Diagnostic value of glypican-3 in serum and liver for primary hepatocellular carcinoma

AIM:To evaluate the diagnostic value of glypican-3(GPC3) in serum and liver for primary hepatocellular carcinoma(HCC).METHODS:Serum levels of GPC3 and α-fetoprotein(AFP) were measured in 75 patients with primary HCC and 32 patients with liver cirrhosis.Expression of GPC3 and AFP in 58 HCC and 12 cirrhotic specimens was detected with immunohistochemical staining.RESULTS:When the cut-off value of serum GPC3 was set at 300 ng/L,its sensitivity and specificity for HCC were 47.0% and 93.5%,respectively.Among the 14 patients with HCC at stage according to the Barcelona Clinic Liver Cancer staging system,the serum GPC3 level was higher than 300 ng/L in 50%(7/14) patients,the serum AFP level was not ≥ 400 μg/L in any patient.Combined serum AFP and GPC3 significantly increased the sensitivity to the diagnosis of HCC.The GPC3 expression was detected in cytoplasm of HCC cells but not in hepatocytes and bile ducts of benign tumors.Among the 58 HCC patients,the GPC3 was expressed in 100%(28/28) patients with their serum AFP level ≥ 400 μg/L,and in 90%(27/30) patients with their AFP level < 400 μg/L,respectively.The GPC3 was weakly or negatively expressed in all paracarcinomatous and cirrhotic tissue samples.AFP positive HCC cells were only found in 1 out of the 58 HCC patients.CONCLUSION:GPC3 protein is a sensitive and specific serum marker for diagnosis of early HCC.Its expression in liver tissues can be used to discriminate tumor cells from benign hepatic cells.

Effects of resveratrol in experimental and clinical non-alcoholic fatty liver disease

The prevalence of obesity and related conditions like non-alcoholic fatty liver disease(NAFLD) is increasing worldwide and therapeutic options are limited.Alternative treatment options are therefore intensively sought after.An interesting candidate is the natural polyphenol resveratrol(RSV) that activates adenosinmonophosphate-activated protein kinase(AMPK) and silent information regulation-2 homolog 1(SIRT1).In addition,RSV has known anti-oxidant and anti-inflammatory effects.Here,we review the current evidence for RSVmediated effects on NAFLD and address the different aspects of NAFLD and non-alcoholic steatohepatitis(NASH) pathogenesis with respect to free fatty acid(FFA) flux from adipose tissue,hepatic de novo lipogenesis,inadequate FFA β-oxidation and additional intra- and extrahepatic inflammatory and oxidant hits.We review the in vivo evidence from animal studies and clinical trials.The abundance of animal studies reports a decrease in hepatic triglyceride accumulation,liver weight and a general improvement in histological fatty liver changes,along with a reduction in circulating insulin,glucose and lipid levels.Some studies document AMPK or SIRT1 activation,and modulation of relevant markers of hepatic lipogenesis,inflammation and oxidation status.However,AMPK/SIRT1-independent actions are also likely.Clinical trials are scarce and have primarily been performed with a focus on overweight/obese participants without a focus on NAFLD/NASH and histological liver changes.Future clinical studies with appropriate design are needed to clarify the true impact of RSV treatment in NAFLD/NASH patients.

Evolution and predictive factors of thyroid disorder due to interferon alpha in the treatment of hepatitis C

AIM： To study predictive factors of thyroid dysfunction associated with interferon-alpha （IFNa） therapy in chronic hepatitis C （CHC） and to describe its long-term evolution in a large population without previous thyroid dysfunction. METHODS： We performed a follow-up of thyroid function and detection of thyroid antibodies in 301 patients treated for CHC with IFNα from 1999 to 2004. RESULTS： Thyroid disorder developed in 30/301 （10%） patients with a mean delay of 6 ± 3.75 mo： 13 patients had hyperthyroidism, 11 had hypothyroidism, and 6 had biphasic evolution. During a mean follow-up of 41.59 ± 15.39 mo, 9 patients with hyperthyroidism, 3 with hypothyroidism, and 4 with biphasic evolution normalized thyroid function in 7.88 ± 5.46 mo. Recovery rate of dysthyroidism was not modified by treatment discontinuation, but was better for patients with negative thyroid antibodies before antiviral treatment （P = 0.02）. Women had significantly more dysthyroidism （P = 0.05）. Positive thyroid peroxidase and thyroglobulin antibodies were more frequent before antiviral treatment in patients who developed dysthyroidism （P 〈 0.0003 and P = 0.0003, respectively）. In a multivariate model, low fibrosis was found to be a predictive factor of dysthyroidism （P = 0.039）.CONCLUSION： In this monocentric population of CHC, dysthyroidism, especially hyperthyroidism, developed in 10% of patients, Low fibrosis was found to be a predictive factor of dysthyroidism, Thyroid disorder recovered in 16/30 patients （53%） and recovery was better in the non-autoimrnune form,

Development and predictive validity of the cirrhosis-associated ascites symptom scale: A cohort study of 103 patients

AIM To develop a scale of domains associated with the health-related quality-of-life(HRQOL) in patients with cirrhosis-related ascites.METHODS We initially undertook literature searches and a qualitative study in order to design a cirrhosis-associated ascites symptom(CAS) scale describing symptoms with a potential detrimental impact on health related quality of life(HRQL)(the higher the score, the worse the symptoms). Discriminatory validity was assessed in a validation cohort including cirrhotic patients with(1) tense/severe;(2) moderate/mild; or(3) no ascites(controls). Patients also completed chronic liver disease questionnaire(CLDQ) and the Euro QoL 5-Dimensions 5-Level(EQ-5D-5L) questionnaire evaluating HRQL. The relation between scale scores was analysed using Spearman correlations. RESULTS The final CAS scale included 14 items. The equivalent reliability was high(Chronbach's alpha 0.88). The validation cohort included 103 patients(72% men, mean age 62.4 years). The mean scores for each question in the CAS scale were higher for patients with severe/tense ascites than for mild/moderate ascites and controls. Compared with controls(mean = 9.9 points), the total CAS scale score was higher for severe/tense ascites(mean = 23.8 points) as well as moderate/mild ascites(mean = 18.6 points)(P < 0.001 both groups). We found a strong correlation between the total CAS and CLDQ score(rho = 0.82, P < 0.001) and a moderate correlation between the CAS and the EQ-5D-5L score(0.67, P < 0.001). CONCLUSION The CAS is a valid tool, which reflects HRQOL in patients with ascites.

Epidemiological profiles of human immunodeficiency virus and hepatitis C virus infections in Malian women:Risk factors and relevance of disparities

AIM:To document the epidemiologic patterns and risk factors of human immunodeficiency virus(HIV)and hepatitis C virus(HCV)infections in Mali in order to develop prevention means for both diseases.METHODS:Two prospective studies were conducted in Bamako in 2009 among 1000 pregnant women(i.e.,young women)who consulted six reference health centers,and in 2010,among 231 older women who attended general practice in two hospitals.Antibody tests and molecular analysis(performed only for HCV)were used to quantify the frequencies of both infections.The data were collected from patients recruited through a questionnaire.Transmission risk factors of both diseases were identified by univariate and multivariate analysis.RESULTS:HCV seroprevalence was 0.2% for young and 6.5% for older women.HIV prevalence was similar in both populations(4.1% vs 6.1%).In older women,the analysis of risk factors highlighted an association between HCV infection and episodes of hospitalization(P < 0.01).The study did not show an association between HIV infection and the variables such as hospitalization,transfusion,tattoo,dental care,and endoscopy.A significant decrease of HIV seroprevalence was detected in young women who used condoms for contraception more than for other purposes(P < 0.01).By contrast,HIV seroprevalence was significantly increased in young women using condoms mainly to prevent sexual infections rather than for contraception(P < 0.01).No HCV/HIV coinfection was detected in our study.CONCLUSION:Risk factors and epidemiologic data of HIV and HCV as well as the absence of co-infection strongly suggest epidemiological disparities between these diseases.

Prevalence of HIV and HCV infections in two populations of Malian women and serological assays performances

AIM: To estimate the prevalence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in women in Mali and to evaluate the performance of serological assays.

Susceptibility patterns and virulence genotypes of Helicobacter pylori affecting eradication therapy outcomes among Egyptian patients with gastroduodenal diseases

BACKGROUND Helicobacter pylori(H.pylori)is a significant human pathogen that is responsible for a variety of illnesses,including mucosa-associated lymphoid tissue lymphoma,gastric cancer,peptic ulcers,and gastritis.AIM To investigate the frequency of H.pylori infection and its resistance patterns among Egyptian patients and to determine the influence of H.pylori virulence genetic determinants on the eradication success of 14-d triple therapy regimen.METHODS H.pylori infections were investigated in 72 patients with gastroduodenal complications suggestive of H.pylori infection.The cagA and vacA genotypes of cultured strains were studied using polymerase chain reaction.The patients underwent 14 d of triple-therapy treatment.The treatment response was examined using histology and a rapid urease test 6 wk after therapy discontinuation.RESULTS The intention-to-treat eradication rate was 59.2%(95%CI:48.2%-70.3%).Rates of H.pylori resistance to clarithromycin,amoxicillin,and metronidazole were 52.8%,81.9%,and 100%,respectively.Successful eradication of H.pylori was more significantly associated with vacA s1-positive strains[adjusted odds ratio(aOR)=0.507,95%CI:0.175-0.822].A significant association was found between failed eradication rate and H.pylori strains resistant to clarithromycin(aOR=0.204,95%CI:-0.005 to 0.412)and amoxicillin(aOR=0.223,95%CI:0.026-0.537).CONCLUSION This study’s low H.pylori eradication rate following 14-d triple therapy is concerning and worrying.H.pylori pan-resistance to metronidazole followed by the high resistance to ciprofloxacin,amoxicillin,and clarithromycin in this research is challenging and of great concern.

Subclinical proximal tubulopathy in hepatitis B:The roles of nucleot(s)ide analogue treatment and the hepatitis B virus

BACKGROUND The recommended monitoring tools for evaluating nucleot(s)ide analogue renal toxicity,such as estimated glomerular filtration rate(eGFR)and phosphatemia,are late markers of proximal tubulopathy.Multiple early markers are available,but no consensus exists on their use.AIM To determine the 24 mo prevalence of subclinical proximal tubulopathy(SPT),as defined with early biomarkers,in treated vs untreated hepatitis B virus(HBV)-monoinfected patients.METHODS A prospective,non-randomized,multicenter study of HBV-monoinfected patients with a low number of renal comorbidities was conducted.The patients were separated into three groups:Naïve,starting entecavir(ETV)treatment,or starting tenofovir disoproxil(TDF)treatment.Data on the early markers of SPT,the eGFR and phosphatemia,were collected quarterly.SPT was defined as a maximal tubular reabsorption of phosphate/eGFR below 0.8 mmoL/L and/or uric acid fractional excretion above 10%.The prevalence and cumulative incidence of SPT at month 24(M24)were calculated.Quantitative data were analyzed using analyses of variance or Kruskal-Wallis tests,whereas chi-squared or Fisher’s exact tests were used to analyze qualitative data.Multivariate analyses were used to adjust for any potential confounding factors.RESULTS Of the 196 patients analyzed,138(84 naïve,28 starting ETV,and 26 starting TDF)had no SPT at inclusion.At M24,the prevalence of SPT was not statistically different between naïve and either treated group(21.1%vs 30.7%,P<0.42 and 50.0%vs 30.7%,P=0.32 for ETV and TDF,respectively);no patient had an eGFR lower than 50 mL/min/1.73 m²or phosphatemia less than 0.48 mmoL/L.In the multivariate analysis,no explanatory variables were identified after adjustment.The cumulative incidence of SPT over 24 mo(25.5%,13.3%,and 52.9%in the naïve,ETV,and TDF groups,respectively)tended to be higher in the TDF group vs the naïve group(hazard ratio:2.283,P=0.05).SPT-free survival at M24 was 57.6%,68.8%,and 23.5%for the naïve,ETV,and TDF groups,respectively.The median survival time without SPT,evaluated only in the TDF group,was 5.9 mo.CONCLUSION The prevalence and incidence of SPT was higher in TDF-treated patients compared to naïve patients.SPT in the naïve population suggests that HBV can induce renal tubular toxicity.

Effects and safety of natriuretic peptides as treatment of cirrhotic ascites:A systematic review and meta-analysis

BACKGROUND Natriuretic peptides are involved in the cascade of pathophysiological events occurring in liver cirrhosis,counterbalancing vasoconstriction and anti-natriuretic factors.The effects of natriuretic peptides as treatment of cirrhotic ascites have been investigated only in small studies,and definitive results are lacking.AIM To examine the effects and safety of natriuretic peptides in cirrhosis patients with ascites.METHODS We searched MEDLINE,Web of Science,Scopus,Cochrane Library and Embase for all available studies applying intravenous administration of any natriuretic peptide to patients suffering from cirrhotic ascites.Inclusion was not limited by treatment duration or dose,or by follow-up duration.Both randomised controlled trials and non-randomised studies were eligible for inclusion.The primary outcome was change in renal sodium excretion.Secondary outcomes included safety measures and changes in renal water excretion,plasma aldosterone concentration,and plasma renin activity.RESULTS Twenty-two studies were included.Atrial natriuretic peptide(ANP)was the only intensively studied treatment.Sodium excretion increased in response to continuous ANP infusion and was more pronounced when infusion rates of>30 ng/kg/min were administered compared with≤30 ng/kg/min(P<0.01).Moreover,natriuresis was significantly higher in study subgroups with mild/moderate ascites compared with moderate/severe and refractory ascites(P<0.01).ANP infusions increased renal water excretion,although without reaching a statistically significant dose-response gradient.Plasma aldosterone concentration and plasma renin activity were significantly lower at baseline in study subgroups achieving a negative sodium balance in response to an ANP administration compared with treatment non-responders(P<0.01).Blood pressure decreases occurred less frequently when ANP doses≤30 ng/kg/min were applied.The quality of evidence for a natriuretic response to ANP was low,mainly due to small sample sizes and considerable between-study heterogeneity.Data were sparse for the other natriuretic peptides;B-type natriuretic peptide and urodilatin.CONCLUSION Intravenous ANP infusions increase sodium excretion in patients with cirrhotic ascites.Continuous infusion rates>30 ng/kg/min are the most effective.However,safety increases with infusion rates≤30 ng/kg/min.

Predictors of early rebleeding and mortality after acute variceal haemorrhage in patients with cirrhosis

The upper gastrointestinal bleeding from esophageal or gastric varices is the most dangerous complication of portal hypertension. The purpose of this study was to identify the predictors of early rebleeding and mortality after a bleeding episode. Patients and Methods: It was a retrospective study including 215 patients admitted in our department of hepatology and gastroenterology at the Hassan II University Hospital of Fez, from January 2001 to January 2010. Results: The mean age of our patients was 51 years. Thirty percent of patients had cirrhosis due to virus (B or C). The majority of patients (79%) had only esophageal varices. Fifty patients (23%) had a bleeding recurrence. Twenty-five patients (11.5%) died during the first ten days, of which 52% had presented rebleeding (p = 0.01). In 30% of cases, the rebleeding was secondary to a fall of pressure ulcers. Univariate analysis showed that early mortality of patients was significantly associated with advanced age (p = 0.018), low prothrombin time (PT) (p = 0.022), low serum sodium (p = 0.03), low platelet count (p = 0.05), and elevated transaminases (p = 0.02). Conclusion: The survival of cirrhotic patients after a bleeding episode was influenced by advanced age, a low rate of PT, of serum sodium, and of the platelet count, and elevated transaminases.

Obeticholic acid for severe bile acid diarrhea with intestinal failure:A case report and review of the literature

Bile acid diarrhea results from excessive amounts of bile acids entering the colon due to hepatic overexcretion of bile acids or bile acid malabsorption in the terminal ileum. The main therapies include bile acid sequestrants, such as colestyramine and colesevelam, which may be given in combination with the opioid receptor agonist loperamide. Some patients are refractory to conventional treatments. We report the use of the farnesoid X receptor agonist obeticholic acid in a patient with refractory bile acid diarrhea and subsequent intestinal failure. A 32-year-old woman with quiescent colonic Crohn's disease and a normal terminal ileum had been diagnosed with severe bile acid malabsorption and complained of watery diarrhea and fatigue. The diarrhea resulted in hypokalemia and sodium depletion that made her dependent on twice weekly intravenous fluid and electrolyte infusions. Conventional therapies with colestyramine, colesevelam, and loperamide had no effect. Second-line antisecretory therapies with pantoprazole, liraglutide, and octreotide also failed. Third-line treatment with obeticholic acid reduced the number of stools from an average of 13 to an average of 7 per 24h and improved the patient's quality of life. The fluid and electrolyte balances normalized. The effect was sustained during follow-up for 6 mo with treatment at a daily dosage of 25 mg. The diarrhea worsened shortly after cessation of obeticholic acid. This case report supports the initial report that obeticholic acid may reduce bile acid production and improve symptoms in patients with bile acid diarrhea.

Serum Vitamin D Levels and Severity of Liver Dysfunction in Cirrhotic Patients

Background and objective: Cirrhosis affects hundreds of millions of patients all around the world. Vitamin D deficiency is frequently observed in chronic hepatic disease. Vitamin D level may be an important survival marker in advanced liver cirrhosis. Material and Methods: The study is a sectional one of the descriptive-analytical type, where 90 of the patients with hepatic cirrhoses were selected with census sampling method. In all the cirrhotic patients, for diagnosis in clinical findings, the serological marker, autoantibodies were stable;biochemical endoscopy and imaging were the histological evidence and examinations and were then analyzed by SPSS version 22 software. Results: Based on the study, from the aspect of Child-Pugh classification, the highest vitamin D levels had the highest value in Child-Pugh class A with a frequency of 13 (43%) in the form of insufficiency, and had the highest value in Child-Pugh class B and C in the form of slight deficiency. Conclusion: It was specified based on the results obtained from the research that different vitamin D levels and liver failure severity have a significant relationship with each other (p < 0.05) in patients suffering from hepatic cirrhosis, such that the serum vitamin D level decreases as liver failure severity increases.

Barriers for resuming endoscopy service in the context of COVID-19 pandemic:A multicenter survey from Egypt

BACKGROUND The current coronavirus disease 2019(COVID-19)pandemic has affected routine endoscopy service across the gastroenterology community.This led to the suspension of service provision for elective cases.AIM To assess the potential barriers for resuming the endoscopy service in Egypt.METHODS A national online survey,four domains,was disseminated over a period of 4 wk in August 2020.The primary outcome of the survey was to determine the impact of the COVID-19 pandemic on the endoscopy service and barriers to the full resumption of a disabled center(s).RESULTS A hundred and thirteen Egyptian endoscopy centers participated in the survey.The waiting list was increased by≥50% in 44.9% of areas with clusters of COVID-19 cases(n=49)and in 35.5% of areas with sporadic cases(n=62).Thirty nine(34.8%)centers suffered from staff shortage,which was considered a barrier against service resumption by 86.4% of centers in per-protocol analysis.In multivariate analysis,the burden of cases in the unit locality,staff shortage/recovery and the availability of separate designated rooms for COVID-19 cases could markedly affect the resumption of endoscopy practice(P=0.029,<0.001 and 0.02,respectively)and Odd’s ratio(0.15,1.8 and 0.16,respectively).CONCLUSION The COVID-19 pandemic has led to restrictions in endoscopic volumes.The staff shortage/recovery and the availability of COVID-19 designed rooms are the most important barriers against recovery.Increasing working hours and dividing endoscopy staff into teams may help to overcome the current situation.

Correlation of magnetic resonance signal characteristics and perfusion parameters assessed by volume perfusion computed tomography in hepatocellular carcinoma:Impact on lesion characterization

AIM: To find out if magnetic resonance(MR)-signal characteristics of hepatocellular carcinomas(HCC) correlate with perfusion parameters assessed by volume perfusion computed tomography(VPCT).METHODS: From October 2009 to January 2014, 26(mean age, 69.3 years) patients with 36 HCC lesions who underwent both VPCT and MR liver imaging were analysed. We compared signal intensity in the T1 wand T2w-images and wash-in/wash-out kinetics on postcontrast MR images with mean values of blood flow(BF, mL/100 mL per minute), blood volume(BV, mL/100 mL), k-trans(mL/100 mL per minute), arterial liver perfusion(mL/100 mL per minute), portal venous perfusion and hepatic perfusion index(HPI, %) obtained by VPCT. Signal intensity on magnetic resonance imaging(MRI) was classified hyper/iso/hypointense compared with surrounding liver parenchyma. RESULTS: Signal intensity on native T1w- and T2 wimages was hyper/iso/hypo in 4/16/16 and 21/14/1 lesions, respectively. Wash-in and wash-out contrast kinetics were found on MRI in 33 of 36 lesions(91.7%) and 25 of 36 lesions(69.4%), respectively. The latter was observed significantly more often in higher graded lesions(P < 0.005). HPI was 94.7% ± 6.5%. There was no significant relationship between lesion's MRsignal intensity, MR signal combinations, size and any of the VPCT-perfusion parameters. However HPI was constantly high in all HCC lesions.CONCLUSION: VPCT parameters add limited value to MR-lesion characterization. However in HCC lesions with atypical MR signal characteristics HPI can add a parameter to ensure HCC diagnosis.

Targeting GPR65 alleviates hepatic inflammation and fibrosis by suppressing the JNK and NF-κB pathways

Background:G-protein coupled receptors(GPCRs)are recognized as attractive targets for drug therapy.However,it remains poorly understood how GPCRs,except for a few chemokine receptors,regulate the progression of liver fibrosis.Here,we aimed to reveal the role of GPR65,a proton-sensing receptor,in liver fibrosis and to elucidate the underlying mechanism.Methods:The expression level of GPR65 was evaluated in both human and mouse fibrotic livers.Furthermore,Gpr65-deficient mice were treated with either bile duct ligation(BDL)for 21 d or carbon tetrachloride(CCl4)for 8 weeks to investigate the role of GPR65 in liver fibrosis.A combination of experimental approaches,including Western blotting,quantitative real-time reverse transcription-polymerase chain reaction(qRT-PCR),and enzyme-linked immunosorbent assay(ELISA),confocal microscopy and rescue studies,were used to explore the underlying mechanisms of GPR65’s action in liver fibrosis.Additionally,the therapeutic potential of GPR65 inhibitor in the development of liver fibrosis was investigated.Results:We found that hepatic macrophage(HM)-enriched GPR65 was upregulated in both human and mouse fibrotic livers.Moreover,knockout of Gpr65 significantly alleviated BDL-and CCl4-induced liver inflammation,injury and fibrosis in vivo,and mouse bone marrow transplantation(BMT)experiments further demonstrated that the protective effect of Gpr65knockout is primarily mediated by bone marrow-derived macrophages(BMMs).Additionally,in vitro data demonstrated that Gpr65 silencing and GPR65 antagonist inhibited,while GPR65 overexpression and application of GPR65 endogenous and exogenous agonists enhanced the expression and release of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6)and transforming growth factor-β(TGF-β),all of which subsequently promoted the activation of hepatic stellate cells(HSCs)and the damage of hepatocytes(HCs).Mechanistically,GPR65 overexpression,the acidic pH and GPR65 exogenous agonist induced up-regulation of TNF-αand IL-6 via the Gαq-Ca^(2+)-JNK/NF-κB pathways,while promoted the expression of TGF-βthrough the Gαq-Ca^(2+)-MLK3-MKK7-JNK pathway.Notably,pharmacological GPR65 inhibition retarded the development of inflammation,HCs injury and fibrosis invivo.Conclusions:GPR65 is a major regulator that modulates the progression of liver fibrosis.Thus,targeting GPR65 could be an effective therapeutic strategy for the prevention of liver fibrosis.

Regression of hepatic fibrosis after pharmacological therapy for nonalcoholic steatohepatitis

The global incidence of nonalcoholic fatty liver disease(NAFLD)is escalating considerably.NAFLD covers a range of liver conditions from simple steatosis to the more severe form known as nonalcoholic steatohepatitis,which involves chronic liver inflammation and the transformation of hepatic stellate cells into myofibroblasts that generate excess extracellular matrix,leading to fibrosis.Hepatocyte ballooning is a key catalyst for fibrosis progression,potentially advancing to cirrhosis and its decompensated state.Fibrosis is a critical prognostic factor for outcomes in patients with NAFLD;therefore,those with substantial fibrosis require timely intervention.Although liver biopsy is the most reliable method for fibrosis detection,it is associated with certain risks and limitations,particularly in routine screening.Consequently,various noninvasive diagnostic techniques have been introduced.This review examines the increasing prevalence of NAFLD,evaluates the noninvasive diagnostic techniques for fibrosis,and assesses their efficacy in staging the disease.In addition,it critically appraises current and emerging antifibrotic therapies,focusing on their mechanisms,efficacy,and potential in reversing fibrosis.This review underscores the urgent need for effective therapeutic strategies,given the dire consequences of advanced fibrosis.

Dapagliflozin as an oral antihyperglycemic agent in the management of diabetes mellitus in patients with liver cirrhosis

BACKGROUND The use of dapagliflozin in patients with cirrhosis has been relatively restricted due to concerns regarding its overall safety and pharmacological profile in this population.AIM To determine the safety and effectiveness of dapagliflozin in the co-management of diabetes mellitus and cirrhosis with or without ascites.METHODS The patients studied were divided into two groups:100 patients in the control group received insulin,while 200 patients received dapagliflozin.These patients were classified as Child A,B,or C based on the Child–Pugh classification.Child A or B and Child C were administered doses of 10 mg and 5 mg of dapagliflozin,respectively.RESULTS The rate of increased diuretics dose was markedly elevated in the group that received insulin compared to the group that received dapagliflozin.In addition,dapagliflozin treatment substantially reduced weight,body mass index,and fasting blood glucose compared to the insulin group during follow-up.However,there were no significant differences in hemoglobin A1c,liver function,or laboratory investigations between both groups during the follow-up period.The incidence of hypoglycemia,hepatic encephalopathy,variceal bleeding,and urinary tract infection was significantly higher in the insulin group compared to the dapagliflozin group.In contrast,the dapagliflozin group experienced significantly higher rates of frequent urination and dizziness.In addition,the insulin group exhibited a marked worsening of ascites compared to the dapagliflozin group.CONCLUSION Dapagliflozin demonstrated safety and efficacy in the treatment of diabetic patients who have cirrhosis with or without ascites.This resulted in an improvement of ascites,as well as a decrease in diuretic dose and Child–Pugh score.

Role of macroscopic on-site evaluation of endoscopic ultrasoundguided fine-needle aspiration/biopsy:Results of a multicentric prospective study

BACKGROUND The concept of macroscopic on-site evaluation(MOSE)was introduced in 2015 when the endoscopist observed better diagnostic yield when the macroscopically visible core on MOSE was superior to 4 mm.Recent studies suggest that MOSE by the endoscopist may be an excellent alternative to rapid on-site evaluation,and some classi-fications have been published.Few studies have assessed the adequacy of histologic cores in MOSE during endoscopic ultrasound-guided fine-needle aspiration/biopsy(EUS-FNA/FNB).AIM To evaluate the performance of MOSE during EUS-FNA/FNB.METHODS This multicentric prospective study was conducted in 16 centers in 3 countries(Egypt,Iraq,and Morocco)and included 1108 patients with pancreatic,biliary,or gastrointestinal pathology who were referred for EUS examination.We prospectively analyzed the MOSE in 1008 patients with available histopathological reports according to 2 classifications to determine the adequacy of the histological core samples.Data management and analysis were performed using a Statistical Package for Social Sciences(SPSS)version 27.RESULTS A total of 1074 solid lesions were biopsied in 1008 patients with available cytopathological reports.Mean age was 59 years,and 509 patients(50.5%)were male.The mean lesion size was 38 mm.The most frequently utilized needles were FNB-Franseen(74.5%)and 22 G(93.4%),with a median of 2 passes.According to 2 classifications,618 non-bloody cores(61.3%)and 964 good samples(95.6%)were adequate for histological evaluation.The overall diagnostic yield of cytopathology was 95.5%.The cytological examination confirmed the diagnosis of malignancy in 861 patients(85.4%),while 45 samples(4.5%)were inconclusive.Post-procedural adverse events occurred in 33 patients(3.3%).Statistical analysis showed a difference between needle types(P=0.035)with a high sensitivity of FNB(97%).The analysis of the relationship between the MOSE-score and the final diagnosis showed a significant difference between the different scores of the MOSE(P<0.001).CONCLUSION MOSE is a simple method that allows endoscopists to increase needle passes to improve sample quality.There is significantly higher FNB sensitivity and cytopathology diagnostic yield with good MOSE cores.

Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis

Hepatocellular carcinoma (HCC) is the commonest primary malignant cancer of the liver in the world. Given that the burden of chronic liver disease is expected to rise owing to increasing rates of alcoholism, hepatitis B and C prevalence and obesity-related fatty liver disease, it is expected that the incidence of HCC will also increase in the foreseeable future. This article summarizes the international epidemiology, the risk factors and the pathogenesis of HCC, including the roles of viral hepatitis, toxins, such as alcohol and aflatoxin, and insulin resistance.

Current treatment of ulcerative colitis

Ulcerative colitis (UC) is a chronic disease featuring re- current inflammation of the colonic mucosa. The goal of medical treatment is to rapidly induce a steroid-free remission while at the same time preventing complica- tions of the disease itself and its treatment. The choice of treatment depends on severity, localization and the course of the disease. For proctitis, topical therapy with 5-aminosalicylic acid (5-ASA) compounds is used. More extensive or severe disease should be treated with oral and local 5-ASA compounds and corticosteroids to induce remission. Patients who do not respond to this treatment require hospitalization. Intravenous steroids or, when refractory, calcineurin inhibitors (cyclosporine, tacrolimus), tumor necrosis factor-α antibodies (infliximab) or immunomodulators (azathioprine, 6-mercaptopurine) are then called for. Indications for emergency surgery include refractory toxic megacolon, perforation, and continuous severe colorectal bleeding. Close collaboration between gastroenterologist and surgeon is mandatory in order not to delay surgical therapy when needed. This article is intended to give a general, practice-orientated overview of the key issues in ulcerative colitis treatment. Recommendations are based on published consensus guidelines derived from national and international guidelines on the treatment of ulcerative colitis.