups, respectively. Identified DPs included a Westernized type and Mediterranean type, with high and moderate food intakes. In the context of literacy, independent factors associated with CD were age above 80 years, living in Beirut, frailty, and adopting a Westernized (OR = 3.08, 95% CI: 1.22-7.8) and a high-intake Mediterranean DP (OR = 2.11, 95% CI: 1.05-4.22). In the context of illiteracy, the same factors were associated with CD, but not DP nor frailty, with an age cut-off at 78 years. In a Lebanese sample of older adults, factors associated with CD depend on the level of literacy, with DP only associated with CD in the context of literacy.

Perception and Attitude of Lebanese IBD Patients During the COVID-19 Pandemic.

Objective: The emergence of the COVID pandemic affected daily living and healthcare access of IBD patients, due to delays of elective procedures and in-hospital treatments. Our aim is to determine the repercussions of the pandemic on the daily habits of IBD patients and on their compliance to follow-up and treatment. Methods: This was a cross-sectional observational study. A questionnaire was administered in between 2020 and 2022 to IBD patients in a tertiary center in Lebanon. The outcomes measured were patient perceptions regarding COVID and how it affected their treatment. Results: A total of 201 answers were included in the analysis with male predominance. Two-thirds had Crohn's disease. Near 80% were afraid of being infected by COVID-19 and 87.6% were afraid of physical contact. 91.5% reduced their daily habits and 96.0% have used personal protective equipment. 47.3% of the patients report that there are factors that reduced their worries, the most common factor being contacting their physician (61.0%). The main source of information was the treating physician (37.8%). A quarter of patients think that their condition predisposed to COVID-19 infection and about two-thirds believe that immunosuppressive therapy did so. The same amount reported concern regarding visiting the hospital. 27.4% preferred telemedicine and 44.8% preferred over-The-phone consultation to an in-person visit. Three-quarters were in favor of vaccination. 59.6% delayed their in-center treatment, which was associated with a reduction in daily life activities. 13.9% wanted to discontinue their treatment, which was associated with smoking, cardiovascular, and rheumatological comorbidities, but only 4% did so. Conclusion: The pandemic had significant repercussions on the everyday life of IBD patients, with some preferring to consult via telemedicine and others considering stopping their treatment.

Serum MFAP4, a novel potential biomarker for liver cirrhosis screening, correlates with transient elastography in NAFLD patients.

Background and Aim: Non-alcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in different countries. Liver fibrosis is considered as the most appropriate predictor of NAFLD-associated outcome. Microfibrillar-associated protein 4 (MFAP4) is a glycoprotein located in the extracellular matrix. Circulatory MFAP4 has been suggested as a noninvasive biomarker for the assessment of hepatitis C virus and alcoholic liver disease associated liver fibrosis. In this study, we aimed to investigate the association between serum MFAP4 and liver fibrosis severity in NAFLD patients. Methods: A case-control study was conducted in which NAFLD patients (n = 25) and healthy participants (n = 12) were recruited. Liver fibrosis/cirrhosis was assessed by transient elastography (TE) and biochemical parameters were collected. Serum MFAP4 was measured by sandwich ELISA based on two monoclonal anti-MFAP4 antibodies and calibrated with a standard of recombinant MFAP4. Results: Serum MFAP4 levels increased with fibrosis severity and were highly upregulated in patients with cirrhosis (F4 fibrosis stage). In addition, serum MFAP4 levels positively correlated with TE measurement and showed significant association with the severely advanced fibrotic stage in NAFLD patients, in multiple linear regression analysis following adjustment for age, gender, and body mass index. Conclusion: This study suggests the use of MFAP4 as a potential diagnostic noninvasive biomarker for cirrhosis screening in NAFLD patients.

Genetic predisposition to porto-sinusoidal vascular disorder: A functional genomic-based, multigenerational family study.

BACKGROUND AND AIMS: Porto-sinusoidal vascular disorder (PSVD) is a group of liver vascular diseases featuring lesions encompassing the portal venules and sinusoids unaccompanied by cirrhosis, irrespective of the presence/absence of portal hypertension. It can occur secondary to coagulation disorders or insult by toxic agents. However, the cause of PSVD remains unknown in most cases. Hereditary cases of PSVD are exceptionally rare, but they are of particular interest and may unveil genetic alterations and molecular mechanisms associated with the disease. APPROACH AND RESULTS: We performed genome sequencing of four patients and two healthy individuals of a large multigenerational Lebanese family with PSVD and identified a heterozygous deleterious variant (c.547C>T, p.R183W) of FCH and double SH3 domains 1 ( FCHSD1 ), an uncharacterized gene, in patients. This variant segregated with the disease, and its pattern of inheritance was suggestive of autosomal dominant with variable expressivity. RNA structural modelling of human FCHSD1 suggests that the C-to-T substitution at position 547, corresponding to FCHSD1R183W , may increase both messenger RNA (mRNA) and protein stability and its interaction with MTOR-associated protein, LST8 homolog, a key protein of the mechanistic target of rapamycin (mTOR pathway). These predictions were substantiated by biochemical analyses, which showed that FCHSD1R183W induced high FCHSD1 mRNA stability, overexpression of FCHSD1 protein, and an increase in mTORC1 activation. This human FCHSD1 variant was introduced into mice through CRISPR/Cas9 genome editing. Nine out of the 15 mice carrying the human FCHSD1R183W variant mimicked the phenotype of human PSVD, including splenomegaly and enlarged portal vein. CONCLUSIONS: Aberrant FCHSD1 structure and function leads to mTOR pathway overactivation and may cause PSVD.

Validity and reliability of a food frequency questionnaire for community dwelling older adults in a Mediterranean country: Lebanon.

BACKGROUND: Food frequency questionnaires (FFQ) is an easy and inexpensive tool that can be used to evaluate nutrient and dietary trends of groups and individuals. Few studies in the East Mediterranean region tailored FFQs to describe dietary intakes of older adults. The purpose of the study is therefore to assess the validity and reproducibility of a FFQ, designed for use with older adults living in a Mediterranean Arabic speaking country, Lebanon. METHODS: The FFQ is composed of a list of 90 food items, commonly consumed by adults above 60 years of age. Validity of the FFQ was tested using the mean of two 24-hours dietary recalls (24HDR), and reproducibility, by repeating the questionnaire within a one-month period, along the second dietary recall. Our study included 42 and 76 participants, for the repoducibility and validity analysis respectively. Subjects were randomly selected from 2 of the 8 governorates in the country. RESULTS: FFQ reproducibility showed a mean relative difference of 1.03% without any significant difference between all paired components of nutrients. Intra class correlation (ICC) showed good and excellent reliability for caloric intake and all macronutrients, moderate to good reliability for all remaining nutrients, except for poly-unsaturated fatty acids, vitamins A, B12 and fibers. Correlation coefficients for all nutrients were fair to strong. Both administrations of the FFQ showed good internal validity. Validation of FFQ showed a mean relative difference between FFQ and mean 24HDR at 19.5%. Agreements between the 2 methods, for classifying individuals in the same or adjacent quartile, for nutrient intake and nutrient adequacy, were 80 and 78.2% respectively. Mean Kappa coefficient was 0.56 and energy-adjusted correlations were within the recommended values for all items except for vitamin A and B12. Adjusting for nutrient-dense food intake improved the agreement for theses 2 vitamins to 0.49 and 0.56, respectively. CONCLUSION: The proposed FFQ can be considered a valid tool to help describe nutrient intake of older individuals in an Arabic speaking Mediterranean country. It could serve for possible use in the East Mediterranean region for the evaluation of regular dietary intake of community-dwelling older adults.

Identification of a Variant in APOB Gene as a Major Cause of Hypobetalipoproteinemia in Lebanese Families.

Familial hypobetalipoproteinemia (FHBL) is a codominant genetic disorder characterized by reduced plasma levels of low-density lipoprotein cholesterol and apolipoprotein B. To our knowledge, no study on FHBL in Lebanon and the Middle East region has been reported. Therefore, we conducted genetic studies in unrelated families and probands of Lebanese origin presenting with FHBL, in order to identify the causes of this disease. We found that 71% of the recruited probands and their affected relatives were heterozygous for the p.(Arg490Trp) variant in the APOB gene. Haplotype analysis showed that these patients presented the same mutant haplotype. Moreover, there was a decrease in plasma levels of PCSK9 in affected individuals compared to the non-affected and a significant positive correlation between circulating PCSK9 and ApoB levels in all studied probands and their family members. Some of the p.(Arg490Trp) carriers suffered from diabetes, hepatic steatosis or neurological problems. In conclusion, the p.(Arg490Trp) pathogenic variant seems a cause of FHBL in patients from Lebanese origin, accounting for approximately 70% of the probands with FHBL presumably as a result of a founder mutation in Lebanon. This study is crucial to guide the early diagnosis, management and prevention of the associated complications of this disease.

Dietary Patterns and Risk Factors of Frailty in Lebanese Older Adults.

Factors associated with frailty, particularly dietary patterns, are not fully understood in Mediterranean countries. This study aimed to investigate the association of data-driven dietary patterns with frailty prevalence in older Lebanese adults. We conducted a cross-sectional national study that included 352 participants above 60 years of age. Sociodemographic and health-related data were collected. Food frequency questionnaires were used to elaborate dietary patterns via the K-mean cluster analysis method. Frailty that accounted for 15% of the sample was twice as much in women (20%) than men (10%). Identified dietary patterns included a Westernized-type dietary pattern (WDP), a high intake/Mediterranean-type dietary pattern (HI-MEDDP), and a moderate intake/Mediterranean-type dietary pattern (MOD-MEDDP). In the multivariate analysis, age, waist to height ratio, polypharmacy, age-related conditions, and WDP were independently associated with frailty. In comparison to MOD-MEDDP, and after adjusting for covariates, adopting a WDP was strongly associated with a higher frailty prevalence in men (OR = 6.63, 95% (CI) (1.82-24.21) and in women (OR = 11.54, 95% (CI) (2.02-65.85). In conclusion, MOD-MEDDP was associated with the least prevalence of frailty, and WDP had the strongest association with frailty in this sample. In the Mediterranean sample, a diet far from the traditional one appears as the key deleterious determinant of frailty.

Hemophagocytic lymphohistiocytosis, a new cause of death during 'post-acute COVID-19 syndrome?' A case report.

'Post-acute coronavirus disease 2019 (COVID-19) syndrome' is a new term that was coined to describe a constellation of persistent symptoms and new complications following recovery from COVID-19 initial illness. Identifying post-COVID-19 complications is crucial for early diagnosis and subsequent initiation of therapies to ensure more favorable outcomes. Severe COVID-19-related hemophagocytic lymphohistiocytosis (HLH) has been previously described during the acute phase of the infection. It is characterized by hyperinflammation, multi-organ involvement, and hemophagocytosis. We report the case of a 69-year-old woman who presented, two weeks after recovery from COVID-19, with hyperosmolar state and high inflammatory markers. Bone marrow aspirate, flow cytometry, extensive viral panel and total body scan were performed. Review of bone marrow aspirate smear showed hemophagocytosis. Flow cytometry, viral panel, and total body scan were normal. The diagnosis of post COVID-19-related HLH was made. Unfortunately, the patient died despite adequate treatment. To our knowledge, this is the first case establishing a high probability of COVID-19-related HLH given its occurrence two weeks following a documented biological and clinical recovery. Awareness and early recognition of HLH features following COVID-19 recovery should prompt timely initiation of therapy.

Real world experience with the all-oral interferon free regimen for the treatment of chronic hepatitis c virus infection in the Lebanese population.

INTRODUCTION: The treatment of hepatitis C has dramatically improved since the introduction of the new Direct-Acting Antivirals (DAAs). The aim of this study is to assess the effectiveness and safety of all oral DAAs with or without ribavirin in the treatment of hepatitis C virus (HCV) in treatment naïve and experienced Lebanese population. METHODOLOGY: We reviewed all cases approved for hepatitis C treatment with DAAs according to the Lebanese guidelines for treatment of HCV at the Ministry of Public Health from October 2015 till December 2016. Available data concerning age, sex, mode of transmission, genotype (GT) and subtype, fibrosis stage, previous treatment (if present), new DAAs treatment, and sustained virological response at week 12 (SVR12) were collected. RESULTS: During a period of 15 months (October 2015 to December 2016), 186 patients were treated with DAAs. 57% were male and the mean age was 54.3 years. The source of infection was unknown in 51% of cases and blood transfusion in 35.5% of cases. Genotype 1 was the most predominant genotype (45%), followed by GT4 (34%) and GT3 (12%). 71.6% of patients had advanced fibrosis before starting DAAs and 57% were cirrhotic. 42% of patients were treatment experienced (85% pegylated interferon and ribavirin). Different DAAs regimens were used according to the Lebanese guidelines for treatment of HCV: Ledipasvir/Sofosbuvir (38.7%), Sofosbuvir/Daclatasvir (16.1%), Sofosbuvir/Velpatasvir (1.6%), Sofosbuvir/RBV (7.5%), Ombitasvir/Paritaprevir/Ritonavir (17.5%) and Ombitasvir/Paritaprevir/Ritonavir -Dasabuvir (18.8%). Ribavirin was used in 51.6% of cases. SVR12 was achieved in 93% of patients (relapse in 4%, loss of follow up and/or severe adverse effect in 3%). SVR 12 was achieved in 93%, 96% and 94% of GT1, GT3 and GT4 cases respectively. SVR12 was seen in 91.3% of cirrhotic patients vs. 98.7% of F0-F3 patients. (p = 0.047).  There was no difference in SVR12 between treatment naïve and experienced patients. Hepatocellular carcinoma developed in 5 patients (2.9%) during the study period. CONCLUSION: This is the first real world Lebanese data of HCV treatment with DAAs. The study population was significant for a large number of patients with cirrhotic (50%) and treatment experienced patients (42%). SVR12 was achieved in 93% of patients with no difference between treatment naïve and experienced patients. SVR12 was lower in patients with cirrhosis compared to patients with lower stage of fibrosis (91.3% vs. 98.7%).

Prevalence of hepatitis C virus genotypes and subtypes in Lebanese population and major high risk groups.

BACKGROUND AND STUDY AIMS: The prevalence of hepatitis C in Lebanon is low. It is estimated at 0.2% of the total population. The aim of our study is to evaluate the exact prevalence of each genotype on a large scale population and in each potential source of infection. PATIENTS AND METHODS: We reviewed all the data in the Ministry of Public Health related to patients who have submitted their file for treatment during a period of 9years ranging from January 2005 till December 2013. RESULTS: The genotype distribution in 1031 Lebanese patients was as following: Genotype 1 was the most predominant representing 47% followed by genotype 4 representing 34% then genotype 3 representing14%. Concerning sex distribution and routes of infection, there was a male predominance in intravenous drug users (IVDU), whereas approximately equal distribution was noted in haemodialysis and transfusion groups. A female predominance was noted in the "unknown" mode of infection. Concerning age distribution and routes of infection, a mean age of 27 was noted in the IVDU group, whereas mean age of 60 in the transfusion group and 50 in the haemodialysis group. In patients who acquired the infection post transfusion or during haemodialysis, genotype 1 was the most predominant, whereas in IVDU, genotype 3 was the most predominant. Concerning sub-genotyping: subtype 1b was the most predominant (84%) in genotype 1. in genotype 2 subtype b with 75%, all genotype 3 were subtype a, in genotype 4 subtype a represents 50% of genotype followed by subtype e in 30%. CONCLUSION: Our data concerning Lebanese population demonstrate that genotype 1 is the most prevalent genotype followed by genotype 4. In IVU, we noted genotype-3 and -1 being the most prevalent in relation to clustering in this high risk group. This distribution differs from most surrounding countries and all other Arab countries.

Omental ischemia.

Omental ischemia is a rare cause of acute abdomen. Clinical diagnosis is usually difficult because clinical signs and symptoms are similar to other common causes of abdominal pain. The most common differential diagnosis is acute appendicitis. Diagnosis is mainly based on ultrasound, and especially computed tomography scan analysis. There is, at present, no standard treatment modality for omental ischemia. When diagnosed by radiological imaging, omental ischemia can be managed conservatively. We hereby review incidence, etiology, pathology, clinical presentation, differential diagnosis, biological anomalies, radiological features, and treatment options of omental ischemia.

Isolated fever induced by mesalamine treatment.

Adverse reactions to mesalamine, a treatment used to induce and maintain remission in inflammatory bowel diseases, particularly ulcerative colitis, have been described in the literature as case reports. This case illustrates an unusual adverse reaction. Our patient developed an isolated fever of unexplained etiology, which was found to be related to mesalamine treatment. A 22-year-old patient diagnosed with ulcerative colitis developed a fever with rigors and anorexia 10 d after starting oral mesalamine while his colitis was clinically resolving. Testing revealed no infection. A mesalamine-induced fever was considered, and treatment was stopped, which led to spontaneous resolution of the fever. The diagnosis was confirmed by reintroducing the mesalamine. One year later, this side effect was noticed again in the same patient after he was administered topical mesalamine. This reaction to mesalamine seems to be idiosyncratic, and the mechanism that induces fever remains unclear. Fever encountered in the course of a mesalamine treatment in ulcerative colitis must be considered a mesalamine-induced fever when it cannot be explained by the disease activity, an associated extraintestinal manifestation, or an infectious etiology.

Unusual etiology of epigastric pain.

BACKGROUND: Epigastric pain is a common presenting complaint encountered in urgent care settings. Although peptic, biliary, and pancreatic pathologies are the most frequent findings, other rare diagnoses also can be found. OBJECTIVES: We report an unusual case of acute epigastric pain in which abdominal ultrasound was of great support in revealing the diagnosis. CASE REPORT: A 64-year-old man presented to the Emergency Department after rapid onset of acute epigastric pain. Abdominal ultrasound showed a multi-cystic heterogeneous mass between the stomach and the liver. Abdominal computed tomography scan confirmed the gastric origin of the mass and showed torsion signs. Urgent laparotomy was performed with tumor excision. The diagnosis of pedunculated exophytic gastric stromal tumor was made and long-term follow-up was arranged. CONCLUSIONS: Acute presentation revealed the presence of the tumor, which was excised surgically.

Migration in two directions.

BACKGROUND: Percutaneous endoscopic gastrostomy (PEG), the modality of choice for long-term enteral access, is generally a safe procedure but can be associated with many potential complications. OBJECTIVES: Report two different and late complications of PEG in two patients fed at home, leading them to the emergency department. CASE REPORT: A 75-year-old man and a 14-year-old young man with PEG presented to the emergency department with two different complications related to the gastrostomy tube. The first patient developed fever and deterioration in mental status due to parietal abscess which developed secondary to the migration of the internal button of the gastrostomy tube in the abdominal wall. He was treated with antibiotics and the gastrostomy tube was extracted. The second one presented upper gastrointestinal bleeding due to intestinal perforation at the level of the internal button of the gastrostomy tube. Bleeding and perforation were treated conservatively and he had a good evolution. CONCLUSION: Persons taking care of patients with PEG tube must be aware of potential complications. The position and the permeability of the tube must be systematically checked before feeding and medical advice should immediately be asked for in case of doubt or in the presence of any alarming sign.

Effect of intravenous crystalloid infusion on postoperative nausea and vomiting after thyroidectomy: a prospective, randomized, controlled study.

BACKGROUND AND OBJECTIVE: Intravenous administration of compound sodium lactate (CSL) 30 ml kg to women undergoing gynaecological laparoscopy reduced the incidence of vomiting, nausea and antiemetic use when compared with 10 ml kg. The aim of this study was to evaluate the effect of intravenous fluid administration on nausea and vomiting after thyroidectomy. METHODS: With ethics committee approval, 100 patients scheduled for thyroid surgery were included in this prospective, controlled, double blind study. Patients were randomized into two groups: the CSL-10 group (n = 50) received CSL 10 ml kg and the CSL-30 group received CSL 30 ml kg; the administration of fluid was completed by the end of surgery. Standardized anaesthesia was performed. The incidence of nausea and vomiting and need for antiemetics and analgesic therapy were assessed by a blinded observer at 0.5, 2, 6, 12, 18 and 24 h after surgery. Patients' satisfaction was also recorded (0-100). RESULTS: The incidence of nausea (64%) was similar in both groups (P = 0.1). The incidence of vomiting was 34% in the CSL-10 group and 32% in the CSL-30 group (P = 0.83). Antiemetics (P = 0.84) and analgesic consumption (P = 0.72) did not differ significantly between the two groups. Patients' satisfaction was also comparable (P = 0.39). CONCLUSION: Intravenous administration of CSL 30 ml kg to patients undergoing thyroidectomy did not reduce the incidence of nausea, vomiting and antiemetic use when compared with CSL 10 ml kg.