The conclusion of reducing acute rejection after liver transplantation by machine perfusion should be extrapolated with caution

There is a theory that the unavoidable graft damage caused by ischemia-reperfusion injury(IRI)during liver transplantation(LT)can lead to severe IRI-related inflammation and trigger an early activation of the innate immune response mediated by T-cells,which potentially worsening the acute cellular rejection(ACR)cascade.As a result,machine perfusion(MP)has been placed great expectations for the potential to diminish post-LT ACR and other related immune responses by alleviating IRI through removing harmful substances and restoring cellular metabolism homeostasis(1,2).However,there has been much debate about MP’s benefits on ACR as relative data is limited.

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.

β-cryptoxanthin and fatty liver disease:new insights

β-cryptoxanthin is a nutritionally important xanthophyll found in orange-fleshed tropical and citrus fruits,including papaya,oranges,and tangerines(1).It is also one of the most commonly detected carotenoids in human tissues(1).Uniquely,β-cryptoxanthin is the only regularly consumed dietary xanthophyll to have an intactβ-ionone ring,thus in addition to functioning as an antioxidant it can also be metabolized to vitamin A.A limited number of past studies have shown a beneficial effect ofβ-cryptoxanthin supplementation in animal models of hepatic steatosis(2).As discussed below,the recent publication by Liu et al.from the group led by Dr.Xiang-Dong Wang has provided new insight into the benefits ofβ-cryptoxanthin supplementation in the context of fatty liver disease(3).

“Digging in the Dirt”faecal microRNAs as dietary biomarkers of host-microbe interactions

The role of diet and nutrition in maintaining a healthy lifestyle has become a central part of chronic disease prevention(1).Chronic conditions such as cancer,Inflammatory bowel disease(IBD)and obesity are more prevalent in people with poor diets(2).Food consumption is controlled by physiological systems such as the gut-microbiome and distinct neuroendocrine pathways that overlap to promote host nutritional gain resulting in people living longer healthier lives(3).A recent analysis of the global burden of disease by the World Health Organization(WHO),noted that factors associated with poor diet,including obesity and malnutrition,critically undermine health and wellbeing.They note that undernutrition,deficiencies in key nutrients and obesity have high social and economic impacts.Cardiovascular disease,cancer,diabetes,and respiratory diseases account for 77%of all diseases and are responsible for 86%of all premature deaths(4).There is an appreciation that diets that reduce or eliminate red meats and animal fats results in the reduction of many of the indicators of poor diet,such as body mass index(BMI)and levels of cholesterol in the blood.

Safety and feasibility of laparoscopic pancreatoduodenectomy

Laparoscopic pancreaticoduodenectomy(LPD)has been safely performed by experts with favorable surgical outcomes.However,the feasibility of LPD remains controversial.LPD is generally considered a challenging operation that requires advanced laparoscopic techniques.In particular,pancreatic reconstruction can be safely performed by only laparoscopic experts.Thus,guidelines created by LPD experts are valuable in indicating the future direction of LPD.Qin et al.developed practical guidelines regarding the safety and feasibility of LPD with 28 international experts from eight countries(1).To create these guidelines,the first summit on minimally invasive pancreatico-biliary surgery was held in Wuhan,China,to promote the development of LPD.Based on a systematic literature review and expert opinions,16 statements were created by the experts.These statements provide useful guidelines not only for surgical trainees who will attempt LPD but also for specialized surgeons.This expert consensus will contribute to the safe implementation of LPDs in the future.

Editorial on“Laparoscopic versus open liver resection for hepatocellular carcinoma in elderly patients:a propensity score matching analysis”

We read with great interest the article of Delvecchio et al.published in a recent issue of HPB journal(1).The authors compared short-and long-term outcomes of laparoscopic and open liver resection(OLR)in elderly patients with hepatocellular carcinoma(HCC)using 1-1 propensity score matching(PSM).

Comment on:liver venous deprivation(LVD)or associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)?A retrospective multicentric study

We read with interest the recently published paper by Chebaro et al.(1).The authors compared liver venous deprivation(LVD)and associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)which are two novel techniques used to achieve increased hypertrophy of the future liver remnant(FLR)in view of extensive liver resections(2,3).

Optimization of the future remnant liver:review of the current strategies in Europe

Liver resection still represent the treatment of choice for liver malignancies,but in some cases inadequate future remnant liver(FRL)can lead to post hepatectomy liver failure(PHLF)that still represents the most common cause of death after hepatectomy.Several strategies in recent era have been developed in order to generate a compensatory hypertrophy of the FRL,reducing the risk of post hepatectomy liver failure.Portal vein embolization,portal vein ligation,and ALLPS are the most popular techniques historically adopted up to now.The liver venous deprivation and the radio-embolization are the most recent promising techniques.Despite even more precise tools to calculate the relationship among volume and function,such as scintigraphy with^(99m)Tc-mebrofenin(HBS),no consensus is still available to define which of the above mentioned augmentation strategy is more adequate in terms of kind of surgery,complexity of the pathology and quality of liver parenchyma.The aim of this article is to analyse these different strategies to achieve sufficient FRL.

Surgical treatment of ovarian cancer liver metastasis

In addition to hepatocellular carcinoma,metastatic liver cancer(MLC)is another focus of hepatic surgeon.Good outcome of patients with liver metastasis(LM)from colorectal cancer or neuroendocrine tumor have been achieved.Ovarian cancer liver metastasis(OCLM)has its unique oncological characteristics and a variety of metastasis patterns,which brings a challenge to hepatic surgeon.Hepatic surgeons hold different views and techniques from gynecologists,which makes differences in the evaluation and treatment of the disease.We reviewed recent studies and,in combination with our own clinical experience,attempted to introduce the progress of surgical treatment of liver metastases from OC.In our experience,both preoperative imaging and surgical procedures are based on the assurance of R0 resection.R0 cytoreductive surgery(CRS)is the most favorable determinant for the prognosis of OC patients,and R0 liver resection(LR)is a component of R0 CRS.Gynecologists and hepatic surgeons should do their own preoperative and intraoperative evaluation for the extrahepatic and intrahepatic metastasis respectively.During the operation,regardless of the miliary nodules dissemination between the right hemidiaphragm and liver capsule,liver parenchymal infiltration(LPI)or liver parenchymal metastasis(LPM),1–2 cm resection margin should be emphasized.For patients with liver portal lymph node metastasis(LPLNM),hepatic portal skeletonization should be performed,rather than portal lymph node dissection.The operation should be as radical as possible to ensure the patients to achieve good prognosis.

Surgical resection plus radiofrequency ablation for the treatment of multifocal hepatocellular carcinoma

Background:To compare the efficacy and safety of surgical resection plus radiofrequency ablation(SR-RFA)with transarterial chemoembolization(TACE)in patients with multifocal hepatocellular carcinoma(HCC)beyond the Milan criteria.Methods:From 2009 to 2015,a total of 469 consecutive patients with multifocal HCC beyond the Milan criteria(≤5 nodules)treated with SR-RFA(n=59)or TACE(n=410)were analyzed.Their overall survival(OS)rate was compared through propensity score matching(PSM)analysis at a ratio of 1:2,and 141 patients were identified(SR-RFA,n=47;TACE,n=94).Subgroup analysis was conducted according to factors associated with treatment options.Results:Before PSM,the 1-,2-and 3-year OS rates were 81.5%,68.3%and 64.3%in the SR-RFA group and 58.7%,35.5%and 24.4%in the TACE group,respectively(all P<0.001).After PSM,the 1-,2-and 3-year OS rates in the SR-RFA group were 81.8%,68.7%and 63.4%,whereas those in the TACE group were 59.3%,36.1%and 19.4%,respectively(all P<0.001).Subgroup analysis also revealed a survival advantage of SR-RFA over TACE in each subgroup.The 30-day mortality rate was 1.22%in the TACE group and nil in the SR-RFA group(P=0.861).Conclusions:SR-RFA provides better a long-term survival rate than TACE for patients with multifocal HCC beyond the Milan criteria.SR-RFA may serve as an alternative treatment for patients with multifocal HCC in a selected patient population.

Lymphovascular tumor embolus might be a risk factor for peritoneal metastasis after laparoscopic hepatectomy for hepatocellular carcinoma

Laparoscopic hepatectomy has been applied to treat hepatocellular carcinoma(HCC)(1-7).Previous reports show that laparoscopic procedure is as safe as the open procedure,and the long-term results are also inspiring.However,there are still doubts about whether laparoscopic procedure would increase the possibility of peritoneal metastasis and what the risk factors may be.This issue has not been found or mentioned in these recent reports.However,we here present two patients with HCC who developed peritoneal metastasis after laparoscopic hepatectomy.Risk factors for peritoneal metastasis after laparoscopic hepatectomy merits further study.

Complete portal vein occlusion after cyanoacrylate sclerotherapy in biliary atresia treated by living donor liver transplantation with intraoperative portal vein stenting via segment 4 portal vein stump

IntroductionLiving donor liver transplantation(LDLT)is a durable treatment for end-stage liver disease due to biliary atresia(BA)with excellent graft and patient survivals as shown in our previous study(1).Vascular complications are a major cause of graft failure in LDLT,particularly in children,where size disparity between donor and recipient vessels is often unavoidable.

Hepatocellular carcinoma and intrahepatic cholangiocarcinoma incidence between 2006 and 2015 in China: estimates based on data from 188 population-based cancer registries

Background:Hepatocellular carcinoma(HCC)and intrahepatic cholangiocarcinoma(ICC)are the most common subtypes of primary liver cancer,but nationwide incidence of both liver cancer subtypes have never been reported in China.We aimed to estimate the most recent incidence of HCC and ICC and temporal trends in China based on the most updated data from high qualified population-based cancer registries(covering 13.1%of the national population),in comparison to those in the United States at the same period.Methods:We used data from 188 Chinese population-based cancer registries covering 180.6 million population of China to estimate the nationwide incidence of HCC and ICC in 2015.And 22 population-based cancer registries’data were used to estimate the trends of HCC and ICC incidence from 2006 to 2015.Multiple imputation by chained equations method was used to impute liver cancer cases with unknown subtype(50.8%).We used data from 18 population-based registries from the Surveillance,Epidemiology,and End Results program to analyze incidence of HCC and ICC in the United States.Results:In China,an estimated 301,500 and 61,900 newly diagnosed HCC and ICC occurred in 2015.The overall age-standardized rates(ASRs)of HCC incidence decreased by 3.9%per year.For ICC incidence,the overall ASR was relatively stable,but increased in the population of over 65 years old.Subgroup analysis by age showed that the ASR of HCC incidence had the sharpest decline in population who were less than 14 years old and received neonatally hepatitis B virus(HBV)vaccination.In the United States,though the incidence of HCC and ICC were lower than those in China,the overall HCC and ICC incidence increased by 3.3%and 9.2%per year.Conclusions:China still faces with a heavy burden of liver cancer incidence.Our results may further support the beneficial effect of Hepatitis B vaccination on reduction of HCC incidence.Both healthy lifestyle promotion and infection control are needed for future liver cancer control and prevention for China and the United States.

Clinical practice guidelines for acute-on-chronic liver failure: are we ready for reaching global consensus?

The concept of acute-on-chronic liver failure(ACLF)has gained increasing awareness during the last decade.It considers liver cirrhosis as a systemic disease where precipitating events lead to a sudden deterioration,decompensation and extrahepatic organ failures.Disease severity is determined by the number and types of organ failures and patients with ACLF have a distinct and worse prognosis than patients with acute decompensation but not fulfilling ACLF criteria(1-3).

LEARN algorithm:a novel option for predicting non-alcoholic steatohepatitis

Background:There is an unmet need for accurate non-invasive methods to diagnose non-alcoholic steatohepatitis(NASH).Since impedance-based measurements of body composition are simple,repeatable and have a strong association with non-alcoholic fatty liver disease(NAFLD)severity,we aimed to develop a novel and fully automatic machine learning algorithm,consisting of a deep neural network based on impedance-based measurements of body composition to identify NASH[the bioeLectrical impEdance Analysis foR Nash(LEARN)algorithm].Methods:A total of 1,259 consecutive subjects with suspected NAFLD were screened from six medical centers across China,of which 766 patients with biopsy-proven NAFLD were included in final analysis.These patients were randomly subdivided into the training and validation groups,in a ratio of 4:1.The LEARN algorithm was developed in the training group to identify NASH,and subsequently,tested in the validation group.Results:The LEARN algorithm utilizing impedance-based measurements of body composition along with age,sex,pre-existing hypertension and diabetes,was able to predict the likelihood of having NASH.This algorithm showed good discriminatory ability for identifying NASH in both the training and validation groups[area under the receiver operating characteristics(AUROC):0.81,95%CI:0.77-0.84 and AUROC:0.80,95%CI:0.73-0.87,respectively].This algorithm also performed better than serum cytokeratin-18 neoepitope M30(CK-18 M30)level or other non-invasive NASH scores(including HAIR,ION,NICE)for identifying NASH(P value<0.001).Additionally,the LEARN algorithm performed well in identifying NASH in different patient subgroups,as well as in subjects with partial missing body composition data.Conclusions:The LEARN algorithm,utilizing simple easily obtained measures,provides a fully automated,simple,non-invasive method for identifying NASH.

Sengstaken-Blakemore tubes:a rescue system during liver transplantation

A 52-year-old woman has undergone liver transplantation(LT)owing to fulminant viral hepatitis,MELD 42.The first cadaveric graft allocated was a large-for-size graft.LT was performed with a piggyback side-to-side cavocaval anastomosis.At the end of the procedure,the removal of the abdominal retractor produced,due to a narrow ribcage,a caval compression with liver congestion because of a reduced caval outflow.

Combination therapies for advanced hepatocellular carcinoma: a beacon of light or a castle in the air

The review article by Zhang et al.(1)critically discussed the efficacy of combination therapies for advanced hepatocellular carcinoma(HCC)and the factors affecting efficacy and overall survival(OS)with a particular emphasis on timing and sequence of combination therapies to improve OS.The role of interventional therapies such as radio-frequency ablation(RFA)and chemoembolization were also discussed-although ablation is well-established for the treatment of small tumors,cancer,it may not be appropriate for tumors near the liver capsule or adjacent to blood vessels due to a higher risk of complications and local recurrence from untreated perivascular cells.

Validation study of postoperative liver failure and mortality risk scores after liver resection for perihilar cholangiocarcinoma

Background:Surgery for perihilar cholangiocarcinoma(PHCC)remains a challenging procedure with high morbidity and mortality.The Academic Medical Center(Amsterdam UMC)and Memorial Sloan Kettering Cancer Center proposed a postoperative mortality risk score(POMRS)and post-hepatectomy liver failure score(PHLFS)to predict patient outcomes.This study aimed to validate the POMRS and PHLFS for PHCC patients at Hokkaido University.Methods:Medical records of 260 consecutive PHCC patients who had undergone major hepatectomy with extrahepatic bile duct resection without pancreaticoduodenectomy at Hokkaido University between March 2001 and November 2018 were evaluated to validate the PHLFS and POMRS.Results:The observed risks for PHLF were 13.7%,24.5%,and 39.8%for the low-risk,intermediate-risk,and high-risk groups,respectively,in the study cohort.A receiver-operator characteristic(ROC)analysis revealed that the PHLFS had moderate predictive value,with an analysis under the curve(AUC)value of 0.62.Mortality rates based on the POMRS were 1.7%,5%,and 5.1%for the low-risk,intermediate-risk,and high-risk groups,respectively.The ROC analysis demonstrated an AUC value of 0.58.Conclusions:This external validation study showed that for PHLFS the threshold for discrimination in an Eastern cohort was reached(AUC>0.6),but it would require optimization of the model before use in clinical practice is acceptable.The POMRS were not applicable in the eastern cohort.Further external validation is recommended.

Prognostic risk scores for liver transplantation: game changers or statistical artworks?

Several prognostic liver transplant-related risk scores for hepatocellular carcinoma(HCC)have been developed in recent years.The most prominent scores,displayed in Table 1,are based exclusively on HCC-related variables(1-6).Given that non-HCC-related variables can also influence post-transplant outcomes,Goldberg et al.sought to develop a continuous risk score predicting post-transplant survival for patients using both HCC-and non-HCC-related variables(1).

Gallbladder volvulus

Background Like colon or stomach,gallbladder can twist,leading to a volvulus;an entity first described by Wendel in 1898(1).Gallbladder volvulus(GV)is a relatively rare disease occurring when the gallbladder rotates on its own axis,along the cystic duct(Figure 1).Different types of rotation have been described:incomplete vs.complete(≤180°vs.>180°)and clockwise vs.anticlockwise(2).As the rotation might involve the cystic artery,blood supply may be compromised,resulting in ischemia and eventually necrosis.GV constitutes an acute abdominal condition associated with poor outcomes,if not diagnosed and treated in time.