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The risk factors for drug-induced liver injury (DILI) involve host factors (including general non-genetic factors and idiosyncratic genetic and immune factors), drug-related factors, and environmental factors. The pathogenesis of DILI can be classified as intrinsic (or direct) hepatotoxicity, idiosyncratic hepatotoxicity, and indirect hepatotoxicity, as well as tumorigenicity and carcinogenicity of some drugs to the liver. The pathogenesis of different types of hepatotoxicity not only has significant differences, but also has internal correlation at multiple links. The three-step model centered on mitochondrial permeability transition (MPT) and a two-stage model with liver cell regeneration and liver tissue repair capacity as the determinants of different outcomes display the mechanism progress of DILI from different perspectives. Clarification of the complex pathogenesis of DILI needs long-term collection of clinical cases and systematic studies, which is of great significance for the scientific prevention, diagnosis, and treatment of DILI. [ABSTRACT FROM AUTHOR]

Cholestatic liver disease (CSLD) is a group of liver diseases which can cause cholestasis and has a complex etiology. Its pathogenesis remains unclear, and there are still no effective treatment measures. In the recent decade, new achievements have been made on various aspects of CSLD, which provides more help to accurate diagnosis and treatment and reflects many pending issues which need further research. This article introduces the research advances and problems in CSLD from the following six aspects: the “ascending” pathophysiology of CSLD, mechanisms of cholestasis-induced liver fibrosis and related management measures, association of enterohepatic circulation and intestinal microbiota with CSLD, pathogenesis and diagnosis/treatment of drug-induced cholestasis, pathogenesis and management of liver failure-associated cholestasis, and research advances in treatment targets and drug research and development for CSLD. [ABSTRACT FROM AUTHOR]

Due to a lack of specific biomarkers,the diagnosis of drug-induced liver injury(DILI) mainly depends on the method of exclusion. The Roussel Uclaf Causality Assessment Method(RUCAM) scale is the most widely used causality assessment scale and is relatively objective,but it is still waiting for further improvement. Another method is global introspection or expert opinion,which is relatively subjective,and the simplified global introspection method is commonly used in clinical practice. The Structured Expert Opinion Procedure(SEOP)created by the US DILI network(DILIN) is very complicated and time-consuming and thus cannot be used in clinical practice. The drug rechallenge test(DRT) with a positive result is considered the gold standard for the diagnosis of DILI,but DILI cannot be excluded based on the negative result of DRT. The value of lymphocyte transformation test(LTT),modified LTT,monocyte-derived hepatocyte-like cell lactate-dehydrogenase release test,and various predictive models for drug hepatotoxicity in the diagnosis of DILI awaits further assessment.The differential diagnosis of autoimmune-mediated DILI and traditional autoimmune liver diseases usually depends on liver biopsy,the type and titer of autoantibody,and response to glucocorticoids. Reasonable timing of drug withdrawal and application of anti-inflammatory liver-protecting drugs may help most DILI patients recover. Generally,the prophylactic use of anti-inflammatory liver-protecting drugs is not recommended,except in special situations. In-depth studies are needed for the precise diagnosis and prevention/treatment of DILI. [ABSTRACT FROM AUTHOR]

Dual infection with hepatitis C virus ( HCV) and hepatitis B virus ( HBV ) has significantly different clinical, immunological, and virological features from single infection with HCV or HBV , which brings various challenges to clinical diagnosis/treatment and management. Direct - acting antiviral agents used for effective control of HCV infection may cause HBV activation, onset of hepatitis B, and even liver failure. Therefore, during the antiviral treatment of HCV infection, it is of great importance to select appropriate anti - HBV therapy and follow-up management strategies based on the status of HCV/HBV dual infection. [ABSTRACT FROM AUTHOR]

Up to now, the diagnosis of drug-induced liver injury (DILI) still relies on the exclusive method, and the Roussel Uclaf Causality Assessment Method (RUCAM) is the most commonly used scale. Since the release of the first version of RUCAM scale in 1993, the second version was released in 2015, in which the definition and scoring criteria of each key element were revised appropriately and explained in detail. The Structured Expert Opinion Process (SEOP) was designed by the workgroup of DILI network prospective study, but since it is too complicated and time- and energy-consuming, its application in clinical practice is limited. This article introduces the research and development history and application method of RUCAM, as well as the modifications made in the 2015 version of RUCAM, and briefly compares the difference in bias between RUCAM and SEOP in the diagnosis of DILI. It is pointed out that both RUCAM and SEOP have marked interobserver and intraobserver variabilities, and therefore, it is necessary to explore a more objective, reproducible, accurate, and convenient strategy for the diagnosis of DILI. [ABSTRACT FROM AUTHOR]

In patients with liver disease such as viral hepatitis and liver cirrhosis, renal injury and renal insufficiency can be generally classified as acute kidney injury (AKI), chronic kidney disease, and acute-on-chronic nephropathy. AKI can be classified as stage 1 (risk stage), stage 2 (injury stage), and stage 3 (failure stage). Traditionally hepatorenal syndrome is classified as types Ⅰ and Ⅱ, and in recent years, type Ⅲ hepatorenal syndrome with organic renal injury has been proposed. Hepatorenal disorder(HRD) is used to describe any renal disease which occurs in patients with liver cirrhosis. At present, sensitive and accurate biochemical parameters used to evaluate renal function in patients with liver disease in clinical practice include estimated glomerular filtration rate, increase in serum creatinine within unit time, and serum cystatin C level, and urinary microalbumin level also plays an important role in the early diagnosis of nephropathy. Causes of liver disease, severity, complications including infection, nutritional status, therapeutic drugs, and underlying nephropathy may be associated with renal injury and renal insufficiency in patients with liver disease and should be differentiated. [ABSTRACT FROM AUTHOR]

In March 2022, EASL released a new version of the clinical practice guidelines on haemochromatosis. Haemochromatosis is characterized by elevated transferrin saturation（TSAT） and progressive iron overload mainly involving the liver, and early diagnosis and venesection can prevent liver cirrhosis, hepatocellular carcinoma, diabetes, arthritis, and other complications. For patients with p.Cys282 Tyr homozygous mutation of the hemochromatosis gene HFE, haemochromatosis can be diagnosed if serum iron parameters show TSAT >45% and ferritin >200 μg/L in female patients, or TSAT >50% and ferritin >300 μg/L in male patients and postmenopausal female patients. If a patient has elevated TSAT and ferritin and belongs to other HFE genotypes, magnetic resonance or liver biopsy is needed to confirm iron overload in the liver. Liver fibrosis stage and damage to other organs should be carefully assessed at the time of diagnosis, which will help to determine management strategies. Hepatocellular carcinoma should be screened for patients with progressive liver fibrosis. The goal of venesection is to achieve ferritin <50 μg/L during the induction stage and ferritin <100 μg/L during the maintenance stage. [ABSTRACT FROM AUTHOR]

Drug-induced liver injury( DILI) with extrahepatic adverse drug reaction( EHADR) is the injury of extrahepatic organs which is caused by the same drug inducing liver injury and may occur simultaneously or successively with DILI,such as the skin,gastrointestinal tract,blood system,cardiovascular system,and bone and joint system,and it should be taken seriously in clinical practice. DILI with EHADR is not rare,and its pathogenesis may be associated with various factors including the physicochemical properties,distribution,metabolism,excretion,biological activity,and immunological properties of drugs,host genetic background,and underlying diseases. The diagnosis and treatment of DILI with EHADR is more challenging than that of DILI alone. [ABSTRACT FROM AUTHOR]

Drug-induced cholestasis (DRIC) mainly includes cholestasis-type and mixed-type drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method scale should be used to determine the causality between drug and cholestasis and other etiologies should be excluded. Liver biopsy may help with differential diagnosis. Drugs should be stopped after the development of DRIC to avoid stimulation, and ursodeoxycholic acid should be administered for treatment. DRIC has a complex pathogenesis, which involves the direct toxicity of drugs and their metabolites on hepatocytes and the biliary tree, immune and inflammatory response, gene polymorphism and inhibition of key enzymes and transporters in the pathways of drug metabolism and efflux, and HLA gene polymorphisms. Clarification of these pathogeneses helps with the early warning, prevention, and optimized treatment of DRIC. [ABSTRACT FROM AUTHOR]

Objective To investigate the effect of synergistic intervention of interferonα(IFNα) and thymopentin(TP5) on the mRNA expression of apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 A(APOBEC3 A) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 B(APOBEC3 B) in HepG2. 2. 15 cells. Methods HepG2. 2. 15 cells were divided into blank control group, IFNα treatment group, TP5 treatment group, and IFNα + TP5 treatment group, and at 12, 24, 48, and 72 hours of treatment, quantitative real-time PCR was used to measure the mRNA expression of APOBEC3 A and APOBEC3 B in HepG2. 2. 15 cells. An analysis of variance was used for comparison of continuous data between multiple groups, and the least significant difference t-test was used for further comparison between two groups. Results Compared with the blank control group, the IFNα treatment group and the IFNα + TP5 treatment group had a significant increase in the mRNA expression of APOBEC3 A at 12, 24, 48, and 72 hours of treatment(all P < 0. 001). Compared with the IFNα treatment group, the IFNα + TP5 treatment group had a significant increase in the mRNA expression of APOBEC3 A at these four time points(all P < 0. 001). TP5 treatment had no significant influence on the mRNA expression of APOBEC3 A at each time point(all P > 0. 05). There was no significant difference in the mRNA expression of APOBEC3 B between the blank control group and the treatment groups(all P > 0. 05). Conclusion IFNα combined with TP5 can significantly upregulate the mRNA expression of APOBEC3 A in HepG2. 2. 15 cells. [ABSTRACT FROM AUTHOR]