Pre-MASLD:Should it be defined separately?

Nonalcoholic fatty liver disease(NAFLD)is one of the most common chronic liver diseases,yet it has not received sufficient attention[1].Over the past two decades,the overall global prevalence of NAFLD has risen from 25%to 37%[2].The disease burden of NAFLD is fueled by the epidemic of obesity and diabetes[3].It is estimated that more than half of patients with diabetes have NAFLD.

Risk factors for alcohol-related liver injury in the island population of China: A population-based case-control study

AIM:To investigate the association of alcohol dose, duration of drinking and obesity with abnormal alcohol-related liver injury indicators, the prevalence of alcohol-related liver injury in the island population of China.METHODS:Randomized multistage stratified cluster sampling from the island population of China was used in the population-based case-control study. Then interview, physical examination, laboratory assessments and ultrasonography were done. RESULTS:Daily alcohol intake ≥ 20 g, duration of drinking ≥ 5 years and obesity were closely related to alcohol-related liver injury (P < 0.05). The odds-ratio (OR) (95% CI) was 1.965 (1.122-3.442), 3.412 (1.789-6.507) and 1.887 (1.261-2.824), respectively. The prevalence rate of alcohol-related liver injury in ≥ 20 g daily alcohol intake group and < 20 g daily alcohol intake group was 37.14% and 12.06%, respectively. The prevalence rate of alcohol-related liver injury in ≥ 5 years drinking group and < 5 years drinking group was 34.44% and 8.53%, respectively. No significant dose-response relation was found between daily alcohol intake and abnormal alcohol-related liver injury indicators as well as between duration of drinking and abnormal alcohol-related liver injury indicators. There was no significant difference in the prevalence of alcohol-related liver injury between beer drinking group and yellow rice wine drinking group, hard liquor drinking group, multiple drinking group.CONCLUSION:The risk threshold of daily alcohol intake is 20 g and duration of drinking inducing alcohol-related liver injury 5 years in the island population of China. Liver injury induced by obesity should be concerned.

Role of endoplasmic reticulum stress in the pathogenesis of nonalcoholic fatty liver disease

Nonalcoholic fatty liver disease(NAFLD)has emerged as a common public health problem in recent decades.However,the underlying mechanisms leading to the development of NAFLD are not fully understood.The endoplasmic reticulum(ER)stress response has recently been proposed to play a crucial role in both the development of steatosis and progression to nonalcoholic steatohepatitis.ER stress is activated to regulate protein synthesis and restore homeostatic equilibrium when the cell is stressed due to the accumulation of unfolded or misfolded proteins.However,delayed or insufficient responses to ER stress may turn physiological mechanisms into pathological consequences,including fat accumulation,insulin resistance,inflammation,and apoptosis,all of which play important roles in the pathogenesis of NAFLD.Therefore,understanding the role of ER stress in the pathogenesis of NAFLD has become a topic of intense investigation.This review highlights the recent findings linking ER stress signaling pathways to the pathogenesis of NAFLD.

Allyl isothiocyanate ameliorates lipid accumulation and inflammation in nonalcoholic fatty liver disease via the Sirt1/AMPK and NF-κB signaling pathways

BACKGROUND Allyl isothiocyanate(AITC),a classic anti-inflammatory and antitumorigenic agent,was recently identified as a potential treatment for obesity and insulin resistance.However,little is known about its direct impact on the liver.AIM To investigate the effect and underlying mechanism of AITC in nonalcoholic fatty liver disease(commonly referred to as NAFLD).METHODS To establish a mouse and cellular model of NAFLD,C57BL/6 mice were fed a high fat diet(HFD)for 8 wk,and AML-12 cells were treated with 200μM palmitate acid for 24 h.For AITC treatment,mice were administered AITC(100 mg/kg/d)orally and AML-12 cells were treated with AITC(20μmol/L).RESULTS AITC significantly ameliorated HFD-induced weight gain,hepatic lipid accumulation and inflammation in vivo.Furthermore,serum alanine aminotransferase and aspartate aminotransferase levels were markedly reduced in AITC-treated mice.Mechanistically,AITC significantly downregulated the protein levels of sterol regulatory elementbinding protein 1(SREBP1)and its lipogenesis target genes and upregulated the levels of proteins involved in fatty acidβ-oxidation,as well as the upstream mediators Sirtuin 1(Sirt1)and AMPactivated protein kinaseα(AMPKα),in the livers of HFD-fed mice.AITC also attenuated the nuclear factor kappa B(NF-κB)signaling pathway.Consistently,AITC relieved palmitate acid-induced lipid accumulation and inflammation in AML-12 cells in vitro through the Sirt1/AMPK and NF-κB signaling pathways.Importantly,further studies showed that the curative effect of AITC on lipid accumulation was abolished by siRNA-mediated knockdown of either Sirt1 or AMPKαin AML-12 cells.CONCLUSION AITC significantly ameliorates hepatic steatosis and inflammation by activating the Sirt1/AMPK pathway and inhibiting the NF-κB pathway.Therefore,AITC is a potential therapeutic agent for NAFLD.

Current status of Helicobacter pylori eradication and risk factors for eradication failure

BACKGROUND The Helicobacter pylori(H.pylori)eradication rate is decreasing in the general population of China.AIM To evaluate the H.pylori eradication status in real-world clinical practice and to explore factors related to eradication failure.METHODS Patients with H.pylori infection who were treated with standard 14-d quadruple therapy and received a test of cure at a provincial medical institution between June 2018 and May 2019 were enrolled.Demographic and clinical data were recorded.Eradication rates were calculated and compared between regimens and subgroups.Multivariate analysis was performed to identify predictors of eradication failure.RESULTS Of 2610 patients enrolled,eradication was successful in 1999(76.6%)patients.Amoxicillin-containing quadruple regimens showed a higher eradication rate than other quadruple therapy regimens(83.0%vs 69.0%,P<0.001).The quadruple therapy containing amoxicillin plus clarithromycin achieved the highest eradication rate(83.5%).Primary therapy had a higher eradication rate than rescue therapy(78.3%vs 66.5%,P<0.001).In rescue therapy,the amoxicillinand furazolidone-containing regimens achieved the highest eradication rate(80.8%).Esomeprazole-containing regimens showed a higher eradication rate than those containing other proton pump inhibitors(81.8%vs 74.9%,P=0.001).Multivariate regression analysis found that older age,prior therapy,and use of omeprazole or pantoprazole were associated with an increased risk of eradication CONCLUSION The total eradication rate is 76.6%.Amoxicillin-containing regimens are superior to other regimens.Age,prior therapy,and use of omeprazole or pantoprazole are independent risk factors for eradication failure.

Association of caveolin-3 and cholecystokinin A receptor with cholesterol gallstone disease in mice

AIM: To investigate the role of caveolin-3 (CAV3) and cholecystokinin A receptor (CCKAR) in cholesterol gallstone disease (CGD).

Screening for pancreatic cancer in familial high-risk individuals: A systematic review

AIM:To analyze the benefits and harms of pancreatic cancer screening in familial high-risk individuals(HRIs).METHODS:Studies were identified by searching PubMed,EBSCO,ClinicalTrials.gov and the Cochrane database from database inception to June 2014.We also obtained papers from the reference lists of pertinent studies and systematic reviews.Englishlanguage trials and observational studies were searched.The key words used as search terms were "screening" and "surveillance".Cost-effectiveness,diagnostic rate,survival rate,mortality and adverse events were the outcomes of interest.Age,sex,lifestyle and other confounding factors were also considered.However,anticipating only a few of these studies,we also included observational studies with or without control groups.We also included studies concerning the anxiety associated with pancreatic cancer risk and other psychological changes in familial HRIs.We extracted details on study design,objectives,population characteristics,inclusion criteria,year of enrollment,method of screening,adjusted and unadjusted mortality,cost-effectiveness and adverse events from the included studies.Studies were assessed using the Reporting of Observational studies in Epidemiology(STROBE) checklist.RESULTS:Sixteen studies on pancreatic cancer screening were included.Five studies included control groups,nine were observational studies without control groups,and the other two studies investigated the worry associated with pancreatic cancer risk.We found that pancreatic cancer screening resulted in a high curative resection rate(60%vs 25%,P = 0.011),longer median survival time(14.5 mo vs 4 mo,P < 0.001),and higher 3-year survival rate(20%vs 15.0%,P =0.624).We also found that familial HRIs had a higher diagnostic rate of pancreatic tumors than controls(34%vs 7.2%,P< 0.001).In patients who underwent regular physical examinations,more stage I pancreatic cancers were observed(19%vs 2.6%,P= 0.001).In addition,endoscopic ultrasonography,which was the main means of detection,diagnosed 64.3%of pancreatic cancers.In comparison,endoscopic retrograde cannulation of the pancreas,magnetic resonance imaging,and computed tomography diagnosed 28.6%,42.9%,and21.4%,respectively.For mass lesions,instant surgery was recommended because of the beneficial effects of post-operative chemotherapy.However,in patients with intraductal papillary mucinous neoplasms,we did not find a significant difference in outcome between surgery and follow-up without treatment.Moreover,pancreatic cancer screening in familial HRIs had a greater perceived risk of pancreatic cancer(P< 0.0001),higher levels of anxiety regarding pancreatic cancer(P< 0.0001),and increased economic burden.CONCLUSION:Pancreatic cancer screening in familial HRIs is associated with a higher detection rate and longer survival,although screening may influence psychological function and increase the economic burden.

Gastric foreign body granuloma caused by an embedded fishbone:A case report

Fishbones are the most commonly ingested foreign bodies that cause gastrointestinal tract penetration. However, fishbones embedded in the gastrointestinal tract that lead to foreign body granulomas that mimic submucosal tumors are rare. Herein, we describe a 56-year-old woman who presented with a 20-day-history of upper abdominal pain. Endoscopy revealed an elevated lesion in the gastric antrum. An abdominal computed tomography scan showed a mass in the gastric antrum and a linear calcified lesion in the mass. An endoscopic ultrasonography examination revealed a 3.9 cm &#x000d7; 2.2 cm, irregular, hypoechoic mass with indistinct margins in the muscularis propria layer. The patient was initially diagnosed as having a submucosal tumor, and subsequent surgical resection showed that the lesion was a foreign body granuloma caused by an embedded fishbone. Our case indicated that the differential diagnosis of a foreign body granuloma should be considered in cases of elevated lesions in the gastrointestinal tract.

Construction of a convolutional neural network classifier developed by computed tomography images for pancreatic cancer diagnosis

BACKGROUND Efforts should be made to develop a deep-learning diagnosis system to distinguish pancreatic cancer from benign tissue due to the high morbidity of pancreatic cancer.AIM To identify pancreatic cancer in computed tomography(CT)images automatically by constructing a convolutional neural network(CNN)classifier.METHODS A CNN model was constructed using a dataset of 3494 CT images obtained from 222 patients with pathologically confirmed pancreatic cancer and 3751 CT images from 190 patients with normal pancreas from June 2017 to June 2018.We established three datasets from these images according to the image phases,evaluated the approach in terms of binary classification(i.e.,cancer or not)and ternary classification(i.e.,no cancer,cancer at tail/body,cancer at head/neck of the pancreas)using 10-fold cross validation,and measured the effectiveness of the RESULTS The overall diagnostic accuracy of the trained binary classifier was 95.47%,95.76%,95.15%on the plain scan,arterial phase,and venous phase,respectively.The sensitivity was 91.58%,94.08%,92.28%on three phases,with no significant differences(χ2=0.914,P=0.633).Considering that the plain phase had same sensitivity,easier access,and lower radiation compared with arterial phase and venous phase,it is more sufficient for the binary classifier.Its accuracy on plain scans was 95.47%,sensitivity was 91.58%,and specificity was 98.27%.The CNN and board-certified gastroenterologists achieved higher accuracies than trainees on plain scan diagnosis(χ2=21.534,P<0.001;χ2=9.524,P<0.05;respectively).However,the difference between CNN and gastroenterologists was not significant(χ2=0.759,P=0.384).In the trained ternary classifier,the overall diagnostic accuracy of the ternary classifier CNN was 82.06%,79.06%,and 78.80%on plain phase,arterial phase,and venous phase,respectively.The sensitivity scores for detecting cancers in the tail were 52.51%,41.10%and,36.03%,while sensitivity for cancers in the head was 46.21%,85.24%and 72.87%on three phases,respectively.Difference in sensitivity for cancers in the head among the three phases was significant(χ2=16.651,P<0.001),with arterial phase having the highest sensitivity.CONCLUSION We proposed a deep learning-based pancreatic cancer classifier trained on medium-sized datasets of CT images.It was suitable for screening purposes in pancreatic cancer detection.

Association between serumα-L-fucosidase andnon-alcoholic fatty liver disease:Cross-sectional study

AIM: To explore the association between serum α-Lfucosidase(Af U) and non-alcoholic fatty liver disease(NAf LD).METHODS: A total of 16473 individuals(9456 men and 7017 women) were included in the current study, who presented for a health examination at the first Affiliated hospital of Zhejiang University School of medicine in 2014. The baseline characteristics of the cohort were compared by NAf LD status. Linear regression analysis and stepwise multiple regression analysis were applied to assess the risk factors for NAf LD. Receiver operating characteristic curve was used to determine the sensitivity and specificity of Af U in the diagnosis of NAf LD.RESULTS: The prevalence rates of NAf LD and metabolic syndrome(met S) were 38.0% and 25.4%, respectively. The NAf LD group had significantly higher Af U levels than the non-NAf LD group(28.7 ± 7.9 U/L vs 26.0 ± 7.3 U/L, P < 0.001) and the prevalence rate of NAf LD increased with progressively higher serum Af U levels. Af U was positively correlated with met S and its five components: central obesity, hypertriglyceridemia, low high-density lipoprotein cholesterol, and elevated blood pressure and fasting glucose. Stepwise multiple logistic regression analysis showed that Af U was associated with an increased risk of NAf LD(OR = 1.009, 95%CI: 1.003-1.014, P < 0.001). The best cut-off value of Af U for the diagnosis of NAf LD was 27.5 U/L. The area under the curve(diagnostic efficacy index) was 0.606. The sensitivity and specificity were 54.6% and 61.8%, respectively. CONCLUSION: Af U level is significantly associated with NAf LD, and elevated Af U level is an independent risk factor for NAf LD.

Esophageal granular cell tumors:Report of 9 cases and a literature review

Esophageal granular cell tumors(GCTs) are rare tumors of the esophagus.We evaluated the clinical and pathologic features of 9 esophageal GCT patients(5 men and 4 women) from our institute and reviewed the related disease literature.Patient age ranged from 25 to 53 years(mean:41 years).All the patients were asymptomatic or presented with non-specific symptoms.Most GCTs occurred in the distal esophagus and were less than 6 mm in diameter.Computational analysis showed that the average gray-scale endoscopic ultrasound images of esophageal GCTs were greater than that of esophageal leiomyomas.Eight patients were treated by endoscopic resection,and 1 patient underwent surgical excision.No post-therapy recurrence or metastasis developed during follow-up(mean:36.4 mo,range:1-72 mo).

Association between serum alpha-fetoprotein levels and fatty liver disease: A cross-sectional study

AIM: To investigate the association between serum alpha-fetoprotein (AFP) levels and fatty liver disease (FLD) in a Chinese population.

Olfactomedin-4 in digestive diseases: A mini-review

Olfactomedin-4(OLFM4, GW112, h GC-1) is a glycoprotein belonging to the olfactomedin family. The expression of OLFM4 is strong in the small intestine, colon and prostate, and moderate in the stomach and bone marrow. Previous studies have revealed that OLFM4 is closely associated with many digestive diseases. Up-regulation of OLFM4 has been detected in the Helicobacter pylori(H. pylori)-infected gastric mucosa, inflammatory bowel disease tissue and gastrointestinal malignancies, including gastric cancer, colorectal cancer, pancreatic cancer and gallbladder cancer. Downregulation of OLFM4 has also been detected in some cases, such as in poorly differentiated, advancedstage and metastatic tumors. Studies using OLFM4-deficient mouse models have revealed that OLFM4 acts as a negative regulator of H. pylori-specific immune responses and plays an important role in mucosal defense in inflammatory bowel disease. Patients with OLFM4-positive gastric cancer or colorectal cancer have a better survival rate than OLFM4-negative patients. However, the prognosis is worse in pancreatic cancer patients with high levels of expression of OLFM4. The NF-κB, Notch and Wnt signaling pathways are involved in the regulation of OLFM4 expression in digestive diseases, and its role in pathogenesis is associated with anti-inflammation, apoptosis, cell adhesion and proliferation. OLFM4 may serve as a potential specific diagnostic marker and a therapeutic target in digestive diseases. Further studies are required to explore the clinical value of OLFM4.

Metabolic dysfunction is associated with steatosis but no other histologic features in nonalcoholic fatty liver disease

BACKGROUND Recently,nonalcoholic fatty liver disease(NAFLD)has been renamed metabolicassociated fatty liver disease(MAFLD).Based on the definition for MAFLD,a group of non-obese and metabolically healthy individuals with fatty liver are excluded from the newly proposed nomenclature.AIM To analyze the histologic features in the MAFLD and non-MAFLD subgroups of NAFLD.METHODS Eighty-three patients with biopsy-proven NAFLD were separated into MAFLD and non-MAFLD groups.The diagnosis of MAFLD was established as hepatic steatosis along with obesity/diabetes or evidence of metabolic dysfunction.The histologic features were compared according to different metabolic disorders and liver enzyme levels.RESULTS MAFLD individuals had a higher NAFLD activity score(P=0.002)and higher severity of hepatic steatosis(42.6%Grade 1,42.6%Grade 2,and 14.8%Grade 3 in MAFLD;81.8%Grade 1,13.6%Grade 2,and 4.5%Grade 3 in non-MAFLD;P=0.007)than the non-MAFLD group.Lobular and portal inflammation,hepatic ballooning,fibrosis grade,and the presence of nonalcoholic steatohepatitis(NASH)and significant fibrosis were comparable between the two groups.The higher the liver enzyme levels,the more severe the grades of hepatic steatosis(75.0%Grade 1 and 25.0%Grade 2 in normal liver function;56.6%Grade 1,39.6%Grade 2,and 3.8%Grade 3 in increased liver enzyme levels;27.8%Grade 1,27.8%Grade 2,and 44.4%Grade 3 in liver injury;P<0.001).Patients with liver injury(alanine aminotransferase>3×upper limit of normal)presented a higher severity of hepatocellular ballooning(P=0.021).Moreover,the grade of steatosis correlated significantly with hepatocellular ballooning degree(r=0.338,P=0.002)and the presence of NASH(r=0.466,P<0.001).CONCLUSION Metabolic dysfunction is associated with hepatic steatosis but no other histologic features in NAFLD.Further research is needed to assess the dynamic histologic characteristics in NAFLD based on the presence or absence of metabolic disorders.

A novel model for predicting fatty liver disease by means of an artificial neural network

Background:The artificial neural network(ANN)emerged recently as a potent diagnostic tool,especially for complicated systemic diseases.This study aimed to establish a diagnostic model for the recognition of fatty liver disease(FLD)by virtue of the ANN.Methods:A total of 7,396 pairs of gender-and age-matched subjects who underwent health check-ups at the First Affiliated Hospital,College of Medicine,Zhejiang University(Hangzhou,China)were enrolled to establish the ANN model.Indices available in health check-up reports were utilized as potential input variables.The performance of our model was evaluated through a receiver-operating characteristic(ROC)curve analysis.Other outcome measures included diagnostic accuracy,sensitivity,specificity,Cohen’s k coefficient,Brier score,and Hosmer-Lemeshow test.The Fatty Liver Index(FLI)and the Hepatic Steatosis Index(HSI),retrained using our training-group data with its original designated input variables,were used as comparisons in the capability of FLD diagnosis.Results:Eight variables(age,gender,body mass index,alanine aminotransferase,aspartate aminotransferase,uric acid,total triglyceride,and fasting plasma glucose)were eventually adopted as input nodes of the ANN model.By applying a cut-off point of 0.51,the area under ROC curves of our ANN model in predicting FLD in the testing group was 0.908[95%confidence interval(CI),0.901-0.915]—significantly higher(P<0.05)than that of the FLI model(0.881,95%CI,0.872-0.891)and that of the HSI model(0.885;95%CI,0.877-0.893).Our ANN model exhibited higher diagnostic accuracy,better concordance with ultrasonography results,and superior capability of calibration than the FLI model and the HSI model.Conclusions:Our ANN system showed good capability in the diagnosis of FLD.It is anticipated that our ANN model will be of both clinical and epidemiological use in the future.