Epidemiology and natural history of Wilson's disease in the Chinese: A territory-based study in Hong Kong between 2000 and 2016

AIM To investigate the epidemiology and natural history of Wilson's disease in the Chinese.METHODS Data were retrieved via electronic search of hospital medical registry of the Hong Kong Hospital Authority,which covers all the public healthcare services. We identified cases of Wilson's disease between 2000 and 2016 by the International Classification of Diseases(ICD)-9 code. We analyzed the incidence rate,prevalence and adverse outcomes of Wilson's disease.RESULTS We identified 211 patients(male cases 104; female cases 107; median age 27.2 years,IQR: 17.1-38.6 years; duration of follow-up 8.0 years,IQR: 5.0-14.0 years). The average annual incidence rate was 1.44 per million person-years while the prevalence was 17.93 per million. Between 2000 and 2016,there was a decrease in the annual incidence rate from 1.65 to 1.23 per million person-years(P = 0.010),whereas there was an increase in the annual prevalence from 7.80 to 25.20 per million(P < 0.001). Among the 176 cases with hepatic involvement,38(21.6%) had cirrhosis,three(1.7%) developed hepatocellular carcinoma,24(13.6%) underwent liver transplantations,and 26(14.8%) died. Seven patients had concomitant chronic viral hepatitis B or C. The 5-year and 10-years rates of overall survival were 92.6% and 89.5%,and for transplant-free survival rates 91.8% and 87.4%,respectively. Cirrhosis and possibly chronic viral hepatitis were associated with poorer overall survival. CONCLUSION There was a significant increase in the prevalence of Wilson's disease in Hong Kong. The prognosis was favorable except for those with cirrhosis or concomitant viral hepatitis.

Effects of SARS-CoV-2 infection on incidence and treatment strategies of hepatocellular carcinoma in people with chronic liver disease

BACKGROUND Chronic liver disease(CLD)was associated with adverse clinical outcomes among people with severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection.AIM To determine the effects of SARS-CoV-2 infection on the incidence and treatment strategy of hepatocellular carcinoma(HCC)among patients with CLD.METHODS A retrospective,territory-wide cohort of CLD patients was identified from an electronic health database in Hong Kong.Patients with confirmed SARS-CoV-2 infection[coronavirus disease 2019(COVID-19)+CLD]between January 1,2020 and October 25,2022 were identified and matched 1:1 by propensity-score with those without(COVID-19-CLD).Each patient was followed up until death,outcome event,or November 15,2022.Primary outcome was incidence of HCC.Secondary outcomes included all-cause mortality,adverse hepatic outcomes,and different treatment strategies to HCC(curative,non-curative treatment,and palliative care).Analyses were further stratified by acute(within 20 d)and post-acute(21 d or beyond)phases of SARS-CoV-2 infection.Incidence rate ratios(IRRs)were estimated by Poisson regression models.RESULTS Of 193589 CLD patients(>95%non-cirrhotic)in the cohort,55163 patients with COVID-19+CLD and 55163 patients with COVID-19-CLD were included after 1:1 propensity-score matching.Upon 249-d median follow-up,COVID-19+CLD was not associated with increased risk of incident HCC(IRR:1.19,95%CI:0.99-1.42,P=0.06),but higher risks of receiving palliative care for HCC(IRR:1.60,95%CI:1.46-1.75,P<0.001),compared to COVID-19-CLD.In both acute and post-acute phases of infection,COVID-19+CLD were associated with increased risks of allcause mortality(acute:IRR:7.06,95%CI:5.78-8.63,P<0.001;post-acute:IRR:1.24,95%CI:1.14-1.36,P<0.001)and adverse hepatic outcomes(acute:IRR:1.98,95%CI:1.79-2.18,P<0.001;post-acute:IRR:1.24,95%CI:1.13-1.35,P<0.001),compared to COVID-19-CLD.CONCLUSION Although CLD patients with SARS-CoV-2 infection were not associated with increased risk of HCC,they were more likely to receive palliative treatment than those without.The detrimental effects of SARS-CoV-2 infection persisted in post-acute phase.

Psychometrics of the chronic liver disease questionnaire for Southern Chinese patients with chronic hepatitis B virus infection

AIM： To test the psychometric properties of a Chinese [（Hong Kong） HK] translation of the chronic liver disease questionnaire （CLDQ）. METHODS： A Chinese （HK） translation of the CLDQ was developed by iterative translation and cognitive debriefing. It was then administered to 72 uncomplicated and 78 complicated chronic hepatitis B （CriB） patients in Hong Kong together with a structured questionnaire on service utilization, and the Chinese （HK） SF-36 Health Survey Version 2 （SF-36v2）. RESULTS： Scaling success was ≥ 80% for all but three items. A new factor assessing sleep was found and items of two （Fatigue and Systemic Symptoms） subscales tended to load on the same factor. Internal consistency and test-retest reliabilities ranged from 0.58-0.90 for different subscales. Construct validity was confirmed by the expected correlations between the SF-36v2 Health Survey and CLDQ scores. Mean scores of CLDQ were significantly lower in complicated compared with uncomplicated CHB, supporting sensitivity in detecting differences between groups.CONCLUSION： The Chinese （HK） CLDQ is valid, reliable and sensitive for patients with CHB. Some modifications to the scaling structure might further improve its psychometric properties,

Understanding the role of PIN1 in hepatocellular carcinoma

PIN1 is a peptidyl-prolyl cis/trans isomerase that binds and catalyses isomerization of the specific motif comprising a phosphorylated serine or threonine residue preceding a proline(p Ser/Thr-Pro) in proteins. PIN1 can therefore induce conformational and functional changes of its interacting proteins that are regulated by proline-directed serine/threonine phosphorylation. Through this phosphorylation-dependent prolyl isomerization, PIN1 fine-tunes the functions of key phosphoproteins(e.g., cyclin D1, survivin, β-catenin and x-protein of hepatitis B virus) that are involved in the regulation of cell cycle progression, apoptosis, proliferation and oncogenic transformation. PIN1 has been found to be over-expressed in many cancers, including human hepatocellular carcinoma(HCC). It has been shown previously that overexpression of PIN1 contributes to the development of HCC invitro and in xenograft mouse model. In this review, we first discussed the aberrant transcription factor expression, miR NAs dysregulation, PIN1 gene promoter polymorphisms and phosphorylation of PIN1 as potential mechanisms underlying PIN1 overexpression in cancers. Furthermore, we also examined the role of PIN1 in HCC tumourigenesis by reviewing the interactions between PIN1 and various cellular and viral proteins that are involved in β-catenin, NOTCH, and PI3K/Akt/mT OR pathways, apoptosis, angiogenesis and epithelial-mesenchymal transition. Finally, the potential of PIN1 inhibitors as an anti-cancer therapy was explored and discussed.

Antralization at the edge of proximal gastric ulcers:Does Helicobacter pylori infection play a role?

AIM: To determine the prevalence of antralization at the edge of proximal gastric ulcers, and the effect ofH. pylori eradication on the mucosal appearances. METHODS: Biopsies were taken from the antrum, body and the ulcer edge of patients with benign proximal gastric ulcers before and one year after treatment. Gastric mucosa was classified as antral, transitional or body type.H. pylori positive patients receivedeither triple therapy, or omeprazole. RESULTS: Patients with index ulcers in the incisura, body or fundus (n=116) were analyzed. Antral-type mucosa was more prevalent at the ulcer edge inH. pylori-positive patients thanH.pylori-negative patients (93% vs 60%, OR=8.95,95%CI: 2.47-32.4, P=0.001). At one year, there was a significant reduction in the prevalence of antralization (from 93 % to 61%, P=0.004) at the ulcer edge in patients with H. pyloribeing eradicated. However, there was no difference in the prevalence of antralization at the ulcer edge in those with persistent infection. CONCLUSION: H. pylori infection is associated with antralization at the edge of proximal gastric ulcers, which may be reversible in some patients after eradication of the infection.

Gastrointestinal infection-related disseminated intravascular coagulation mimicking Shiga toxin-mediated hemolytic uremic syndrome-implications of classical clinical indexes in making the diagnosis:A case report and literature review

BACKGROUND Thrombocytopenia associated with acute kidney injury is a challenging disorder. Thrombotic microangiopathy (TMA) is a potentially life- or organ-threatening syndrome that can be induced by several disorders or medical interventions. There is overlap between the clinical presentation and pathophysiology of thrombotic thrombocytopenia purpura and hemolytic uremic syndrome (HUS), and to a lesser extent, disseminated intravascular coagulation (DIC). We describe a case to illustrate the potential diagnostic difficulty, especially at initial presentation. CASE SUMMARY We reported a case of a 44-year-old woman that presented with diarrhea, thrombocytopenia, schistocytes, elevated serum lactate dehydrogenase (LDH) level and acute kidney injury. While the clinical presentation resembled that of Shiga toxin–induced HUS, the disease course was more consistent with gastrointestinal infection-related DIC. To aid in the accurate diagnosis of TMA and other associated disorders, we have undertaken a review and provided a clear interpretation of some typical biomarkers including schistocytes, LDH and platelet count, coagulation profile and more specific indexes of ADAMTS13, complement profile, and the isolation of Shiga toxin-producing Escherichia coli (commonly referred to as STEC). CONCLUSION The use and correct interpretation of classical indexes of schistocyte, LDH, and platelet count is vital in diagnosing TMA and associated disorders. Understanding the characteristics of these biomarkers in the context of thrombocytopenia purpura, HUS and DIC will facilitate the accurate diagnosis and early initiation of appropriate treatment.

Research on the allelopathic potential of wheat

Objective: This paper mainly discusses the Allelopathic potential of Wheat. Methods: This paper is prepared by reviewing the latest academic literatures. Result: The green revolution in the 1960s caused an increase in the demand for food. The agricultural sector and farmers tended to spend more time on the agricultural work but the crop yield was suppressed by the weeds. Hence, the usage of herbicide insecticides, fungicides and others chemicals had been increased. Although herbicides are efficient for weed controls, the continuous uses had gradually stimulated the weeds developing an effecttive resistance to the chemicals. Wheat (Triticum aestivum L.) is known as allelopathic against crops and weeds. Allelopathy of wheat (Triticum aestivum L.) has been extensively examined for its potentials in weeds management. The allelopathic activity of wheat has been attributed to hydroxamic acids, the related compounds and phenolic acids. Therefore, it could effectively reduce herbicide uses in order to maintain an eco-friendly environment and a cost-effective weed control.

Exploratory use of ultrasound to determine whether demyelination following carpal tunnel syndrome co-exists with axonal degeneration

Carpal tunnel syndrome （CTS） accompanied by secondary axonal degeneration cannot be clearly dis- criminated using the current cross-validated ultrasound severity classification system. This study aimed at exploring cut-off values of ultrasound parameters, including wrist cross-sectional area （W-CSA）, wrist perimeter （W-P）, ratio of cross-sectional area （R-CSA） and perimeter （R-P）, changes of CSA and P from wrist to one third distal forearm （△CSA＆AP） for differentiation. Seventy-three patients （13 male and 60 female） were assigned into group A （demyelination only, n = 40） and group B （demyelination with secondary axonal degeneration, n = 33） based on the outcomes of nerve conduction studies （NCS）. Receiver Operative Characteristics （ROC） curves were plotted to obtain sensitivity, specificity, and accuracy of cut- off values for all the ultrasound parameters. The overall identified cut-off values （W-CSA 12.0 mm2, W-P 16.27 mm, R-CSA 1.85, R-P 1.48, △CSA 6.98 mm2, △P 5.77 mm） had good sensitivity （77.1-88.6%）, fair specificity （40-62.2%） and fair-to-good accuracy （0.676-0.758）. There were also significant differences in demographics （age and severity gradation, P 〈 0.001）, NCS findings （wrist motor latency and conduction velocity, P 〈 0.0001; wrist motor amplitude, P 〈 0.05; distal sensory latency, P 〈 0.05; sensory amplitude, P 〈 0.001） and ultrasound measurements （W-CSA, W-P, R-CSA, R-P, △CSA＆△P, P 〈 0.05） between groups. These findings suggest that ultrasound can be potentially used to differentiate demyelinating CTS with sec- ondary axonal degeneration and provide better treatment guidance.

Treatment of non-small cell lung cancer in the era of targeted therapy

Lung cancer, mostly non-small cell carcinoma (NSCLC), is still a major global problem with devastating outcomes. The majority presents at late stages, in which the chance of cure is minimal. With the better understanding of lung cancer biology, there have been several novel targeted approaches against NSCLC. Anti-angiogenesis has been proven to be an important approach in combination with systemic chemotherapy treatment in NSCLC at the first-line setting. The prototypic monoclonal antibody against vascular endothelial growth factor (VEGF), be- vacizumab, is now approved for clinical use in combination with platinum-based chemotherapy in first-line treatment of advanced non-squamous NSCLC, associated with improved response and survival compared with chemotherapy alone. The most notable example of targeted therapy for lung cancer is epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI). There have been extensive evidences supporting the superiority of EGFR TKI (like gefitinib or erlotinib) over standard platinum-based doublet chemotherapy in first-line treatment of advanced NSCLC carrying EGFR activating mutations. Almost following the same path as EGFR TKI, a novel target (anaplastic lymphoma kinase, ALK) has been identified recently with a very promising targeted agent (crizotinib) that has already been approved for clinical use in NSCLC carrying ALK rearrangements. Over the past decade, there have been undoubtedly growing armamentaria in the treatment of NSCLC, focusing on personalized and targeted approach.

The Hong Kong consensus recommendations on the diagnosis and management of pancreatic cystic lesions

Background:The finding of pancreatic cystic lesions(PCL)on incidental imaging is becoming increasingly common.International studies report a prevalence of 2.2-44.7%depending on the population,imaging modality and indication for imaging,and the prevalence increases with age.Patients with PCL are at risk of developing pancreatic cancer,a disease with a poor prognosis.This publication summarizes recommendations for the diagnosis and management of PCL and post-operative pancreatic exocrine insufficiency(PEI)from a group of local specialists.Methods:Clinical evidence was consolidated from narrative reviews and consensus statements formulated during two online meetings in March 2022.The expert panel included gastroenterologists,hepatobiliary surgeons,oncologists,radiologists,and endocrinologists.Results:Patients with PCL require careful investigation and follow-up due to the risk of malignant transformation of these lesions.They should undergo clinical investigation and pancreas-specific imaging to classify lesions and understand the risk profile of the patient.Where indicated,patients should undergo pancreatectomy to excise PCL.Following pancreatectomy,patients are at risk of PEI,leading to gastrointestinal dysfunction and malnutrition.Therefore,such patients should be monitored for symptoms of PEI,and promptly treated with pancreatic enzyme replacement therapy(PERT).Patients with poor response to PERT may require increases in dose,addition of a proton pump inhibitor,and/or further investigation,including tests for pancreatic function.Patients are also at risk of new-onset diabetes mellitus after pancreatectomy;they should be screened and treated with insulin if indicated.Conclusions:These statements are an accurate summary of our approach to the diagnosis and management of patients with PCL and will be of assistance to clinicians treating these patients in a similar clinical landscape.

Natural history of hepatitis-related hepatocellular carcinoma

Hepatocellular carcinoma （HCC） is an important cause of cancer death in the world. It has great regional differences in the pathology and epidemiology. The variation is greatly influenced by the aetiologies of the disease. Hepatitis B and C infection are the most important risk factors. HCC incidence rates are higher but in decreasing trend in developing countries. However, the figures in the developed countries are contrary. Successful hepatitis B virus （HBV） vacdnation programs, better food hygiene, increased global hepatitis C virus {HCV） prevalence and population migration are the possible explanations. A number of clinical and pathogenic differences exist between HBV- and HCV- related HCC. HBV infection leads to the development of HCC through direct and indirect pathways as it has the ability to integrate into the host genome affecting cellular signaling and growth control. HCV causes HCC mainly through indirect pathways： chronic inflammation, cell deaths and proliferation. As a result, HCC is almost exclusively found in cirrhotic HCV patients while HCC is sometimes found in HBV patients without significant liver cirrhosis. Due to the different severities of liver cirrhosis and HCC extent, therapeutic strategies from resection, liver transplantation to symptoms palliation are available. Poorly differentiated histology, lack of fibrous capsule, large tumour size, early vascular invasion and elevated serum levels of alpha fetoprotein （AFP） are the features for more aggressive disease. Combined with markers of liver reserve and performance status, accurate scoring systems and models have been developed to predict patients＇ survival and match best treatment option.

Risk of gastric cancer development after eradication of Helicobacter pylori

Helicobacter pylori(H. pylori) infection is the most important risk factor for gastric cancer(gc) development through the correa's gastric carcinogenesis cascade. However, H. pylori eradication alone does not eliminate gc, as pre-neoplastic lesions(atrophic gastritis, intestinal metaplasia and dysplasia) may have already developed in some patients. It is therefore necessary to identify patients at high-risk for gastric cancer after H. pylori eradication to streamline the management plan. If the patients have not undergone endoscopy with histologic assessment, the identification of certain clinical risk factors and non-invasive testing(serum pepsinogen) can predict the risk of atrophic gastritis. For those with suspected atrophic gastritis, further risk stratification by endoscopy with histologic assessment according to validated histologic staging systems would be advisable. Patients with higher stages may require long-term endoscopic surveillance. Apart from secondary prevention to reduce deaths by diagnosing gc at an early stage, identifying medications that could potentially modify the gc risk would be desirable. The potential roles of a number of medications have been suggested by various studies, including proton pump inhibitors(PPIs), aspirin, statins and metformin. However, there are currently no randomized clinical trials to address the impact of these medications on gc risk after H. pylori eradication. In addition, most of these studies failed to adjust for the effect of concurrent medications on gc risk. Recently, large population-based retrospective cohort studies have shown that PPIs were associated with an increased gc risk after H. pylori eradication, while aspirin was associated with a lower risk. The roles of other agents in reducing gc risk after H. pylori eradication remain to be determined.

Increasing dietary fiber intake in terms of kiwifruit improves constipation in Chinese patients

AIM： To investigate if increased dietary fiber, in terms of kiwifruit, is effective in Chinese constipated patients. METHODS： 33 constipated patients and 20 healthy volunteers were recruited for a 4-wk treatment of kiwi fruit twice daily. Response during wk 1-4 was defined as an increase in complete spontaneous bowl, motion （CSBM）≥ 1/wk. Secondary efficacy included response during wk 1-4, individual symptoms and scores of bowel habits and constipation. Responses were compared with the baseline run-in period. Colonic transit time and anorectal manometry were performed before and after treatment. RESULTS： Responder rate was 54.5% in the constipated group. The mean CSBM increased after treatment （2.2±2.6 vs 4.4± 4.6, P = 0.013）. There was also improvement in the scores for bothersomeness of constipation （P = 0.02）, and satisfaction of bowel habit （P = 0.001）, and decreased in days of laxative used （P = 0.003）. There was also improvement in transit time （P = 0.003） and rectal sensation （P 〈 0.05）. However, there was no change in the bowel symptoms or anorectal physiology in the healthy subjects. CONCLUSION： Increasing dietary fiber intake is effective in relieving chronic constipation in Chinese population.

Prevention of hepatocellular carcinoma in chronic viral hepatitis B and C infection

Hepatocellular carcinoma(HCC)is a leading cause of cancer-related mortality worldwide,with the majority of cases associated with persistent infection from hepatitis B virus(HBV)or hepatitis C virus(HCV).Natural history studies have identified risk factors associated with HCC development among chronic HBV and HCV infection.High-risk infected individuals can now be identified by the usage of risk predictive scores.Vaccination plays a central role in the prevention of HBV-related HCC.Treatment of chronic HBV infection,especially by nucleoside analogue therapy,could also reduce the risk of HBV-related HCC.Concerning HCV infection,besides the advocation of universal precautions to reduce the rate of infection,pegylated interferon and ribavirin could also reduce the risk of HCV-related HCC among those achieving a sustained virologic response.Recently there has been mounting evidence on the role of chemopreventive agents in reducing HBV-and HCV-related HCC.The continued advances in the understanding of the molecular pathogenesis of HCC would hold promise in preventing this highly lethal cancer.

Rise and fall of anti-obesity drugs

Although it is not generally a life-threatening disease,obesity is becoming a major health problem worldwide.It can be controlled by means of drugs,and,consequently,these are required to be safe as well as effective.In this paper,we summarize the fate of various drugs that have been introduced for clinical use in the treatment of obesity.Fenfluramine and dexfenfluramine were withdrawn because of heart valve damage.Sibutramine suppresses appetite and increases heart rate and blood pressure.In the Sibutramine Cardiovascular OUTcomes trial,an increase in major adverse cardiovascular events prompted its withdrawal in Europe and the United States.Rimonabant is an endocannabinoid receptor antagonist that reduces body weight and ameliorates some cardiovascular risk factors.However,adverse psychiatric side effects led to its withdrawal as well.Orlistat is approved in Europe and the United States for the treatment of obesity,but its use is limited by gastrointestinal side-effects.Ephedrine and caffeine are natural ingredients in foods and supplements that may help the person to lose weight.In the light of several failed attempts,there is a clear need to develop drugs that are effective and safe in the long term in order to successfully combat the phenomenon of obesity.

Management of chronic hepatitis B in severe liver disease

In the past few decades,chronic hepatitis B(CHB)has evolved from a disease that was untreatable and progressive,to one that can be easily controlled with antiviral therapy.However,patients with severe liver disease still remain difficult to treat despite the availability of highly potent nucleos(t)ide analogs.These include those with underlying cirrhosis,severe flares of CHB,hepatocellular carcinoma(HCC),and for those undergoing liver transplantation.For those with established cirrhosis,antiviral therapy should be considered for all,as unpredictable flares can still occur,which can be fatal for those with advanced chronic liver disease.However,even with effective viral suppression,the development of HCC can still occur.For patients with severe flares of CHB,although the use of antiviral can improve long term outcomes,a significant proportion may still die without liver transplantation.The short term prognosis of these patients is dependent on both the severity of flare and underlying pre-existing liver disease.In patients with decompensated cirrhosis,liver failure secondary to severe flares,or those with HCC,liver transplantation may be curative.After liver transplantation,long term antiviral therapy is required to prevent graft loss from recurrent hepatitis B infection.The use of hepatitis B immune globulin(HBIG)in combination with an oral antiviral agent has been the mainstay of post-transplant antiviral regimen for over adecade.With newer and more potent antiviral agents such as tenofovir and entecavir,use of these agents along with HBIG have demonstrated to be effective in preventing significant recurrence in the long term.

Nutrient supplemented serum-free medium increases cardiomyogenesis efficiency of human pluripotent stem cells

AIM: To development of an improved p38 MAPK inhibitor-based serum-free medium for embryoid body cardiomyocyte differentiation of human pluripotent stem cells. METHODS: Human embryonic stem cells (hESC) differentiated to cardiomyocytes (CM) using a p38 MAPK inhibitor (SB203580) based serum-free medium (SB media). Nutrient supplements known to increase cell viability were added to SB medium. The ability of these supplements to improve cardiomyogenesis was evaluated by measurements of cell viability, total cell count, and the expression of cardiac markers via flow cytometry. An improved medium containing Soy hydrolysate (HySoy) and bovine serum albumin (BSA) (SupSB media) was developed and tested on 2 additional cell lines (H1 and Siu-hiPSC). Characterization of the cardiomyocytes was done by immunohistochemistry, electrophysiology and quantitative real-time reverse transcriptionpolymerase chain reaction. RESULTS: hESC cell line, HES-3, differentiating in SB medium for 16 d resulted in a cardiomyocyte yield of 0.07 ± 0.03 CM/hESC. A new medium (SupSB media) was developed with the addition of HySoy and BSA to SB medium. This medium resulted in 2.6 fold increase in cardiomyocyte yield (0.21 ± 0.08 CM/hESC). The robustness of SupSB medium was further demonstrated using two additional pluripotent cell lines (H1, hESC and Siu1, hiPSC), showing a 15 and 9 fold increase in cardiomyocyte yield respectively. The age (passage number) of the pluripotent cells did not affect the cardiomyocyte yields. Embryoid body (EB) cardiomyocytes formed in SupSB medium expressed canonical cardiac markers (sarcomeric α-actinin, myosin heavy chain and troponin-T) and demonstrated all three major phenotypes: nodal-, atrial- and ventricular-like. Electrophysiological characteristics (maximum diastolic potentials and action potential durations) of cardiomyocytes derived from SB and SupSB media were similar. CONCLUSION: The nutrient supplementation (HySoy and BSA) leads to increase in cell viability, cell yield and cardiac marker expression during cardiomyocyte differentiation, translating to an overall increase in cardiomyocyte yield.

Prediction of hepatocellular carcinoma development by aminotransferase to platelet ratio index in primary biliary cholangitis

AIM To investigate the usefulness of aspartate aminotransferase to platelet ratio index(APRI) in predicting hepatocellular carcinoma(HCC) risk in primary biliary cholangitis(PBC).METHODS We identified PBC patients between 2000 and 2015 by searching the electronic medical database of a tertiary center. The hazard ratio(HR) of HCC with different risk factors was determined by Cox proportional hazards model. RESULTS One hundred and forty-four PBC patients were recru-ited. Patients were diagnosed at a median age of 57.8 years [interquartile range(IQR): 48.7-71.5 years), and 41(28.5%) patients had cirrhosis at baseline. The median follow-up duration was 6.9 years(range: 1.0-26.3 years). Twelve patients developed HCC, with an incidence rate of 10.6 cases per 1000 patient-years. The overall 5-, 10-and 15-year cumulative incidences of HCC were 2.3% 95%CI: 0%-4.8%), 8.4%(95%CI: 1.8%-14.5%) and 21.6%(6.8%-34.1%), respectively. Older age(HR = 1.07), cirrhosis(HR = 4.38) and APRI at 1 year after treatment(APRI-r1) > 0.54(HR = 3.94) were independent factors for HCC development. APRI-r1, when combined with treatment response, further stratified HCC risk(log rank P < 0.05). The area under receiver operating curve of APRI-r1 in predicting HCC was 0.77(95%CI: 0.64-0.88).CONCLUSION APRI-r1 can be used to predict the development of HCC in PBC patients. Combination of APRI-r1 with treatment response can further stratify the HCC risk.

Survival outcomes of right-lobe living donor liver transplantation for patients with high Model for End-stage Liver Disease scores

BACKGROUND: Controversy exists over whether living donor liver transplantation (LDLT) should be offered to patients with high Model for End-stage Liver Disease (MELD) scores. This study tried to determine whether a high MELD score would result in inferior outcomes of right-lobe LDLT. METHODS: Among 411 consecutive patients who received right-lobe LDLT at our center, 143 were included in this study. The patients were divided into two groups according to their MELD scores: a high-score group (MELD score ≥25; n=75) and a low-score group (MELD score 【25; n=68). Their demographic data and perioperative conditions were compared. Univariable and multivariable analyses were performed to identify risk factors affecting patient survival. RESULTS: In the high-score group, more patients required preoperative intensive care unit admission (49.3% vs 2.9%; P【0.001), mechanical ventilation (21.3% vs 0%; P【0.001), or hemodialysis (13.3% vs 0%; P=0.005); the waiting time before LDLT was shorter (4 vs 66 days; P【0.001); more blood was transfused during operation (7 vs 2 units; P【0.001); patients stayed longer in the intensive care unit (6 vs 3 days; P【0.001) and hospital (21 vs 15 days; P=0.015) after transplantation;more patients developed early postoperative complications (69.3% vs 50.0%; P=0.018); and values of postoperative peak blood parameters were higher. However, the two groups had comparable hospital mortality. Graft survival and patient overall survival at one year (94.7% vs 95.6%; 95.9% vs 96.9%), three years (91.9% vs 92.6%; 93.2% vs 95.3%), and five years (90.2% vs 90.2%; 93.2% vs 95.3%) were also similar between the groups. CONCLUSIONS: Although the high-score group had signifi-cantly more early postoperative complications, the two groups had comparable hospital mortality and similar satisfactory rates of graft survival and patient overall survival. Therefore, a high MELD score should not be a contraindication to right-lobe LDLT if donor risk and recipient benefit are taken into full account.

Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia

Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.