La piel como reflejo de trastornos hepáticos subyacentes / The skin as a reflection of underlying liver disorders

La piel es el órgano más grande y visible del cuerpo humano; en ella se pueden reflejar diversos hallazgos de enfermedades sistémicas, incluidas las hepatopatías crónicas y agudas, las cuales se asocian a múltiples lesiones dermatológicas como principal manifestación extrahepática. Las manifestaciones cutáneas son comunes pero inespecíficas y pueden encontrarse en diferentes enfermedades; por lo tanto, la piel funciona como una ventana a nuestra salud general, de ahí que el examen clínico de la piel, las uñas y el cabello pueda permitir el reconocimiento adecuado, el diagnóstico y tratamiento temprano de las enfermedades hepáticas y la mejoría de la calidad y esperanza de vida de los pacientes afectados.

La piel es el órgano más grande y visible del cuerpo humano; en ella se pueden reflejar diversos hallazgos de enfermedades sistémicas, incluidas las hepatopatías crónicas y agudas, las cuales se asocian a múltiples lesiones dermatológicas como principal manifestación extrahepática. Las manifestaciones cutáneas son comunes pero inespecíficas y pueden encontrarse en diferentes enfermedades; por lo tanto, la piel funciona como una ventana a nuestra salud general, de ahí que el examen clínico de la piel, las uñas y el cabello pueda permitir el reconocimiento adecuado, el diagnóstico y tratamiento temprano de las enfermedades hepáticas y la mejoría de la calidad y esperanza de vida de los pacientes afectados.

Adenoma Hepatocelular. A propósito de un caso

El Adenoma Hepatocelular (AH) es un tumor hepático benigno, su diagnóstico ha avanzado gracias a los avances en los métodos moleculares, facilitaron dividirlos en subtipos, con diferentes pronósticos e indicaciones terapéuticas. Se presenta el caso clínico de una paciente, de 40 años con hallazgo ecográfico de tumor hepático, la Tomografía de Abdomen y Pelvis voluminosa lesión sólida heterogénea, en la Resonancia Magnética compatible con Adenoma esteatósico (asociado a mutación HNF1 alfa). Se decide tratamiento quirúrgico, con resección de los segmentos 6 y 7. La Anatomía patológica concluye: Compatible con el subtipo inflamatorio. Los Adenoma hepáticos (AH) son tumores raros, solitarios de estirpe epitelial, benignos. Se presentan en mujeres de edad fértil y asociado al consumo de anticonceptivos orales y estrógenos. Estos tumores predominan en hígado derecho, con proliferación de células parecidas a los hepatocitos normales, pero desorganizados y sin arquitectura lobular normal, sin ductos biliares ni tejido conectivo de sostén. Los AH así como el resto de los tumores hepáticos benignos, han aumentado su incidencia de la mano con el avance de la imagenología abdominal. La importancia de la diferenciación con el resto de los tumores hepáticos benignos surge del potencial maligno de éstos. Podemos clasificar a los pacientes según el perfil molecular asociado a marcadores inmunohistoquímicos. Los estudios de imagen son fundamentales para la diferenciación tumoral en diagnóstico y planear la terapéutica. El tratamiento será individualizado, determinada por la clínica, la variedad de subtipos, y la evolución. Debido a la complejidad de la enfermedad, el tratamiento de la HA es uno de los mejores ejemplos de abordaje individualizado en unidades hepatobiliares.

Hepatocellular adenoma (HA) is a benign liver tumor, its diagnosis has advanced thanks to advances in molecular methods, which facilitated its division into subtypes, with different prognoses and therapeutic indications. We present the clinical case of a 40-year-old patient with an ultrasound finding of a liver tumor, a voluminous heterogeneous solid lesion on a CT scan of the abdomen and pelvis, compatible with a steatotic adenoma on MRI (associated with HNF1 alpha mutation). Surgical treatment was decided, with resection of segments 6 and 7. The pathology concluded in short: Compatible with the inflammatory subtype. Hepatic adenomas (HA) are rare, solitary, benign epithelial tumors. They occur in women of childbearing age and associated with the consumption of oral contraceptives and estrogens. These tumors predominate in the right liver, with proliferation of cells similar to normal hepatocytes, but disorganized and without normal lobular architecture, without bile ducts or supporting connective tissue. HA, as well as the rest of the benign liver tumors, have increased their incidence in the hand with the advancement of abdominal imaging. The importance of differentiation with the rest of the benign liver tumors arises from the malignant potential of these. We can classify patients according to the molecular profile associated with immunohistochemical markers. Imaging studies are fundamental for tumor differentiation in diagnosis and therapeutic planning. The treatment will be individualized, determined by the clinic, the variety of subtypes, and the evolution. Due to the complexity of the disease, the treatment of AH is one of the best examples of an individualized approach in hepatobiliary units.

O adenoma hepatocelular (AH) éum tumor benigno do fígado, seu diagnóstico avançougraçasaosavanços dos métodos moleculares, que facilitaramsuadivisão em subtipos, com diferentes prognósticos e indicaçõesterapêuticas. Apresentamos o caso clínico de umadoente de 40 anoscomachadoultrassonográfico de tumor hepático, volumosalesão sólida heterogénea à TC de abdómen e pelve, compatívelcom adenoma esteatótico à RM (associado a mutação HNF1 alfa ). Optou-se por tratamentocirúrgico, comressecção dos segmentos 6 e 7. A patologiaconcluiu-se resumidamente: Compatívelcom o subtipo inflamatório. Os adenomas hepáticos (AH) são tumores epiteliais raros, solitários e benignos. Ocorrem em mulheres em idadereprodutiva e associadasao consumo de anticoncepcionaisorais e estrogênios. Esses tumores predominam no fígadodireito, comproliferação de células semelhantesaoshepatócitosnormais, porém desorganizados e semarquitetura lobular normal, sem ductos biliares outecido conjuntivo de sustentação. O HA, assim como os demais tumores hepáticos benignos, têm aumentado suaincidêncianamãocom o avanço da imagem abdominal. A importância da diferenciaçãocom os demais tumores hepáticos benignos decorre do potencial maligno destes. Podemos classificar os pacientes de acordocom o perfil molecular associado a marcadores imuno-histoquímicos. Os estudos de imagemsãofundamentais para a diferenciação tumoral no diagnóstico e planejamentoterapêutico. O tratamento será individualizado, determinado pela clínica, variedade de subtipos e evolução. Pela complexidade da doença, o tratamento da HA é um dos melhoresexemplos de abordagem individualizada nas unidades hepatobiliares.

Research advances in the immunomodulatory mechanism of galectin-9 and its role in liver diseases / 临床肝胆病杂志

Galectin-9 （Gal-9） is a member of the galectin family that can specifically recognize and bind to galactosides. Recent studies have shown that Gal-9 is highly expressed in the liver and can help to maintain intrahepatic immune homeostasis and perform biological functions in various liver diseases. This article reviews the immunomodulatory functions of Gal-9 and its role in different liver diseases. Studies have shown that Gal-9 has important biological functions in different liver diseases through multiple pathways. Research on the specific immunomodulatory mechanisms and functions of Gal-9 may help to discover the therapeutic role of Gal-9 in liver diseases.

Current research status of animal models for acute-on-chronic liver failure / 临床肝胆病杂志

Acute-on-chronic liver failure has complex conditions， rapid progression， and a high mortality rate， and further studies are still needed to clarify its pathogenesis and etiology. The establishment of animal models for acute-on-chronic liver failure can not only provide a good basis for exploring the pathogenesis of acute-on-chronic liver failure， but also provide an experimental basis for clinical treatment. Through a literature review， this article summarizes the methods commonly used to establish the animal models of acute-on-chronic liver failure， including carbon tetrachloride combined with LPS/GaIN， thioacetamide combined with LPS， serum albumin， and bile duct ligation. This article analyzes the characteristics of various animal models， so as to provide documentary and experimental bases for further exploration of more ideal animal models.

Análise de custos de pacientes cirróticos descompensados recebendo albumina a longo prazo versus tratamento médico padrão nos sistemas de saúde público e privado do Brasil / Albumin versus standard medical treatment in brazilian public and private healthcare systems

ABSTRACT Background: Cirrhosis is one of the final stages of chronic liver disease. Common causes of cirrhosis include alcoholism and viral hepatitis infections. Cirrhosis can progress from an asymptomatic, compensated phase to decompensation and the appearance of overt symptoms. There is no specific treatment for decompensated cirrhosis. The ANSWER trial positioned long-term albumin infusions as a potential treatment for patients with cirrhosis and uncomplicated ascites. Objective: This study assesses the economic impact of albumin infusions following the ANSWER trial regimen in Brazilian patients with decompensated cirrhosis from the public and private healthcare systems perspectives. Methods: The incremental cost per patient per year was calculated for standard medical treatment (SMT) plus long-term albumin infusions versus SMT alone. Costs of diuretics and albumin were obtained from Banco de Preços em Saúde and the Drug Market Regulation Chamber. Costs for complication and procedures were gathered from the published literature. Costs were transformed to 2021 Brazilian reals (BRL). Incidences of clinical complications and treatments were gathered from the ANSWER trial. Univariate sensitivity analysis was performed by increasing and decreasing all inputs by 20%. Results: The cost per patient per year was 118,759 BRL and 189,675 BRL lower for patients treated with SMT and albumin (compared to SMT only) for the public and private healthcare systems, respectively. The additional cost of albumin was offset by reduced complications and treatments (149,526 BRL and 249,572 BRL, respectively). The univariate sensitivity analysis showed cost savings for both healthcare systems in all the scenarios assessed. Conclusion: This economic analysis suggests that, if the ANSWER trial clinical outcomes translate into real-world effectiveness, addition of albumin infusions to SMT in patients with decompensated cirrhosis may lead to cost savings for the public and private healthcare systems in Brazil.

RESUMO Contexto: A cirrose representa o estágio final da doença hepática crônica. Causas comuns de cirrose incluem alcoolismo e infecções por hepatite viral. A cirrose pode progredir de uma fase compensada assintomática para descompensação e aparecimento de sintomas evidentes. Não há tratamento específico para cirrose descompensada. O estudo ANSWER demonstrou que a administração de albumina a longo prazo pode representar um potencial tratamento para pacientes com cirrose e ascite não complicada. Objetivo: Nosso estudo avalia o impacto econômico da administração de albumina a longo prazo seguindo o protocolo do estudo ANSWER em pacientes brasileiros com cirrose descompensada, sob a perspectiva dos sistemas de saúde público e privado. Métodos: O custo incremental por paciente por ano foi calculado para o tratamento médico padrão (SMT) associado a administração de albumina a longo prazo comparado a SMT apenas. Os custos de diuréticos e albumina foram obtidos no Banco de Preços em Saúde e na Câmara de Regulação do Mercado de Medicamentos. Os custos de complicações e procedimentos foram coletados da literatura publicada. Os custos foram transformados em Reais de 2021 (BRL). As incidências de complicações clínicas e tratamentos foram coletadas do estudo ANSWER. Uma análise de sensibilidade univariada foi realizada aumentando e diminuindo todas as variáveis em 20%. Resultados: O custo por paciente por ano foi de R$ 118.759 e R$ 189.675 menor para pacientes tratados com SMT e albumina (comparado apenas com SMT) para os sistemas de saúde público e privado, respectivamente. O custo adicional da albumina foi compensado pela redução de complicações e tratamentos (149.526 BRL e 249.572 BRL, respectivamente). A análise de sensibilidade univariada mostrou redução de custos para ambos os sistemas de saúde em todos os cenários avaliados. Conclusão: Esta análise econômica sugere que, se os resultados clínicos do estudo ANSWER se confirmarem no mundo real, a administração de albumina associada ao SMT em pacientes com cirrose descompensada pode levar a redução de custos para os sistemas de saúde público e privado no Brasil.

Incidental Histopathological Findings Of Liver - A Study Of 100 Autopsy Cases

Introduction: The silent liver diseases are found accidentally during regular health check-ups, examination of other diseases or autopsy examinations. To study the spectrum of histopathological findings of liver and toObjectives: determine the prevalence of silent liver diseases in autopsy cases. A retrospective study wasMaterial And Methods: done in the Department of Pathology, Ramaiah Medical College, Bengaluru from January 2019 to June 2020 on 100 liver autopsy specimens. The majority of the cases with pathological lesions were in the age group of 31-60 yearsResults: with Male: Female ratio of 2.8:1. The most common finding in this study was steatosis (31%), followed by chronic venous congestion (26%), cirrhosis (6%), portal triaditis (6%), steatohepatitis (5%), abscess and cholestasis (1%), tuberculosis (1%) and hepatocellular carcinoma (1%). The autopsy examination of liver by determining the prevalenceConclusion: of silent liver diseases in particular regional population creates public awareness and brings required life style changes.

Helicobacter pylori e as doenças hepatobiliares: atualização 2023 / Helicobacter and hepatobiliary diseases: update 2023

ABSTRACT Helicobacter Pylori (H. pylori) is one of the main infectious causes of gastroduodenal diseases, however, its role in developing different extragastric diseases has been proven. The possible involvement of H. pylori in the pathogenesis of cardiovascular, metabolic, neurodegenerative, skin, and hepatobiliary diseases is suggested. The bacterium has been found in tissue samples from the liver, biliary tract, and gallstones of animals and humans. However, the role of H. pylori infection in the pathogenesis of liver and biliary diseases has not been finally established. The histopathological confirmation of the positive effect of H. pylori eradication is needed. In addition, there are discussions on the clinical significance of other Helicobacter species. The review presents the data available for and against the involvement of H. pylori in hepatobi­liary disease development and progression.

RESUMO Helicobacter pylori (H. pylori) é uma das principais causas infecciosas de doenças gastroduodenais, no entanto, seu papel no desenvolvimento de diferentes doenças extragástricas tem sido comprovado. Sugere-se o possível envolvimento do H. pylori na patogênese de doenças cardiovasculares, metabólicas, neurodegenerativas, cutâneas e hepatobiliares. A bactéria tem sido encontrada em amostras de tecido do fígado, trato biliar e cálculos biliares de animais e humanos. No entanto, o papel da infecção por H. pylori na patogênese de doenças do fígado e das vias biliares ainda não foi estabelecido definitivamente. A confirmação histopatológica do efeito positivo da erradicação do H. pylori é necessária. Além disso, existem discussões sobre a importância clínica de outras espécies de Helicobacter. A revisão apresenta os dados disponíveis a favor e contra o envolvimento do H. pylori no desenvolvimento e progressão das doenças hepatobiliares.

Hematological abnormalities in patients of alcoholic chronic liver disease – A cross-sectional study in a tertiary care hospital in Eastern Zone of India

Background: Alcohol abuse is on increasing trend in world as well as in India, especially in young population. Long-term alcohol intake may leads to alcoholic chronic liver disease which may turns in to end stage liver diseases. Alcoholic chronic liver disease is associated with some hematological abnormalities which if detected at early stage may provide clear therapeutic implications in managing these patients and reducing the adverse events. Aims and Objectives: Our aim of the study was to identify various hematological abnormalities in patients of alcoholic chronic liver disease. Materials and Methods: This hospital-based cross-sectional study includes 100 randomly selected patients with alcoholic chronic liver disease attending Out-Patient Department and admitted in General Medicine ward of Burdwan Medical College satisfying the inclusion and exclusion criteria. Data were analyzed for hemoglobin (Hb), red blood cell (RBC), total leukocyte count (TLC), platelet count, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), MCH concentration, and prothrombin time-international normalized ratio. The mean and standard deviation, percentages, and ratio were calculated and presented in the form of tables with the help of SPSS (IBM) ver-23. P < 0.05 was considered statistically significant. Results: Hematological abnormalities were found more with increased duration of alcohol consumption. Prolonged bleeding time was observed in 23% cases and prolonged clotting time was observed in 21% cases. Maximum patients belonged to Child–Pugh grade C. Hematological abnormalities were more in patients belonging to Child–Pugh grade C. Hb, RBC, platelet, and packed cell volume were significantly lower in patients belonging to Child–Pugh class C, whereas TLC, MCV, and MCH were significantly higher in class C. Conclusion: It can be concluded that related hematological changes, which are common in alcoholic chronic liver disease endanger the lives of these patients. They should be detected and corrected at earliest to minimize morbidity and mortality.

Alcoholic foamy degeneration: an unusual presentation of the alcoholic liver disease diagnosed on autopsy

ABSTRACT Alcoholic foamy degeneration (AFD) is an uncommon presentation of alcoholic liver disease (ALD) with characteristic histologic findings of foamy-looking hepatocytes due to the presence of abundant microvesicles of fat within the cytoplasm predominantly in perivenular and midzonal regions without inflammation and fibrosis. It is underdiagnosed as the patients quickly recover after alcoholic abstinence and are rarely caught on biopsies. AFD has better prognosis than alcoholic hepatitis, and the injury mechanism is different, warranting a different diagnosis. We present an uncommon case of AFD incidentally diagnosed during autopsy in a chronic alcoholic and diabetic man.

Autoimmune hepatitis and primary biliary cholangitis overlap syndrome after COVID-19

ABSTRACT COVID-19 is commonly associated with high serum levels of pro-inflammatory cytokines, and the post-infection status can disturb self-tolerance and trigger autoimmune responses. We are reporting a 45-year-old male who was admitted with fatigue, jaundice, elevated liver enzymes (with cholestatic pattern), and acute kidney injury two weeks after recovering from a mild SARS-CoV-2 infection. Serologies for viral hepatitis and anti-mitochondrial antibody were negative, while anti-nuclear and anti-smooth muscle antibodies were positive. There were no signs of chronic liver disease, and a magnetic resonance cholangiography showed no dilatation of biliary ducts. Histologic evaluation of the liver evidenced numerous foci of lobular necrosis without ductopenia or portal biliary reaction. Considering the autoantibody profile and histologic changes, the medical team started oral prednisone, but there was a suboptimal biochemical response in the outpatient follow-up. Two months later, a second liver biopsy was performed and revealed non-suppurative destructive chronic cholangitis, extensive areas of confluent necrosis with hepatocytes regenerating into pseudorosettes, and numerous plasma cells. According to the Paris Criteria, the patient was then diagnosed with an autoimmune hepatitis-primary biliary cholangitis overlap syndrome (AIH-PBC-OS). After adding azathioprine and ursodeoxycholic acid to the treatment, there was a satisfactory response. This is the second worldwide report of an AIH-PBC-OS triggered by COVID-19, but the first case with a negative anti-mitochondrial antibody. In this setting, histologic evaluation of the liver by an experienced pathologist is a hallmark of achieving the diagnosis and correctly treat the patient.

Occult hepatitis B virus infection in patients with chronic liver disease of different etiology in a Brazilian referral center: comparison of two different hepatitis B virus deoxyribonucleic acid amplification protocols: a cross-sectional study

ABSTRACT BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) deoxyribonucleic acid (DNA) in the liver of individuals with undetectable hepatitis B virus surface antigen (HBsAg) in the serum. The actual prevalence of OBI and its clinical relevance are not yet fully understood. OBJECTIVE: To evaluate the prevalence of HBV DNA in liver biopsies of HBsAg-negative patients with chronic liver disease of different etiologies in a referral center in Brazil and compare two different HBV DNA amplification protocols to detect HBV. DESIGN AND SETTING: This cross-sectional observational study was conducted at the Liver Outpatient Clinic, Hospital das Clínicas, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil, between January 2016 and December 2019. METHODS: HBV DNA was investigated in 104 liver biopsy samples from individuals with chronic liver disease of different etiologies, in whom HBsAg was undetectable in serum by nested-polymerase chain reaction (nested-PCR), using two different protocols. RESULTS: OBI, diagnosed by detecting HBV DNA using both protocols, was detected in 6.7% of the 104 individuals investigated. Both protocols showed a good reliability. CONCLUSION: In addition to the differences in the prevalence of HBV infection in different regions, variations in the polymerase chain reaction technique used for HBV DNA amplification may be responsible for the large variations in the prevalence of OBI identified in different studies. There is a need for better standardization of the diagnostic methods used to diagnose this entity.

Protective effect of Zhizi Dahuang decoction in a mouse model of alcoholic liver disease / 临床肝胆病杂志

ObjectiveTo investigate the effect of Zhizi Dahuang decoction （ZZDHT） in the treatment of alcoholic liver disease （ALD） by improving oxidative stress in hepatic neutrophils. MethodsNetwork pharmacology was used to obtain the chemical components of ZZDHT and their corresponding action targets and analyze the potential targets and functional pathways of ZZDHT in the treatment of ALD. The non-target metabolomics technology was used to observe the changes in the metabolites of ZZDHT in mouse serum and liver. The mice were given ZZDHT at a dose twice as much as the middle dose concentration by gavage， and serum and liver samples were collected at six time points after gavage （10 minutes， 30 minutes， 1 hour， 2 hours， 4 hours， and 6 hours） and were then mixed for mass spectrometry （administration group with 18 mice）， while the 18 mice in the control group were given an equal volume of normal saline by gavage. Ultra-performance liquid chromatography was used for rapid isolation and identification of the metabolites of ZZDHT in serum and liver tissue， and the effective constituents of ZZDHT were validated. Male C57BL/6J mice， aged 8 weeks， were randomly and equally divided into control group， model group， and low-， middle-， and high-dose ZZDHT groups， with 10 mice in each group. All mice except those in the control group were used to establish a mouse model of ALD （NIAAA model mice）， and at the same time， the mice in the administration groups were given low-， middle-， and high-dose ZZDHT by gavage， while those in the control group and the model group were given an equal volume of normal saline by gavage. The serum levels of alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， and triglyceride （TG） were measured； PCR was used to measure the gene expression levels of related inflammation， oxidative stress， and neutrophil indicators in the liver； ELISA was used to measure the levels of related inflammation and oxidative stress indicators in serum； superoxide dismutase （SOD）， glutathione peroxidase （GSH-Px）， and malondialdehyde （MDA） were measured to observe the level of oxidative stress in the liver； HE staining， myeloperoxidase staining， and oil red staining were used to observe liver injury， neutrophil infiltration， and lipid deposition. A one-way 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. ResultsA total of 53 active components and 227 target genes were obtained for ZZDHT， and there were 8685 target genes of ALD， resulting in 222 common target genes between these two groups of genes. Core pathways included the interleukin-6 signaling pathway and the TNF signaling pathway. The non-targeted metabolic analysis of ZZDHT obtained 225 metabolites in mouse liver and 227 metabolites in serum， among which there were 126 common metabolites. The core pathways of liver metabolites included glycerolipid metabolism and inflammatory mediator regulation of TRP channels， and the core pathways of serum metabolites included the AMPK signaling pathway and oxidative phosphorylation， all of which were associated with oxidative stress- and inflammation-related pathways. Compared with the model group， the low-， middle-， and high-dose ZZDHT groups had significant reductions in the serum levels of ALT， AST， and TG （all P<0.05）， and the middle-dose ZZDHT group had significant reductions in the levels of Ly6g， Ncf1， Ncf2， IL-6， TNF-α， IL-1β， MDA， 4-HNE， Gp91， and P22 in the liver （all P<0.05）， a significant increase in the level of SOD （P<0.05）， a significant reduction in the serum level of 4-HNE （P<0.05）， and a significant increase in the level of GSH-Px （P<0.05）. There were significant improvements in fat deposition and neutrophil infiltration in the liver of mice in the middle-dose ZZDHT group （both P<0.05）. ConclusionZZDHT significantly reduces oxidative stress and inflammatory response in NIAAA model mice.

The physiological and pathological role of amyloid protein in the liver / 临床肝胆病杂志

Amyloid protein （AP） is used to describe the fibrous aggregates that form when proteins are misfolded， and it is associated with a series of amyloidosis diseases. When AP is deposited in the liver， it will lead to liver amyloidosis， thereby inducing related pathological changes that affect the normal physiological function of the liver； however， this disease is rarely reported and often neglected in clinical practice. This article reviews the physiological and pathological effects and mechanisms of AP in the liver， so as to improve the understanding of AP-related diseases and provide a reference for related research and clinical treatment.

Clinical features of non－B， non－C hepatocellular carcinoma / 临床肝胆病杂志

ObjectiveTo investigate the change in the proportion of non－B， non－C hepatocellular carcinoma （NBNC－HCC） in hepatocellular carcinoma， and to compare and analyze the clinicopathological features of NBNC－HCC. MethodsA total of 3 090 patients with hepatocellular carcinoma （HCC） who were diagnosed in Sichuan Provincial People’s Hospital from January 2011 to December 2021 were enrolled， and according to the hepatitis markers， they were divided into hepatitis virus infection－associated HCC group with 2 472 patients and NBNC－HCC group with 618 patients. According to the liver disease and metabolic risk factors， the NBNC－HCC group was further divided into metabolic disorder HCC group with 289 patients， alcoholic liver disease （ALD）－associated HCC group with 174 patients， and other HCC group with 155 patients. General information， laboratory markers， and pathological findings were collected from all HCC patients. The Mann－Whitney U test was used for comparison of continuous data between two groups， and the Kruskal－Wallis H test was used for comparison between three groups； the chi－square test was used for comparison of categorical data between groups， and the chi－square trend test was used to investigate the trend of the change in the proportion of NBNC－HCC in HCC. ResultsThe proportion of patients with NBNC－HCC in HCC increased from 13.7% in 2011 to 20.1% in 2021 （χ2=5.529， P=0.019）， and compared with the hepatitis virus infection－associated HCC group， the NBNC－HCC group had a significantly higher proportion of patients with diabetes （28.0% vs 10.3%， χ2=129.482， P<0.001） or hypertension （33.2% vs 15.2%， χ2=105.079， P<0.001）， a significantly lower proportion of patients with liver cirrhosis （44.5% vs 68.4%， χ2=122.563， P<0.001） or vascular invasion （20.4% vs 29.6%， χ2=7.749， P=0.005）， and a significantly higher body mass index （BMI） （Z=－4.015， P<0.001）. Compared with the ALD－HCC group， the metabolic disorder HCC group had a significantly higher BMI， a significantly lower FIB－4 index， and a significantly lower proportion of patients with liver cirrhosis （all P<0.05）. ConclusionThere is a tendency of increase in the proportion of patients with NBNC－HCC in HCC， and NBNC－HCC often coexists with metabolic risk factors such as obesity， diabetes， and hypertension. Patients in the metabolic disorder HCC group may develop liver cancer in the absence of liver cirrhosis or in the early stage of liver fibrosis.

An excerpt of EASL clinical practice guidelines on the management of liver diseases in pregnancy （2023） / 临床肝胆病杂志

Recently， the European Association for the Study of the Liver organized the development of the clinical practice guidelines for the management of liver diseases in pregnancy， which include 105 recommendations for the clinical management of liver diseases in pregnancy. This article gives an excerpt of the main contents of the guidelines.

Chinese expert consensus on clinical management of hepatopathy－related thrombocytopenia / 临床肝胆病杂志

@#Hepatopathy－related thrombocytopenia refers to a decrease in platelet count caused by liver disease or its treatment， and the incidence rate of this disease is associated with the course and severity of liver disease. The direct effect of thrombocytopenia on the clinical outcome of patients with liver disease is an increased risk of bleeding， and its indirect effect involves delay or discontinuation of treatment due to the potential risk of bleeding. The pathophysiological mechanisms of hepatopathy－related thrombocytopenia involve reduced platelet production， abnormal platelet distribution， and increased destruction or consumption. Current treatment strategies aiming at different mechanisms include thrombopoietic agents， surgery， immunosuppressants， and platelet transfusion， but their clinical application needs further standardization. In order to improve the clinical management of hepatopathy－related thrombocytopenia in China in terms of diagnosis， typing， and rational selection of treatment regimens， National Clinical Research Center for Infectious Diseases organized experts to discuss and develop these consensus statements with reference to the latest evidence of evidence－based medicine in this field.

Research advances in animal models of cholestatic liver disease / 临床肝胆病杂志

Cholestatic liver diseases (CLD) are a series of diseases due to impaired bile flow and accumulation of bile acid in the liver and/or systemic circulation caused by immune, genetic, and environmental factors. The pathogenesis of CLD remains unclear and CLD is difficult to treat. As a substitute for human diseases, animal models can provide a platform for exploring the etiology and pathogenesis of the disease and finding appropriate therapeutic targets. This article reviews the current research advances in the animal models of CLD.

Role and potential significance of peroxisome proliferator-activated receptors in liver diseases / 临床肝胆病杂志

Peroxisome proliferator-activated receptors (PPAR) are members of the nuclear estrogen receptor family, and they are involved in a variety of physiological and pathological processes in the human body and play important roles in cellular metabolism, inflammation, and cancer. At present, there are three known subtypes of PPAR, i.e., α, β/δ, and γ. Studies have shown that PPARs are highly expressed in the liver and are widely involved in various physiological and pathological activities such as liver energy metabolism, oxidative stress, and inflammation, and they are also closely associated with the progression of liver diseases. This article reviews the role of PPAR in common liver diseases such as viral hepatitis, metabolic associated fatty liver disease, cholestatic liver disease, liver fibrosis, and primary liver cancer, and the current status of their application in the treatment of liver diseases.

Role of the nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling pathway in alcoholic liver disease / 临床肝胆病杂志

The incidence rate of alcoholic liver disease (ALD) is increasing year by year China, and there is a gradual increase in disease burden among Chinese people. Oxidative stress response in hepatocytes is an important pathogenic mechanism of ALD. The nuclear factor erythroid 2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is an important endogenous anti-oxidative stress pathway in the body, and Nrf2 is activated in response to oxidative stress and exerts its transcriptional activity to induce high HO-1 expression. HO-1 is an important oxidative stress response protein and plays a role in anti-inflammation, anti- oxidation, and cell apoptosis regulation together with heme hydrolysis products (bilirubin, carbon monoxide, and iron). This article reviews the research advances in the role of the Nrf2/HO-1 signaling pathway in ALD in recent years, so as to find a theoretical basis for the development and progression of ALD and an entry point for treatment.

Effectiveness of increasing alcohol excise taxes in the management of alcohol-associated liver disease in China / 临床肝胆病杂志

Increasing alcohol excise taxes has been confirmed by the World Health Organization as the most cost-effective public policy for reducing alcohol consumption at the population level. In recent years, studies in foreign countries have believed that increasing alcohol excise taxes can improve the burden of alcohol-associated liver disease (ALD), but it is still unclear whether this policy is applicable to ALD management in China. Therefore, with reference to related research evidence in China and globally, this article analyzes the key factors influencing the effectiveness of the policy of increasing alcohol excise taxes from the perspective of ALD management in China, including tax shifting, price elasticity of demand, and unrecorded alcohol, and introduces other public policies that help curb ALD. We think that increasing alcohol excise taxes is currently a useful but not effective policy for improving the burden of ALD in China.