Related Liver Injury Research Articles

LIVER FUNCTION TESTS(LFT) PROFILE IN INTENSIVE CARE UNIT PATIENTS : A PROSPECTIVE OBSERVATIONAL STUDY

Background and study aim: Deranged LFT, commonly noted along with other abnormal blood parameters in ICU patients is both a consequence as well as a signicant cause of patient's morbidity. In this observational study we aim to analyse the patterns of liver injury noted in patients being treated in ICU and suggest various precocious therapeutic measures for better clinical outcomes. We conducted a prospectiveMethods: observational study in ICU patients irrespective of age and gender from January 2020 to February 2022. We analyzed the pattern of liver injury(hepatocellular/cholestatic) and also noted the derangement observed in specic liver parameters secondary to hepatic dysfunction. 974 patients were included in the present study and the study was cleared by institutional ethics committee of the hospital. Of the 974 patientsResults: in study group, 565(58%) found to have abnormal LFT. Among them majority found to have hepatocellular pattern, 441 of 565(78%). Cholestatic pattern was noted in 51 patients(9%) and mixed pattern in 73 patients(13%). The major causes for hepatocellular injury were hypoxic hepatitis(shock/congestion/respiratory failure etc.), noted in 256 patients(58%) and ethanol related liver injury, noted in 146 patients(33%). The major cause for cholestatic pattern as well as mixed pattern was sepsis. Liver dysfunction is a major contributor for signicantConclusion: morbidity and mortality in ICU patients. Deranged LFT was seen in more than half of the patients of our study group. Precocious therapeutic measures like early and aggressive treatment of sepsis, hemodynamic abnormalities and metabolic derangements can prevent or reduce the severity of liver dysfunction there by leading to improved clinical outcomes in measures of morbidity and mortality.

Progressive cholestasis and associated sclerosing cholangitis are frequent complications of COVID-19 in patients with chronic liver disease.

Background and AimsCholestasis is associated with disease severity and worse outcome in COVID‐19. Cases of secondary sclerosing cholangitis (SSC) after severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection have been described.Approach and ResultsHospitalized patients with COVID‐19 between 03/2020 and 07/2021 were included. Patients were stratified as having (i) no chronic liver disease (CLD), (ii) non‐advanced CLD (non‐ACLD), or (iii) advanced CLD (ACLD). Patients with CLD and non–COVID‐19 pneumonia were matched to patients with CLD and COVID‐19 as a control cohort. Liver chemistries before (Pre) and at first, second, and third blood withdrawal after SARS‐CoV‐2 infection (T1–T3) and at last available time point (last) were recorded. A total of 496 patients were included. In total, 13.1% (n = 65) had CLD (non‐ACLD: 70.8%; ACLD: 29.2%); the predominant etiology was NAFLD/NASH (60.0%). COVID‐19–related liver injury was more common among patients with CLD (24.6% vs. 10.6%; p = 0.001). After SARS‐CoV‐2 infection, patients with CLD exhibited progressive cholestasis with persistently increasing levels of alkaline phosphatase (Pre: 91.0 vs. T1: 121.0 vs. last: 175.0 U/L; p < 0.001) and gamma‐glutamyl transferase (Pre: 95.0 vs. T1: 135.0 vs. last: 202.0 U/L; p = 0.001). A total of 23.1% of patients with CLD (n = 15/65) developed cholestatic liver failure (cholestasis plus bilirubin ≥6 mg/dl) during COVID‐19, and 15.4% of patients (n = 10/65) developed SSC. SSC was significantly more frequent among patients with CLD and COVID‐19 than in patients with CLD and non–COVID‐19 pneumonia (p = 0.040). COVID‐19–associated SSC occurred predominantly in patients with NAFLD/NASH and metabolic risk factors. A total of 26.3% (n = 5/19) of patients with ACLD experienced hepatic decompensation after SARS‐CoV‐2 infection.ConclusionsAbout 20% of patients with CLD develop progressive cholestasis after SARS‐CoV‐2 infection. Patients with NAFLD/NASH and metabolic risk factors are at particular risk for developing cholestatic liver failure and/or SSC after COVID‐19.

Impact of SLCO1B1*5 on Flucloxacillin and Co-Amoxiclav-Related Liver Injury.

Background: Idiosyncratic drug-induced liver injury (DILI) is a serious uncommon disease that may develop as a result of the intake of certain drugs such as the antimicrobials flucloxacillin and co-amoxiclav. The reported cases showed significant associations between DILI and various human leukocyte (HLA) markers. The solute carrier organic anion transporter 1B1 (SLCO1B1), a non-HLA candidate gene, was previously reported as a risk factor for liver injury induced by rifampin and methimazole. This study presumed that SLCO1B1 may play a general role in the DILI susceptibility and therefore investigated the association of rs4149056 (SLCO1B1*5, T521C) polymorphism with flucloxacillin- and co-amoxiclav–induced liver injury. Methodology: We recruited 155 and 165 DILI cases of white ancestral origin from various European countries but mainly from the United Kingdom owing to flucloxacillin and co-amoxiclav, respectively. Only adult patients (≥18 years) who were diagnosed with liver injury and who showed i) clinical jaundice or bilirubin >2x the upper limit of normal (ULN), ii) alanine aminotransferase (ALT) >5x ULN or iii) alkaline phosphatase (ALP) >2x ULN and bilirubin > ULN were selected. The population reference sample (POPRES), a European control group (n = 282), was used in comparison with the investigated cases. TaqMan SNP genotyping custom assay designed by Applied Biosystems was used to genotype both DILI cohorts for SLCO1B1 polymorphism (rs4149056). Allelic discrimination analysis was performed using a step one real-time PCR machine. Genotype differences between cases and controls were examined using Fisher’s exact test. GraphPad Prism version 5.0 was used to determine the p-value, odds ratio, and 95% confidence interval. Compliance of the control group with Hardy–Weinberg equilibrium was proven using a web-based calculator available at https://wpcalc.com/en/equilibrium-hardy-weinberg/. Results: A small number of cases failed genotyping in each cohort. Thus, only 149 flucloxacillin and 162 co-amoxiclav DILI cases were analyzed. Genotyping of both DILI cohorts did not show evidence of association with the variant rs4149056 (T521C) (OR = 0.71, 95% CI = 0.46–1.12; p = 0.17 for flucloxacillin cases and OR = 0.87, 95% CI = 0.56–1.33; p = 0.58 for co-amoxiclav), although slightly lower frequency (22.8%) of positive flucloxacillin cases was noticed than that of POPRES controls (29.4%). Conclusion: Carriage of the examined allele SLCO1B1*5 is not considered a risk factor for flucloxacillin DILI or co-amoxiclav DILI as presumed. Testing a different allele (SLCO1B1*1B) and another family member gene (SLCO1B3) may still be needed to provide a clearer role of SLCO1B drug transporters in DILI development–related to the chosen antimicrobials.

THE PATTERN AND LONG TERM FOLLOW UP OF COVID-19 RELATED ABNORMAL LIVER BLOOD TESTS

Objective: Acute COVID-19 is well-known to cause abnormalities in liver blood tests (LBTs). This study aims to identify what are the long-term implications of COVID-19 on LBTs. Methods: A retrospective cohort study that examined the LBTs of patients admitted with COVID-19 both during acute infection and for up to one year. R factor was used to identify type of liver injury. χ² test and Fisher exact was used for statistical analysis with p&lt;0.05 being considered signicant. Results: Data was collected on 373 patients. During acute infection, 57.5% of patients showed at least one raised LBT (ALT, ALP and/or bilirubin). Male patients were more likely to develop LBT abnormalities than females (74.5% versus 25.5%; p&lt;0.001). Increased LBT abnormalities seen in patients requiring ITU admission compared to those with ward based care (87% versus 51% respectively; p&lt;0.001). During short term (1-5 months post discharge) and long-term (&gt;5 months post discharge) follow-up, LBT abnormalities were seen in 31.3% and 24% of patients respectively. In both the acute setting and long-term follow-up, cholestatic or mixed injury types were most commonly seen (acute; 41.1%, 41.6% respectively, long-term; 50.0%, 44.4% respectively) . Discussion: Our data suggests that up to one in four patients have persistent LBT abnormalities up to one year following COVID-19. Future research is needed to investigate the clinical signicance of this LBT abnormalities and whether there are interventions, pharmacological or otherwise, that could reduce COVID-19 related liver injury, both in the acute setting, and longer-term. Summary Box: Many studies have shown that acute COVID-19 infection is commonly associated with liver dysfunction in hospitalised patients and even severe liver failure has been noted. Little however has been published about the long term effect of COVID-19 on the liver prole blood tests. This study complements others looking at acute liver dysfunction during COVID-19 suggesting that severity of COVID-19 is a risk factor for liver blood test abnormalities. The study also suggests that younger patients when hospitalised with COVID-19 are more likely to have abnormal liver blood tests compared to their elderly counterparts. However importantly, this study suggests that around a quarter of patient hospitalised with COVID-19 have persistent liver blood test abnormalities up to one year after discharge. This observational study has highlighted the need for further research to investigate the acute and the long-term clinical signicance of LBT abnormalities from COVID-19. This can then help identify whether there are any interventions, pharmacological or otherwise, that could reduce COVID-19 related liver injury, both in the acute setting, and longer-term.

The expression of cytokeratin and apoptosis-related molecules in echinococcosis related liver injury

The study aimed to investigate the expression of cytokeratin and apoptosis-related molecules in the livers of two types of hepatic echinococcosis mice models and to preliminarily explore the relationship between the expression of cytokeratin and apoptosis in echinococcosis related liver injury. We established a mouse model infected by Echinococcus granulosus and Echinococcus multilocularis and observed the expression of cytokeratin and apoptosis related proteins in the two types of hepatic echinococcosis tissues during different stages by immunohistochemical staining. A co-culture model was established using normal hepatocytes and different concentrations of E. granulosus and E. multilocularis protoscoleces. Cell Counting Kit-8 was used to detect cell proliferation, flow cytometry was used to detect hepatocyte apoptosis, and western blot was used to quantify cytokeratin and apoptosis-related proteins, such as caspase3, caspase9, Bcl-2, and Bax. Surgical specimens were obtained from patients with hepatic echinococcosis to analyze the expressions of cytokeratin, caspase3, caspase9, Bcl-2, and Bax by western blot. The expressions of cytokeratin and caspase3 were analyzed by immunohistochemistry. The qRT-PCR method was used to determine the expression of CK8 and CK18 in the liver tissues. In vivo experiments showed that compared to that in the control group, the cytokeratin and caspase3 proteins in the liver tissues of the two types of hepatic echinococcosis were strongly expressed around the lesions of liver echinococcosis; there was a difference between cytokeratin expression of the two different echinococcosis parasites in the liver. Echinococcus granulosus and Echinococcus multilocularis in the co-culture model in vitro could promote the expression of CK, caspase3, caspase9, and Bax protein, decrease the expression of Bcl-2, promote hepatocyte apoptosis, and inhibit cell proliferation; in clinical samples, we found that compared with that in the normal tissues, the expression of cytokeratin, caspase3, caspase9, and Bax in echinococcus tissues was high, but that in Bcl-2 was low. Furthermore, the expression of CK8 and CK18 mRNA were higher in echinococcus tissues than that in the normal tissues and immunohistochemistry analysis also showed that cytokeratin and caspase3 levels were higher in echinococcus tissues than that in the normal tissues. The expression of cytokeratin and apoptosis-related molecules, reflecting liver damage, is high in the liver and is caused due to hepatic echinococcosis. This study provides the first evidence of cytokeratin could be useful for evaluating liver tissue damage caused by echinococcus infection.

S3674 Drug-Induced Autoimmune Liver Disease (DIAILD)

Introduction: Idiosyncratic drug-induced liver injury (DILI) affects an estimated 19 per 100,000 persons yearly and is a major cause of acute liver failure. Drug-induced autoimmune liver disease (DIAILD) is a poorly defined and under-reported liver disorder, and probably an underestimated liver disease. A small number of drug-induced liver injury (DILI) cases exhibit features typical of autoimmune hepatitis (AIH). To differentiate between true AIH triggered by drugs (DI-AIH) and immune mediated DILI still remains a challenge. Case Description/Methods: We present a 71-year-old ICU nurse with past medical history of hyperlipidemia, hypothyroidism and GERD presenting for nausea, epigastric pain, and chills. Of note, 5 days prior to onset of symptoms she received her vaccine for COVID-19. Medications that she takes at home are cimetidine, Protonix, Lipitor, Synthroid, Zofran, Vitamin A, and D supplementation. Review of systems were pertinent for mild itching, nausea, and chills. Physical exam is unremarkable except for low grade fevers, scleral icterus, and jaundice. Labs are significant for T.bili 13.5, AST 1673, ALT 2372, ALP 246, INR 1.59, ANA 1:160, AFP 169, CT abdomen/pelvis with and without contrast was unremarkable except for mild constipation. Liver biopsy was obtained that revealed submassive hepatic multilobular necrosis with confluent lytic necrosis and cholestasis involving 60-70% of the cores. Portal triads showed surrounding lymphocytic infiltrate without bile duct involvement and active interface hepatitis. active interface hepatitis, . Per pathology report the histological findings were nonspecific and a diagnosis of drug toxicity is the most compatible with given history. She was started on prednisone 40 mg daily and her liver enzymes started to improve. Discussion: In our patient we attributed the acute liver injury secondary to cimetidine from immune mediated DILI. Initially we speculated that covid 19 vaccine could have attributed to her acute hepatitis. However, at the time there were no other cases reported of Covid 19 related acute liver injury;and it could have coincidentally occurred at the same time. It will be interesting to see in the future if Covid 19 vaccine presents similar to this case. Although it is a clinical challenge to differentiate AIH and DI-AIH;it is important to keep both conditions in your differential.

Chronic liver disease not a significant comorbid condition for COVID-19

To explore the role of chronic liver disease (CLD) in COVID-19. A total of 1439 consecutively hospitalized patients with COVID-19 from one large medical center in the United States from March 16, 2020 to April 23, 2020 were retrospectively identified. Clinical characteristics and outcomes were compared between patients with and without CLD. Postmortem examination of liver in 8 critically ill COVID-19 patients was performed. There was no significant difference in the incidence of CLD between critical and non-critical groups (4.1% vs 2.9%, p = 0.259), or COVID-19 related liver injury between patients with and without CLD (65.7% vs 49.7%, p = 0.065). Postmortem examination of liver demonstrated mild liver injury associated central vein outflow obstruction and minimal to moderate portal lymphocytic infiltrate without evidence of CLD. Patients with CLD were not associated with a higher risk of liver injury or critical/fatal outcomes. CLD was not a significant comorbid condition for COVID-19.

Triptolide and atorvastatin synergistically promote hepatotoxicity in cultured hepatocytes and female Sprague-Dawley rats by inhibiting pregnane X receptor-mediated transcriptional activation of CYP3A4

Triptolide (TP), an active component of Tripterygium wilfordii Hook. F, has been widely used in China for treating autoimmune and inflammatory diseases, and has also been validated by modern science and developed as a candidate anti-cancer treatment. However, liver toxicity of TP has seriously hindered its use and development, the clinical features and primary toxicological mechanism have been unclear. Considering the major target regulation mechanism of TP is the suppression of global transcription regulated by RNAPII, which is closed related with the detoxification of drugs. This paper tries to verify the synergistic liver injury and its mechanism of TP when co-administered with CYP3A4 substrate drug. The experiments showed that TP dose-dependently blocked transcriptional activation of CYP3A4 in both hPXR and hPXR-CYP3A4 reporter cell lines, lowered the mRNA and protein expression of PXR target genes such as CYP3A1, CYP2B1, and MDR1, and inhibited the functional activity of CYP3A in a time- and concentration-dependent manner in sandwich-cultured rat hepatocytes (SCRH) and female Sprague-Dawley (f-SD) rats. Furthermore, TP combined with atorvastatin (ATR), the substrate of CYP3A4, synergistically enhanced hepatotoxicity in cultured HepG2 and SCRH cells (CI is 0.38 and 0.29, respectively), as well as in f-SD rats, with higher exposure levels of both drugs. These results clearly indicate that TP inhibits PXR-mediated transcriptional activation of CYP3A4, leading to a blockade on the detoxification of itself and ATR, thereby greatly promoting liver injury. This study may implies the key cause of TP related liver injury and provides experimental data for the rational use of TP in a clinical scenario.

Preliminary study on the protective effect of glycosyltransferase Colgalt2 gene deletion on acetaminophen-induced liver injury

Objective: To investigate the protective effect of Colgalt2 gene deletion on acute liver injury induced by acetaminophen (APAP) in mice. Methods: Colgalt2(+/+) wild-type control mice and Colgalt2(-/-) mice (all C57BL/6J strains) were selected as the research subject. APAP solution was injected intraperitoneally to establish a mouse model of acute liver injury. The mouse were divided into four groups: Colgalt2(+/+) wild-type control group, Colgalt2(+/+) wild-type drug group (APAP 500 mg/kg), Colgalt2(-/-) control group, and Colgalt2(-/-) drug group (APAP 500 mg/kg). The survival rate was measured to plot survival curve. Liver function was evaluated by detecting serum ALT and AST levels. Liver histopathological changes were observed by HE staining to evaluate the condition of liver injury. Western blot was used to detect protein c-Jun N-terminal kinase (JNK)-related liver injury. Results: Compared with Colgalt2(+/+) mice, the survival rate was significantly increased after giving APAP to Colgalt2(-/-) mice (86.7% vs. 40%), and liver cell necrosis and inflammatory cell infiltrates of Colgalt2(+/+) mice were milder. Serum ALT, and AST level was significantly decreased [ALT: (5 291.9 ± 1 016.34) U/L vs. (1 616.9 ± 330.65) U/L, P = 0.000; AST: (4 978.0 ± 1 028.43) U/L vs. (1 851.0 ± 437.55) U/L, P = 0.000]. The expression level of JNK was significantly decreased in liver tissue. Conclusion: Colgalt2 gene deletion has a protective effect on acute liver injury induced by acetaminophen (APAP) in mice. Therefore, Colgalt2 may be a potential therapeutic option for acetaminophen-induced hepatotoxicity.

COVID-19 Related to Liver Impairment and Its Impact on Chronic Liver Disease

By late December 2019, a novel beta-coronavirus, named as COVID-19 (2019-nCoV), was discovered in Wuhan, Hubei Province, China which epidemiologically linked to a Huanan seafood market in Wuhan. Coronavirus Disease 2019 or COVID-19 cases are growing rapidly from Wuhan to many countries, finding the health care system unprepared to face this threat. No effective drugs are clinically approved to manage the disease and strategies to protect the most vulnerable from developing severe illness and infection is still unclear. Information on how COVID-19 virus infection may affects many organs, especially the liver and the relevance of pre-existing liver disease in patients as a risk factor for the infection or disease severity are still scarce and inconclusive. Besides, the recommendation and consideration in liver transplant patients, hepatocellular carcinoma, or patient on immunosuppressive therapy still need further analysis Therefore, the information on the mechanism and treatment of COVID-19 related liver injury in patients with or without pre-existing liver disease should be considered.

Sestrin2 protects against bavachin induced ER stress through AMPK/mTORC1 signaling pathway in HepG2 cells

Bavachin (BV), a natural flavonoid compound derived from Psoralea corylifolia L, has been reported to be a potential hepatotoxin. Our previous studies have found that BV can induce endoplasmic reticulum (ER) stress-related cell apoptosis, but the molecular mechanism underlying BV-induced ER stress remains obscure. Sestrin2, a highly conserved stress-inducible protein, is involved in the cellular responses of various stress conditions and homeostatic regulation. However, whether Sestrin2 participated in the ER stress related hepatotoxicity against BV is still elusive. In the present study, we aim to investigate the role of BV on liver injury of mice and the impact of Sestrin2 on BV-induced ER stress in HepG2 cells. The results in mice showed that BV induced ER stress related liver injury with increased Sestrin2 expression involvement. Knockdown of Sestrin2 with siRNA aggravated BV-induced ER stress significantly in HepG2 cells. Further mechanistic study uncovered that inhibition of mTORC1 with rapamycin blocked BV-induced ER stress, and treatment with Sestrin2 siRNA blocked the inhibition effect of AMPK to mTORC1. Therefore, constant mTORC1 would lead to accumulation of misfolded or unfolded proteins and aggravated ER stress. Collectively, our study indicates that Sestrin2 confers protection against BV-induced ER stress via activating of the AMPK/mTORC1 pathway.

No association between COVID-19 related liver injury and the course of disease: a retrospective study

Objective Several studies have reported on liver injury during COVID-19. However, the definition and timing of liver injury is different among the published articles. The aim of the present study is to evaluate whether COVID-19 related liver injury at the time of first presentation is associated with the course of the disease. Methods We conducted a single center retrospective study at Amphia Hospital in Breda, The Netherlands, from February 1 through April 30, 2020. Patients with reverse transcription polymerase chain reaction confirmed COVID-19 were included. We excluded patients with known chronic liver disease, harmful alcohol consumption or patients on certain antibiotics prior to admission. The clinical characteristics and outcomes of patients with and without COVID-19 related liver injury were compared. Liver injury was defined as elevated alanine aminotransferase and/or alkaline phosphatase at the time when the first positive COVID-19 sample was obtained. Results We included 382 patients with COVID-19 infection. The incidence of liver injury was 41.6% (n = 159). Being female was associated with liver injury (p < .05). Liver injury was not associated with a more severe course of the disease in terms of hospitalization, length of hospital stay, intensive care unit admission and mortality. Conclusion COVID-19 related liver injury at the time of diagnosis of COVID-19 does not seem to be associated with a more severe course of the disease in our hospital.

Appropriate chemopreventive strategy for anti-tubercular therapy related liver injury is unsettled: Results from a systematic review and network meta-analysis

ABSTRACT Background Role of chemoprophylaxis for prevention of antitubercular therapy-related drug-induced liver injury (ATT-DILI) is uncertain. Methods Electronic databases were searched for randomized trials reporting on chemoprophylaxis agents for prevention of ATT-DILI. We included studies evaluating the role of a drug in comparison to controls/placebo. The primary outcome was the occurrence of ATT-DILI. We performed a Bayesian random-effects network meta-analysis to calculate odds ratios (ORs) and 95% credible intervals (CrI) for those arms where at least two studies were available. Additional comparative studies for these arms were also identified. Results Fourteen studies were identified and seven included in the meta-analysis. The agents used for prevention of ATT-DILI were silymarin/silibinin (4 trials), N-acetylcysteine (NAC) (3 studies), herbal preparations (5 studies) and one study each for cholecalciferol and carnitine. Compared with controls/placebo, the odds of occurrence of hepatotoxicity with NAC was 7 * 10−17 (95% CrI: 2.8 * 10−53, 0.0053) and Silymarin was 0.68 (95% CrI: 0.084, 4.6). NAC had the highest probability of rank 1 (0.99) which was followed by Silymarin (0.004). Conclusion N-acetyl cysteine, but not Silymarin/Silibinin, appears to be beneficial in prevention of ATT-DILI. However, the results were limited by the possible risk of bias in included studies, variable definitions of ATT-DILI and limited number and category of patients.

Systemic inflammation as fuel for acute liver injury in COVID-19

BackgroundA cytokine storm conceivably contributes to manifestations of corona virus disease (COVID-19). Inflammatory cytokines such as interleukin-6 (IL-6) cause acute liver injury while serum detectability indicates systemic inflammation. AimsWe explored a link between systemic IL-6, related acute phase proteins and liver injury in hospitalized COVID-19 patients. Methods655 patients with suspected COVID-19 were screened in the emergency department at the University Hospital of Innsbruck, Austria, between February and April 2020. 96 patients (∼15%) were hospitalized with COVID-19. 15 patients required intensive-care treatment (ICT). Plasma aminotransferases, alkaline phosphatase, bilirubin, and gamma glutamyl transferase, as well as IL-6, C-reactive protein (CRP), ferritin and lactate dehydrogenase (LDH) were determined by standard clinical assays. ResultsOf all hospitalized COVID-19 patients, 41 (42%) showed elevated aspartate aminotransferase (AST) concentration. COVID-19 patients with elevated AST exhibited significantly higher IL-6 (p < 0.001), ferritin (p < 0.001), LDH (p < 0.001) and CRP (p < 0.05) serum concentrations compared to patients with normal AST. Liver injury correlated with systemic IL-6 (p < 0.001), CRP (p < 0.001), ferritin (p < 0.001) and LDH (p < 0.001) concentration. In COVID-19 patients requiring ICT, correlations were more pronounced. ConclusionSystemic inflammation could be a fuel for hepatic injury in COVID-19.

Drug and herbal/dietary supplements-induced liver injury: A tertiary care center experience.

Drug-induced liver injury (DILI) and herbal/dietary supplements (HDS) related liver injury present unique diagnostic challenges. Collaboration between the clinician and the pathologist is required for an accurate diagnosis and management. To report our experience on the clinical-pathological findings of hepatic injury caused by drugs/HDS. A retrospective review of clinically proven cases of DILI/HDS who presented to our institution from January 1, 2013 to December 31, 2017 was performed. Slides were reviewed for histopathological patterns of injury and correlated with the causative agent. Out of 600 patients presenting with unexplained rise in liver enzymes undergoing biopsy, 107 were suspected to have DILI/HDS. Of these, 53 had a directly linked exposure to drug/herbal supplements. Fifteen patients were excluded for concurrent known liver disease. Thirty-eight patients with clinically proven DILI/HDS were finally included. Thirty-eight cases of DILI/HDS with a male:female of 1:1.5 and mean age of 51 ± 3 years were identified. DILI was identified in 84.2% cases while HDS injury in 15.8%. Acute hepatitis (42.1%) was the most common pattern of injury while granulomatous hepatitis (2.6%) was the least common. We found one case of acute-cholestasis due to rivaroxaban and two cases of cholestatic-hepatitis due to rizatriptan and trimethobenzamide-hydrochloride that, to the best of our knowledge, have not been previously reported. One case of steatohepatitis due to trimethoprim-sulfamethoxazole and three unusual cases of cholestatic-hepatitis with bile duct injury and steatosis due to dronedarone, C4-Extreme and hydroxycut, were also seen. Of our cohort, 81.6% of the patients fared well with discontinuation of drug and 18.4% underwent transplant; of which 42.9% were deceased. We describe the clinical findings, histopathological patterns of injury and clinical outcomes caused by drugs. In particular, we report a few previously unreported/ rarely observed clinical and histopathological patterns of hepatic injury.

SARS-CoV-2 May Not Aggravate Liver Injury in Patients with Hepatitis B Virus Infection

COVID-19 has become a global pandemic and garnered international attention. Although the clinical features of COVID-19 related liver injury have been investigated, there have been no reports and studies on the clinical characteristics of COVID-19 patients co-infected with Hepatitis B Virus (HBV). This study was aimed to evaluate whether SARS-CoV-2/HBV co-infection could influence liver function and the disease outcome. All 326 confirmed COVID-19 cases in Shanghai Public Health Clinical Center (The COVID-19 designated hospital in Shanghai, China) from January 20, 2020 to February 24, 2020 were enrolled and followed up until February 29 in this study. The clinical, laboratory data and the length of stay were collected and analyzed retrospectively. 20 patients with HBV co-infection (6.1%) and 306 patients (93.9%) without HBV infection showed no differences in the level of liver function parameters. However, compared with HBsAg- patients [145.4 mg/L (103.9-179.2)], HBsAg+ patients had a lower level of prealbumin [(102.3 mg/L (76.22-160.2), P=.0367]. There were also no significant differences for the discharge rate and the length of stay between two groups. Our study is the first to elaborate on the clinical characteristics of SARS-CoV-2/HBV co-infection patients and no evidence shows SARS-CoV-2/HBV co-infection could aggravate liver injury or extend hospitalization time. Funding Statement: This study was funded by the first-class discipline construction project of Fudan university (ISF162005),Shanghai Science and Technology Development Fund (No.17411969500), National Science and Technology Major Project (2017ZX10203202-003-007) and Shanghai Public Health Clinical Center Fund (2020YJKY01, XKJS-2019HBV-06, KY-GW-2019-32) joined in hepatitis prevention and control procedures. Declaration of Interests: All authors declare that they have no competing interests. Ethics Approval Statement: This study was approved by the Ethics Committee of the Shanghai Public Health Clinical Center (2019-S047-02, Review date: Jan 13, 2020) and was exempted from the need for informed consent from patients.

Etiological evaluation of the elevated transaminases in children

Objective: We aimed to determine the etiology of hypertransaminasemia in children, demonstrate the differences according to the age and evaluate course of transaminases.Method: We retrospectively analyzed the medical records of children who presented with elevated transaminase levels for at least 2 months, aged between 3 months and 18 years, for demographic features, laboratory, radiologic and histopathological findings.Results: Among total 292 children, 194 (66.4%) were male and 98 (33.6%) were female. The mean age was 6.5±5.4 years. The 45.9% of the children had no complaints at presentation. Majority of the patients had mildly elevated transaminases (81.6%). The most common etiology was non-alcoholic fatty liver disease (NAFLD) (25.7%). The NAFLD was more prevelant in patients older than 5 years-old (p<0.001). The second cause was infectious diseases (97.8% were viral infections) and more prevelant in patients younger than 2 years-old (p=0.043). In 34.1 % of the children, no overt cause of hypertransaminasemia was identified. The patients with unidentified etiology were significantly younger, but had higher mean aspartate aminotransferase (AST) levels than the patients in whom the etiology was identified (p= <0.0001, p=0.008 respectively). The normalization of transaminases was seen in 40.4% of the patients at mean 5.4±4.4 months. The shortest normalization time was observed in drug related liver injury (DILI) among all other etiologies (p=0.015). Conclusions: The most common cause of hypertransaminasemia in childhood were NAFLD and viral infections, which varies by age. A stepwise approachment to hypertransaminasemia leads to early diagnosis.

Drug-Induced Liver Injury in GI Practice.

Although drug‐induced liver injury (DILI) is a rare clinical event, it carries significant morbidity and mortality, leaving it as the leading cause of acute liver failure in the United States. It is one of the most challenging diagnoses encountered by gastroenterologists. The development of various drug injury networks has played a vital role in expanding our knowledge regarding drug‐related and herbal and dietary supplement–related liver injury. In this review, we discuss what defines liver injury, epidemiology of DILI, its biochemical and pathologic patterns, and management.

Guidelines for safe use of Polygoni Multiflori Radix

Polygoni Multiflori Radix is a commonly used traditional Chinese medicine in clinical treatment and health care. However, the related liver injury has been frequently reported, which has attracted extensive attention. Fortunately, in recent years, the scholars have made substantial progress in revealing the basic properties, main causes, material basis and molecular mechanism of Polygoni Multiflori Radix related liver injury. The basic characteristics and biomarkers of its susceptible subjects have been found. It indicated that Polygoni Multiflori Radix is only at risk of liver injury for a small number of specific subjects but safe for the majority. To provide detailed guidance for the rational use of Polygoni Multiflori Radix and related preparation, we compiled this guideline based on existing research and knowledge. The guideline has been issued by the China Association of Chinese Medicine(No. T/CACM 1328-2019).

6-Gingerol ameliorates sepsis-induced liver injury through the Nrf2 pathway

Sepsis-induced liver injury is very common in intensive care units. Here, we investigated the effects of 6-gingerol on sepsis-induced liver injury and the role of the Nrf2 pathway in this process. 6-Gingerol is the principal ingredient of ginger that exerts anti-inflammatory and antioxidant effects. Using cecal ligation and puncture (CLP) to induce polymicrobial sepsis and related liver injury, we found that mice pre-treated with 6-Gingerol showed less incidences of severe liver inflammation and death than untreated CLP groups. 6-Gingerol administration also inhibited the expression of pyroptosis-related proteins, including NOD-like receptor protein 3 (NLRP3), IL-1β, and caspase-1. Consistent with these findings, 6-gingerol reduced the effects of pyroptosis induced by lipopolysaccharide (LPS) and adenosine 5′-triphosphate (ATP) in RAW 264.7 cells, as evidenced by IL-1β and caspase-1 protein levels in the supernatant and propidium iodide (PI) staining. 6-Gingerol was shown to activate the Nrf2 pathway in vivo and in vitro. Notably, Nrf2 siRNA transfection nullified the inhibitory effects of 6-gingerol on pyroptosis in vitro. In summary, these findings suggested that 6-gingerol alleviated sepsis-induced liver injury by inhibiting pyroptosis through the Nrf2 pathway.