Drug-induced autoimmune hepatitis:A minireview

Drug-induced autoimmune hepatitis(DIAIH)is a specific phenotype of druginduced liver injury that may lead to the devastating outcome of acute liver failure requiring liver transplantation.Drugs implicated in DIAIH include antimicrobials such as nitrofurantoin and minocycline,non-steroidal anti-inflammatory drugs,statins as well as anti-tumor necrosis agents.The clinical features of druginduced liver injury are indistinguishable from idiopathic autoimmune hepatitis(AIH)as both may have positive AIH-related autoantibodies,elevated immunoglobulin G,as well as similar histopathological findings.In patients who show no clinical improvement,or there is progressive liver injury despite cessation of the suspected drug,a liver biopsy should be considered,whereby the presence of advance fibrosis on histology favors the diagnosis of idiopathic AIH.Empirical treatment with corticosteroids may be required in patients with non-resolving liver injury.A typical clinical scenario supportive of DIAIH includes a history of drug exposure with spontaneous resolution of liver injury after drug withdrawal and the absence of relapse after rapid steroid taper.In this article we report two cases of DIAIH secondary to Sorafenib and Atorvastatin along with a review of currently available literature.Early identification and treatment often lead to a favorable outcome in DIAIH.

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.

Hepatitis C virus cures after direct acting antiviral-related drug-induced liver injury: Case report

The United States Food and Drug Administration recently warned that the direct acting antiviral(DAA) combination hepatitis C virus(HCV) treatment of Paritaprevir, Ombitasvir, Dasabuvir, Ritonavir, and Ribavirin(PODr + R) can cause severe liver injury in patients with advanced liver disease. Drug induced liver injury was observed in a small number of patients with decompensated cirrhosis treated with other DAAs, but has not been reported in patients with compensated cirrhosis. We report a case of a 74-year-old woman with chronic HCV and Child-Pugh class A cirrhosis(compensated cirrhosis) treated with PODr + R. The patient presented on day 14 of PODr + R therapy with jaundice and new-onset ascites. Her total bilirubin level increased to 23 mg/dL and international normalized ratio rose to 1.65, while aminotransferase levels remained relatively stable. Hepatitis C treatment was discontinued on day 24 and she gradually recovered. Follow-up testing showed that she achieved a sustained virologic response. In conclusion, hepatic decompensation developed within two weeks of starting treatment withPODr + R in a patient with Child-Pugh class A cirrhosis and was characterized by jaundice and ascites with stable aminotransferase levels. Careful monitoring is warranted in patients with HCV-related cirrhosis treated with PODr + R.

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.

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

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.

Serious drug-induced liver disease secondary to ezetimibe

Ezetimibe is the f irst member of a new family of lipid- lowering drugs that inhibits uptake of dietary and bili- ary cholesterol. It was approved by the FDA in 2002 for hypercholesterolemia alone or in combination with statins. Its use has been spreading over the last years. Ezetimibe was considered a safe drug. We report a case of a woman who developed a serious hepatocellular drug-induced liver disease after 4 mo therapy with 10 mg daily of ezetimibe. After withdrawal of the drug, the patient recovered slowly. Ezetimibe may produce seri- ous toxic hepatitis and prompt withdrawal is mandatory in case of a signif icant abnormality in liver testing after beginning or during treatment with ezetimibe.

Halothane hepatitis in Iran:A review of 59 cases

AIM:To study halothane hepatitis (HH) in Iran and its associated risk factors. METHODS: We retrospectively studied files of all cases diagnosed with HH referred to three referral hospitals and four private centers in Iran from April 1994 to September 2006. Information on age at surgery, gender, medications history, obesity, history of previous exposure, previous reaction to halothane, familial history, type of surgery, perioperative hypoxia or sepsis, morbidity and mortality were recorded and analyzed. RESULTS: A total of 59 cases were identifi ed. Forty- eight (81%) were women. The median age at the time of surgery was 44 years (range, 18 to 80 years). Sixty percent of patients were above 40-year-old. Obesity was observed in 22.2%. Previous history of exposures to halothane was noted in 61% of which 50% had history of post-exposure reaction. Coronary artery bypass graft (CABG), cholecystectomy, and cosmetic surgeries (mainly weight reduction) were the most frequent surgeries. The mortality rate was 12.2%. In patients developing encephalopathy, it was as high as 50%. CONCLUSION: HH remains an important cause of morbidity and mortality in centers still using this anesthetic. However, a large percentage of these casescould have been avoided. To lessen occurrence of further cases of HH, the authors suggest that in female patients having a history of surgery (or delivery) with general anesthesia, the use of halothane should be absolutely avoided. Utilization of proper substitutes in adults’ anesthesia is advocated.

Pathogenesis of autoimmune hepatitis

Autoimmune hepatitis(AIH)is a chronic progressive liver disease whose etiology and pathogenesis are not yet clear.It is currently believed that the occurrence of AIH is closely related to genetic susceptibility and immune abnormalities,and other factors such as environment,viral infection and drugs that may cause immune dysfunction.This article reviews the pathogenesis of AIH and describes the latest research results in the past 5 years.

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.

Overview on drug-induced liver injury in Brazil

Drug-induced liver injury(DILI)is an uncommon event in clinical practice,which makes knowing its true incidence difficult.Prospective,retrospective and registry-based studies are the most important methods to obtain epidemiological data on DILI.Latin America(LA)has a historical lack of prospective studies on this topic.New definitions and the creation of hepatotoxicity registries have significantly improved the epidemiological understanding of hepatic drug reactions in several regions of the world.The Latin American DILI network,referred to as LATINDILI,has been created in 2011,and recently published its own DILI recommendations describing the most relevant issues on the management of hepatotoxicity in general,and those based on findings from our own LA experience in particular.Although most of the registries do not carry out population-based studies,they may provide important data related to the prevalence of DILI.The joint work among researchers and the corresponding health and regulatory authorities should be stimulated due to the high impact that hepatotoxicity represents for public health.

Serum markers for detecting histological features of autoimmune hepatitis and predicting prognosis in patients with antinuclear antibody-positive drug-induced liver injury

Aims:Although useful for distinguishing drug-induced liver injury(DILI)from autoimmune hepatitis(AIH),liver biopsy is an invasive examination,and the presence of antinuclear antibody(ANA)positivity in patients with DILI could lead to excessive use of biopsy.Hence,we aimed to identify screening markers for histological features of AIH in patients with ANA-positive DILI and verify their clinical outcomes after 1 year.Methods:This retrospective study included patients with ANA-positive DILI,who underwent liver biopsy between January 2017 and April 2022.Two pathologists identified histological features of AIH.We detected the independent indicators associated with histological features of AIH using logistic regression.We evaluated their diagnostic ability for histological features of AIH using the receiver operating characteristic curve.The followup period to determine clinical outcomes was 1 year after DILI onset.Theχ2 test or Fisher's exact test was used to compare categorical data and the Wilcoxon rank-sum test was used to compare continuous variables.Twosided p<0.05 was considered to indicate significance.Results:The final analysis included 125 patients with ANA-positive DILI,of whom 18 had AIH-like histology.Factors independently associated with AIH-like histology included globulin levels(odds ratio[OR]=1.154,95%confidence interval[CI]=1.046-1.288;p=0.006)and ANA titer≥1:1000(OR=3.531,95%CI=1.136-11.303;p=0.029).The optimal globulin cutoff indicating AIH-like histology was 31.8 g/L.This globulin level in combination with ANA titer≥1:1000(area under the curve=0.785,95%CI=0.738-0.832)provided a sensitivity of 100%and a specificity of 57%for indicating histological features of AIH in patients with ANA-positive DILI.During follow-up,more patients developed AIH in the group with AIH-like histology than in the group without AIH-like histology(35.3%vs.0,p<0.001).Conclusions:For patients with ANA-positive DILI and ANA titer≥1:1000 or globulin≥31.8 g/L,liver biopsy is recommended to determine the presence of histological features of AIH and guide further monitoring.

Risk factors related to significant hepatic inflammation in patients with acute drug-induced liver injury

Background and aims:Currently,research on biopsy-proven acute drug-induced liver injury(DILI)remains limited.This study aimed to identify clinical characteristics and risk factors for significant hepatic inflammation in patients with acute DILI.Methods:An ambispective cohort study was conducted on biopsy-proven acute DILI patients admitted to our hospital from 2012 to 2018.Using the Scheuer scoring system,patients were categorized into G0-2 or G3-4 groups and followed up for 12 months after first admission.Clinical characteristics and outcomes were retrieved from medical records.Results:The median age of the 157 enrolled patients(65.6%female)was 40.4(interquartile range(IQR),31.9-49.1)years.The median latency and length of hospitalization were 30.0(IQR,5.0-60.0)and 18.0(IQR,12.0-26.0)days.The proportions of patients in the G0-2 and G3-4 groups were 54.8%and 45.2%,respectively.Logistic regression analysis revealed that females(odds ratio(OR):2.623,95%confidence interval(CI):1.169-5.887,p=0.019),higher body mass index(OR:1.168,95%CI:1.029-1.325,p=0.016),higher total bilirubin(OR:1.004,95%CI:1.000-1.007,p=0.047),and lower prothrombin activity(OR:0.976,95%CI:0,957-0.995,p=0.013)were associated with significant hepatic inflammation.The predominance of the hepatocellular injury pattern(60.5%)at admission transformed into a predominance of the cholestatic pattern(60.5%)at discharge.During follow-up,23 patients(14.6%)developed chronic DILI,with nine patients(5.7%)progressing to cirrhosis.Moreover,15 female patients(9.6%)developed autoimmunity(3cases in the G0-2 group vs 12 cases in the G3-4 group,p<0.05).Conclusion:Acute DILI patients with high-risk factors were more likely to develop significant hepatic inflammation,and females with significant inflammation were at a higher risk of developing autoimmunity during follow-up.

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.

Immune checkpoint inhibitor-related hepatotoxicity:A review

The application of immune checkpoint inhibitors(ICI)in advanced cancer has been a major development in the last decade.The indications for ICIs are constantly expanding into new territory across different cancers,disease stages and lines of therapy.With this increased use,adverse events including immune checkpoint inhibitor-related hepatotoxicity(ICH)have emerged as an important clinical problem.This along with the introduction of ICI as first-and second-line treatments for advanced hepatocellular carcinoma makes ICH very relevant to gastroenterologists and hepatologists.The incidence of ICH varies between 1%-20%depending on the number,type and dose of ICI received.Investigation and management generally involve excluding differential diagnoses and following a stepwise escalation of withholding or ceasing ICI,corticosteroid treatment and adding other immunosuppressive agents depending on the severity of toxicity.The majority of patients with ICH recover and some may even safely recommence ICI therapy.Guideline recommendations are largely based on evidence derived from retrospective case series which highlights a priority for future research.

In drug-induced, immune-mediated hepatitis, interleukin-33 reduces hepatitis and improves survival independently and as a consequence of FoxP3+ T-cell activity

Immune-mediated,drug-induced hepatitis is a rare complication of halogenated volatile anesthetic administration.IL-4-regulated Th2-polarized reactions initiate this type and other types of hepatitis,while the mechanisms that regulate the severity remain elusive.IL-33 is an innate,IL-4-inducing,Th2-polarizing cytokine that has been detected in patients with liver failure and has been associated with upregulated ST2+Foxp3+CD4+CD25+T cells;however,roles for IL-33 in drug-induced hepatitis are unclear.We investigated IL-33 in an anesthetic,immune-mediated hepatitis modeled in BALB/c,IL-33−/−and ST2−/−mice,as well as in patients with anesthetic hepatitis.The hepatic IL-33 and ST2 levels were elevated in BALB/c mice(p<0.05)with hepatitis,and anti-IL-33 diminished hepatitis(p<0.05)without reducing IL-33 levels.The complete absence of IL-33 reduced IL-10(p<0.05)and ST2+Foxp3+CD4+CD25+T cells(p<0.05),as well as reduced the overall survival(p<0.05),suggesting suppressive roles for IL-33 in anesthetic,immune-mediated hepatitis.All of the mice demonstrated similar levels of CD4+T-cell proliferation following direct Tcell receptor stimulation,but we detected splenic IL-33 and ST2-negative Foxp3+CD4+CD25+T cells in ST2−/−mice that developed less hepatitis than BALB/c mice(p<0.05),suggesting that ST2-negative Foxp3+CD4+CD25+T cells reduced hepatitis.In patients,serum IL-33 and IPEX levels were correlated in controls(r2=0.5,p<0.05),similar to the levels in mice,but not in anesthetic hepatitis patients(r2=0.01),who had elevated IL-33(p<0.001)and decreased IPEX(p<0.01).Our results suggest that,in anesthetic,immune-mediated hepatitis,IL-33 does not regulate the CD4+T-cell proliferation that initiates hepatitis,but IL-33,likely independent of ST2,reduces hepatitis via upregulation of Foxp3+CD4+CD25+T cells.Further studies are needed to translate the role of IL-33 to human liver disease.

Dangerous dietary supplements: Garcinia cambogia-associated hepatic failure requiring transplantation

Commercial dietary supplements are marketed as a panacea for the morbidly obese seeking sustainable weight-loss. Unfortunately, many claims cited by supplements are unsupported and inadequately regulated. Most concerning, how ever, are the associated harmful side effects, often unrecognized by consumers. Garcinia cambogia extract and Garcinia cambogia containing products are some of the most popular dietary supplements currently marketed for weight loss. Here, we report the first known case of fulminant hepatic failure associated with this dietary supplement. One active ingredient in this supplement is hydroxycitric acid, an active ingredient also found in weight-loss supplements banned by the Food and Drug Administration in 2009 for hepatotoxicity. Heightened awareness of the dangers of dietary supplements such as Garcinia cambogia is imperative to prevent hepatoxicity and potential fulminant hepatic failure in additional patients.

Hepatotoxicity of NONI juice: Report of two cases

NONI juice (Morinda citrifolia) is an increasingly popular wellness drink claimed to be beneficial for many illnesses.No overt toxicity has been reported to date. We present two cases of novel hepatotoxicity of NONI juice. Causality of liver injury by NONI juice was asses-sed. Routine laboratory tests and transjugular or percutaneous liver biopsy were performed. The first patient underwent successful liver transplantation while the second patient recovered spontaneously after cessation of NONI juice.A 29-year-old man with previous toxic hepatitis associated with small doses of paracetamol developed sub-acute hepatic failure following consumption of 1.5 L NONI juice over 3 wk necessitating urgent liver transplantation. A 62-year-old woman without evidence of previous liver disease developed an episode of self-limited acutehepatitis following consumption of 2 L NONI juice for over 3 mo. The most likely hepatotoxic components of Morinda citrifolia were anthraquinones. Physicians should be aware of potential hepatotoxicity of NONI juice.