An excerpt of the EASL clinical practice guidelines on haemochromatosis / 临床肝胆病杂志

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.Cys282Tyr 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.

Pathogenesis of drug-induced liver injury: Current understanding and future needs / 临床肝胆病杂志

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.

Patterns and practice management of occupational exposure of medical staffs in coronavirus disease 2019 isolation wards / 中华传染病杂志

Objective:To explore the patterns and causes of occupational exposure to infectious diseases (OEID) among frontline medical staffs (FMS) in coronavirus disease 2019 (COVID-19) isolation wards (CIW), and the particularity of post-OEID management and the measures to prevent OEID.Methods:A total of 1 061 FMS of Wuhan Huoshenshan Hospital from February 4 to March 21, 2020 were enrolled. The OEID of FMS was investigated and analyzed from the perspectives of FMS physical and psychological conditions, protective equipment, infection-control related regulations and procedures, local air quality, exposure patterns, and the particularity of emergency treatment after exposure.Results:The incidence of OEID among FMS was 2.0%(21/1 061). The nurses and doctors accounted for 95.2%(20/21) and 4.8%(1/21), respectively. The incidences in 17 general wards and two intensive care units (ICU) were 71.4%(15/21) and 28.6%(6/21), respectively. Nearly 90.5%(19/21) and 9.5%(2/21) of the OEID events occurred in contaminated area and potential contaminated area, respectively. About 23.8%(5/21) of the OEID events were air exposure of oral-nasal skin, mucosa and respiratory tract, which was secondary to uncontrollable vomiting, and 76.2%(16/21) were pricking injuries. The inducement factors involved poor quality and inappropriate wearing of some goggles, atomization of the inside of goggles leading to blurring vision, chest distress and decreased sense of touch and operational flexibility related to level-3 protection equipment, poor air quality, FMS physical and psychological conditions, etc. Under the direction of "the Procedures for Handling OEID" , all incidents are properly handled and no FMS was infected by 2019 novel coronavirus and blood-borne pathogens. No new OEID event was found after the strict implement of set of preventive measures.Conclusions:The OEID among FMS in CIW is attributed to multiple causes. The optimized process that takes into account the specificity of OEID management for both COVID-19 and blood-borne infectious diseases can effectively prevent potential post-exposure infections. And reasonable precautions can fully reduce the risk of OEID of FMS in CIW.

The pathogenesis, diagnosis, and treatment of drug-induced liver injury with extrahepatic adverse drug reactions / 临床肝胆病杂志

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.

Several issues worthy of reference and discussion of 2019 edition of the European Association for the Study of the Liver guideline for drug-induced liver injury / 中华肝脏病杂志

The 2019 European Association for the Study of the Liver (EASL) Clinical Practice Guidelines (hereinafter referred to as the EASL Guidelines) extracted the required evidence from detailed research materials, and rigorously graded and condensed the varying strengths of evidence into 32 recommendations and 14 statements (recommendations and reminders) for drug-induced Liver Injury (DILI). This guideline has important reference values for helping clinicians to further improve their understanding of DILI and the level of clinical diagnosis, treatment and prevention; however, there are still several issues worthy of further discussion.

Current status of the pathogenesis, diagnosis, and treatment of drug-induced cholestasis / 临床肝胆病杂志

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.

Current status and research interests of the diagnosis and treatment of cholestatic liver disease / 临床肝胆病杂志

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.

Diagnosis and treatment of drug-induced liver injury / 临床肝胆病杂志

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.

Features and management of patients with hepatitis C virus/hepatitis B virus dual infection associated with the application of direct-acting antiviral agents / 临床肝胆病杂志

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.

Current status and future views of indicators for clinical outcome of antiviral treatment in patients with hepatitis B virus infection / 中华肝脏病杂志

The optimal clinical outcomes are the original intention and base to form the short-term, long-term and special goals of antiviral treatment in patients with hepatitis B virus (HBV) infection. The immediate indicators for assessment of antiviral clinical outcomes, which usually need prolonged follow-up, include the liver histopathological changes, the occurrence and severity of liver cirrhosis and hepatocellular carcinoma (HCC), mortality and survival rates, survival time and life quality, prevention rates of Mother-to-Child Transmission and HBV reinfection after liver transplantation, etc.

Strengthening the clinical research in long-term therapy of hepatitis B: beginning with the end in mind / 中华肝脏病杂志

Chronic hepatitis B is a serious public health issue in China. The clinical management of hepatitis B is effective with the emergence of antiviral agents. The outcome of long-term therapy and nucleos(t)ide analogues stopping rules are currently unresolved issues and unmet needs. Thus, we need to pay more attention to clinical research to build large-sample and long-term follow-up cohorts and begin with the end in mind. We believe that the way to resolve the issues above will be found with the efforts of generations.

Several issues regarding evaluation of renal injury and renal insufficiency in patients with liver disease / 临床肝胆病杂志

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.

Advances in Roussel Uclaf Causality Assessment Method for diagnosis of drug-induced liver injury and its comparison with structured expert opinion process / 临床肝胆病杂志

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.

RUCAM scale-based diagnosis, clinical features and prognosis of 140 cases of drug-induced liver injury / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To analyze the etiology, clinical features and prognosis of liver injuries caused by different drugs.</p><p><b>METHODS</b>The types of suspected drugs related to liver injury, clinical manifestations, liver biochemical parameters, clinical outcomes and other associated data were retrospectively assessed for 140 patients with drug-induced liver injury (DILI). The Roussel Uclaf Causality Assessment Method (RUCAM) was used to assess the causality between drugs and liver injury.</p><p><b>RESULTS</b>The most prevalent agents inducing DILI were Chinese traditional drugs (62.1%), followed by antipyretic analgesic drugs (10%) and antibiotics (5%). The ratio of male to female patients in the study cohort was 1:1.69, with 71 of the total patients (50.7%) being between the ages of 40 and 60 years-old. The RUCAM scale was not less than 3 points for any of the patients.In general, the clinical manifestations and biochemical results were not specific. The percentages of hepatocellular injury type, cholestatic injury type and mixed injury type were 51.4%, 30.7% and 17.9% respectively. The median age of patients with cholestatic liver injury was 55.6 years, which was older than that of patients with hepatocellular injury (47.1 years) or mixed injury (49.9 years).</p><p><b>CONCLUSION</b>Although antipyretic analgesics and antibiotics are considered as common drugs that can induce DILI, Chinese traditional drugs have emerged as another important group of liver injurious agents. Cholestatic DILI was found to occur more often in elderly patients than in younger patients.</p>

Investigation of the epidemiological and clinical characteristics of an outbreak of tsutsugamushi disease in Anhui Province / 中华传染病杂志

Objective To investigate the epidemiological and clinical characteristics of an outbreak of tsutsugamushi disease in Chuzhou region, Anhui Province, and to clarify the new changes of epidemic focus of tsutsugamushi disease in China. Methods Field epidemiological investigation and analysis of clinical features were done. The detections of specific antibodies against Rickettsia tsutsugamushi were conducted to diagnose tsutsugamushi disease using colloidal gold immunochromatography assay combined with Well-Felix reaction. The geomorphic and climatic characteristics of the new epidemic focus were investigated. Results The outbreak occurred from October to November, 2007. The epidemic focus located on mountainous brushland regions, and the air temperature fluctuated from 20-4 ℃. Nineteen cases of tsutsugamushi disease in the new-found epidemic focus were finally diagnosed, 9 cases out of them were hospitalized, another 9 had recovered when diagnosed by serological tests; the remaining one had classical manifestations of tsutsugamushi disease but did not receive the serological test for certain cause. The main clinical symptoms were chilly in 14 cases, fever in 19 cases, headache in 15 cases; among the 9 hospitalized patients, the symptoms were lymphadenectasis in 8 inpatients, skin rash in 7 inpatients, splenomegaly in 4 inpatients and skin eschar and ulcer in 7 inpatients and Weil-Felix reaction by OXκantigen positive in 4 cases; the specific antibodies against Rickettsia tsutsugarnushi of 18 tested cases were all positive. No severe complications occurred in all patients. Before the first case was identified, all other cases were not diagnosed in time and did not receive correct antibiotic treatment. Nine hospitalized patients recovered rapidly with the treatment of doxycycline. Conclusions The outbreak of tsutsugamushi disease in Anhui Province in 2007 is type of emerged in autumn and transitional epidemic focus. There is epidemic focus of tsutsugamushi disease in northern region of Anhui Province. Doxycycline is rapid and effective for the treatment of tsutsugamushi disease.

The exploration and practice of standardized training for medical specialist of obstetrics and gynecology / 中华医学教育探索杂志

The standardized training for residents (medical specialists) is an important aspect to fulfill the post-graduated medical education in China. It not only can bring up outstanding qualified specialists,but also is in line with international trends in medical education. According to the situation and existing problems of current standardized training for obstetrics and gynecology specialist,a lot of advice was given for further improvement of the standardization of training in obstetrics and gynecology specialist.

Design and activity assessment of HDV ribozymes to trans-cleave HCV RNA / 第三军医大学学报

Objective　To study the probability of using hepatitis D virus (HDV) ribozyme as a kind of anti-hepatitis-C-virus (HCV) gene thera-py drugs. Methods　The natural HDV genomic ribozyme′s stem Ⅳ was optimized and its substrate-binding region reconstructed, thus three recombinant HCV-specific HDV genomic ribozymes RzC1, RzC2 and RzC3 were obtained. HCV RNA 5'-noncoding region and 5'-fragment of C region (HCV RNA5'-NCR-C) were transcribed from plasmid pHCV-neo by T7 phage RNA polymerase in vitro, and radiolabelled at its 5'-end. The trans-cleaving reaction was performed by mixing the ribozymes and substrate at mol ratio 100∶1 under conditions as follows: 37℃, pH7.5, Mg2+ 20 mmol/L and deionized formamide 2.5 mol/L. Percentage of trans-cleaved products were calculated at different time points and used as the activity indicator of the three ribozymes. Results　RzC1, RzC2 trans-cleaved more substrate when the time extended, and got to 24.9%,20.3% after reac-ting for 90 minutes respectively; RzC3 was not able to trans-cleave its substrate. Conclusion　Recombinant HDV genomic ribozymes have the ability to trans-cleave HCV RNA, but the appropriate target sequence should be selected.

The pathogenesis, diagnosis, and treatment of drug-induced liver injury with extrahepatic adverse drug reactions / 临床肝胆病杂志

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.