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.

Viral etiologies of acute liver failure

Acute liver failure(ALF)is a rare cause of liver-related mortality worldwide,with an estimated annual global incidence of more than one million cases.While drug-induced liver injury,including acetaminophen toxicity,is the leading cause of ALF in the Western world,viral infections remain a significant cause of ALF and the most common cause in many developing nations.Given the high mortality rates associated with ALF,healthcare providers should be aware of the broad range of viral infections that have been implicated to enable early diagnosis,rapid treatment initiation when possible,and optimal management,which may include liver transplantation.This review aims to provide a summary of viral causes of ALF,diagnostic approaches,treatment options,and expected outcomes.

Changes in the etiology of liver cirrhosis and the corresponding management strategies

We read with interest the article by Xing Wang,which was published in the recent issue of the World Journal of Hepatology 2023;15:1294-1306.This article focuses particularly on the prevalence and trends in the etiology of liver cirrhosis(LC),prognosis for patients suffering from cirrhosis-related complications and hepatocellular carcinoma(HCC),and management strategies.The etiology of cirrhosis varies according to geographical,economic,and population factors.Viral hepatitis is the dominant cause in China.Vaccination and effective treatment have reduced the number of people with viral hepatitis,but the overall number is still large.Patients with viral hepatitis who progress over time to LC and HCC remain an important population to manage.The increased incidence of metabolic syndrome and alcohol consumption is likely to lead to a potential exponential increase in metabolic dysfunction-associated steatotic liver disease(MASLD)-associated LC and alcoholic liver disease in the future.Investigating the evolution of the etiology of LC is important for guiding the direction of future research and policy development.These changing trends indicate a need for greater emphasis on tackling obesity and diabetes,and implementing more effective measures to regulate alcohol consumption in order to reduce the occurrence of MASLD.In an effort to help cope with these changing trends,the authors further proposed countermeasures for healthcare authorities doctors,and patients.

Necroptosis contributes to non-alcoholic fatty liver disease pathoetiology with promising diagnostic and therapeutic functions

Nonalcoholic fatty liver disease(NAFLD)is the most prevalent type of chronic liver disease.However,the disease is underappreciated as a remarkable chronic disorder as there are rare managing strategies.Several studies have focused on determining NAFLD-caused hepatocyte death to elucidate the disease pathoe-tiology and suggest functional therapeutic and diagnostic options.Pyroptosis,ferroptosis,and necroptosis are the main subtypes of non-apoptotic regulated cell deaths(RCDs),each of which represents particular characteristics.Considering the complexity of the findings,the present study aimed to review these types of RCDs and their contribution to NAFLD progression,and subsequently discuss in detail the role of necroptosis in the pathoetiology,diagnosis,and treatment of the disease.The study revealed that necroptosis is involved in the occurrence of NAFLD and its progression towards steatohepatitis and cancer,hence it has potential in diagnostic and therapeutic approaches.Nevertheless,further studies are necessary.

Advancements in Liver Tumor Detection:A Comprehensive Review of Various Deep Learning Models

Liver cancer remains a leading cause of mortality worldwide,and precise diagnostic tools are essential for effective treatment planning.Liver Tumors(LTs)vary significantly in size,shape,and location,and can present with tissues of similar intensities,making automatically segmenting and classifying LTs from abdominal tomography images crucial and challenging.This review examines recent advancements in Liver Segmentation(LS)and Tumor Segmentation(TS)algorithms,highlighting their strengths and limitations regarding precision,automation,and resilience.Performance metrics are utilized to assess key detection algorithms and analytical methods,emphasizing their effectiveness and relevance in clinical contexts.The review also addresses ongoing challenges in liver tumor segmentation and identification,such as managing high variability in patient data and ensuring robustness across different imaging conditions.It suggests directions for future research,with insights into technological advancements that can enhance surgical planning and diagnostic accuracy by comparing popular methods.This paper contributes to a comprehensive understanding of current liver tumor detection techniques,provides a roadmap for future innovations,and improves diagnostic and therapeutic outcomes for liver cancer by integrating recent progress with remaining challenges.

Thrombotic complications post liver transplantation:Etiology and management

Liver transplantation(LT)is the life saving therapeutic option for patients with acute and chronic end stage liver disease.This is a routine procedure with excellent outcomes in terms of patient survival and quality of life post LT.Orthotopic LT(OLT)patients require a critical care as they are prone to variety of post-operative vascular,cardiovascular,biliary,pulmonary and abdominal complications.Thrombotic complications(both arterial and venous)are not uncommon post liver transplant surgery.Such vascular problems lead to increased morbidity and mortality in both donor and graft recipient.Although thromboprophylaxis is recommended in general surgery patients,no such standards exist for liver transplant patients.Drastic advancements of surgical and anesthetic procedures have improvised survival rates of patients post OLT.Despite these,haemostatic imbalance leading to thrombotic events post OLT cause significant graft loss and morbidity and even lead to patient’s death.Thus it is extremely important to understand pathophysiology of thrombosis in LT patients and shorten the timing of its diagnosis to avoid morbidity and mortality in both donor and graft recipient.Present review summarizes the current knowledge of vascular complications associated with LT to highlight their impact on short and long-term morbidity and mortality post LT.Also,present report discusses the lacunae existing in the literature regarding the risk factors leading to arterial and venous thrombosis in LT patients.

Liver as a new target organ in Alzheimer's disease:insight from cholesterol metabolism and its role in amyloid-beta clearance

Alzheimer's disease,the primary cause of dementia,is characterized by neuropathologies,such as amyloid plaques,synaptic and neuronal degeneration,and neurofibrillary tangles.Although amyloid plaques are the primary characteristic of Alzheimer's disease in the central nervous system and peripheral organs,targeting amyloid-beta clearance in the central nervous system has shown limited clinical efficacy in Alzheimer's disease treatment.Metabolic abnormalities are commonly observed in patients with Alzheimer's disease.The liver is the primary peripheral organ involved in amyloid-beta metabolism,playing a crucial role in the pathophysiology of Alzheimer's disease.Notably,impaired cholesterol metabolism in the liver may exacerbate the development of Alzheimer's disease.In this review,we explore the underlying causes of Alzheimer's disease and elucidate the role of the liver in amyloid-beta clearance and cholesterol metabolism.Furthermore,we propose that restoring normal cholesterol metabolism in the liver could represent a promising therapeutic strategy for addressing Alzheimer's disease.

Elafibranor, a dual PPARα and PPARδ agonist, reduces alcoholassociated liver disease: Lessons from a mouse model

Metabolic dysfunction-associated steatotic liver disease(MASLD)is a highly prevalent liver pathology in need of novel pharmacological treatments to complement lifestyle-based interventions.Nuclear receptor agonists have been under scrutiny as potential pharmacological targets and as of today,resmetirom,a thyroid hormone receptor b agonist,is the only approved agent.The dual PPARαandδagonist elafibranor has also undergone extensive clinical testing,which reached the phase III clinical trial but failed to demonstrate a beneficial effect on MASLD.As alcohol-associated liver disease and MASLD can be interconnected,whether elafibranor might be affective against liver disease caused by alcohol consumption is worth investigating.Writing recently in the World Journal of Gastroenterology,Koizumi et al reported using a mouse model of alcoholassociated liver disease and found that hepatic steatosis,liver fibrosis,and hepatocyte apoptosis were alleviated by administration of elafibranor.Although preclinical in nature,these data support the potential beneficial action of elafibranor in alcohol-induced MASLD,warranting the testing of this molecule in patients with steatotic liver disease caused by alcohol consumption.

Advancements in liver retraction techniques for laparoscopic gastrectomy

Traditionally,liver retraction for laparoscopic gastrectomy is done via manual methods,such as the placement of retractors through the accessory ports and using a Nathanson retractor.However,these techniques often posed issues including extra abdominal incisions,risk of liver injury or ischaemia,and the potential for compromised visualization.Over the years,the development of innovative liver retraction techniques has significantly improved the safety and efficacy of laparoscopic gastrectomy and similar other hiatal procedures.This editorial will comment on the article by Lin et al,and compare this to the other liver retractor techniques available for surgeons and highlight the pros and cons of each technique of liver retraction.

High metabolic dysfunction-associated steatotic liver disease prevalence in type 2 diabetes: Urgent need for integrated screening and lifestyle intervention

This letter discusses the recent study by Mukherjee et al,which identifies a significant prevalence of metabolic dysfunction-associated steatotic liver disease(MASLD)among newly diagnosed type 2 diabetes mellitus(T2DM)patients in Bihar,India,and underscores the pressing need for integrated MASLD mana-gement within T2DM care.With 72.3%of the study cohort affected by MASLD,implementing routine liver function tests and ultrasound screenings is recom-mended as a standard practice in diabetes care,especially in regions with high prevalence rates.The study also advocates for dietary and lifestyle modifications,particularly the reduction of saturated fats,to slow MASLD progression.Patient education on monitoring body mass index and waist circumference,coupled with the integration of these metrics into digital health records,could enhance patient involvement and support proactive health management.Moreover,the letter emphasizes the advantages of developing a region-specific MASLD risk model that incorporates local dietary patterns and socioeconomic factors.Continued research into genetic and environmental determinants of MASLD remains es-sential for advancing our understanding of its etiology and informing targeted public health strategies.

Prediction of posthepatectomy liver failure in patients withhepatocellular carcinoma through ultrasound elastography

In this article,we comment on the article by Cheng et al published in recently.Posthepatectomy liver failure(PHLF)remains a leading cause of hepatectomyrelated mortality and can be evaluated according to liver reserve function.Liver stiffness(LS)measured by ultrasonic elastography and spleen area demonstrate a strong correlation with hepatic proliferation,fibrosis,and portal vein congestion,thus indirectly reflecting liver reserve function.This article highlights a meticulous study aimed at investigating the potential of two-dimensional shear wave elastography in assessing LS,as well as its integration with spleen area,surgical factors,and laboratory indicators,for predicting the risk of PHLF in hepatocellular carcinoma patients.In this article,we discussed the non-invasive elastography modality by ultrasound and magnetic resonance imaging to assess LS.Based on literature data,we subsequently suggested that several risk factors may contribute to PHLF,including excessive intrahepatic neutrophil accumulation,the formation of neutrophil extracellular traps,end-stage liver disease scores,and albumin-bilirubin scores.Therefore,a more comprehensive study incor-porating detailed information requires further investigation.

Assessment of skeletal muscle alterations and circulating myokines in metabolic dysfunction-associated steatotic liver disease:A crosssectional study

BACKGROUND Skeletal muscle alterations(SMAs)are being increasingly recognized in patients with metabolic dysfunctionassociated steatotic liver disease(MASLD)and appear to be associated with deleterious outcomes in these patients.However,their actual prevalence and pathophysiology remain to be elucidated.AIM To determine the prevalence of SMAs and to assess the significance of circulating myokines as biomarkers in patients with MASLD.METHODS Skeletal muscle strength and muscle mass were measured in a cross-sectional study in a cohort of 62 patients fulfilling MASLD criteria,recruited from the outpatient clinics of a tertiary level hospital.The degree of fibrosis and liver steatosis was studied using abdominal ultrasound and transitional elastography.Anthropometric and metabolic characteristics as well as serum levels of different myokines were also determined in the MASLD cohort.Statistical analysis was performed comparing results according to liver fibrosis and steatosis.RESULTS No significant differences were found in both skeletal muscle strength and skeletal muscle mass in patients with MASLD between different stages of liver fibrosis.Interestingly,serum levels of fibroblast growth factor-21(FGF21)were significantly higher in patients with MASLD with advanced hepatic fibrosis(F3-F4)than in those with lower fibrosis stages(F0-F2)(197.49±198.27 pg/mL vs 95.62±83.67 pg/mL;P=0.049).In addition,patients with MASLD with severe hepatosteatosis(S3)exhibited significantly higher serum levels of irisin(1116.87±1161.86 pg/mL)than those with lower grades(S1-S2)(385.21±375.98 pg/mL;P=0.001).CONCLUSION SMAs were uncommon in the patients with MASLD studied.Higher serum levels of irisin and FGF21 were detected in patients with advanced liver steatosis and fibrosis,respectively,with potential implications as biomarkers.

Hepatitis B virus infection and metabolic dysfunction associated steatotic liver disease:Rising pandemic with complex interaction

Due to sedentary lifestyle and rising prevalence of obesity,patients with general population and those who are infected with chronic hepatitis B are found to have metabolic dysfunction associated steatotic liver disease(MASLD).Both chronic hepatitis B virus(HBV)infection and MASLD can damage hepatocytes in their own way,but concomitant HBV-MASLD has its own clinical implications.Cherry on top is the presence of diabetes mellitus,hypertension or obesity which added more chances of unfavorable outcomes in these patients.In this article,we co-mment on the article by Wang et al published in the recent issue.This article provides a comprehensive overview of the complex interaction between HBV-MASLD,HBV alone and MASLD alone patients.We discuss key findings from recent studies,including the promising outcomes observed in patients with concurrent HBV and MASLD,warrants further research.The insights presented here offer renewed understanding of this complex interaction.

Delivering Care

Gertrude Nyathi walks calmly into Zimbabwe’s Mahusekwa Hospital for antenatal care in Mashonaland,where she is expected to give birth in the next five months.In a country where medical facilities are obsolete,patients flock to seek medical care at the Chinese-aided hospital,seen by many as a game changer in Marondera district.

Reducing invasiveness in liver surgery-where is the limit?

In this article,we comment on the article by Wang et al published in the recent issue of the World Journal of Gastroenterology Surgery.Most prominent advancements in liver surgery in the last two decades are related to refinements in surgical technique(extraglissonean approach)and advancements in surgical technology(laparoscopy and robotics).In this article,authors present both these aspects:Laparoscopic segmentectomy using extraglissonean approach.Furthermore,they describe segmental resections of all 8 segments which is the main novelty that can be observed in the article.By now,extraglissonean approach was thoroughly described mainly in hepatectomies or lateral sectionectomies.Various“hilar gates”are defined which allows safe liver resection by ligating Glissonean pedicles first which is then followed by parenchymal resection.We here focus on past,present and future perspectives of extraglissonean approach and laparoscopic liver resections and comment the value of the presented article.

Prognostic value of combined detection of alpha-fetoprotein,plasma prothrombin activity,and serum prealbumin in acute-on-chronic liver failure

BACKGROUND Acute-on-chronic liver failure(ACLF)is a liver disease based on chronic liver disease,which is significantly influenced by clinical treatment regimen and disease status,and despite the existence of multiple prognostic assessment indicators for ACLF,the overall sensitivity and accuracy are relatively low.AIM To investigate the prognostic value of the combined detection of alpha-fetoprotein(AFP),plasma prothrombin activity(PTA),and serum prealbumin(PA)in ACLF.METHODS This retrospective study included 87 patients with ACLF admitted from February 2021 to February 2023 and categorized them into the survival(n=47)and death(n=40)groups according to their clinical outcomes 3 months posttreatment.All the participants underwent AFP,PTA,and PA level measurements upon admission.Baseline data,as well as AFP,PTA,and PA levels,were comparatively analyzed.Pearson correlation coefficients were utilized to analyze the correlations of AFP,PTA,and PA with different survival outcomes in patients with ACLF.Receiver operating characteristic(ROC)curves and areas under the curves were used to evaluate the predictive value of AFP,PTA,and PA for ACLF prognosis.RESULTS AFP,PTA,and PA levels were markedly decreased in the death group than in the survival group(P<0.05).Pearson analysis indicated a positive association of the AFP,PTA,and PA levels with the survival of patients with ACLF(P<0.05).ROC curve analysis determined the sensitivity and specificity of the combined diagnosis at 91.24%and 100.00%,respectively,both of which were notably increased compared to the single-index diagnosis.The ROC of their combined diagnosis was 0.989,significantly surpassing 0.907,0.849,and 0.853 of AFP,PTA,and PA,respectively.No statistically significant variance was determined in the sensitivity and specificity of the combined diagnosis vs the single detection(P>0.05).CONCLUSION The combined detection of AFP,PTA,and PA levels demonstrates favorable diagnostic value for the short-term prognosis of patients with ACLF,featuring high sensitivity and specificity.

Relevant clinical factors for early extubation in living-donor liver transplantation: A single-center retrospective cohort study

BACKGROUND Clinical guidelines for early extubation after liver transplantation remain lacking,with significant variations in the rates of early extubation across transplantation centers.AIM To identify clinical factors,including the use of epidural analgesia,associated with early extubation in living-donor liver transplantation(LDLT).METHODS The medical records of LDLT recipients were analyzed in this study,categorizing them based on extubation timing as delayed(leaving the operating room without extubation)or early(tracheal tube removed immediately after surgery).A multivariate binary logistic regression analysis was performed.Subgroup analysis was conducted,excluding patients contraindicated for epidural analgesia owing to significant coagulopathy.RESULTS Total of 159 patients,93(58.5%)underwent early extubation.Relevant clinical factors of early extubation were shorter anhepatic time[adjusted odds ratio(OR)=0.439,95%confidence interval(CI):0.232-0.831;P=0.011],absence of high-dose vasoactive drug use at the end of surgery(OR=0.235,95%CI:0.106-0.519;P<0.001),and the use of epidural analgesia(OR=15.730,95%CI:1.919-128.919;P=0.010).In a subgroup analysis of 67 patients,epidural analgesia remained a relevant clinical factor for early extubation(adjusted OR=19.381,95%CI:2.15-174.433;P=0.008).CONCLUSION Shorter anhepatic time,absence of high-dose vasoactive drug use at the end of surgery,and the use of epidural analgesia are relevant clinical factors of early extubation following LDLT.

Parameter changes and influencing factors in sixty patients with interventional surgery for liver cancer diagnoses

BACKGROUND The development of hepatocellular carcinoma(HCC)is influenced by multiple factors.Interventional therapy offers an effective treatment option for patients with unresectable intermediate-to-advanced HCC.Interventional therapy can induce electrocardiographic(ECG)abnormalities that may be associated with liver dysfunction,electrolyte disorders,and cardiac injury.AIM To explore the ECG alterations and determinants following interventional therapy in patients with HCC.METHODS Sixty patients undergoing interventional treatment for liver cancer were selected as study participants.According to the results of the dynamic ECG examination 1 day after surgery,the patients were divided into an abnormal group(n=21)and a nonabnormal group(n=39).With the help of dynamic ECG examination,the ECG parameters were compared and the baseline data of patients was recorded in the two groups.RESULTS The 24 hours QT interval variability,24 hours normal atrial polarization to ventricular polarization(R-R)interval(standard deviation),24 hours consecutive 5 minutes normal R-R interval,and 24 hours continuous 5 minutes normal R-R interval(standard deviation mean)were lower than patients in the nonabnormal group(P<0.05).The logistic analysis showed that age>60 years,liver function grade B,and postoperative body temperature 38°C were risk factors for abnormal dynamic electrocardiogram in patients with liver cancer intervention(P<0.05).CONCLUSION Interventional therapy for HCC can lead to ECG abnormalities,underscoring the clinical need for enhanced cardiac monitoring to mitigate myocardial complications.

Mild liver injury following withdrawal of long-term prednisonetherapy: A case report

BACKGROUND Liver injury manifesting as hepatic enzyme abnormalities,has been occasionally identified to be a feature of primary or secondary Addison's disease,an uncommon endocrine disease characterized by adrenal insufficiency.There have been no more than 30 reported cases of liver injury explicitly attributed to Addison's disease.Liver injury resulting from adrenal insufficiency due to glucocorticoid withdrawal is exceptionally rarer.CASE SUMMARY A 42-year-old man presented with fatigue and mildly elevated transaminases.Laboratory investigations and imaging studies excluded common etiologies of liver injury.Based on the fact that the patient discontinued long-term therapy with prednisone approximately 2 weeks before he was found to have elevated transaminase levels and the observation that his cortisol was lower than the normal value,he was diagnosed as having hypertransaminasemia secondary to adrenal insufficiency caused by glucocorticoid withdrawal.The patient was infused intravenously with compound diisopropylamine dichloroacctate and compound glycyrrhizin,and his transaminase levels returned to normal after 1 week.Approximately 2 years later,the patient received hydroprednisone treatment for 2 days in an endoscopic sinus surgery.Eight days after he discontinued the hydroprednisone treatment,he developed symptoms reminiscent of glucocorticoid withdrawal syndrome.These symptoms resolved spontaneously after 1 week.Intriguingly,the patient did not develop hepatic dysfunction this time.CONCLUSION The present case,showing some unusual clinical features,highlights the importance of education of clinicians and patients to avoid improper discontinuation of glucocorticoid therapy and complete history taking for prompt recognition.

What is the role of nonalcoholic fatty liver disease in pulmonary carcinoma development?

This article summarizes the epidemiological characteristics and clinical manifest-ations of nonalcoholic fatty liver disease(NAFLD).The incidence of NAFLD has been increased dramatically and become the leading cause of chronic liver disease worldwide.In addition to its adverse outcomes of liver fibrosis,cirrhosis,and hepatocellular carcinoma,and related complications,NAFLD has recently been found to be associated with the high-risk extrahepatic carcinomas,such as various types of lung cancer(i.e.,lung adenocarcinoma,squamous cell carcinoma,and small cell lung cancer).The presence of hepatic steatosis also predisposes lung cancer to liver metastasis,but has better response to immune checkpoint inhibi-tors.Whether other factors(i.e.,gender,smoking,etc.)are associated with NAFLD and lung cancer remains controversial.We also comment on the reciprocal rela-tionships between NAFLD and components of metabolic syndrome.Most meta-bolic syndrome components are suggested to facilitate lung cancer development via activating insulin/insulin-like growth factor axis.In addition,suppressed anti-tumor immunity and accelerated tumor progression could be attributed to the cell-specific metabolic reprogramming in condition of high-fat diet and related obesity.These findings may reveal the role of NAFLD in pulmonary carcinoma and help develop new treatment strategies for this disease.