Transition process in children with chronic liver diseases:what is the challenging point?

Pediatric chronic liver diseases encompass a wide spectrum of hepatopathies with a relevant health medical and financial burden(1,2).In addition to inherited disorders(e.g.,Alagille syndrome,metabolic disorders,etc.),there are numerous chronic liver conditions including metabolic dysfunction-associated steatotic liver disease(MASLD)and autoimmune liver diseases affecting morbidity,quality of life,and life expectancy of these young patients(3,4).To complicate matters,the exact prevalence of childhood chronic liver diseases is still unknown since their asymptomatic course especially in the early stages but increasing rates are reported worldwide(1,5,6).Moreover,management of these chronic conditions represents a great challenge for clinicians as it requires a lifelong multi-disciplinary approach(1).Worthy of note,advances in the knowledge of pathophysiological mechanisms underlying liver diseases greatly improved their natural history with increased survival rates into adulthood(1,3).Given that,adult hepatologists are increasingly dealing with most of these conditions(3).

Is it now possible to transition from laparoscopic liver resection to robotic liver resection?

Minimally invasive surgery(MIS)has significantly progressed and emerged as the preferred approach for various gastrointestinal procedures,including gastrectomy,cholecystectomy,and various colorectal surgeries(1).However,the widespread acceptance of robotic surgery in liver resection has encountered obstacles,attributed to factors such as the lack of appropriate surgical instruments,the intricate learning curve,and safety apprehensions.Nonetheless,the utilization of MIS in liver resection is linked to decreased blood loss,reduced post-operative pain,shorter hospital stays,and lower morbidity rates compared to both open and laparoscopic liver resection procedures(2).

Update on herbal and dietary supplement-induced liver injury:current gaps and future directions

Drug-induced liver injury(DILI)is a rare but potentially life-threatening condition,which accounts for the majority of acute liver failure cases in the US and EU.Unlike direct hepatoxicity,which is mainly caused by acetaminophen,idiosyncratic DILI is unpredictable and occurs unrelated to the dose or frequency of the medication.Interestingly,DILI cannot only be caused by a large variety of prescription drugs,but also by herbal and dietary supplements(HDS).While HDS-DILI has already played a role in Asian countries like China or Korea for a long time,there is also an increasing incidence of HDS-DILI in countries with formerly less HDS-DILI cases such as the US,presumably due to a rising usage of those remedies(1).

Managing portal hypertension in patients with liver cirrhosis and hepatocellular carcinoma:non-invasive diagnosis and systemic treatment considerations

Portal hypertension(PH)represents a crucial complication of liver cirrhosis that significantly impacts a patient’s prognosis.Controlling portal venous pressure requires a combination of medical and interventional treatments.However,it’s important to note that the presence of other conditions in patients,such as hepatocellular carcinoma(HCC),can influence the treatment approaches for PH and subsequently affect the overall outcomes.Clinicians should consider that condition when developing treatment strategies to enhance patient outcomes(1).

Patient with unresectable colorectal liver metastases and asymptomatic primary tumor:end of the debate!

In patients with definitively unresectable colorectal liver metastases,whether the primary tumor should be resected prior to chemotherapy is an old question.Several retrospective studies(1-5)and a meta-analysis with individual data(6)had suggested that primary resection of the primary tumor followed by chemotherapy was associated with better survival than the chemotherapy-first strategy.The prevention of complications related to the primary tumor(occlusion,perforation,bleeding)as well as a better response to chemotherapy were usual justifications to explain the superiority of primary tumor resection-first.However,the absence of any randomized study made it difficult to conclude on this question due to the numerous selection biases related to these retrospective analyses.

Functional assessment of liver regeneration after major hepatectomy

Background: Liver regeneration is crucial to restore the functional liver mass after liver resection. The aim of this study was to evaluate the early postoperative changes in remnant liver function, volume and liver stiffness after major liver resection and their correlation with postoperative outcomes. Methods: Patients undergoing major liver resection (≥3 segments) between February and November 2018 underwent both functional assessment using technetium-99m mebrofenin hepatobiliary scintigraphy (HBS) and CT-volumetry of the (future) remnant liver on preoperative day 1, the 5th postoperative day, and 4-6 weeks after resection. At the same time points, patients underwent transient elastography (TE) for the assessment of liver stiffness. Severe postoperative complications (Clavien-Dindo ≥ 3A) and mortality were correlated with the functional and volumetric increases of the remnant liver. Liver failure was graded according to the International Study Group of Liver Surgery (ISGLS) criteria. Results: A total of 18 patients were included of whom 10 (56%) had severe complications and one patient (5%) developed liver failure. Function and volume of the remnant liver had increased by the 5th postoperative day from 6.9 (5.4-10.9) to 9.6 (6.7-13.8) %/min/m2, P=0.004 and from 795.5 (538.3-1,037.5) to 1,080.0 (854.0-1,283.3) mL, P<0.001, respectively. After 4-6 weeks, remnant liver volume had further increased [from 1,080.0 (854.0-1,283.3) to 1,222.0 (1,016.0-1,380.5) mL, P=0.035], however, liver function did not show any significant, further increase [from 9.6 (6.7-13.8) to 10.9 (8.8-13.6) %/min/m2, P=0.177]. Liver elasticity of the future remnant liver (FRL) increased [from 10.8 (5.7-18.7) to 17.5 (12.4-22.6) kPa, P=0.018] and gradually recovered after 4-6 weeks to a median of 10.9 (5.7-18.8) kPa (T3 vs. T4, P=0.079). Patients who had severe postoperative complications did not show a significant increase in liver function on the 5th postoperative day (P=0.203), despite increase of volume (P<0.01). Conclusions: Functional regeneration of the remnant liver predominantly occurs during the first 5 days after resection. In case of severe complications, functional regeneration is delayed, in contrast to volume increase.

Controlling cholesterol entry into mitochondria,a key step for hepatocarcinogenesis in non-alcoholic steatohepatitis-related hepatocellular carcinoma

Hepatocellular carcinoma(HCC)is the sixth most common cancer and the second leading cause of cancer-related death worldwide(1).Unfortunately,the incidence and mortality of HCC are increasing steadily in formerly low-risk countries(2).Although the contribution of patients infected with hepatitis B virus(HBV)and hepatitis C virus(HCV)has dramatically decreased due to the use of highly effective antiviral agents,increasing epidemiologic evidence indicates a link between non-alcoholic fatty liver disease(NAFLD)and the risk of HCC(1).It is important to highlight that the prevalence of NAFLD has increased in parallel with the obesity,metabolic syndrome,and type 2 diabetes mellitus pandemic.Among patients with NAFLD,the incidence of HCC is around 0.44 per 1,000 person-years(3).

Whole grain intake and pancreatic cancer risk

Cancer is one of the leading causes of death worldwide,and there is evidence that dietary factors contribute significantly to cancer risk(1).Whole grain foods are associated with a lower risk of several chronic diseases,including cancer,and are recommended as part of a healthy diet(1,2).Over the past 10 years,multiple meta-analyses have shown that whole grain intake is associated with lower risk of total and site-specific cancer incidence and mortality(3).

A comparative study of pancreas transplantation between type 1 and 2 diabetes mellitus

Background:Pancreas transplantation remains the best long-term treatment option to achieve physiological euglycemia and insulin independence in patients with labile diabetes mellitus(DM).It is widely accepted as an optimal procedure for type 1 DM(T1DM),but its application in type 2 DM(T2DM)is not unanimously acknowledged.Methods:In total,146 diabetes patients undergoing pancreas transplantation were included in this study.Clinical data and outcomes were compared between the T1DM and T2DM groups.Results:Majority(93%)of the pancreas transplantations in T2DM were for uremic recipients.Complications occurred in 106(73%)patients,including 70(48%)with early complications before discharge and 79(54%)with late complications during follow-up period.Overall,rejection of pancreas graft occurred in 37(25%)patients.Total rejection rate in T2DM recipients was significantly lower than that in T1DM.The short-and long-term outcomes for endocrine function in terms of fasting blood sugar and hemoglobin A1c levels and graft survival rates are comparable between the T2DM and T1DM groups.Conclusions:T2DM is not inferior to T1DM after pancreas transplantation in terms of surgical risks,immunological and endocrine outcomes,and graft survival rates.Therefore,pancreas transplantation could be an effective option to treat selected uremic T2DM patients without significant insulin resistance.

Optimizing future remnant Iiver prior to major hepatectomies:increasing volume while decreasing morbidity and mortality

Post hepatectomy liver failure(PHLF)remains the most dreaded complication in major hepatectomies.Adequate future remnant liver(FRL)plays a pivotal role in prevention of PHLF.Pre-operative portal vein embolization(PVE)has become standard of care for increasing the FRL in preparation for major hepatectomies.Associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)has also been used,though has demonstrated a substantial risk of morbidity and mortality.However,there are many situations in which PVE achieves an inadequate extent of hypertrophy,potential increasing the risk of PHLF.Panaro and colleagues explore their data with a prospective review of preoperative PVE versus liver venous deprivation(LVD)regarding intra and post-operative complications,as well as,histologic findings(1).This study adds to a growing body of literature assessing the benefit of LVD over PVE and ALPPS both,in regards to increased rate of hypertrophy,improvement in FRL,in the face of similar morbidity/mortality rates compared to PVE.

The role of fluid restriction in abdominal surgery

Recently,Myles et al.(1)published a multi-center randomized controlled trial(RCT)concluding that compared to liberal fluid regimen,restricted fluid regimen did not improve clinical outcomes in patients after abdominal surgery.Perioperative fluid management plays an important role in postoperative care.As fluid accumulation was associated with poor outcomes in surgical patients(2),restricted fluid protocol was investigated to alleviate this situation.However,the conclusions remain conflicting.In contrast to Myles et al.'s finding,the benefits of restricted fluid protocol have been reported in several RCTs(PMID:12044376,14578723,21948211).

Nonalcoholic fatty liver disease in obese adolescents: the role of genetic polymorphisms

Nonalcoholic fatty liver disease(NAFLD)has recently become an emerging health problem worldwide(1).The pathogenetic mechanisms involved in the development and progression of NAFLD are due to genetic predisposition that expresses a metabolic profile associated with high energy food intake(2).The most accurate estimate of the worldwide prevalence of NAFLD is 24–25%of the general population,and ranges from 5–18%in Asia to 20–30%in the Western countries(1,3).Nowadays,the reason for this variability is not clear yet.However,it is plausible that genetic factors could play a major role in pathogenesis and the advances in genomics,transcriptomics,and proteomics have highlighted new pathogenic pathways.In fact,increasing literature data support the role of single nucleotide polymorphisms(SNPs),and in particular the SNPs of genes involved in insulin signaling,lipid homeostasis,and oxidative stress,not only in the susceptibility to develop NAFLD,but also in the severity of liver damage and in the etiology of multisystemic metabolic disorders(4).The development of the Genome Wide Association Study technology has allowed the identification of many SNPs involved in the onset of NAFLD,since they can change the stages of development,the rate of progression,and the efficacy of treatment(5).Recently,Tricòet al.investigate the clinical and genetic features associated with pediatric NAFLD in a prospective study in a large multiethnic cohort of obese adolescents(6).A total of 503 subjects,identified as"The Yale Pediatric NAFLD cohort",were enrolled,including 191(38.0%)Caucasians,134(26.6%)African Americans,and 178(35.4%)Hispanics.

Gut microbiome beats two to zero host genome

The gut microbiota and its genomic scaffold, exceeding the human one nearly 500 times, substantially affect human health and diseases. Host-microbe interactions, exerted through microbial biochemical and immunological activities, contain pathogen burden, control neurological and endocrine signalling, enterocyte wellness, energy biosynthesis, gut dysbiosis, complement gaps of host metabolic pathways, finally contributing to human physiology and disease within the gastrointestinal district and through gut-liver and gut-brain axis (1). Regardless substantial advances in correlating microbiota modulation and perturbation with various influencers, the specific impact of internal and external stimuli need to be definitely assigned though causality relationships beyond correlative measures. Host origin or genetic background, age, sanitation, delivery mode, breast-feeding and weaning, infections, diet, drugs, but also exercise, sleep, stress have been reviewed in a wide range of recent literature (2). All external (i.e., food, pathogens) and internal (i.e., microbiota) host modulating factors, both, can be conceptually synthetized by the term "exposome" which we are exposed to in the lifetime and which drives both individual enterophenotypes and disease phenotypes (3). Integrative descriptive and functional charts of microbiota allow the description of the microbiota-host Holobionts system, relationship that can be employed in understanding personalized physiology and nutrition, thus providing patient-tailored therapies (Figure 1). To investigate microbiota unbalance and passage from healthy to disease or unhealthy status, individual baseline compositions and variations within an individual's own range are required.

Left hepatectomy with concomitant cavo-atrial and biliary tumor thrombectomy for invasive hepatocellular carcinoma:a video report

Introduction Representing the prevalent primary hepatic malignancy,hepatocellular carcinoma(HCC)is concurrently the sixth most common cancer worldwide and the third dominant cause of mortality due to cancer(1,2).The preponderance of such neoplasms is secondary to cirrhosis,primarily induced by viral hepatitis,alcohol abuse or exposure to other hepatotoxins.Over the last decades,however,metabolic disorders such as obesity and insulin resistance,have established as key players in the chronic damage of liver parenchyma,eventually contributing to the development of the large spectrum of chronic hepatopathies known as non-alcoholic fatty liver disease(NAFLD)(3).

Will the magnetic resonance imaging proton density fat fraction replace liver biopsy as the gold standard for detecting steatosis?

Accompanied with the ongoing epidemics of obesity and metabolic syndrome arising from the westernization of lifestyles, the incidence of nonalcoholic fatty liver disease (NAFLD) has been getting higher worldwide in the last decades (1).

Resection post-radio-embolization in patients with single large hepatocellular carcinoma

We read with interest this article evaluating the results of transarterial radioembolization(TARE)in the management of large(≥5 cm)initially unresectable hepatocellular carcinoma(HCC)(1).The aim of this retrospective study was to compare the results of upfront resection(single,resectable large HCC)with resection preceded by TARE(single,initially unresectable large HCC).The authors retrospectively analyzed the 216 patients managed with a single HCC larger than 5 cm,between 2015 and 2020 in their center.Patients were divided into two groups:upfront surgery(n=144,66.7%)or TARE if considered unresectable(n=72,33.3%).Then,among those who had undergone TARE,a further dichotomy was made between those who had undergone surgery(“TARE-surgery”,n=20,9%)and those who had not(“TARE-only”,n=52,24%).

Shrinking fat,healing liver:unlocking the metabolic dysfunction associated steatohepatitis puzzle

Metabolic dysfunction associated steatohepatitis(MASH)is a silent epidemic,hiding in the shadows of obesity,and often silently advancing towards the grave complication of cirrhosis.The distinction between MASH and simple hepatic steatosis,which is under the spectrum of metabolic dysfunction-associated steatotic liver disease(MASLD),is highly desired as it provides critical information about the prognosis of the patient.Noninvasive indicators,such as fibrosis-4(FIB-4)index and nonalcoholic fatty liver disease(NAFLD)fibrosis score that includes conventional laboratory data and clinical parameters.

Parenchymal sparing anatomical liver resections for hepatocellular carcinoma

The rationale of the performance of anatomic resection(AR)of the liver in case of hepatocellular carcinoma(HCC)is the removal of portal pedicle feeding the tumor because of the tumor’s tendency to invade the portal veins(1).This technical approach is expected to be effective from an oncological perspective for a disease such as HCC,which is associated with a high rate of intrahepatic recurrence(2,3).In the eighties,Makuuchi et al.proposed the systematic subsegmentectomy(4)reporting excellent results(5),and later some other authors reported new techniques to identify the portal territory of a given HCC and perform a true AR of the liver(5-7).

Association of Pringle maneuver with postoperative recurrence and survival following hepatectomy for hepatocellular carcinoma: a multicenter propensity score and competing-risks regression analysis

Background:The application of Pringle maneuver(PM)during hepatectomy reduces intraoperative blood loss and the need for perioperative transfusion,but its effect on long-term recurrence and survival for patients with hepatocellular carcinoma(HCC)remains controversial.We sought to determine the association between the application of PM and post-hepatectomy oncologic outcomes for patients with HCC.Methods:Patients who underwent curative hepatectomy for HCC at 9 Chinese hospitals from January 2010 to December 2018 were identified.Using two propensity score methods[propensity score matching(PSM)and inverse probability of treatment weight(IPTW)],cumulative recurrence rate and cancer-specific mortality(CSM)were compared between the patients in the PM and non-PM groups.Multivariate competing-risks regression models were performed to adjust for the effect of non-cancer-specific mortality and other prognostic risk factors.Results:Of the 2,798 included patients,2,404 and 394 did and did not adopt PM(the PM and non-PM groups),respectively.The rates of intraoperative blood transfusion,postoperative 30-day mortality and morbidity were comparable between the two groups(all P>0.05).In the PSM cohort by the 1:3 ratio,compared to 382 patients in the non-PM group,1,146 patients in the PM group also had the higher cumulative 5-year recurrence rate and CSM(63.9%and 39.1%vs.55.3%and 31.6%,both P<0.05).Similar results were also yielded in the entire cohort and the IPTW cohort.Multivariate competing-risks regression analyses demonstrated that no application of the PM was independently associated with lower recurrence rate and CSM based on various analytical cohorts[hazard ratio(HR),0.82 and 0.77 in the adjusted entire cohort,HR 0.80 and 0.73 in the PSM cohort,and HR 0.80 and 0.76 in the IPTW cohort,respectively].Conclusions:The findings suggested that no application of PM during hepatectomy for patients with HCC reduced the risk of postoperative recurrence and cancer-specific death by approximately 20–25%.

Wilson’s disease:practical information for general physicians

Wilson’s disease is an autosomal-recessive disorder with an ATP7B mutation that causes a functional failure of the copper-transporting protein ATP7B(1,2).As a result,unbound copper in the blood increases,and due to copper accumulation,multiple organs show various symptoms,e.g.,Kayser-Fleischer rings,acute liver failure,liver cirrhosis,liver cancer,dysarthria,tremors,character changes,renal disorders,rheumatological symptoms,endocrinopathy,heart failure,and arrhythmias(3,4).This disease afflicts approximately 1 in 40,000 people,with approximately 1 carrier for every 100 people,and early diagnosis is difficult.