Drug-induced, mixed-type hepatitis following ingestion of Cordyceps sinensis.

The use of herbal and dietary supplements is increasing worldwide. Consumers consider it as a natural, and therefore safe and healthy alternative to conventional synthetic drugs and do not expect adverse effects. However, numerous herbal and dietary supplements have been associated with adverse hepatic reactions of variable severity. Recognition of adverse hepatic reactions following the ingestion of herbal and dietary supplements is sometimes difficult since clinical presentation can resemble that of other etiologies unrelated to xenobiotics. Pharmacovigilance is based on spontaneous reporting and, thus, many incidents probably remain unrecorded due to lack of awareness among users and prescribers. The present report describes the first case of cholestatic hepatitis after the intake of an herbal supplement containing Cordyceps sinensis. Causality was considered probable after exclusion of alternative causes, a close temporal relationship, and an immediate dechallenge response with a full remission.

Development of a modified lymphocyte transformation test for diagnosing drug-induced liver injury associated with an adaptive immune response.

Drug-induced liver injury (DILI) is a growing problem. Diagnostic methods to differentiate DILI caused by an adaptive immune response from liver injury of other causes or to identify the responsible drug in patients receiving multiple drugs, herbals and/or dietary supplements (polypharmacy) have not yet been established. The lymphocyte transformation test (LTT) has been proposed as a diagnostic method to determine if a subject with an apparent hypersensitivity reaction has become sensitized to a specific drug. In this test, peripheral blood mononuclear cells (PBMC) collected from a subject are incubated with drug(s) suspected of causing the reaction. Cell proliferation, measured by the incorporation of [3H]-thymidine into new DNA, is considered evidence of a drug-specific immune response. The objectives of the current studies were to: (1) develop and optimize a modified version of the LTT (mLTT) and (2) investigate the feasibility of using the mLTT for diagnosing DILI associated with an adaptive immune response and identifying the responsible drug. PBMC collected from donors with a history of drug hypersensitivity reactions to specific drugs (manifested as skin rash) were used as positive controls for assay optimization. Following optimization, samples collected from 24 subjects enrolled in the U.S. Drug-Induced Liver Injury Network (DILIN) were tested in the mLTT. Using cytokine and granzyme B production as the primary endpoints to demonstrate lymphocyte sensitization to a specific drug, most samples from the DILIN subjects failed to respond. However, robust positive mLTT responses were observed for two of four samples from three DILIN subjects with hepatitis due to isoniazid (INH). We conclude that the mLTT, as performed here on frozen and thawed PBMC, is not a reliable test for diagnosing DILI caused by all drugs, but that it may be useful for confirming the role of the adaptive immune response in DILI ascribed to INH.

Does Citrulline Have Protective Effects on Liver Injury in Septic Rats?

Citrulline (Cit) supplementation was proposed to serve as a therapeutic intervention to restore arginine (Arg) concentrations and improve related functions in sepsis. This study explored whether citrulline had positive effects on liver injury and cytokine release in the early stages of sepsis. The cecal ligation and puncture (CLP) model was utilized in our study. Rats were divided into four groups: normal, Cit, CLP, and CLP+Cit. The CLP group and CLP+Cit group were separated into 6-, 12-, and 24-hour groups, according to the time points of sacrifice after surgery. Intragastric administration of L-citrulline was applied to rats in Cit and CLP+Cit groups before surgery. Serum AST and ALT levels and levels of MDA, SOD, NO, and iNOS in the liver tissues were evaluated. Plasma concentrations of Cit and Arg were assessed using HPLC-MS/MS. Serum concentrations of cytokines and chemokines were calculated by Luminex. Results showed SOD activities of CLP+Cit groups were significantly higher than that of CLP groups, contrasting with the MDA and NO levels which were significantly lower in CLP+Cit groups than in CLP groups. In addition, plasma concentrations of TNF-α, IL-6, and IL-1ß were significantly lower in the CLP+Cit 6-hour group than in the CLP 6-hour group.

Malestar e ictericia. Hepatitis tóxica por Copalchi / Illness and jaundice. Copalchi toxic hepatitis

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To chew or not to chew: that's the question.

A 25-year-old Somalian man was referred to the department of internal medicine because of nausea, vomiting and jaundice of recent onset. On physical examination, he was frankly icteric without clinical signs of chronic liver disease. Laboratory data showed evidence of acute hepatitis. Viral serologic tests for hepatitis A, B, C and E were negative. Antinuclear antibodies (ANA) were positive (titre 1 : 1280; speckled pattern, NV < 1 : 40) as well anti-actin antibodies (titre 75 UA, NV < 20). A liver biopsy was performed and showed a feature compatible with toxic hepatitis. On further questioning, the patient admitted to daily chew Khat when he was living in Somalia. We concluded to Khat-induced toxic hepatitis together with high-titre anti-nuclear antibody mimicking serologic patterns of auto-immune hepatitis.

A Case Report of Supplement-Induced Hepatitis in an Active Duty Service Member.

The incidence of drug-induced hepatic injury has been increasing as a result of more widespread use of workout supplements containing anabolic steroids to increase muscle mass. Synthetic androgenic steroids are shown to cause cholestatic liver injury, but the exact mechanism of injury is not completely understood. We present a case of a healthy, young, active duty Army male soldier who developed pruritis and jaundice shortly after starting to take a body-building supplement containing anabolic steroids, and was subsequently found to have significant biopsy proven drug-induced liver injury.

Autoimmune liver diseases.

Autoimmune liver diseases are characterized histologically by a dense mononuclear cell infiltrate in the portal tract and serologically by high levels of transaminases and immunoglobulin G (IgG) and positive autoantibodies, in the absence of a known etiology. In pediatrics, there are three liver disorders in which liver damage is likely to arise from an autoimmune attack: autoimmune hepatitis (AIH); autoimmune sclerosing cholangitis (ASC); and de novo autoimmune hepatitis after liver transplantation. The exact pathogenesis of AIH is still unknown, but it is known that unidentified environmental factors, and occasionally drugs, might trigger disease in genetically-susceptible individuals. The clinical spectrum of disease is very wide, ranging from asymptomatic individual with abnormal liver function test to fulminant liver failure. The diagnosis is based on the combination of biochemical and histological parameters, and exclusion of other liver diseases. It is a relatively rare but devastating disease, which progresses rapidly unless immunosuppressive treatment is started promptly. Standard therapy consists of a combination of corticosteroids and azathioprine, which is efficacious in 80% of patients. Alternative therapies are increasingly being explored in patients who do not respond to the standard treatment and/or have intolerable side effects. The purpose of this review was to provide an overview of the current knowledge on pediatric autoimmune liver disease.

Neonatal jaundice.

Neonatal jaundice lasting greater than 2 weeks should be investigated. Pale stools and dark or yellow urine are evidence of liver disease, which should be urgently investigated. The neonatal hepatitis syndrome has many causes, and a structured approach to investigation is mandatory. It should be possible to confirm or exclude biliary atresia within one week, so that definitive surgery is not delayed unnecessarily. Babies with the neonatal hepatitis syndrome should have vigorous fat-soluble vitamin supplementation, including parenteral vitamin K if coagulation is abnormal. The prognosis for infants with idiopathic neonatal hepatitis and multifactorial cholestasis is excellent.

Hepatotoxicidade induzida por sulfassalazina: relato de caso / Hepatotoxicity induced by sulfasalazine: case report

A sulfassalazina é ainda muito utilizada nas doenças inflamatórias intestinais, sobretudo na retocolite ulcerativa leve e moderada. Entretanto, seu uso é relacionado a vários efeitos colaterais, incluindo disfunção hepática grave.Este é um relato do caso de paciente masculino, 21 anos, portador de retocolite ulcerativa moderada, com queixa de inapetência, febre, artralgia e icterícia, há sete dias. Antecedente pessoal de uso de sulfassalazina 4 g/dia há seis semanas. Ao exame físico apresentava-se ictérico, com exantema em membros e edema de membros inferiores. Exames complementares mostravam aumento de bilirrubinas, enzimas hepáticas e canaliculares e da proteína C reativa. Com o diagnóstico de hepatotoxicidade por sulfassalazina, foi suspensa a medicação e introduzido prednisona 20 mg/dia e ciprofloxacino 1 g/dia. Recebeu alta no terceiro dia de internação após melhora clínica e laboratorial. Atualmente encontra-se assintomático e em uso de azatioprina 150 mg/dia.

The sulfasalazine is widely used in inflammatory bowel disease, especially in mild and moderate ulcerative rectocolitis. However, its use is related to several side effects, including severe liver dysfunction. We report the case of male patient, 21 years, with the moderate ulcerative rectocolitis, complaining of inappetence, fever, arthralgia and jaundice for seven days. Personal history includes use of sulfasalazine 4 g/day during six weeks. The physical examination revealed jaundiced, with members in rash and lower extremity edema. Laboratory exams showed an increase in bilirubin, liver enzymes and canalicular and C-reactive protein. With the diagnosis of hepatotoxicity by sulfasalazine, this medication was suspended, and introduced prednisone 20 mg/day and ciprofloxacin 1g/day. He was discharged on the third day of admission after clinical and laboratorial improvement. Currently, he is asymptomatic and in use of azathioprine 150 mg/day.

[Study on Chinese medical syndrome identification in patients with post-hepatitis cirrhosis by soft independent modelling of class analogy].

OBJECTIVE: To explore the feasibility of Chinese medical syndrome identification in patients with post-hepatitis cirrhosis (PHC) by soft independent modeling of class analogy (SIMCA). METHODS: After variants were normalized, SIMCA was used to analyze clinical symptoms, physical signs, and biological parameters in 268 PHC patients, and the obtained distance of SIMCA was used to identify the syndromes of PHC. Some incorrect reasons were then tested by Mann-Whitney test. RESULTS: The recognition rates of 5 Chinese medical syndromes (Gan depression and Pi deficiency syndrome, Gan-Shen yin-deficiency syndrome, Pi-Shen yang-deficiency syndrome, inner accumulation of dampness-heat syndrome, and stasis-heat accumulation syndrome) were 72.9% in the nearest class, and 17.91% in the sub-near class, as well as the total recognition rate was 90.3%. The highest recognition rate (95.24%) presented in the recognition on Gan-Shen yin-deficiency syndrome. Among some vital symptom variants of nearest class, significant difference could be found between identified and un-identified syndromes (P < 0.05). CONCLUSION: Identification of Chinese medical syndromes by SIMCA has rather higher goodness-of-fit with clinical practice, to set up a SIMCA depended syndrome identifying system could offer a useful reference for Chinese medical syndrome identification.

[Study on near infrared spectrum in the application of the BP neural network in the tongue diagnosis for hepatitis patients].

For a quick and noninvasive examination of the tongue for potential hepatitis patients, a study was conducted on the relation between the reflectivity of near infrared spectrum on the tongues of the healthy people and the hepatitis patients. Spectral data, 25 items for each case, are to be collected from the left and right side tongue, left and right sublingual venae, and tip of the tongue from the healthy people and the hepatitis patients. Then a three-layer neural network structure was established with all the data input after normalization reflectivity pretreatment. With the establishment of a BP neural network model, 40 data from each part of the body were selected as training samples. The rest 10 were adopted for prediction, which later was proved to be 100% correct with relative deviation values of less than 0.2. The research findings show that the proposed application of BP neural network in the spectral noninvasive examination of the tongue for identification of different case diagnosis is important for reference.

Severe hepatotoxicity following ingestion of Herbalife nutritional supplements contaminated with Bacillus subtilis.

BACKGROUND/AIMS: Nutritional supplements are widely used. Recently, liver injury after consumption of Herbalife preparations was reported but the underlying pathogenesis remained cryptic. METHODS: Two patients presented with cholestatic hepatitis and pruritus, and cirrhosis, respectively. Viral, alcoholic, metabolic, autoimmune, neoplastic, vascular liver diseases and synthetic drugs as the precipitating causes of liver injury were excluded. However, both patients reported long-term consumption of Herbalife products. All Herbalife products were tested for contamination with drugs, pesticides, heavy metals, and softeners, and examined for microbial contamination according to standard laboratory procedures. Bacteria isolated from the samples were identified as Bacillus subtilis by sequencing the 16S rRNA and gyrB genes. RESULTS: Causality between consumption of Herbalife products and disease according to CIOMS was scored "probable" in both cases. Histology showed cholestatic and lobular/portal hepatitis with cirrhosis in one patient, and biliary fibrosis with ductopenia in the other. No contamination with chemicals or heavy metals was detected, and immunological testing showed no drug hypersensitivity. However, samples of Herbalife products ingested by both patients showed growth of Bacillus subtilis of which culture supernatants showed dose- and time-dependent hepatotoxicity. CONCLUSIONS: Two novel incidents of severe hepatic injury following intake of Herbalife products contaminated with Bacillus subtilis emphasize its potential hepatotoxicity.

[Results of the participation of 360 laboratories of Russia in the external quality assessment program for HBsAG tests].

During their first participation in the external quality assessment program (EQAP), 78-81% of the laboratories detect positive samples of control panels containing 0.125 IU/ml of HBsAg; 95-97% of them identify negative samples of the control panels. The high efficiency of EQAP was established when the results of the same laboratories that had participated in two cycles were compared. For correct detection of positive samples of the control panel, it is necessary to use disposable containers and tips for example for solutions of conjugate concentrate, tetramethylbenzidine, buffer for conjugate dilution, and citrate-phosphate solution. The ranges of 95% confidence interval were established for the individual values of CV values of the commercial preparation ILC-HBsAg in the laboratories: from 0 to 11.3% with estimated convergence and from 0 to 14.2% with estimated reproducibility. In making an intralaboratory control of the quality of HBsAg test using ILC-HBsAg, one should be guided by the test accuracy indices given in the application sheet.

Lay beliefs about hepatitis among North American Chinese: implications for hepatitis prevention.

The objective was to learn about the hepatitis prevention behavior of relatively unacculturated North American Chinese adults, along with their knowledge, beliefs, and perceptions with regard to hepatitis, screening, and vaccination. Forty Chinese men and women, aged 18-64, were recruited from immigrant communities in Seattle, Washington, and Vancouver, British Columbia. Semi-structured interviews (Cantonese or Mandarin) were audiotaped, translated, transcribed verbatim, and coded. Open coding, axial coding, constant comparison methods, and QSR NUD*IST 5 software was used for analysis. Findings were validated using eight focus groups. Findings indicated that many interviewees lack accurate knowledge with regard to hepatitis, often confusing the different types. Perceived causes of hepatitis included potentially harmful food (e.g., fried foods or potentially contaminated foods), alcohol, contact with infected individuals, stress, and inadequate rest. Preventive strategies associated with Chinese health beliefs included the use of Chinese herbal medicine, maintaining a stress-free mind, strengthening the body's natural defenses, and getting enough sleep. Other preventive strategies were the practice of good hygiene, vaccination, and the avoidance of contact with infected persons. Vaccination was not seen as primary, as 65% of those who had heard of hepatitis vaccination did not cite it as a means for hepatitis prevention until asked. Also, participants lacked information about the types and purposes of hepatitis vaccination and were worried about side effects. In conclusion, any attempt to promote hepatitis testing and vaccination among the North American Chinese should take traditional beliefs and practices into consideration.

HHH syndrome (hyperornithinaemia, hyperammonaemia, homocitrullinuria), with fulminant hepatitis-like presentation.

We report a 3-year-old Italian patient with the hyperornithinaemia, hyperammonaemia, homocitrullinuria (HHH) syndrome who presented with neurological deterioration after an intercurrent infection. Hyperammonaemia, coagulopathy and moderate hypertransaminasaemia were detected on hospital admission. Severe hepatocellular necrosis with hypertransaminasaemia (aspartate aminotransferase 20,000 UI/L, alanine aminotransferase 18,400 UI/L) and coagulopathy (PT < 5%) rapidly developed within few days, prompting evaluation for liver transplantation. A protein-restricted diet and arginine supplementation were immediately started, with a rapid improvement of the patient's neurological conditions and normalization of liver function tests and blood ammonia. The diagnosis of HHH syndrome was based on the presence of the typical metabolic abnormalities. Molecular analysis of the SLC25A15 gene showed that the patient was heterozygous for two novel mutations (G113C and M273K). The diagnosis of HHH syndrome should be considered in patients with fulminant hepatitis-like presentations. Early identification and treatment of these patients can be life-saving and can avoid liver transplantation.