hepatitis

摘要： BACKGROUND The antidepressant escitalopram is widely prescribed for the treatment of depression.It is generally well-tolerated,and cholestasis is not mentioned in its summary of product characteristics(Sm PC).We present a case of cholestatic and cytolysis liver injury due to escitalopram and a Vigi Base?study.CASE SUMMARY A 68-year-old man was admitted to our emergency unit due to clinical jaundice associated with hepatitis,pruritus and dark urine.We tested the patient for the most common etiologies of jaundice,including hemolysis,viral hepatitis,cirrhosis,carcinoma,cholangitis,cholelithiasis and intrahepatic or extrahepatic obstruction.The etiological study was negative,and an adverse drug reaction was the sole possible explanation.The patient was receiving treatment with escitalopram.Two days after its withdrawal,pruritus was resolved.Ten days after withdrawal,clinical jaundice disappeared.It took a month and three weeks after withdrawal for the patient to have normalized liver function tests.To our knowledge,this is the first reported case of cholestasis where treatment with escitalopram was the only possible cause,with a highly probable causality.In addition,we determined whether escitalopram is associated with hepatotoxicity and cholestasis by performing a disproportionality analysis.All cases of hepatobiliary disorders induced by escitalopram and reported in the World Health Organization pharmacovigilance database(Vigi Base?)were analyzed to characterize this toxicity.We found that patients treated with escitalopram had an increased risk of hepatitis[odds ratio(OR)=1.938(1.186-3.166)]and cholestasis[OR=1.866(1.279-2.724)][OR(95%confidence interval)].The median duration between the introduction of escitalopram and the occurrence of acute hepatitis and/or cholestasis was ten days+/-seven days.CONCLUSION Although extremely rare,this case report,the review of the literature and the pharmacovigilance update confirm that escitalopram can cause drug-induced hepatotoxicity and cholestasis,generally within a week after initiation.Thus,escitalopram should be withdrawn immediately if an iatrogenic cause cannot be excluded.If its responsibility is ascertained,escitalopram should be consequently contraindicated.In addition,serotoninergic antidepressants in patients with nonsevere depression are ineffective and harmful.Finally,the Sm PC of escitalopram should be updated to alert for this risk and give clear clinical guidelines.

摘要： BACKGROUND Primary liver cancer(PLC)is a major contributor to cancer-related deaths.Data on global and country-specific levels and trends of PLC are essential for understanding the effects of this disease and helping policymakers to allocate resources.AIM To investigate the association between the burden of PLC and socioeconomic development status.METHODS Cancer mortality and incidence rates were obtained from the Global Burden of Disease(GBD)2019,and the data were stratified by country and territory,sex,and the Socio-demographic Index(SDI)level.The association between the attributable etiology of PLC and socioeconomic development status,represented using the SDI,was described.The attributable etiology of PLC included hepatitis B,hepatitis C,alcohol use,and nonalcoholic steatohepatitis.The association between the attributable etiology of PLC and SDI was further stratified by sex and geographical location.A confidence analysis was also performed based on bootstrap draw.RESULTS The age-standardized incidence rate of PLC was 6.5[95%confidence intervals(CI):5.9-7.2]per 100000 person-years,which decreased by-27.5%(-37.0 to-16.6)from 1990 to 2019.Several countries located in East Asia,South Asia,West Africa,and North Africa shouldered the heaviest burden of PLC in 2019.In terms of incidence rates,the first leading underlying cause of PLC identified was hepatitis B,followed by hepatitis C,alcohol use,and nonalcoholic steatohepatitis.Regarding stratification using the SDI,the incidence rate of PLC was the highest for high and middle SDI locations.Further,the leading attributable etiologies of PLC were hepatitis B for the middle and high middle SDI locations while hepatitis C and nonalcoholic steatohepatitis for the high SDI locations.CONCLUSION The pronounced association between socioeconomic development status and PLC burden indicates socioeconomic development status affects attributable etiologies for PLC.GBD 2019 data are valuable for policymakers implementing PLC cost-effective interventions.

摘要： Classical acute viral hepatitis(AVH)has an uncomplicated outcome.Acute liver failure has a grave prognosis.Atypical manifestations of AVH are a group of disorders that causes significant morbidity and dilemmas in children.These include prolonged cholestasis,relapsing hepatitis,ascitic form of AVH,late-onset hepatic failure(LOHF),intravascular hemolysis,and provoking an autoimmune trigger leading to autoimmune hepatitis.These entities cause significant liver dysfunction or worsening and are often difficult to differentiate from chronic liver disease(CLD).Ascitic form of AVH,LOHF,decompensated CLD and acute-onchronic liver failure have significant overlapping features that need to be carefully dissected out.In many cases,only on long-term follow-up,these clinical entities can be separately identified.Intravascular hemolysis is usually caused by associated glucose-6-phosphate dehydrogenase deficiency.Rarely CLD such as Wilson disease and autoimmune hepatitis can also present with hemolysis in the initial presentation,which can mimic AVH with hemolysis.Identifying deviations from typical manifestations aid in avoiding unnecessary investigations,allowing focused therapy and alleviating anxiety.

摘要： Fibrolamellar carcinoma(FLC)is a rare variant of hepatocellular carcinoma(HCC),comprising 1%–9%of all HCCs.FLC is a poorly understood malignancy,which seems to be more prevalent in young patients with no underlying liver diseases.The term“fibrolamellar”is derived from thick fibrous collagen bands surrounding the tumor cells.Unlike HCC,cirrhosis and viral hepatitis infection are not predisposing to FLC,and it is not associated with elevations in serum alpha-fetoprotein.FLC patients often present with vague abdominal pain,nausea,malaise,and weight loss.Most cases present are at an advanced stage at the time of initial diagnosis.However,curative treatment options can still be offered to up to 70%of patients.Surgery(resection/liver transplantation)is the mainstay of treatment and the only potentially curative option.FLCs have been less chemoresponsive than the conventional HCC,however,in advanced cases,multimodality treatments can be effective.Recent advances in molecular studies of FLC have found a unique DNAJB1–PRKACA fusion transcript in most of the cases studied.The review aims to describe clinical characteristics,diagnostic methods,and therapeutic modalities for this rare tumor to raise awareness among clinicians and surgeons.

摘要： Objective:To systematically explore the effect and mechanism of melastomatis dodecandri herba(Melastoma dodecandrum Lour.)in the treatment of hepatitis based on network pharmacology.Method:We evaluated the hepatoprotective effects of M.dodecandrum in concanavalin A(Con A)-induced hepatitis in mice by assessing survival rate,histological analysis,serum transaminases,and related cytokines.Then the mechanism of action was predicted by a network pharmacology-based strategy.Based on the results,we measured the hepatic expression of related genes at mRNA level and proteins related to the phosphoinositide 3-kinase(PI3K)/protein kinase B(Akt)and nuclear factorkappa B(NF-кB)pathways.Results:Our study results clearly demonstrated that M.dodecandrum pretreatment significantly alleviated liver injury.This was demonstrated by an increase in survival rate,decreased severity of liver damage,and reduced serum transaminase levels compared with those in the Con A group.Moreover,M.dodecandrum significantly reduced the serum levels of tumor necrosis factor-a,interleukin-6,and interferon-g and increased the liver levels of superoxide dismutase,which indicated that M.dodecandrum exhibits anti-inflammatory and antioxidant activities.On the basis of network pharmacology,50 nodes were selected as major hubs based on their topological importance.Pathway enrichment analyses indicated that the putative targets of M.dodecandrum mostly participate in various pathways associated with the anti-inflammation response,which implies the underlying mechanism by which M.dodecandrum acts on hepatitis.Real-time fluorescent quantitative PCR analysis showed that M.dodecandrum downregulates the mRNA expression of interleukin-6,Toll-like receptor 7,interleukin-1 receptor-associated kinase-4,NF-кB and tumor necrosis factor-a in liver tissues.Western blotting showed that M.dodecandrum pretreatment protected against inflammation through activating the PI3K-Akt pathway by upregulating phosphorylated Akt(p-Akt)expression and suppressing NF-кB activation by inhibiting the phosphorylation of IKK,IkBa,and p65.Conclusion:The present work demonstrated the hepatoprotective effects of M.dodecandrum by regulating the PI3K/Akt and NF-кB pathways in Con A-induced mice,which provide insights into the treatment of hepatitis using M.dodecandrum.

摘要： The article by Lan et al.[1],published on 30 October 2021 in Hepatology,showed the relationship between the natural flavonoid compound breviscapine and nonalcoholic steatohepatitis(NASH).The researchers demonstrated that breviscapine might be a novel therapeutic candidate for the treatment of NASH.It can be proven that breviscapine prevents metabolic stress-induced NASH progression through direct inhibition of the TGF-β-activated Kinase 1(TAK1)signaling pathway.

摘要： On April 6,2022,the United Kingdom Health Security Agency(UKHSA)released an alert on cases of hepatitis of unknown etiology in children[1].On April 15,2022,World Health Organization(WHO)published the first notice of this condition[2].Later on,similar cases were reported from the UK,other European countries,and other parts of the world.

摘要： Immunological checkpoint inhibitors(ICIs)have revolutionized therapy of many different malignanices.Concomitant immune-mediated adverse effects are common and can affect many organs such as the skin,lungs,gastrointestinal and endocrine organs as well as the liver.Liver injury has been reported in 3%-8%of patients with grade III-IV hepatitis in retrospective studies.The liver injury is characterized by hepatocellular injury resembling autoimmune hepatitis biochemically but not immunologically as patients with ICI induced hepatoxicity rarely have auto-antibodies or IgG elevation.The role for liver biopsy(LB)in patients with suspected liver injury due to ICIs is controversial and it is not clear whether results of a LB will change clinical management.LB can be helpful when there is diagnostic uncertainty and pre-existing liver disease is suspected.Although there are no distinctive histological features,the finding of granulomas and endothelitis may suggest a specific type of hepatitis induced by ICIs.The natural history of hepatotoxicity of ICI therapy is not well known.Recent studies have demonstrated that 33%-50%of patients improve spontaneously with discontinuation of ICIs.In patients with jaundice and/or coagulopathy corticosteroids are used.The high doses of corticosteroids with 1-2 mg/kg/d of methylprednisolone recommended by the oncological societies are controversial.Recently it has shown that initial treatment with 1 mg/kg/d provided similar liver tests improvement which was also associated with a reduced risk of steroid-induced adverse effects in comparison with higher-dose regimens.Secondary immunosuppression mostly with mycophenolate mofetil has been reported to be helpful.

摘要： Common variable immunodeficiency (CVID) is one of the most prevalent primary immunodeficiency disorders, characterized by an alteration in the maturation of B lymphocytes. Patients with this condition are redisposed to a higher risk of infections. Despite being an immune deficiency disorder, the prevalence of autoimmune disorders is reported in more than 20% of patients. The likelihood of patients’ gastrointestinal tract being affected is relatively low, close to 6%. We present the case of a 22-year-old man with a history of CVID without medical treatment, who presented with upper gastrointestinal bleeding secondary to esophageal varices due to cirrhotic portal hypertension. Infectious and toxic causes of cirrhosis were ruled out. Histological changes compatible with autoimmune hepatitis (AIH) were documented by liver biopsy. The diagnosis of autoimmune diseases is a challenge in the presence of IDCV, we highlight the importance of establishing a timely diagnosis and an intentional search for these conditions to offer timely treatment and avoid late complications.

摘要： BACKGROUND Hereditary hemochromatosis(HH)has an increased risk of hepatocellular cancer(HCC)both due to genetic risks and iron overload as iron overload can be carcinogenic;HH impacts the increasing risk of HCC,not only through the development of cirrhosis but concerning hepatic iron deposition,which has been studied further recently.AIM To evaluate HH yearly trends,patient demographics,symptoms,comorbidities,and hospital outcomes.The secondary aim sheds light on the risk of iron overload for developing HCC in HH patients,independent of liver cirrhosis complications.The study investigated HH(without cirrhosis)as an independent risk factor for HCC.METHODS We analyzed data from National Inpatient Sample(NIS)Database,the largest national inpatient data collection in the United States,and selected HH and HCC cohorts.HH was first defined in 2011 International Classification of Disease-9th edition(ICD-9)as a separate diagnosis;the HH cohort is extracted from January 2011 to December 2019 using 275.01(ICD-9)and E83.110(ICD-10)diagnosis codes of HH.Patients were excluded from the HH cohort if they had a primary or secondary diagnostic code of cirrhosis(alcoholic,non-alcoholic,and biliary),viralhepatitis,alcoholic liver disease,non-alcoholic fatty liver disease(NAFLD),and non-alcoholic steatohepatitis(NASH).We removed these patients from the HH cohort to rule out bias or ICD-10 diagnostic errors.The HCC cohort is selected from January 2011 to December 2019 using the ICD-9 and ICD-10 codes of HCC.We selected a non-HCC cohort with the 1:1 fixed ratio nearest neighbor(greedy)propensity score method using the patients'age,gender,and race.We performed multivariate analysis for the risk factors of HCC in the HCC and non-HCC matched cohort.We further analyzed HH without cirrhosis(removing HH patients with a diagnosis of cirrhosis)as an independent risk factor of HCC after adjusting all known risk factors of HCC in the multivariate model.RESULTS During the 2011-2019 period,a total of 18031 hospitalizations with a primary or secondary diagnosis of HH(excluding liver diseases)were recorded in the NIS database.We analyzed different patients’characteristics,and we found increments in inpatient population trend with a Ptrend<0.001 and total hospital cost of care trend from$42957 in 2011 to$66152 in 2019 with a Ptrend<0.001 despite no change in Length of Stay over the last decade.The multivariate analyses showed that HH without cirrhosis(aOR,28.8;95%CI,10.4–80.1;P<0.0001),biliary cirrhosis(aOR,19.3;95%CI,13.4–27.6;P<0.0001),non-alcoholic cirrhosis(aOR,17.4;95%CI,16.5–18.4;P<0.0001),alcoholic cirrhosis(aOR,16.9;95%CI,15.9–17.9;P<0.0001),hepatitis B(aOR,12.1;95%CI,10.85–13.60;P<0.0001),hepatitis C(aOR,8.58;95%CI,8.20–8.98;P<0.0001),Wilson disease(aOR,4.27;95%CI,1.18–15.41;P<0.0001),NAFLD or NASH(aOR,2.96;95%CI,2.73–3.20;P<0.0001),alpha1-antitrypsin deficiency(aOR,2.10;95%CI,1.21–3.64;P<0.0001),diabetes mellitus without chronic complications(aOR,1.17;95%CI,1.13–1.21;P<0.0001),and blood transfusion(aOR,1.80;95%CI,1.69–1.92;P<0.0001)are independent risk factor for liver cancer.CONCLUSION Our study showed an increasing trend of in-hospital admissions of HH patients in the last decade.These trends were likely related to advances in diagnostic approach,which can lead to increased hospital utilization and cost increments.Still,the length of stay remained the same,likely due to a big part of management being done in outpatient settings.Another vital part of our study is the significant result that HH without cirrhosis is an independent risk factor for HCC with adjusting all known risk factors.More prospective and retrospective large studies are needed to re-evaluate the HH independent risk in developing HCC.