Osteonecrosis of both knees in a woman with Crohn's disease

Osteonecrosis is a very rare complication of Crohn’s disease (CD). It is not clear if it is related to corticosteroid therapy or if it occurs as an extraintestinal manifestation of inflammatory bowel disease. We present the case of a patient with CD who presented with osteonecrosis of both knees. A 22 years old woman was diagnosed with CD in April 2012 (Montreal Classification A2L1 + L4B3p). She was started on prednisolone (40 mg/d), azathioprine (100 mg/d) and messalazine (3 g/d). In July 2012, due to active perianal disease, infliximab therapy was initiated. In September 2012, she had a pelvic abscess complicated by peritonitis and an ileal segmental resection and right hemicolectomy were performed. In December 2012 she was diagnosed with bilateral septic arthritis of both knees with walking impairment. She was treated with amoxicillin-clavulanic acid, started a physical rehabilitation program and progressively improved. However, then, bilateral knee pain exacerbated by movement developed. Magnetic resonance imaging showed multiple osseous medullary infarcts in the distal extremity of the femurs, proximal extremity of the tibiae and patellas and no signs of subchondral collapse, which is consistent with osteonecrosis. The patient recovered completely and maintains therapy with azathioprine and messalazine. A review of the literature is also done.

Hospital costs, length of stay and prevalence of hip and knee arthroplasty in patients with inflammatory bowel disease

To examined the prevalence of hip and knee arthroplasty in patients with inflammatory bowel disease (IBD) by comparing the diagnostic codes for these procedures in patients with IBD and a control group of patients. METHODSThe National Inpatient Sample database (NIS) is part of the Healthcare Cost and Utilization Project (HCUP), the largest publicly available inpatient healthcare database in the United States. The NIS samples about 20% of discharges from all community hospitals participating in HCUP, representative of more than 95% of the United States population, with approximately 7000000 hospitalizations reported annually. NIS contains data on diagnoses, procedures, demographics, length of stay (LOS), co-morbidities and outcomes. ICD-9-CM diagnostic codes for primary hospitalizations for arthroplasty of the hip or knee with a co-diagnosis of IBD [combining both Crohn’s disease (CD) and ulcerative colitis (UC)] were used to identify study subjects for cost and LOS analysis for NIS from 1999-2012. Statistical analysis: 1: 2 propensity score matching between IBD vs a control group based on following factors: Patient age, gender, race, total co-morbidities, # of procedures, admission type, insurance, income quartiles, and hospital bed size, location and hospital teaching status. Categorical variables were reported as frequency and compared by χ2 tests or Fisher’s exact tests. Individual 1:3 matching was also performed for patients carrying diagnostic codes for CD and for patients with the diagnostic code for UC. After matching, continuous variables were rcompared with Wilcoxon signed rank or Paired T-tests. Binary outcomes were compared with the McNemar’s test. This process was performed for the diagnosis of hip or knee arthroplasty and IBD (CD and UC combined). Prevalence of the primary or secondary diagnostic codes for these procedures in patients with IBD was determined from NIS 2007. RESULTSCosts and mortality were similar for patients with IBD and controls, but LOS was significantly longer for hip arthroplasties patients with IBD, (3.85 +/-2.59 d vs 3.68 +/-2.54 d, respectively, P = 0.009). Costs, LOS and survival from the procedures was similar in patients with CD and UC compared to matched controls. These results are shown in Tables 1-10. The prevalence of hip arthroplasty in patients with IBD was 0.5% in 2007, (170/33783 total patients with diagnostic codes for IBD) and was 0.66% in matched controls (P = 0.0012). The prevalence of knee arthroplasty in patients with IBD was 1.36, (292/21202 IBD patients) and was 2.22% in matched controls (P < 0.0001). CONCLUSIONCosts and mortality rates for hip and knee arthroplasties are the same in patients with IBD and the general population, while a statistical but non-relevant increase in LOS is seen for hip arthroplasties in patients with IBD. Compared to the general population, arthroplasties of the hip and knee are less prevalent in hospitalized patients with IBD.

Unresolved conundrum of the role of physical activity in inflammatory bowel disease:What next?

There is considerable controversy on the role of physical activity in irritable bowel disease(IBD)since published reports are conflicting.It is well known that there is known relapse with specific treatment in IBD.This,in addition to onset of extraintestinal symptoms creates a need to think of alternate approaches.In this context,the current article describes the need of a multi-institutional study with standard protocol of physical activity for documenting its effect on both the primary disease and the extra alimentary manifestations.This paper also points out the possibility of using adjuvant complementary medicine such as yoga,whose effects have been documented in other diseases like irritable bowel syndrome.A third approach could be to focus on the intestinal dysbiosis in IBD and concentrate on research on restoring the microbial flora to normal,to see whether the extraintestinal symptoms are alleviated.

Total knee arthroplasty in patients with Paget's disease of bone: A systematic review

AIM To determine the functional outcomes, complications and revision rates following total knee arthroplasty(TKA) in patients with Paget's disease of bone(PDB). METHODS A systematic review of the literature was performed. Four studies with a total of 54 TKAs were included for analysis. Functional outcomes, pain scores, complications and revision rates were assessed. The mean age was 72.0 years and the mean follow-up was 7.5 years.RESULTS All studies reported significant improvement in knee function and pain scores following TKA. There were 2 cases of aseptic loosening, with one patient requiring revision of the femoral component 10 years after the index procedure. Malalignment, bone loss, soft tissue contractures were the most commonly reported intraoperative challenges. There were five cases(9%) that were complicated by intra-operative patellar tendon avulsion.CONCLUSION The findings support the use of TKA in patients with PDB. The post-operative functional outcomes are largely similar to other patients, however there are specific perioperative challenges that have been highlighted, in particular the high risk for patellar tendon avulsion.

Microglial response to aging and neuroinflammation in the development of neurodegenerative diseases

Cellular senescence and chronic inflammation in response to aging are considered to be indicators of brain aging;they have a great impact on the aging process and are the main risk factors for neurodegeneration.Reviewing the microglial response to aging and neuroinflammation in neurodegenerative diseases will help understand the importance of microglia in neurodegenerative diseases.This review describes the origin and function of microglia and focuses on the role of different states of the microglial response to aging and chronic inflammation on the occurrence and development of neurodegenerative diseases,including Alzheimer's disease,Huntington's chorea,and Parkinson's disease.This review also describes the potential benefits of treating neurodegenerative diseases by modulating changes in microglial states.Therefore,inducing a shift from the neurotoxic to neuroprotective microglial state in neurodegenerative diseases induced by aging and chronic inflammation holds promise for the treatment of neurodegenerative diseases in the future.

The role of exosomes in adult neurogenesis:implications for neurodegenerative diseases

Exosomes are cup-shaped extracellular vesicles with a lipid bilayer that is approximately 30 to 200 nm in thickness.Exosomes are widely distributed in a range of body fluids,including urine,blood,milk,and saliva.Exosomes exert biological function by transporting factors between different cells and by regulating biological pathways in recipient cells.As an important form of intercellular communication,exosomes are increasingly being investigated due to their ability to transfer bioactive molecules such as lipids,proteins,mRNAs,and microRNAs between cells,and because they can regulate physiological and pathological processes in the central nervous system.Adult neurogenesis is a multistage process by which new neurons are generated and migrate to be integrated into existing neuronal circuits.In the adult brain,neurogenesis is mainly localized in two specialized niches:the subventricular zone adjacent to the lateral ventricles and the subgranular zone of the dentate gyrus.An increasing body of evidence indicates that adult neurogenesis is tightly controlled by environmental conditions with the niches.In recent studies,exosomes released from different sources of cells were shown to play an active role in regulating neurogenesis both in vitro and in vivo,thereby participating in the progression of neurodegenerative disorders in patients and in various disease models.Here,we provide a state-of-the-art synopsis of existing research that aimed to identify the diverse components of exosome cargoes and elucidate the therapeutic potential of exosomal contents in the regulation of neurogenesis in several neurodegenerative diseases.We emphasize that exosomal cargoes could serve as a potential biomarker to monitor functional neurogenesis in adults.In addition,exosomes can also be considered as a novel therapeutic approach to treat various neurodegenerative disorders by improving endogenous neurogenesis to mitigate neuronal loss in the central nervous system.

Revisiting endovascular treatment in below-the-knee disease. Are drug-eluting stents the best option？

Patients with below-the-knee arterial disease are primarily individuals suffering from critical limb ischemia(CLI), while a large percentage of these patients are also suffering from diabetes or chronic renal failure or both. Available data from randomized controlled trials and their meta-analysis demonstrated that the use of infrapopliteal drug-eluting stents(DES), in short-to medium-length lesions, obtains significantly better results compared to plain balloon angioplasty and bare metal stenting with regards to vascular restenosis, target lesion revascularization, wound healing and amputations. Nonetheless, the use of this technology in every-day clinical practice remains limited mainly due to concerns regarding the deployment of a permanent metallic scaffold and the possibility of valid future therapeutic perspectives. However, in the majority of the cases, these concerns are not scientifically justified. Large-scale, multicenter randomized controlled trials, investigating a significantly larger number of patients than those already published, would provide more solid evidence and consolidate the use of infrapopliteal DES in CLI patients. Moreover, there is still little evidence on whether this technology can be as effective for longer below-the-knee lesions, where a considerable number of DES is required. The development and investigation of new, longer balloon-expanding or perhaps selfexpanding DES could be the answer to this problem.

Association Between Knee Alignment,Disease Severity and Subchondral Trabecular Bone Microarchitecture in Patients with Knee Osteoarthritis

Objective Most patients with knee osteoarthritis(OA)have alignment deformity with the change of Hip-knee-ankle(HKA)angle.The knee alignment influences load distribution at the tibial plateau.Meanwhile,change of subchondral trabecular bone microstructure is related to load bearing and OA progression.However,the relationship between knee alignment on the changes of subchondral trabecular bone microstructure and OA severity have been poorly investigated.The main goal of this work was to investigate variation in tibial plateaus subchondral trabecular bone microstructure in knee OA patients and their association with the severity of OA with the change of knee alignment.Methods Seventy-one knee OA patients planning to undergo total knee arthroplasty were enrolled in this study.The HKA angle and OA disease severity(OARSI score,compartment-specific Kellgren-Lawrence(K-L)grade and OARSI Atlas grade)based on full-leg standing posteroanterior radiographs were evaluated preoperatively in all patients.The tibial plateau collected during surgery was first used for micro-computed tomography(μCT)to analyze the subchondral trabecular bone microstructures,and then used for pathological sections to analyze cartilage degeneration(OARSI score).Pearson and spearman correlations were used to examine linear relationships between knee alignment,OA disease severity and subchondral trabecular bone microstructure.Patients were then divided into group I(HKA angle exceeds 0°in the valgus direction),group II(varus angle<10°)and group III(varus angle≥10°).The differences in subchondral trabecular bone microstructural parameters between the three groups were analyzed by the one-way ANOVA with a post hoc Tukey test.Results HKA angle was significantly correlated with all tibial plateau subchondral trabecular bone microstructure parameters.Regardless of the medial or lateral tibia,HKA angle was most strongly correlated with bone volume fraction(BV/TV),M:(r=0. 613,P<0.01);L:(r=-0.490,P<0.01).In addition,for the media-to-lateral ratios(M:L)of the subchondral trabecular bone microstructure parameters,the HKA angle is positively correlated with M:L BV/TV(r=0.658,P<0.01),M:L trabecular number(Tb.N)(r=0.525,,P<0.01),M:L trabecular thickness(Tb.Th)(r=0.636,P<0.01),and negatively correlated with M:L trabecular separation(Tb.Sp)(r=-0.636,P<0.01)and M:L Specific Bone Surface(BS/BV)(r=-0.792,P<0.01).The BV/TV,Tb.N,and Tb.Th of the medial tibia were sequentially incremented in the order of groupⅠ,Ⅱ,Ⅲof knee alignment,while the Tb.Sp and BS/BV were decreased in this order.The lateral tibia is the opposite.In addition,most of the severity indices of OA are associated with subchondral trabecular bone microstructures,of which OARSI score and BV/TV in medial tibia are the most relevant(r=0.787,P<0.01).HKA angle is significantly correlated with all OA severity grades in medial compartment,but only with OARSI score and Bone sclerosis grade in lateral compartment.Conclusions Tibial plateau subchondral trabecular bone microarchitecture is associated with the HKA angle and OA severity.With the increase of varus angle and the severity of OA,the subchondral trabecular bone in medial tibia has more obvious sclerosis changes and vice versa,suggesting that knee malalignment may promote abnormal subchondral trabecular bone remodeling by altering joint load distribution,thereby affecting the progression of OA.

Relationship between Serum Levels of Some Trace Elements, Disease Duration and Severity in Patients with Knee Osteoarthritis

Background: Many trace elements in the biological system, including boron, are involved in various vital processes related to health and diseases. Boron has been proved to have a role in decreasing inflammatory pain, joint stiffness and other disabling symptoms associated with osteoarthritis (OA). Aims and Objective: The purpose of the present study was to evaluate the relationship between serum concentrations of copper (Cu), zinc (Zn), selenium (Se), manganese (Mn) and magnesium (Mg) with disease duration and severity in patients with knee OA. Methods: A total of 43 patients with knee OA were clinically evaluated and serum concentrations of Cu, Zn, Se, Mn and Mg were measured, and the results were compared with those of healthy controls. Trace elements levels were correlated with disease duration and severity. Results: Serum Cu and the value of Cu/Zn were significantly elevated in OA patients and positively correlated with disease duration and severity. Serum Zn, Se and Mn were significantly lower in patients compared with controls;Zn and Se were found to be negatively and significantly correlated with disease duration and severity. Conclusion: Patients with knee OA had higher levels of Cu and larger value of Cu/Zn and lower levels of serum Zn and Se;these changes were potentially correlated with the duration and severity of disease.

A Case of Muscle Contraction-Induced Ischemic Limb Hyperemia in a Patient with Peripheral Arterial Disease during Incremental Repeat Isometric Knee Extensor Workloads

Background: To determine whether muscle contraction-induced leg blood flow (LBF) during exercise may be altered in a patient with an ischemic limb due to peripheral arterial disease (PAD) compared with the non-PAD limb. Case Presentation: A 66-year-old male patient with intermittent claudication due to PAD in the right leg (ankle brachial pressure index, 0.69) showed complete obstruction in both common iliac arteries including internal/external segments with collaterals above the femoral artery and popliteal artery with collaterals, and in the healthy left non-PAD-leg (1.06). He attempted unilateral repeat isometric knee extensions at a target contraction rhythm with each leg at incremental contraction intensities (5%, 10%, and 30% of maximum voluntary contraction [MVC] for 3 min at each intensity). Blood velocity/flow (Doppler ultrasound) in the femoral artery, blood pressure, and leg vascular conductance (LVC) were measured. Isometric thigh MVC strength pre-exercise was similar between the PAD-leg (48.0 kg) and non-PAD-leg (48.7 kg). Pre-exercise LBF (ml/min) was also similar between the PAD-leg (316) and non-PAD-leg (327). Blood pressure increases were similar during exercise. Average exercising LBF in ml/min in the last 1 min at each intensity was higher in the PAD-leg than the non-PAD-leg: 1087 vs. 471 at 5%, 2097 vs. 712 at 10%, and 2656 vs. 1517 at 30% MVC with a close positive linear relationship between LBF and %MVC in the non-PAD-leg (r = 0.999, P < 0.01), in agreement with previous findings, but less significant in the PAD-leg (r = 0.879, P = NS), indicating intense vasodilation (increasing LVC) in the PAD-leg compared with the non-PAD-leg. Conclusion: Knee extensor exercising LBF in the femoral artery was dissimilar between the PAD-leg and non-PAD-leg at the same exercise intensity, even though pre-exercising LBF was the same. Further research on the time-course in hemodynamics during leg exercise in PAD might potentially provide insight for the cardiovascular adjustment in severity of arteriosclerosis, stenosis and/or collaterals reserve.

Elafibranor:A promising treatment for alcoholic liver disease,metabolic-associated fatty liver disease,and cholestatic liver disease

Liver diseases pose a significant threat to human health.Although effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient outcomes.This article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of Gastroenterology.We summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current research.We also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated steatohepatitis.Our goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

Perianal Crohn’s disease:Still more questions than answers

In this editorial we comment on the article by Pacheco et al published in a recent issue of the World Journal of Gastroenterology.We focus specifically on the burden of illness associated with perianal fistulizing Crohn’s disease(PFCD)and the diagnostic and therapeutic challenges in the management of this condition.Evol-ving evidence has shifted the diagnostic framework for PFCD from anatomical classification systems,to one that is more nuanced and patient-focused to drive ongoing decision making.This editorial aims to reflect on these aspects to help clinicians face the challenge of PFCD in day-to-day clinical practice.

Meta-analysis of factors influencing anterior knee pain after total knee arthroplasty

BACKGROUND Total knee arthroplasty(TKA)is a mature procedure recommended for correcting knee osteoarthritis deformity,relieving pain,and restoring normal biomechanics.Although TKA is a successful and cost-effective procedure,patient dissatisfaction is as high as 50%.Knee pain after TKA is a significant cause of patient dissatisfaction;the most common location for residual pain is the anterior region.Between 4%and 40%of patients have anterior knee pain(AKP).AIM To investigate the effect of various TKA procedures on postoperative AKP.METHODS We searched PubMed,EMBASE,and Cochrane from January 2000 to September 2022.Randomized controlled trials with one intervention in the experimental group and no corresponding intervention(or other interventions)in the control group were collected.Two researchers independently read the title and abstract of the studies,preliminarily screened the articles,and read the full text in detail according to the selection criteria.Conflicts were resolved by consultation with a third researcher.And relevant data from the included studies were extracted and analyzed using Review Manager 5.4 software.RESULTS There were 25 randomized controlled trials;13 were comparative studies with or without patellar resurfacing.The meta-analysis showed no significant difference between the experimental and control groups(P=0.61).Six studies were comparative studies of circumpatellar denervation vs non-denervation,divided into three subgroups for meta-analysis.The two-subgroup meta-analysis showed no significant difference between the experimental and the control groups(P=0.31,P=0.50).One subgroup meta-analysis showed a significant difference between the experimental and control groups(P=0.001).Two studies compared fixed-bearing TKA and mobile-bearing TKA;the results meta-analysis showed no significant difference between the experimental and control groups(P=0.630).Two studies compared lateral retinacular release vs non-release;the meta-analysis showed a significant difference between the experimental and control groups(P=0.002);two other studies compared other factors.CONCLUSION Patellar resurfacing,mobile-bearing TKA,and fixed-bearing TKA do not reduce the incidence of AKP.Lateral retinacular release can reduce AKP;however,whether circumpatellar denervation can reduce AKP is controversial.

Perianal disease in inflammatory bowel disease:Broadening treatment and surveillance strategies for anal cancer

The perianal disease affects up to one-third of individuals with Crohn's disease(CD),causing disabling symptoms and significant impairment in quality of life,particularly for those with perianal fistulising CD(PFCD).The collaborative effort between gastroenterologists and surgeons is essential for addressing PFCD to achieve fistula closure and promote luminal healing.Limited fistula healing rates with conventional therapies have prompted the emergence of new biological agents,endoscopic procedures and surgical techniques that show promising results.Among these,mesenchymal stem cells injection is a particularly hopeful therapy.In addition to the burden of fistulas,individuals with perianal CD may face an increased risk of developing anal cancer.This underscores the importance of surveillance programmes and timely interventions to prevent late diagnoses and poor outcomes.Currently,there is no established formal anal screening programme.In this review,we provide an overview of the current state of the art in managing PFCD,including novel medical,endoscopic and surgical approaches.The discussion also focuses on the relevance of establishing an anal cancer screening programme in CD,intending to propose a risk-based surveillance algorithm.The validation of this surveillance programme would be a significant step forward in improving patient care and outcomes.

Antisense therapy:a potential breakthrough in the treatment of neurodegenerative diseases

Neurodegenerative diseases are a group of disorders characterized by the progressive degeneration of neurons in the central or peripheral nervous system.Currently,there is no cure for neurodegenerative diseases and this means a heavy burden for patients and the health system worldwide.Therefore,it is necessary to find new therapeutic approaches,and antisense therapies offer this possibility,having the great advantage of not modifying cellular genome and potentially being safer.Many preclinical and clinical studies aim to test the safety and effectiveness of antisense therapies in the treatment of neurodegenerative diseases.The objective of this review is to summarize the recent advances in the development of these new technologies to treat the most common neurodegenerative diseases,with a focus on those antisense therapies that have already received the approval of the U.S.Food and Drug Administration.

NADPH oxidase 4(NOX4)as a biomarker and therapeutic target in neurodegenerative diseases

Diseases like Alzheimer’s and Parkinson’s diseases are defined by inflammation and the damage neurons undergo due to oxidative stress. A primary reactive oxygen species contributor in the central nervous system, NADPH oxidase 4, is viewed as a potential therapeutic touchstone and indicative marker for these ailments. This in-depth review brings to light distinct features of NADPH oxidase 4, responsible for generating superoxide and hydrogen peroxide, emphasizing its pivotal role in activating glial cells, inciting inflammation, and disturbing neuronal functions. Significantly, malfunctioning astrocytes, forming the majority in the central nervous system, play a part in advancing neurodegenerative diseases, due to their reactive oxygen species and inflammatory factor secretion. Our study reveals that aiming at NADPH oxidase 4 within astrocytes could be a viable treatment pathway to reduce oxidative damage and halt neurodegenerative processes. Adjusting NADPH oxidase 4 activity might influence the neuroinflammatory cytokine levels, including myeloperoxidase and osteopontin, offering better prospects for conditions like Alzheimer’s disease and Parkinson’s disease. This review sheds light on the role of NADPH oxidase 4 in neural degeneration, emphasizing its drug target potential, and paving the path for novel treatment approaches to combat these severe conditions.

Alanine aminotransferase predicts incident steatotic liver disease of metabolic etiology: Long life to the old biomarker!

Alanine aminotransferase(ALT)serum levels increase because of hepatocellular damage.Metabolic dysfunction-associated fatty liver disease(MAFLD),which identifies steatotic liver disease(SLD)associated with≥2 metabolic abnormalities,has prominent sexual differences.The Metabolic Syndrome defines a cluster comprising abdominal obesity,altered glucose metabolism,dyslipidemia,and hypertension.Male sex,body mass index,glucose,lipids,ferritin,hypertension,and age independently predict ALT levels among blood donors.Over the last few decades,the reference range of ALT levels has been animatedly debated owing to attempts to update sex-specific reference ranges.With this backset,Chen et al have recently published a study which has two main findings.First,>80%of indi-viduals with MAFLD had normal ALT levels.Second,there was a linear increa-sing trend in the association between cumulative excess high-normal ALT levels and the rate of incident MAFLD.This study has biologically credible findings.However,it inaccurately considered sex differences in the MAFLD arena.Therefore,future studies on SLD owing to metabolic dysfunction should adopt locally determined and prospectively validated reference ranges of ALT and carefully consider sex differences in liver enzymes and MAFLD pathobiology.

Metabolic dysfunction-associated steatotic liver disease:Navigating terminological evolution,diagnostic frontiers and therapeutic horizon-an editorial exploration

Metabolic dysfunction-associated steatotic liver disease(MASLD),once known as non-alcoholic fatty liver disease(NAFLD),represents a spectrum of liver disorders characterized by lipid accumulation within hepatocytes.The redefinition of NAFLD in 2023 marked a significant reposition in terminology,emphasizing a broader understanding of liver steatosis and its associated risks.MASLD is now recognized as a major risk factor for liver cirrhosis,hepatocellular carcinoma,and systemic complications such as cardiovascular diseases or systemic inflammation.Diagnostic challenges arise,particularly in identifying MASLD in lean individuals,necessitating updated diagnostic protocols and investing in non-invasive diagnostic tools.Therapeutically,there is an urgent need for effective treatments targeting MASLD,with emerging pharmacological options focusing on,among others,carbohydrate and lipid metabolism.Additionally,understanding the roles of bile acid metabolism,the microbiome,and dietary interventions in MASLD pathogenesis and management holds promise for innovative therapeutic approaches.There is a strong need to emphasize the importance of collaborative efforts in understanding,diagnosing,and managing MASLD to improve physicians’approaches and patient outcomes.

Metabolic-associated fatty liver disease and sarcopenia:A double whammy

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity pandemic.MAFLD,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and sarcopenia.Understanding the interplay between MAFLD and these comorbidities is important to design optimal therapeutic strategies.Sarcopenia can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and cirrhosis.Sarcopenia can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical factors.Therefore,it is crucial to thoroughly understand how we deal with these diseases,especially when they coexist.We explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

Update in lean metabolic dysfunction-associated steatotic liver disease

BACKGROUND A new nomenclature consensus has emerged for liver diseases that were previously known as non-alcoholic fatty liver disease(NAFLD)and metabolic dysfunction-associated fatty liver disease(MAFLD).They are now defined as metabolic dysfunction-associated steatotic liver disease(MASLD),which includes cardiometabolic criteria in adults.This condition,extensively studied in obese or overweight patients,constitutes around 30%of the population,with a steady increase worldwide.Lean patients account for approximately 10%-15%of the MASLD population.However,the pathogenesis is complex and is not well understood.AIM To systematically review the literature on the diagnosis,pathogenesis,characteristics,and prognosis in lean MASLD patients and provide an interpretation of these new criteria.METHODS We conducted a comprehensive database search on PubMed and Google Scholar between January 2012 and September 2023,specifically focusing on lean NAFLD,MAFLD,or MASLD patients.We include original articles with patients aged 18 years or older,with a lean body mass index categorized according to the World Health Organization criteria,using a cutoff of 25 kg/m2 for the general population and 23 kg/m2 for the Asian population.RESULTS We include 85 studies in our analysis.Our findings revealed that,for lean NAFLD patients,the prevalence rate varied widely,ranging from 3.8%to 34.1%.The precise pathogenesis mechanism remained elusive,with associations found in genetic variants,epigenetic modifications,and adaptative metabolic response.Common risk factors included metabolic syndrome,hypertension,and type 2 diabetes mellitus,but their prevalence varied based on the comparison group involving lean patients.Regarding non-invasive tools,Fibrosis-4 index outperformed the NAFLD fibrosis score in lean patients.Lifestyle modifications aided in reducing hepatic steatosis and improving cardiometabolic profiles,with some medications showing efficacy to a lesser extent.However,lean NAFLD patients exhibited a worse prognosis compared to the obese or overweight counterpart.CONCLUSION MASLD is a complex disease comprising epigenetic,genetic,and metabolic factors in its pathogenesis.Results vary across populations,gender,and age.Limited data exists on clinical practice guidelines for lean patients.Future studies employing this new nomenclature can contribute to standardizing and generalizing results among lean patients with steatotic liver disease.