Drug induced autoimmune hepatitis:An unfortunate case of herbal toxicity from Skullcap supplement:A case report

BACKGROUND The surge in traditional herbal dietary supplement(HDS)popularity has led to increased drug-induced liver injuries(DILI).Despite lacking evidence of efficacy and being prohibited from making medical claims,their acceptance has risen over sevenfold in the last two decades,with roughly 25%of United States(US)adults using these supplements monthly.An estimated 23000 emergency room visits annually in the US are linked to HDS side effects.NIH-funded research suggests HDS contribute to 7-20%of DILI cases,with similar trends in Europe—Spain reporting 2%and Iceland up to 16%.Patients with acute liver failure from HDS undergo liver transplantation more frequently than those from prescription medicines.Here we describe a case of drug-induced autoimmune hepatitis due to Skullcap supplements,this association appears to be the first documented instance in literature.CASE SUMMARY A middle-aged Caucasian woman,previously healthy,presented with sudden jaundice.Four months earlier,her liver enzymes were normal.She mentioned recent use of Skullcap mushroom supplements.Tests for chronic liver disease were negative.The first liver biopsy indicated severe resolving drug-induced liver injury.Despite treatment,she was readmitted due to worsening jaundice.Followup tests raised concerns about autoimmune hepatitis.A subsequent biopsy confirmed this diagnosis.The patient responded as expected to stopping the medication with improvement in liver enzymes.CONCLUSION This scenario highlights an uncommon instance of DILI caused by Skullcap supplements.It's crucial for hepatologists to recognize this connection due to the increasing prevalence of herbal supplements.

A rare cause of drug-induced hepatitis in an immunocompromised patient and the role of glutathione

The Food and Drug Administration (FDA) has issued a warning on numerous herbal drugs, including many popular products at General Nutrition Centers (GNC), regarding unstudied hepatotoxicity. There have been recent reports of GNC products such as hydroxycut and herbalife, causing drug-induced hepatitis. Herbal medications are over-the-counter products and are not investigated thoroughly by the FDA. Given that the mostcommon outpatient laboratory abnormality is elevated liver transaminases, a sign of hepatocellular toxicity; it is not surprising that some of these products end up causing hepatic dysfunction, especially when taken in large volume. There are numerous herbal supplements that are hepatotoxic, however, these medications have a much more significant effect in human immunodeficiency virus (HIV)/ acquired immune deficiency syndrome patients, which is secondary to depleted glutathione. We present a rare case of drug induced hepatitis secondary to herbal medications used to treat HIV and elucidate the role of glutathione depletion in immunocompromised patients.

CD4+Foxp3+CD25+/-Tregs characterize liver tissue specimens of patients suffering from drug-induced autoimmune hepatitis:A clinical-pathological study

Background: The diagnosis of drug-induced autoimmune hepatitis(DIAIH) and its differentiation from idiopathic autoimmune hepatitis(AIH) is challenging. This study aimed to differentiate DIAIH from AIH by comparing the biochemical changes, histological features, and frequencies of CD4~+Foxp3~+CD25+/-regulatory T cells(Tregs) in liver tissues or peripheral blood lymphocytes.Methods: A total of 15 DIAIH patients and 24 AIH patients who underwent liver biopsies at initial presentation were enrolled in this study. The liver histological changes were assessed by HE staining. The phenotypic recognition and distribution of CD4~+Foxp3~+CD25+/-Tregs in liver tissues were evaluated by single/double immunostains in serial sections. The CD4~+Foxp3~+CD25+/-Tregs in peripheral blood were analyzed by flow cytometry.Results: The median values of ALT and AST were 404.50 U/L and 454.10 U/L in DIAIH patients and309.50 U/L and 315.00 U/L in AIH patients, respectively. More importantly, for the first time we found that patients with DIAIH had higher levels of serum ALT and AST, more severe degree of lobular inflammation,higher frequencies of zone 3 necrosis and higher number of lobular CD4~+Foxp3~+CD25~-Tregs compared with AIH(P < 0.05). Furthermore, there were positive correlations in DIAIH between the degree of lobular inflammation and either the AST/ALT level or the number of lobular CD4~+Foxp3~+CD25~-Tregs(P < 0.05).However, the frequency of peripheral blood CD4~+Foxp3~+CD25+/-Tregs were not significantly different between DIAIH and AIH.Conclusions: The differences of ALT, AST and the number of lobular CD4~+Foxp3~+CD25~-Tregs between patients with DIAIH and those with AIH are clinically helpful in differentiating these two diseases in their early stage.

Care strategies for patients with severe drug-induced hepatitis

Objective: The aim of this study is to analyse the clinical characteristics of 32 patients with severe drug-induced hepatitis, reinforce the practice of unique nursing and holistic nursing, improve the therapeutic effect, reduce the patients’ mortality, and increase their quality of life. Methods: We give patients individualized dietary guidance, medication nursing, and psychological care according to the characteristics of severe hepatitis and its complications, using com- prehensive medical treatment and combined signs of Traditional Chinese Medicine. Results: Overall, 22 (68.8%) out of 32 cases were improved, 8 (25.0%) cases died, and 2 (6.2%) cases were discharged of free will. In addition, the average hospital stay was 28.75 days. Conclusion: This study indicates that dietary guidance for the patients with severe drug-induced hepatitis varies with the individual. The result embodies the concept of Traditional Chinese Medicine that different treatment for the same disease and different diet for the same disease. Special nursing enriches the connotation of holistic nursing. Both of them are vital for improving the survival rate and promoting rehabilitation of patients with severe drug-induced hepatitis.

Carbimazole Drug-Induced Hepatitis during Treatment of Graves’ Disease: About Four Cases at Dakar Teaching Hospital

Introduction: Mostly reported common side effects of carbimazole are cutaneous allergies and severe agranulocytosis. However, hepatotoxicity is rarely described. Thus, we report four observations of carbimazole drug-induced hepatitis during the treatment of Graves’ disease, which imputability is likely and probably an immuno-allergic mechanism. Observations: They were four women whose average age was 43 years, with extreme ages of 32 and 54. Patients were monitored and treated with carbimazole in doses contained between 40 mg and 60 mg per day. Clinical manifestations of liver injury were mainly dominated by cholestatic jaundice, found in 100% of our patients. A painful sensitivity of the right hypochondrium was concomitant with jaundice for two patients. The jaundice time to onset after the beginning of treatment with carbimazole varies between 1 month and 6 months. They all had acute hepatitis. The biological assays used to determine the type of liver injury showed, in all cases, a mixed, cholestatic and cytolytic hepatitis. Therapeutically, in all patients, carbimazole was stopped as soon as the suspicion of its incrimination in the occurrence of liver damage was set up. They all had a substitution of carbimazole with benzylthiouracil. Evolution was favorable for all patients, after therapeutic substitution. It was marked by disappearance of jaundice and normalization of the liver biological parameters within a maximum delay of two months after stopping carbimazole use. Conclusion: Treatment with synthetic antithyroid drugs, particularly carbimazole that is most widely used in our regions, requires clinical and biological monitoring. This surveillance, which is often difficult in Africa because of the limited economic resources, can lead to the occurrence of side effects such as potentially serious drug-induced hepatitis, but which has been favorable in our observations.

Induced pluripotent stem cells for therapy personalization in pediatric patients:Focus on drug-induced adverse events

Adverse drug reactions(ADRs)are major clinical problems,particularly in special populations such as pediatric patients.Indeed,ADRs may be caused by a plethora of different drugs leading,in some cases,to hospitalization,disability or even death.In addition,pediatric patients may respond differently to drugs with respect to adults and may be prone to developing different kinds of ADRs,leading,in some cases,to more severe consequences.To improve the comprehension,and thus the prevention,of ADRs,the set-up of sensitive and personalized assays is urgently needed.Important progress is represented by the possibility of setting up groundbreaking patient-specific assays.This goal has been powerfully achieved using induced pluripotent stem cells(iPSCs).Due to their genetic and physiological species-specific differences and their ability to be differentiated ideally into all tissues of the human body,this model may be accurate in predicting drug toxicity,especially when this toxicity is related to individual genetic differences.This review is an up-to-date summary of the employment of iPSCs as a model to study ADRs,with particular attention to drugs used in the pediatric field.We especially focused on the intestinal,hepatic,pancreatic,renal,cardiac,and neuronal levels,also discussing progress in organoids creation.The latter are three-dimensional in vitro culture systems derived from pluripotent or adult stem cells simulating the architecture and functionality of native organs such as the intestine,liver,pancreas,kidney,heart,and brain.Based on the existing knowledge,these models are powerful and promising tools in multiple clinical applications including toxicity screening,disease modeling,personalized and regenerative medicine.

drug-induced autoimmune liver disease:a diagnostic dilemma of an increasingly reported disease

The aetiology of autoimmune hepatitis(AIH) is uncer-tain but the disease can be triggered in susceptible patients by external factors such as viruses or drugs.AIH usually develops in individuals with a genetic back-ground mainly consisting of some risk alleles of the major histocompatibility complex(HLA).Many drugs have been linked to AIH phenotypes,which sometimes persist after drug discontinuation,suggesting that they awaken latent autoimmunity.At least three clini-cal scenarios have been proposed that refers to drug- induced autoimmune liver disease(DIAILD):AIH with drug-induced liver injury(DILI); drug induced-AIH(DI-AIH); and immune mediated DILI(IM-DILI).In addi-tion,there are instances showing mixed features of DI-AIH and IM-DILI,as well as DILI cases with positive autoantibodies.Histologically distinguishing DILI from AIH remains a challenge.Even more challenging is the differentiation of AIH from DI-AIH mainly relying in histological features; however,a detailed standard-ised histologic evaluation of large cohorts of AIH and DI-AIH patients would probably render more subtle features that could be of help in the differential diag-nosis between both entities.Growing information on the relationship of drugs and AIH is being available,being drugs like statins and biologic agents more fre-quently involved in cases of DIAILD.In addition,there is some evidence on the fact that patients diagnosed with DIAILD may have had a previous episode of hepa-totoxicity.Further collaborative studies in DIAILD will strengthen the knowledge and understanding of this intriguing and complex disorder which might represent different phenotypes across the spectrum of

S-1 induced hepatic steatosis in patients with pancreatic cancer:Retrospective analysis

To determine whether S-1 induces hepatic steatosis in patients being treated for pancreatic cancer. METHODSThis retrospective study evaluated 22 patients who received oral S-1 as a first-line treatment for pancreatic cancer between January 2008 and July 2015 at the Ishikawa Prefectural Central Hospital. Patients underwent abdominal computed tomography (CT) scans before chemotherapy and within 3 mo from the start of treatment. CT numbers of the liver and spleen were measured before and after S-1 administration. Steatosis was diagnosed when the ratio of the CT number of the liver to that of the spleen (liver/spleen ratio) was < 0.9. RESULTSMedian patient age was 68 years (range, 48-85 years), and median body mass index was 21 kg/m2 (range, 18-27 kg/m2). Of the 22 patients, six (27%) regularly consumed alcohol, and five (23%) had liver metastases. The mean ratio of CT number of the liver to the spleen was significantly higher before administration of S-1 (1.27 vs 1.09, P = 0.012) compared with after. Of the 22 patients, five (23%) had hepatic steatosis and 17 (77%) did not. The pretreatment demographic and clinical characteristics of these two groups showed no significant differences. The relationship between liver/spleen ratio and alanine transaminase activity in these patients. A statistically significant inverse correlation was observed (r = -0.417, P < 0.027). CONCLUSIONOf the 22 patients with pancreatic cancer, five (23%) experienced S-1 induced hepatic steatosis. Care should be taken during S-1 treatment of patients with pancreatic cancer.

Effect of IFNα-2a on Fas expression and apoptosis rate of peripheral blood cytotoxic T cells in patients with hepatitis B

Interferon(IFN) with antiviral and im-munomodulatory activities is one of the most important therapeutic agents for the treatment of chronic hepatitis. The apoptotic effect of IFN is influenced by cell type and the types of IFN, which suppresses proliferation and induces apoptosis in some cell types while inhibiting apoptosis in others. The aim of this study was to explore the effect of IFNα-2a on Fas expression and the apoptosis rate of peripheral blood cytotoxic T cells (CTLs) in patients with hepatitis B. METHODS:Peripheral blood mononuclear cells were isolated from 26 patients with hepatitis B including 16 patients with chronic hepatitis B and 10 patients with chronic severe hepatitis B. Fas expression and apoptosis rate of CTLs were analyzed with flow cytometry before and after IFNα-2a treatment. RESULTS:Before IFNα-2a treatment, Fas expression and apoptosis rate of CTLs from patients with chronic hepatitis B were significantly higher than those from patients with chronic severe hepatitis B and healthy controls respectively. No significant difference was observed between Fas expression and apoptosis rate of CTLs from patients with chronic severe hepatitis B and healthy controls. After IFNα-2a treatment,Fas expression and apoptosis rate of CTLs from different groups were compared with those before IFNα-2a treatment, showing no significant difference despite alternation of different degree. CONCLUSIONS:Activation induced cell death (AICD) exists in peripheral blood CTLs from patients with hepatitis B. No effect of IFNα-2a exerts on Fas expression and apoptosis rate of Fas in patients with hepatitis B.

Potential triggering factors of acute liver failure as a first manifestation of autoimmune hepatitis-a single center experience of 52 adult patients

AIM To investigate potential triggering factors leading to acute liver failure(ALF) as the initial presentation of autoimmune hepatitis(AIH).METHODS A total of 565 patients treated at our Department between 2005 and 2017 for histologically-proven AIH were retrospectively analyzed. However, 52 patients(9.2%) fulfilled the criteria for ALF defined by the "American Association for the Study of the Liver(AASLD)". According to this definition, patients with "acute-on-chronic" or "acute-on-cirrhosis" liver failure were excluded. Following parameters with focus on potential triggering factors were evaluated: Patients' demographics, causation of liver failure, laboratory data(liver enzymes, MELD-score, autoimmune markers, virus serology), liver histology, immunosuppressive regime, and finally, outcome of our patients.RESULTS The majority of patients with ALF were female(84.6%) and mean age was 43.6 ± 14.9 years. Interestingly, none of the patients with ALF was positive for antiliver kidney microsomal antibody(LKM). We could identify potential triggering factors in 26/52(50.0%) of previously healthy patients presenting ALF as their first manifestation of AIH. These were drug-induced ALF(57.7%), virus-induced ALF(30.8%), and preceding surgery in general anesthesia(11.5%), respectively. Unfortunately, 6 out of 52 patients(11.5%) did not survive ALF and 3 patients(5.7%) underwent liver transplantation(LT). Comparing data of survivors and patients with non-recovery following treatment, MELDscore(P < 0.001), age(P < 0.05), creatinine(P < 0.01), and finally, ALT-values(P < 0.05) reached statistical significance. CONCLUSION Drugs, viral infections, and previous surgery may trigger ALF as the initial presentation of AIH. Advanced age and high MELD-score were associated with lethal outcome.

Autoimmune hepatitis and anti-tumor necrosis factor alpha therapy:A single center report of 8 cases

This article describes cases of anti-tumor necrosis factor(TNF)-α-induced autoimmune hepatitis and evaluates the outcome of these patients in relation to their immunosuppressive strategy. A retrospective analysis of medical records was performed in our center, in order to detect cases of autoimmune hepatitis(AIH) associated with anti-TNF biologic agents. We describe and analyze eight cases of AIH following anti-TNF therapy, 7 with infliximab and 1 with adalimumab. A distinction should be made between induction of autoimmunity and clinically evident autoimmune disease. Liver biopsy is useful in detecting the role of the TNF-α antagonist in the development of AIH. The lack of relapse after discontinuing immunosuppressive therapy favors, as in this case series, an immune-mediated drug reaction as most patients with AIH have a relapse after treatment is suspended. Although AIH related to anti-TNF therapy is rare, a baseline immunological panel along with liver function tests should be performed in all patients with autoimmune disease before starting biologics.

Viral hepatitis prevalence in patients with active and latent tuberculosis

AIM: To assess the prevalence of hepatitis B virus(HBV) and hepatitis C virus(HCV) infection and association with drug induced liver injury(DILI) in patients undergoing anti-tuberculosis(TB) therapy.METHODS: Four hundred and twenty nine patients with newly diagnosed TB- either active disease or latent infection- who were due to commence antiTB therapy between September 2008 and May 2011 were included. These patients were prospectively tested for serological markers of HBV, HCV and human immunodeficiency virus(HIV) infections- hepatitis B core antigen(HBc Ag), hepatitis B surface antigen(HBs Ag), hepatitis B e antigen, Ig G and Ig M antibody to HBc Ag(anti-HBc), HCV Ig G antibody and HIV antibody using a combination of enzyme-linked immunosorbent assay, Western blot assay and polymerase chain reaction techniques. Patients were reviewed at least monthly during the TB treatment initiation phase. Liver function tests were measured prior to commencement of antiTB therapy and 2-4 wk later. Liver function tests were also performed at any time the patient had significant nausea, vomiting, rash, or felt non-specifically unwell. Fisher's exact test was used to measure significance in comparisons of proportions between groups. A P value of less than 0.05 was considered statistically significant.RESULTS: Of the 429 patients, 270(62.9%) had active TB disease and 159(37.1%) had latent TB infection. 61(14.2%) patients had isolated anti-HBc positivity, 11(2.6%) were also HBs Ag positive and 7(1.6%) were HCV-antibody positive. 16/270 patients with active TB disease compared to 2/159 patients with latent TB infection had markers of chronic viral hepatitis(HBs Ag or HCV antibody positive; P = 0.023). Similarly the proportion of HBs Ag positive patients were significantly greater in the active vs latent TB infection group(10/43 vs 1/29, P = 0.04). The prevalence of chronic HBV or HCV was significantly higher than the estimated United Kingdom prevalence of 0.3% for each. We found no association between DILI and presence of serological markers of HBV or HCV. Three(5.3%) patients with serological markers of HBV or HCV infection had DILI compared to 25(9.5%) patients without; P = 0.04.CONCLUSION: Viral hepatitis screening should be considered in TB patients. DILI risk was not increased in patients with HBV/HCV.

Khat(Catha Edulis) as a possible cause of autoimmune hepatitis

AIM:To investigate the potential role of khat in triggering auto immune hepatitis.METHODS:Patients with a history of khat use and acute hepatitis were identified using the computer database in the hepatology department at the Royal Hallamshire Hospital.They were then assessed for probability of having autoimmune hepatitis using the revised autoimmune hepatitis scoring criteria.RESULTS:Six patients were identified.All of them had presented with acute hepatitis on a background of khat.All were male and five of these patients were of Somali origin,while one patient was from Yemen.The patients were given points on the modified autoimmune hepatitis score which is based on their liver enzymes,autoimmune screen,exclusion of viral hepatitis alcohol and drugs,immunoglobulin levels and liver histology.The patients were given a score of-4 for khat use due to its potential to cause drug induced liver injury.Five of these patients scored between 10 and 15 points,placing them in the probable group for having autoimmune hepatitis.All of these patients were treated with prednisolone and demonstrated a good response to immunosuppression.CONCLUSION:One possibile cause of hepatotoxicity with khat could be via triggering of autoimmune hepatitis in a genetically susceptible individual.Further studies are needed for confirmation.

Hepatobiliary manifestations in inflammatory bowel disease: The gut,the drugs and the liver

Abnormal liver biochemical tests are present in up to30%of patients with inflammatory bowel disease(IBD),and therefore become a diagnostic challenge.Liver and biliary tract diseases are common extraintestinal manifestations for both Crohn’s disease and ulcerative colitis(UC),and typically do not correlate with intestinal activity.Primary sclerosing cholangitis(PSC)is the most common hepatobiliary manifestation of IBD,and is more prevalent in UC.Approximately 5%of patients with UC develop PSC,with the prevalence reaching up to 90%.Cholangiocarcinoma and colon cancer risks are increased in these patients.Less common disorders include autoimmune hepatitis/PSC overlap syndrome,IgG4-associated cholangiopathy,primary biliary cirrhosis,hepatic amyloidosis,granulomatous hepatitis,cholelithiasis,portal vein thrombosis,liver abscess,and non-alcoholic fatty liver disease.Hepatitis B reactivation during immunosuppressive therapy is a major concern,with screening and vaccination being recommended in serologically negative cases for patients with IBD.Reactivation prophylaxis with entecavir or tenofovir for 6to 12 mo after the end of immunosuppressive therapy is mandatory in patients showing as hepatitis B surface antigen(HBsAg)positive,independently from viral load.HBsAg negative and anti-HBc positive patients,with or without anti-HBs,should be closely monitored,measuring alanine aminotransferase and hepatitis B virus DNA within 12 mo after the end of therapy,and should be treated if the viral load increases.On the other hand,immunosuppressive therapy does not seem to promote reactivation of hepatitis C,and hepatitis C antiviral treatment does not influence IBD natural history either.Most of the drugs used for IBD treatment may induce hepatotoxicity,although the incidence of serious adverse events is low.Abnormalities in liver biochemical tests associated with aminosalicylates are uncommon and are usually not clinically relevant.Methotrexaterelated hepatotoxicity has been described in 14%of patients with IBD,in a dose-dependent manner.Liver biopsy is not routinely recommended.Biologics-related hepatotoxicity is rare,but has been shown most frequently in patients treated with infliximab.Thiopurines have been associated with veno-occlusive disease,regenerative nodular hyperplasia,and liver peliosis.Routine liver biochemical tests are recommended,especially during the first month of treatment.All these conditions should be considered in IBD patients with clinical or biochemical features suggestive of hepatobiliary involvement.Diagnosis and management of these disorders usually involve hepatologists and gastroenterologists due to its complexity.

红细胞分布宽度-血小板比值评估自身免疫性肝炎患者肝纤维化严重程度的回顾性研究

目的比较自身免疫性肝炎(AIH)、药物性肝损伤(DILI)的临床资料差异,并评估AIH患者肝纤维化严重程度的影响因素及其诊断效能。方法回顾2015年6月-2022年8月期间苏州市中西医结合医院收治的AIH患者45例(AIH组),男4例、女41例;DILI患者86例(DILI组),男23例、女63例;AIH、DILI诊断符合要求。使用Metavir系统对肝纤维化程度进行评分,其中<F2期为非显著肝纤维化,≥F2期为显著肝纤维化,比较两者临床资料信息,采用单变量和多变量分析影响AIH患者晚期肝纤维化的因素。应用ROC曲线以及AUC值评估红细胞分布宽度-血小板(RPR)对AIH肝纤维化严重程度诊断的准确性。结果AIH患者年龄、皮肤瘙痒、ALP、球蛋白、TBA、PT及RDW分别为54(48,63)岁、6例(13.3%)、154(119,278)U/L、36.1(31.2,44.0)g/L、50.4(17.8,140.6)μmol/L、11.8(11.2,13.4)s及15.1(13.6,16.4)%,均显著高于DILI[50(41,58)岁、0(0)、121(82,187)U/L、28.3(24.6,31.8)g/L、25.6(8.9,108.4)μmol/L、11.2(10.8,12.3)s及14.1(13.0,15.5)%,P<0.05];而AIH患者男性、PLT水平分别为4例(8.9%)、162(126,203)×109/L,均显著低于DILI[23例(26.7%)、204(173,352)×109/L,P<0.05]。单变量分析显示,非显著、显著肝纤维化AIH患者IgA、RDW、FIB-4、GPR及RPR差异有统计学意义;多变量分析发现,IgA、GPR及RPR升高,AIH患者显著肝纤维化风险显著增加,而年龄、性别、IgG、RDW、APRI及FIB-4与AIH患者显著肝纤维化之间无明显关联。RPR对AIH患者显著肝纤维化的截断点、ROC值、敏感度及特异度分别为-2.3、0.82、82.3%(14/17)及78.6%(22/28)。结论AIH患者的组织学肝纤维化程度与RPR和血清IgA水平显著相关。

Immune-mediated liver injury following COVID-19 vaccination

Liver injury secondary to vaccination is a rare adverse event that has recently come under attention thanks to the continuous pharmacovigilance following the widespread implementation of coronavirus disease 2019(COVID-19)vaccination protocols.All three most widely distributed severe acute respiratory syndrome coronavirus 2 vaccine formulations,e.g.,BNT162b2,mRNA-1273,and ChAdOx1-S,can induce liver injury that may involve immune-mediated pathways and result in autoimmune hepatitis-like presentation that may require therapeutic intervention in the form of corticosteroid administration.Various mechanisms have been proposed in an attempt to highlight immune checkpoint inhibition and thus establish causality with vaccination.The autoimmune features of such a reaction also prompt an in-depth investigation of the newly employed vaccine technologies.Novel vaccine delivery platforms,e.g.,mRNA-containing lipid nanoparticles and adenoviral vectors,contribute to the inflammatory background that leads to an exaggerated immune response,while patterns of molecular mimicry between the spike(S)protein and prominent liver antigens may account for the autoimmune presentation.Immune mediators triggered by vaccination or vaccine ingredients per se,including autoreactive antibodies,cytokines,and cytotoxic T-cell populations,may inflict hepatocellular damage through wellestablished pathways.We aim to review available data associated with immunemediated liver injury associated with COVID-19 vaccination and elucidate potential mechanisms underlying its pathogenesis.

Autoimmune hepatitis in human immunodeficiency virus infection: Case report and literature review

The infection due to human immunodeficiency virus(HIV) is characterized by the progressive reduction of CD4+ T lymphocytes and the compromise of other cell lines of the immune system, resulting in immunosuppression. In this context, autoimmune diseases could be considered contradictory, however, cases of autoimmune diseases during this infection have been described, including autoimmune hepatitis(AIH), which is uncommon and has few case reports within medical literature, none of them from Latin America. In this case report where a patient with an HIV infection on combined antiretroviral treatment developed acute elevation of transaminases, hyperbilirubinemia, and deterioration in hepatic synthetic function. Although initially an antiretroviral drug-induced liver injury was suspected, during the study a diagnosis of autoimmune hepatitis was proven, which required treatment with corticosteroid and azathioprine, obtaining a satisfactory response and managing to continue the antiretroviral therapy. Autoimmune diseases in HIV infection must be taken into account. In the case of hepatitis in patients with HIV on antiretroviral treatment, the differentiation between viral hepatitis caused by autoimmune diseases or medications is essential to establish an adequate treatment, and avoid the suspension of the antiretroviral therapy.

70例慢性肝炎型DILI患者临床血清学特征及病理特点分析

目的:观察慢性肝炎型药物性肝损伤(DILI)患者的临床血清学特征及病理损伤程度。方法:回顾性观察70例经肝穿刺组织病理明确诊断为慢性肝炎型DILI患者的临床特征、用药史、合并基础病、血清学指标、影像特征及病理损伤程度等资料。结果:慢性肝炎型DILI患者女性明显多于男性,以45~60岁多见,平均(52.6±11.4)岁。最常见用药是中药或中成药(27.1%),其次是抗生素类(21.4%),联合用药占比32.9%;前三位并发症分别是高血压(22.9%)、糖尿病(17.1%)、甲状腺功能亢进(8.6%);17.1%患者存在过敏史;反复发作的有患者41例(58.6%),平均反复发作次数2.1次。血清学指标以ALT、AST、TBil、LY%轻度升高为主,有45例(64.3%)患者伴自身抗体阳性,以抗核抗体最常见(41.4%),炎症活动以中或重度为主,纤维化程度以轻或中度为主。结论:慢性肝炎型DILI患者多见于中年女性,易反复发作,中药或中成药是最常见用药类型,常伴有异常的自身免疫反应,炎症与纤维化程度常不同步。

1例维迪西妥单抗联合卡度尼利单抗治疗晚期膀胱癌致免疫相关性肝炎的病例分析

目的分析维迪西妥单抗联合卡度尼利单抗致免疫相关性肝炎的不良反应,为临床合理、安全使用卡度尼利单抗和维迪西妥单抗提供参考。方法临床药师通过回顾1例晚期膀胱癌患者使用维迪西妥单抗联合卡度尼利单抗治疗导致免疫相关性肝炎的临床表现、诊治思路、治疗结局,对病例进行分析。结果经过糖皮质激素治疗后,患者转氨酶及胆红素水平恢复,免疫相关性肝炎分级降至1级以下。结论免疫相关性肝炎临床表现不典型,不及时处理可能导致生命危险,医生应根据临床症状及相关检查及时发现免疫相关性肝炎并给予早期治疗,以预防严重不良反应。

药物诱导的自身免疫样肝炎的研究进展

药物诱导的自身免疫样肝炎(DI-ALH)是药物性肝损伤的一种特殊临床表型,与自身免疫性肝炎有相似的临床特征和实验室检查,多数时候通过肝组织活检也无法直接区分,因此正确鉴别DI-ALH与自身免疫性肝炎是临床实践中的重难点。本文总结了DI-ALH的发病机制、临床特点、诊治、预后的研究进展,为临床医生提供此类疾病的诊治思路。