Clinical manifestation score and characterization of cytokines and lymphocytes of dimethylacetamide-induced toxic hepatitis in spandex workers.

Occupational exposure to dimethylacetamide (DMAc) has been reported to cause toxic hepatitis. Sixty spandex workers were included in this study to research the clinical manifestations and expression of cytokines and lymphocytes in DMAc-induced toxic hepatitis. Chinese drugs (reduced glutathione and Hugan tablets) were used to treat them. The manifestations including jaundice, asthenia, appetite, nausea, emesis, abdominal distension, yellow urine, and dizziness were scored. The percentages of patients rated as 0-3, 4-6, 7-9, and 10-12 points were 33.3%, 43.3%, 21.7%, and 1.7%, respectively, before treatment, and all patients showed 0-3 points after the treatment. The ultrasonic and CT imaging revealed diffuse intrahepatic hypodensity, intrahepatic calcification, signs of liver injury, and splenomegaly, which improved after therapy. Blood analysis showed that ALT, AST, TBIL, IL-6, IL-10, TNF-α, IFN-γ, CD3+%, and CD4+/CD8+ statistically decreased after drug treatment. Correlation analysis demonstrated positive linear correlations between ALT and TBIL, AST and TBIL, IL-10 and ATL, IL-10 and AST, IL-10 and TBIL, IFN-γ and IL-6, IFN-γ and TNF-α, and CD3+% and ALT. Pro-inflammatory cytokines and lymphocytes in DMAc-induced toxic hepatitis reflected an active immune state that decreased after treatment. IL-10 may inhibit the immune response in this disease, as a protective mechanism.

[Treatment of toxic hepatitis in COVID-19 patients].

BACKGROUND: The article reflects the clinical significance of the early diagnosis of toxic hepatitis in patients who have undergone a new coronavirus infection with the determination of clinical and laboratory predictors of the response to therapy. A dynamic analysis of the effectiveness of toxic hepatitis therapy in patients of three experimental groups and a control group is presented. AIM: The aim of the present study is to increase the effectiveness of the treatment of toxic hepatitis in patients who have undergone COVID-19. MATERIALS AND METHODS: On the basis of the newly created infection centers of the Central Clinical Hospital "RZhD-Medicine" and Vishnevsky 3-rd Central Military Clinical Hospital 996 patients with COVID-19, who had clinical and laboratory signs of toxic liver damage (cytolytic and/or cholestatic syndromes) against the background of COVID-19 therapy. RESULTS: On the 14th day from the start of therapy in group 3, there was a significant decrease in the clinical manifestations of jaundice in 163 (72.8%) patients, on the 21st day of treatment, this symptom was stopped in all patients. In groups 1 and 2, the decrease in clinical manifestations of jaundice was significantly lower - 122 (55.2%) and 134 (58.8%); p<0.05. At the end of therapy, no manifestations of jaundice were observed in all experimental groups, while in the control group, symptom reduction was achieved only in 47 (14.5%) patients. CONCLUSION: The use of drugs with hepatoprotective effect in the form of monotherapy in groups 1 (UDCA) and 2 (ademethionine) showed a low therapeutic effect with positive dynamics of clinical and laboratory indicators of toxic hepatitis activity. The use of combined treatment in group 3 (UDCA and ademethionine) demonstrated the maximum therapeutic effect, pronounced positive dynamics in the form of normalization of clinical and laboratory indicators of toxic hepatitis activity.

[Effects of triterpenoids in fatty products on liver condition of laboratory animals with acute toxic hepatitis].

One of the principles of prevention and non-medicamentous treatment of liver diseases, including hepatitis of different etiology, is the normalization of the diet through the consumption of food with physiologically active ingredients, in particular betulin, which helps to eliminate the causes of metabolic and oxidative disorders within liver cells. The aim of the research was to assess in vivo the influence of triterpene alcohol betulin extracted from Betula pendula Roth. birch bark in fat-containing products (for example mayonnaise) on the blood biochemical parameters and liver morphological structure of rats with initiated acute toxic hepatitis. Material and methods. Hepatoprotective and antioxidant activities of betulin as part of mayonnaise samples has been investigated in vivo on the model of toxic hepatitis initiated by carbon tetrachloride in male Wistar rats weighing 210-265 g. The animals were divided into 4 groups of 10 animals each: CG-1 - intact, CG-2 and MG - with carbon tetrachloride initiated toxic hepatitis. rats of the main groups were orally administered mayonnaise once a day at a dosage of 1 ml for 21 days after the formation of the model pathology: OG-1 with the added betulin (1 mg per 1 kg of body weight), OG-2 without betulin. Disorders of metabolic and oxidative processes in liver cells of animals were evaluated by biochemical indicators of blood plasma: the level of glucose, albumin, total cholesterol, triglycerides and urea and the activity of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase and γ-glutamyltransferase. Oxidative stress in rats was estimated by the activity of catalase and superoxide dismutase in blood hemolysate (at a dilution of 1:200 and 1:10, respectively); the total prooxidant (in blood plasma) and total antioxidant (in blood hemolysate at a dilution of 1:10) activity were determined spectrophotometrically (colored complexes of TWIN-80 oxidation products with thiobarbituric acid). The morphological structure of rats' liver was estimated by microscopy of prepared cuts of hepatic tissue. Results. Based on biochemical parameters of rat blood plasma, it has been established that the administration of mayonnaise with betulin prevents the development of cytolic syndrome and suppresses the process of peroxidation by directly neutralizing free radicals. Aspartate aminotransferase and alkaline phosphatase activity in blood plasma of the experimental animals of the main group MG-1 reduced by 20.7 and 35.2% compared with indicators of the rats of the main group MG-2. Glucose concentration normalized to the level of the control group CG-1. The concentration of bilirubin and triglycerides decreased by 22.9 and by 48.1%, which indicates a significant reduction in the indicators of cholestatic syndrome in the group of animals OG-1 compared to OG-2. The total prooxidant activity and the concentration of thiobarbiturate-reactive products decreased compared to the CG-2 and MG-2 groups, which indicates the suppression of oxidative stress and, as a result, an improvement in liver conditions of animals with toxic hepatitis even when taking a fat-containing product. In liver histopeparates of animals receiving mayonnaise with betulin, necrobotic changes were less pronounced in comparison with the group MG-2. They were estimated at 1 point: small-drip dystrophy spots were found, haemorrhages in the interregional septum with inflammatory infiltration in the course of hemorrhages against the presence of necrosis hepatocytes with pronounced adipose dystrophy in the centres of the lobules, step necrosis with signs of replacing the damaged hepatocytes of the connective tissue, accompanied by centrolobular hemorrhages in MG-2 rats. Conclusion. Introduced into the composition of mayonnaise betulin, reduces the development of cytolic syndrome in toxic hepatitis and suppresses the process of peroxidation, on the basis of which fat-containing foods with betulin can be recommended for clinical examination as specialized products in acute and chronic liver diseases, including complicated cholestasis.

Early therapeutic plasma exchange may improve treatment outcomes in severe acute toxic Hepatitis.

BACKGROUND AND OBJECTIVES: Acute toxic hepatitis can result in a different clinical course from a completely curable disease to subacute hepatitis, chronic hepatitis, and fulminant hepatitis failure, which is quite mortal. For this purpose, therapeutic plasma exchange (TPE) can be used for improving treatment outcomes by reducing the harmful substances caused with and/or without liver function in acute toxic hepatitis. We aimed to evaluate treatment outcomes in severe acute toxic hepatitis patients who applied early TPE procedure. MATERIALS AND METHODS: A total of 335 patients who received TPE between 2010-2021 were retrospectively screened and 59 (male/female, 30/29; min/max-age, 22-84) patients with acute toxic hepatitis who underwent TPE in the first 24 h were included in the study. TPE was performed in patients who had high total bilirubin level (>10 mg/dL). Laboratory parameters of the patients before and after the TPE procedure, number of patients developed complications of acute toxic hepatitis and mortality rates were evaluated for effectiveness of TPE. RESULTS: Acute toxic hepatitis was associated with hepatotoxic drugs in 44 (74.5 %), herbal medication 6 (10.2 %), mushroom poisoning 6 (10.2 %) and with substance abuse 3 (5.1 %) in patients. When the patients were compared based on INR, liver function tests, ammonia, lactate and Model For End-Stage Liver Disease (MELD) score at baseline, 48 h after TPE (independently of TPE number) and before final state a statistically significant decrease was observed in all parameters (p < 0.05). Fifty three (90 %) of patients improved without complications, the remaining 6 (10 %) patients were diagnosed with fulminant hepatitis. All these remaining patients died before liver transplantation (LTx) could be performed. CONCLUSION: TPE is a safe, tolerable therapy option and early TPE may improve treatment outcomes in severe acute toxic hepatitis.

Monooxygenase System and NO Metabolism in Liver Microsomes of Rats with Toxic Hepatitis and the Effect of Sesquiterpene Lactones.

We analyzed changes in activities of enzymes of phases I and II of xenobiotic biotransformation and parameters of NO metabolism in liver microsomes of rats with toxic CCl4-induced hepatitis after a 14-day course of sesquiterpene lactones from Artemisia leucodes (10 mg/kg). It was found that toxic hepatitis was associated with significant inhibition of NADPH-cytochrome c-reductase, benzo(a)pyrene hydroxylase, and NADPH-diaphorase, reduced cytochrome P-450 content, and enhanced induction of nitrate/nitrite reductase with accumulation of NO metabolites in the liver. Administration of sesquiterpene lactones stimulated activity of the studied components of the cytochrome P-450 system and promoted recovery of the NOergic system components; the effects were most pronounced in 7 and 14 days after treatment.

A Case of Autoimmune Hepatitis after Occupational Exposure to N,N-Dimethylformamide.

N,N-dimethylformamide (DMF), a widely used solvent in the chemical industry, is known to induce toxic hepatitis. However, there have been no reported cases of DMF-associated autoimmune hepatitis. A 31-year-old healthy man working at a glove factory since July 2015 had intermittently put his bare hands into a diluted DMF solution for his first 15 days at work. After 2 months, he felt nausea, fatigue, and hand cramping, and a jaundice followed. His laboratory findings showed positive autoantibodies and elevated immunoglobulin G (IgG), and his liver biopsy pathology was typical of autoimmune hepatitis (AIH). Prednisolone and azathioprine therapy began, and he recovered rapidly without adverse events. Though his liver chemistry was normalized, the IgG level remained persistently upper normal range. His 2nd liver biopsy performed in April 2019 showed mild portal activity, and he was well under a low dose immunosuppressive therapy up to April 2020. This case warns of the hazard of occupational exposure to DMF, and clinicians should be aware of DMF-related AIH for timely initiation of immunosuppressive therapy.

Serum level of interleukin-6 (IL-6) and N-terminal propeptide of procollagen type I (PINP) in patients with liver diseases.

INTRODUCTION: The aim of this study was to evaluate the concentration of interleukin-6 and N-terminal propeptide of procollagen type I and their relationship in liver diseases of different etiologies. MATERIAL AND METHODS: Serum samples were obtained from 30 healthy volunteers and patients suffering from alcoholic cirrhosis (AC) - 31, non-alcoholic cirrhosis (NAC) - 28 and toxic hepatitis (HT) - 23 patients. Cirrhotic patients were classified according to Child-Pugh score. IL-6 and PINP concentrations were determined according to the electrochemiluminescence immunoassay. RESULTS: The mean serum IL-6 concentration was significantly higher in AC (mean ± SD:21.52 ± 15.01 pg/mL), NAC (20.07 ± 32.12 pg/mL) and HT (15.14 ± 17.18 pg/mL) when compared to the control group (C) (1.67 ± 0.42 pg/mL) (Mann-Whitney U test: p < .001 for all comparisons). The mean serum PINP concentration was significantly higher only in patients with AC (104.32 ± 54.50 ng/mL) in comparison with the control group (54.70 ± 19.83 ng/mL; p < .001). The mean values of IL-6 and PINP significantly differed between liver diseases (ANOVA rank Kruskal-Wallis test: p = .020 and p < .001, respectively). Accordingly, the serum levels of IL-6 and PINP were significantly higher in patients with AC than that in NAC (p < .001 and p = .022, respectively). IL-6 and PINP concentrations appeared to vary depending on the severity of liver damage (p < .001 for both). The concentrations of IL-6 and PINP were significantly higher in class C (31.88 ± 21.51 pg/mL; 132.73 ± 65.63 ng/mL, respectively) than that in class A (6.12 ± 9.00 pg/mL; 57.32 ± 28.85 ng/mL, respectively) (p < .001 for both). There were also significant differences in IL-6 concentrations between Child-Pugh class B (27.88 ± 24.45 pg/mL) and class A (6.12 ± 9.00 pg/mL; p < .001). CONCLUSIONS: We conclude that serum concentrations of IL-6 and PINP change in liver diseases, and those changes reflect the severity of liver disease.

Drug-induced liver injury: a cohort study on patients referred to the Danish transplant center over a five year period.

OBJECTIVE: The idiosyncratic subtype of drug-induced liver injury (DILI) is a rare reaction to medical treatment that in severe cases can lead to acute liver failure and death. The aim of this study was to describe the presentation and outcome of DILI and to identify potential predictive factors of poor outcome. MATERIALS AND METHODS: We identified all patients diagnosed with DILI at the Department of Hepatology, Rigshospitalet, from March 2007 to November 2012. The following parameters were registered from patient files: drug causing DILI, symptoms, comorbidity, biochemistry, treatment and outcome. RESULTS: Of 43 patients, 25 (58%) were female with a mean age of 54 years. The two most frequent causes of DILI were Disulfiram (30%) and antibiotics (19%). The most common symptoms were jaundice, nausea, fatigue and gastrointestinal discomfort. At the time of admission, the most frequent biochemical findings included bilirubin elevated to above 3.2 × ULN, ALT elevated to above 9 × ULN in 86%, INR above 1.4 in 70%. Twenty two patients needed treatment in the liver intensive care unit. Fifteen patients developed acute liver failure with a severe outcome. Six patients were liver transplanted and nine patients died. Jaundice, a moderately elevated bilirubin level or INR at presentation was predictive of severe outcome. CONCLUSION: In this retrospective study, 35% of patients with DILI developed severe acute liver failure and were either liver transplanted or died. Our results underline that DILI may be severe and run a fatal course, and that bilirubin and INR levels may predict poor outcome.

A New Paradigm in Gallstones Diseases and Marked Elevation of Transaminases: An Observational Study.

BACKGROUND: In clinical practice, it is assumed that a severe rise in transaminases is caused by ischemic, viral or toxic hepatitis. Nevertheless, cases of biliary obstruction have increasingly been associated with significant hypertransaminemia. With this study, we sought to determine the true etiology of marked rise in transaminases levels, in the context of an emergency department. MATERIAL AND METHODS: We retrospectively identified all patients admitted to the emergency unit at Centro Hospitalar e Universitário de Coimbra between 1st January 2010 and 31st December 2010, displaying an increase of at least one of the transaminases by more than 15 times. All patient records were analyzed in order to determine the cause of hypertransaminemia. RESULTS: We analyzed 273 patients - 146 males, mean age 65.1 ± 19.4 years. The most frequently etiology found for marked hypertransaminemia was pancreaticobiliary acute disease (n = 142;39.4%), mostly lithiasic (n = 113;79.6%), followed by malignancy (n = 74;20.6%), ischemic hepatitis (n = 61;17.0%), acute primary hepatocellular disease (n = 50;13.9%) and muscle damage (n = 23;6.4%). We were not able to determine a diagnosis for 10 cases. There were 27 cases of recurrence in the lithiasic pancreaticobiliary pathology group. Recurrence was more frequent in the group of patients who had not been submitted to early cholecystectomy after the first episode of biliary obstruction (p = 0.014). The etiology of hypertransaminemia varied according to age, cholestasis and glutamic-pyruvic transaminase values. CONCLUSION: Pancreaticobiliary lithiasis is the main cause of marked hypertransaminemia. Hence, it must be considered when dealing with such situations. Not performing cholecystectomy early on, after the first episode of biliary obstruction, may lead to recurrence.

Acute interstitial nephritis, toxic hepatitis and toxic myocarditis following multiple Asian giant hornet stings in Shaanxi Province, China.

OBJECTIVES: During July to October 2013, the Asian giant hornet has killed 42 and injured 1,675 people in the southern part of Shaanxi Province, China. This study investigated this unusual and frequent public health event. METHODS: During the 3 months, 103 patients with severe Asian hornet stings were hospitalized in our hospital. Clinical data were collected using a standardized data collection form which included sex, age, length of hospital stay and medical recorder. RESULTS: After physical examination and laboratory investigation, 25.2, 46.6 and 44.7 % of the patients were found with varying degrees of acute interstitial nephritis, acute toxic hepatitis and acute toxic myocarditis, respectively. After timely and appropriate treatment including removal of the stings and the use of intravenous methylprednisolone and antihistamines, the kidney function, liver function and heart function of 99 patients recovered within 1 month, while four patients died. CONCLUSIONS: This study provided a good opportunity for recognizing the effect of Asian giant hornet stings and evaluating this serious public health event.

Hydroxychloroquine-induced toxic hepatitis in a patient with systemic lupus erythematosus: a case report.

Increased serum level of liver enzymes is a common finding in patients with systemic lupus erythematosus (SLE). Hepatotoxic drugs, viral hepatitis and fatty liver are thought to be the main causes of hepatic lesion in these patients. Our aim was to determine the cause of strikingly elevated liver enzymes in a case with systemic lupus presenting with acute abdomen. Liver enzyme abnormality was defined as a 10-fold or greater increase in aspartate aminotransferase and alanine aminotransferase. Acute toxic hepatitis was diagnosed, which rapidly returned to normal after cessation of the suspected causative medication, hydroxychloroquine, and subsequent administration of mycophenolate mofetil. Elevated liver enzymes are a major concern and should be well investigated in SLE patients.

Toxic hepatitis after exposure to humidifier disinfectant: A case series report.

Health damage from humidifier disinfectants is an unprecedented environmental health disaster. Humidifier disinfectants were used broadly in Korea from 1994 to 2011. Most studies have focused on respiratory problems because of the exposure route and primary respiratory symptoms. This overlooks the previous research results that humidifier disinfectants could move to extrapulmonary organs and induce toxic effects. Thus, the objective of this study was to examine toxic hepatitis cases developed after inhaling humidifier disinfectant. We focused on the indications of toxic hepatitis in two pediatric cases and one female adult case. All patients were exposed to humidifier disinfectants in a residential space. These disinfectants all contained polyhexamethylene guanidine (PHMG). Rapid increases in blood hepatic enzyme levels were seen. Two patients were discharged after treatment. Death occurred in one patient who was diagnosed with fulminant hepatitis of unknown cause. This human case series study supports prior knowledge that hepatotoxicity can occur by inhaling humidifier disinfectant.

Ganoderma lingzhi (Reishi Mushroom)-Induced Acute Liver Injury in the Setting of Alcohol Use: A Case Report and Review of the Literature.

As many prior case reports have shown, unregulated supplements and alcohol are both known to cause varying degrees of hepatotoxicity. We present a case of a 47-year-old male who presented to the hospital with headache and abdominal pain after consuming Reishi Mushroom (Ganoderma lingzhi) powder and alcohol. The patient was found to have acute hepatitis with significant transaminitis, which was managed conservatively with N-acetylcysteine and IV fluids. Two-week follow-up labs demonstrated complete resolution of the patient's symptoms and laboratory abnormalities. Despite the growing popularity of mushroom-based supplements, limited research has been done on the systemic effects that can manifest with co-ingestion of other substances such as alcohol.

Acute Cocaine Intoxication: An Approach to Severe Hepatic and Renal Dysfunctions.

Cocaine is a highly addictive substance. Its poisoning can lead to potentially fatal multi-organ dysfunction. We report a case of cocaine overdose with severe multi-organ dysfunction. A healthy 51-year-old man was admitted to the emergency room due to behaviour changes and seizure after inhaling crack. Multiple dysfunctions were developed, with emphasis on liver and kidney dysfunction, due to their severity. The patient had marked hepatic cytolysis with a peak on the third day with alanine aminotransferase (ALT) and aspartate aminotransferase (AST): 7941 and 4453 IU/L, respectively with mild coagulopathy and hyperbilirubinemia. Underwent empirical treatment with acetylcysteine ​​with good clinical response. Also developed anuric AKIN3 acute kidney injury secondary to rhabdomyolysis, requiring treatment with intermittent haemodialysis. The approach to a case with severe multiorgan dysfunction is described, with special emphasis on the use of acetylcysteine. The good evolution of the patient can corroborate the use of this drug as a potential modifier of prognosis.

A case report of toxic hepatitis caused by chloroform in automotive parts manufacturer coating process.

Background: Several cases of chloroform-induced hepatotoxicity have been reported worldwide, but only 2 cases have been reported in Korea. We encountered a case of toxic hepatitis due to chloroform exposure in February 2022 and report the diagnosis process and clinical findings. Case presentation: A 38-year-old employee in charge of the coating after washing (degreasing) at an automotive parts manufacturer complained of jaundice and was diagnosed with acute toxic hepatitis. After the initial diagnosis, he continued to work, his symptoms worsened, and he was hospitalized for 8 days. Liver ultrasonography (elastography) revealed acute hepatitis. The washing agent contained chloroform, which was not listed on the materials safety data sheet, and the concentrations of chloroform in the workplace were up to 4.7 times the time-weighted average. Conclusions: This patient showed typical toxic hepatitis with chloroform; further follow-up studies are required. Both employers and workers should be aware of information on toxic substances and take precautions to avoid exposure.

Toxic hepatitis case with prolonged jaundice due to Favipiravir.

Favipiravir (FPV) is an antiviral drug used in the treatment of severe acute respiratory syndrome coronavirus 2 infection. The main side effects of this drug are teratogenicity and hyperuricemia. Limited information is available on other side effects. Here, we aimed to present our toxic hepatitis case with prolonged jaundice after FPV treatment.

Biomedical evaluation of antioxidant properties of lamb meat enriched with iodine and selenium.

The article presents a study of the antioxidant properties of meat from lambs that received organic forms of iodine and selenium during growth. This meat was included in diets of laboratory animals using a model of acute toxic hepatitis. The experiments resulted in developing and testing a technique that was effective in enriching lamb with bioorganic elements of iodine and selenium and contributed to the activation metabolism in the bodies of animals consuming the meat. The purpose of the presented investigation was to compare the roles of bioorganic iodine and selenium and their combination as antioxidants in rat rations using a model of acute toxic hepatitis induced by carbon tetrachloride. The experimental studies have established a hepatoprotective effect of lamb meat enriched with selenium and iodine on rats suffering from toxic xenobiotic effects. This was confirmed by normalized hematological and biochemical measures in the blood of the experimental rats.

An artificial intelligence algorithm for analyzing acetaminophen-associated toxic hepatitis.

INTRODUCTION: Very little artificial intelligence (AI) work has been performed to investigate acetaminophen-associated hepatotoxicity. The objective of this study was to develop an AI algorithm for analyzing weighted features for toxic hepatitis after acetaminophen poisoning. METHODS: The medical records of 187 patients with acetaminophen poisoning treated at Chang Gung Memorial Hospital were reviewed. Patients were sorted into two groups according to their status of toxic hepatitis. A total of 40 clinical and laboratory features recorded on the first day of admission were selected for algorithm development. The random forest classifier (RFC) and logistic regression (LR) were used for artificial intelligence algorithm development. RESULTS: The RFC-based AI model achieved the following results: accuracy = 92.5 ± 2.6%; sensitivity = 100%; specificity = 60%; precision = 92.3 ± 3.4%; and F1 = 96.0 ± 1.8%. The area under the receiver operating characteristic curve (AUROC) was approximately 0.98. The LR-based AI model achieved the following results: accuracy = 92.00 ± 2.9%; sensitivity = 100%; specificity = 20%; precision = 92.8 ± 3.4%; recall = 98.8 ± 3.4%; and F1 = 95.6 ± 1.5%. The AUROC was approximately 0.68. The weighted features were calculated, and the 10 most important weighted features for toxic hepatitis were aspartate aminotransferase (ALT), prothrombin time, alanine aminotransferase (AST), time to hospital, platelet count, lymphocyte count, albumin, total bilirubin, body temperature and acetaminophen level. CONCLUSION: The top five weighted features for acetaminophen-associated toxic hepatitis were ALT, prothrombin time, AST, time to hospital and platelet count.

Novel Therapies for the Treatment of Drug-Induced Liver Injury: A Systematic Review.

Many drugs with different mechanisms of action and indications available on the market today are capable of inducing hepatotoxicity. Drug-induced liver injury (DILI) has been a treatment challenge nowadays as it was in the past. We searched Medline (via PubMed), CENTRAL, Science Citation Index Expanded, clinical trials registries and databases of DILI and hepatotoxicity up to 2021 for novel therapies for the management of adult patients with DILI based on the combination of three main search terms: 1) treatment, 2) novel, and 3) drug-induced liver injury. The mechanism of action of novel therapies, the potential of their benefit in clinical settings, and adverse drug reactions related to novel therapies were extracted. Cochrane Risk of bias tool and Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment approach was involved in the assessment of the certainty of the evidence for primary outcomes of included studies. One thousand three hundred seventy-two articles were identified. Twenty-eight articles were included in the final analysis. Eight randomized controlled trials (RCTs) were detected and for six the available data were sufficient for analysis. In abstract form only we found six studies which were also anaylzed. Investigated agents included: bicyclol, calmangafodipir, cytisin amidophospate, fomepizole, livina-polyherbal preparation, magnesium isoglycyrrhizinate (MgIG), picroliv, plasma exchange, radix Paeoniae Rubra, and S-adenosylmethionine. The primary outcomes of included trials mainly included laboratory markers improvement. Based on the moderate-certainty evidence, more patients treated with MgIG experienced alanine aminotransferase (ALT) normalization compared to placebo. Low-certainty evidence suggests that bicyclol treatment leads to a reduction of ALT levels compared to phosphatidylcholine. For the remaining eight interventions, the certainty of the evidence for primary outcomes was assessed as very low and we are very uncertain in any estimate of effect. More effort should be involved to investigate the novel treatment of DILI. Well-designed RCTs with appropriate sample sizes, comparable groups and precise, not only surrogate outcomes are urgently welcome.

Novel near-infrared fluorescence probe with large Stokes shift for monitoring CCl4-induced toxic hepatitis.

Toxic hepatitis which is induced by chemical substance is a serious threat to human health. More and more studies have shown that peroxynitrite (ONOO-) is related with the development of toxic hepatitis. So it is important to find a tool to study ONOO- change during the diagnosis and therapy of toxic hepatitis. Herein, a series of novel near-infrared (NIR) fluorescence dyes (DDM-R) with long emission wavelength (740-770 nm) and large Stokes shift (~200 nm) are developed. Among the dyes, DDM-OH with great spectral performance and facilely modified feature is used to construct probe DDM-ONOO-. The probe have the preference of high sensitivity and excellent selectivity for ONOO-. In addition, DDM-ONOO- was applied in detecting exogenous and endogenous ONOO- in cells and further used in detecting ONOO- of CCl4-induced toxic hepatitis in cells by fluorescence imaging, 3D quantification analysis, flow cytometry. More importantly, by visualizing ONOO-, the probe was used to monitor the diagnosis of CCl4-induced toxic hepatitis in mice and evaluate the therapeutic efficacy of hepatoprotective medicines (NAC, SM, DDB). The results show that the probe will provide a powerful tool for the diagnosis and treatment of toxic hepatitis.