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.

Mechanism of action of macrophage efferocytosis in acute and chronic liver diseases and related targeted therapy / 临床肝胆病杂志

Efferocytosis refers to the process by which apoptotic cells are engulfed and cleared by phagocytes， including professional phagocytes， such as macrophages and dendritic cells， and non-professional phagocytes， such as epithelial cells. Liver macrophages are the main cells with the function of efferocytosis in the liver. In recent years， an increasing number of studies have shown that various acute and chronic liver diseases are associated with the efferocytosis function of liver macrophages， including acute liver injury， alcoholic liver disease， nonalcoholic fatty liver disease， autoimmune liver disease， liver fibrosis， and liver cancer. This article elaborates on the expression of molecules associated with the efferocytosis function of macrophages， the process of efferocytosis， and the role of efferocytosis function in different liver diseases， so as to provide new ideas for the treatment of liver diseases.

Application and development of endoscopic techniques in the diagnosis and treatment of liver diseases / 临床肝胆病杂志

Liver disease is one of the most important health problems around the world， and early diagnosis and timely intervention and treatment are the key to preventing liver-related morbidity and mortality rates. The development of endoscopic techniques has provided new diagnostic and intervention methods for liver diseases. This article reviews the application and development of endoscopic techniques in liver diseases from the following aspects： the technical advances and advantages of endoscopic ultrasound-guided liver biopsy； the application and development of endoscopic techniques in the treatment of portal hypertension caused by liver abscess/hepatic cyst and liver diseases， as well as interventional techniques in the treatment of liver tumors； the efficacy and prospects of the endoscopic techniques for weight loss， which are relatively new in China， in the treatment of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Endoscopic techniques may hold promise for wide clinical application and exploration in in liver-related diseases in China， so as to provide more options for patients and doctors.

Research advances in neutrophil extracellular traps and liver diseases / 临床肝胆病杂志

Neutrophils play an immune defense role by releasing the proteases such as neutrophil elastase and myeloperoxidase to form neutrophil extracellular trap （NET） and participate in the inflammatory response of various liver diseases， but the excessive release of NET may worsen liver tissue damage and has thus become one of the risk factors for liver diseases. In recent years， studies have shown that the excessive release of NET can promote the progression of liver diseases （such as viral hepatitis， nonalcoholic steatohepatitis， and hepatic ischemia-reperfusion injury） to liver cancer， and clarifying the mechanism of action of NET is of great importance for the diagnosis and progression of liver diseases. Therefore， this article elaborates on the latest research advances in NET in liver diseases， so as to provide new insights into the diagnosis and treatment of liver diseases and the prevention of liver cancer.

Role of mitophagy in the development and progression of liver-related diseases / 临床肝胆病杂志

Mitophagy is a type of selective autophagy during which cells specifically remove damaged mitochondria in response to nutrient deficiency or external stimulation and thus maintain the integrity of mitochondrial function and cellular homeostasis. In recent years， a large number of studies have shown that dysfunction of mitophagy is closely associated with the development and progression of various liver-related diseases such as nonalcoholic fatty liver disease， drug-related liver injury， viral hepatitis， and hepatocellular carcinoma. This article summarizes the specific mechanisms of mitophagy in regulating liver-related diseases and further elaborates on the potential therapeutic targets of mitophagy in liver-related diseases， in order to provide more effective therapeutic strategies for the clinical treatment of liver diseases.

Clinical significance of benign liver function abnormality / 临床肝胆病杂志

Biochemical liver function tests are important methods to determine liver function in clinical practice， but abnormal liver biochemical parameters are not completely equivalent to liver damage. Some genetic and immune factors can also cause abnormal liver biochemical parameters， but with good prognosis in most cases. This article summarizes the causes of some benign abnormal liver biochemical parameters， so as to help clinicians to broaden their thinking of diagnosis and treatment， take into account genetic and immune factors， and avoid misdiagnosis and mistreatment.

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.

Adenoma Hepatocelular: a propósito de un caso / Hepatocellular adenoma: about a case / Adenoma hepatocelular: sobre um 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.

Liver retransplantation: prognostic scores and results in the state of paraná / Retransplante de fígado: escores prognósticos e resultados no estado do paraná

ABSTRACT BACKGROUND: Hepatic retransplantation is associated with higher morbidity and mortality when compared to primary transplantation. Given the scarcity of organs and the need for efficient allocation, evaluating parameters that can predict post-retransplant survival is crucial. AIMS: This study aimed to analyze prognostic scores and outcomes of hepatic retransplantation. METHODS: Data on primary transplants and retransplants carried out in the state of Paraná in 2019 and 2020 were analyzed. The two groups were compared based on 30-day survival and the main prognostic scores of the donor and recipient, namely Model for End-Stage Liver Disease (MELD), MELD-albumin (MELD-a), Donor MELD (D-MELD), Survival Outcomes Following Liver Transplantation (SOFT), Preallocation Score to Predict Survival Outcomes Following Liver Transplantation (P-SOFT), and Balance of Risk (BAR). RESULTS: A total of 425 primary transplants and 30 retransplants were included in the study. The main etiology of hepatopathy in primary transplantation was ethylism (n=140; 31.0%), and the main reasons for retransplantation were primary graft dysfunction (n=10; 33.3%) and hepatic artery thrombosis (n=8; 26.2%). The 30-day survival rate was higher in primary transplants than in retransplants (80.5% vs. 36.7%, p=0.001). Prognostic scores were higher in retransplants than in primary transplants: MELD 30.6 vs. 20.7 (p=0.001); MELD-a 31.5 vs. 23.5 (p=0.001); D-MELD 1234.4 vs. 834.0 (p=0.034); SOFT 22.3 vs. 8.2 (p=0.001); P-SOFT 22.2 vs. 7.8 (p=0.001); and BAR 15.6 vs. 8.3 (p=0.001). No difference was found in terms of Donor Risk Index (DRI). CONCLUSIONS: Retransplants exhibited lower survival rates at 30 days, as predicted by prognostic scores, but unrelated to the donor's condition.

RESUMO RACIONAL: O retransplante hepático está associado a maior morbimortalidade do que o transplante primário. Dada a escassez de órgãos e a necessidade de alocação eficiente, avaliar parâmetros que possam prever a sobrevida pós-retransmissão é crucial. OBJETIVOS: Analisar os resultados dos retransplantes hepáticos em relação aos principais escores prognósticos. MÉTODOS: Foram analisados os transplantes primários e os retransplantes realizados no Estado do Paraná nos anos de 2019 e 2020. Os dois grupos foram comparados em relação à sobrevida em 30 dias e aos principais escores prognósticos do doador e do receptor: Model for End-Stage Liver Disease (MELD), MELD-albumin (MELD-a), Donor MELD (D-MELD), Survival Outcomes Following Liver Transplantation (SOFT), Preallocation Score to Predict Survival Outcomes Following Liver Transplantation (P-SOFT) e Balance of Risk (BAR). RESULTADOS: Foram incluídos 425 transplantes primários e 30 retransplantes. A principal etiologia da hepatopatia no transplante primário dos pacientes retransplantados foi o etilismo (n=140; 31,0%), e os principais motivos para os retransplantes foram o não funcionamento primário do enxerto (n=10; 33,3%) e a trombose da artéria hepática (n=8; 26,2%). A sobrevida em 30 dias foi maior nos transplantes primários em relação aos retransplantes (80,5% vs 36,7%; p=0,001). Os escores prognósticos foram mais elevados nos retransplantes em relação aos transplantes primários: MELD 30,6 vs 20,7 (p=0,001); MELD-a 31,5 vs 23,5 (p=0,001); D-MELD 1234,4 vs 834,0 (p=0,034); SOFT 22,3 vs 8,2 (p=0,001); P-SOFT 22,2 vs 7,8 (p=0,001); e BAR 15,6 vs 8,3 (p=0,001). Não foi observada diferença em relação ao Índice de Risco do Doador. CONCLUSÕES: Os retransplantes apresentam menor sobrevida em 30 dias, prevista nos escores prognósticos, porém sem relação com a qualidade dos doadores.

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.

Mechanism of action of Dange Jiecheng decoction in a rat model of alcoholic liver disease based on the Kelch-like ECH-associated protein 1/nuclear factor erythroid 2-related factor 2 signaling pathway / 临床肝胆病杂志

Objective To investigate the therapeutic effect of Dange Jiecheng decoction on a rat model of alcoholic liver disease (ALD) and the anti-oxidative stress mechanism of Dange Jiecheng decoction. Methods A total of 96 Sprague-Dawley rats were randomly divided into blank group with 13 rats and ALD group with 83 rats, and the rats in the ALD group were given liquor by gavage to establish a model of ALD. Then the ALD group was randomly divided into model group, high-dose Dange Jiecheng decoction group (24 g/kg), low-dose Dange Jiecheng decoction group (6 g/kg), and Yiganling tablet group (21 mg/kg), with 17 rats in each group. The rats in the blank group and the model group were given normal saline by gavage, and those in the other groups were given corresponding drugs by gavage, for 4 consecutive weeks. HE staining was used to observe the pathological changes of liver tissue; Western blot was used to measure the contents of Kelch-like ECH-associated protein 1 (Keap1), nuclear factor erythroid 2-related factor 2 (Nrf2), and heme oxygenase-1 (HO-1) in liver tissue; quantitative real-time PCR was used to measure the mRNA expression levels of Keap1 and HO-1 in liver tissue. 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. Results Compared with the blank group, the model group had disordered arrangement of hepatocytes with necrosis, massive inflammatory cell infiltration, and a large number of lipid droplet vacuoles, significant increases in the protein and mRNA expression levels of Keap1 ( P < 0.05), and significant reductions in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Compared with the model group, the high- and low-dose Dange Jiecheng decoction groups and the Yiganling tablet group had ordered arrangement of hepatocytes, reductions in hepatocyte necrosis and inflammatory cells, and occasional lipid droplet vacuoles, as well as significant reductions in the protein and mRNA expression levels of Keap1 ( P < 0.05) and significant increases in the protein expression levels of Nrf2 and HO-1 and the mRNA expression level of HO-1 ( P < 0.05). Conclusion By regulating the Keap1/Nrf2 signaling pathway, Dange Jiecheng decoction can promote the nuclear import of Nrf2, upregulate the expression of HO-1, and alleviate oxidative stress response, thereby exerting a protective effect on ALD rats.

Etiological spectrum and clinical features of patients with unexplained liver disease manifesting as isolated jaundice: An analysis of 91 cases / 临床肝胆病杂志

Objective To investigate the etiological and clinical features of patients with unexplained liver disease manifesting as isolated jaundice and the value of whole-exome sequencing in the diagnosis of such diseases. Methods A retrospective analysis was performed for the clinical data of the patients who attended Nanjing Second Hospital due to unexplained liver disease and underwent whole-exome sequencing from February 2017 to December 2021, and according to liver function parameters and imaging data, all cases were classified based on clinical phenotype and were diagnosed based on the whole-exome sequencing report. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between two groups, and the Kruskal-Wallis H test was used for comparison between multiple groups. Results A total of 519 patients underwent whole-exome sequencing, among whom 102 patients with missing or incomplete clinical data were excluded, and finally 417 patients were included in analysis, among whom 91(91/417, 21.82%) had the manifestation of isolated jaundice. The etiology of jaundice was not determined by whole-exome sequencing in 8 patients (8/91, 8.79%). With reference to genetic testing results, 83 patients (83/91, 91.21%) had a confirmed diagnosis, among whom there were 68 patients with hereditary hyperbilirubinemia (68/91, 74.72%), 3 patients with hereditary spherocytosis (3/91, 3.30%), 2 patients with pyruvate kinase deficiency (2/91, 2.20%), and 10 patients with UGT1A1 gene disease combined with other diseases (10/91, 10.99%). Hereditary hyperbilirubinemia was the main etiology, and there were 61 patients with UGT1A1 gene disease (61/91, 67.03%), 5 patients with Dubin-Johnson syndrome (5/91, 5.49%) and 2 patients with Rotor syndrome (2/91, 2.20%). There was a significant difference in indirect bilirubin/total bilirubin ratio between the patients with the different diagnoses above ( H =22.835, P < 0.05), and the patients with UGT1A1 gene disease and other diseases had a significantly higher level of total bilirubin than those with UGT1A1 gene disease alone [95.8 (37.5-187.1) μmol/L vs 51.4 (34.8-267.1) μmol/L, Z =-2.372, P =0.018]. Conclusion Whole-exome sequencing can help with the diagnosis of most cases of unexplained liver disease manifesting as isolated jaundice. Hereditary hyperbilirubinemia is the main etiology, and UGT1A1 gene disease is the most common disease. Whole-exome sequencing can assist the clinical diagnosis of unexplained liver disease manifesting as isolated jaundice.

Application and prospect of cell therapy in clinical treatment of liver diseases / 临床肝胆病杂志

Cell therapy is an emerging therapy different from traditional drug therapy, among which immune cells and mesenchymal stem cells are the two types of most promising cells in the treatment of liver diseases at present, and preliminary results have been achieved for their therapeutic effects. This article summarizes the advances in cell therapy in the field of liver diseases, analyzes the challenges and coping strategies of different cell therapies, and discusses the application prospects of cell therapy in liver-related diseases.

Role of A-kinase anchor protein 12 in chronic liver diseases / 临床肝胆病杂志

A-kinase anchor protein 12 (AKAP12) is a scaffold protein that improves the specificity and efficiency of spatio-temporal signals by assembling intracellular signal proteins into specific complexes. In recent years, the role of AKAP12 in chronic liver diseases has attracted more and more attention. This article introduces the physiological functions of AKAP12 and reviews the role of AKAP12 in chronic liver diseases, in order to lay a foundation for the use of AKAP12 small molecule as a new therapeutic target for chronic liver diseases.

Trends in nano-antimicrobial therapy for severe liver disease with infection / 临床肝胆病杂志

Severe liver disease with infection has always been a key and difficult point in clinical treatment. Through continuous exploration of nanomaterials, researchers have found that nanomaterials can achieve targeted antibacterial and immunomodulatory effects due to their special physicochemical properties. With reference to recent articles and advances, this article reviews the possible mechanisms of nano-therapies for severe liver disease with infection from the aspects of targeted antibacterial effect of nanomaterials without antibiotics, targeted antibacterial effect of nano-drug delivery systems, and targeted immunomodulatory therapy, so as to provide new treatment strategies for the prevention and treatment of severe liver disease with infection in clinical practice.

Role of gasdermin D in the pathological progression of liver diseases / 临床肝胆病杂志

As a novel star molecule, gasdermin D (GSDMD) plays an important role in the amplification of immune inflammatory response and the process of pyroptosis. After being cleaved and activated by caspase-1, the N-terminal of GSDMD is rapidly released, which anchors on the cell membrane and forms pores, thereby leading to pyroptosis, accompanied by the release of a large amount of the strong proinflammatory factors IL-1β and IL-18. Acute/chronic liver inflammatory response and cell death are the common pathological features of liver diseases such as viral hepatitis, alcoholic liver disease, nonalcoholic fatty liver disease, autoimmune liver disease, liver failure, and hepatocellular carcinoma. This article summarizes the basic structural characteristics of GSDMD and elaborates on its important role in the pathological progression of various liver diseases. In addition, it is proposed that prevention and treatment strategies with GSDMD as a potential therapeutic target can provide new ideas for further studies on the clinical prevention and treatment of liver diseases.