Mesenchymal stem cells （MSCs） have emerged as a promising cellular therapy for end-stage liver disease （ESLD） due to their robust self-regenerative， paracrine， and immunomodulatory characteristics， providing new directions for the treatment of advanced liver disease. However， the clinical application of MSCs is significantly limited by the fact that only a small number of MSCs can reach the liver due to massive apoptosis or necrosis during the homing process caused by the influence of the complex microenvironment （inflammation， oxidative stress， and hypoxia） of the injured liver and the fact that a substantial proportion of MSCs become trapped in the pulmonary capillaries following intravenous administration with a lack of sufficient homing receptors or adhesion molecules. Various strategies have been developed to optimize the proliferation， migration， and homing abilities of MSCs， including preconditioning， gene modification， and nanoencapsulation technology. This article elaborates on the influencing factors for the homing ability of MSCs， the strategies to optimize their homing in ESLD， and the mechanism of the homing of MSCs， in order to improve cell transplantation efficiency， promote liver repair and regeneration， and pave the way for the application of MSCs in the treatment of ESLD.

OBJECTIVE:To evaluate the efficacy of exosomes derived from mesenchymal stem cells on animal models of acute liver failure. METHODS:PubMed,Web of Science,Embase,The Cochrane Library,CBM,CNKI,WanFang,and VIP databases were retrieved from inception to January 16,2023.A series of animal experiments on the treatment of acute liver failure animal models by exosomes derived from mesenchymal stem cells were collected.Two evaluators screened the literature and extracted the data independently.The bias risk was evaluated by the SYRCLE tool.The extracted data were analyzed by Revmen 5.4.1 software and Stata 17.0 software. RESULTS:A total of 241 articles were retrieved and 9 animal experiments were included,with 219 animals:110 animals in the model group and 109 animals in the exosome group.The results showed that the survival rate of animals in the exosome group improved significantly[RR=9.34,95%CI(3.91,22.29),P<0.001],the levels of serum alanine transaminase[SMD=-5.31,95%CI(-7.43,-3.19),P<0.001]and aspartate aminotransferase[SMD=-4.47,95%CI(-5.85,-3.10),P<0.001]were reduced obviously.The expressions of interleukin-1β[SMD=-11.54,95%CI(-18.12,-4.95),P=0.000 6],interleukin-6[SMD=-5.75,95%CI(-8.08,-3.41),P<0.001]and tumor necrosis factor-α[SMD=-4.46,95%CI(-6.83,-2.09),P=0.000 2],were suppressed obviously. CONCLUSION:Exosomes derived from mesenchymal stem cells effectively inhibit the inflammatory response,ameliorate liver function of animals with acute liver failure,and improve their survival rate.The results of subgroup analysis showed that the shorter survival time of animals(≤24 hours),the lower dose of transplanted exosomes(<1 mg/kg)and the source of exosomes(adipose-derived mesenchymal stem cells)may affect the efficacy of the exosomes derived from mesenchymal stem cells in the animal model of acute liver failure.This conclusion and its clinical transformation still need to be confirmed by randomized controlled studies with large sample sizes and high quality.

The prognosis of patients with hepatitis C virus infection depends not only on liver lesions， but also on extrahepatic sequelae. Direct-acting antiviral agents （DAAs）， as the first-line drugs in the treatment of hepatitis C， have helped more and more patients achieve sustained virologic response and clinical cure， but its effect on the prognosis of extrahepatic diseases remains unclear. This article reviews the effect of DAAs treatment on the prognosis of extrahepatic diseases in patients with hepatitis C and points out that long-term follow-up monitoring is still required for patients with hepatitis C after cure.

The occurrence rate of primary liver cancer in malignant tumors ranks sixth in the world, and the mortality rate ranks third, with a poor prognosis and a five-year survival rate of less than 5%. Most patients with liver cancer in China are found to be in the intermediate and advanced stages, and a targeted immunotherapy combination has become the main treatment option. However, many patients have underlying liver lesions, and their liver function cannot meet the requirements of targeted immunotherapy, which directly affects the treatment of liver cancer patients. Therefore, it is very important to optimize the patient's liver function in a timely manner so as to obtain the opportunity for anti-tumor therapy. This article reviews the current status and response strategies before liver injury related to targeted immune therapy in patients with primary liver cancer.

Objective:To explore the safety of inactivated novel coronavirus vaccine inoculation and the fluctuating neutralizing antibody in patients with chronic hepatitis B (CHB).Methods:Retrospective and prospective epidemiological research methods were employed. 153 CHB patients who visited the Department of Infectious Diseases at the First Hospital of Shanxi Medical University from September 2021 to February 2022 were selected as the research subjects. Information on vaccination-related adverse reactions was collected. Colloidal gold immunochromatography was used to identify neutralizing antibodies in the body after 3-6 months of vaccination. Statistical analysis was performed using the χ2-test or Fisher's exact test. Results:The positive rates of neutralizing antibodies after inactivated novel coronavirus vaccine inoculation in 153 patients with CHB were 45.50%, 44.70%, 40.00% and 16.20%, respectively, at 3, 4, 5, and 6 months. The neutralizing antibody concentrations were 10.00 (2.95, 30.01) U/ml, 6.08 (3.41, 24.50) U/ml, 5.90 (3.93, 14.68) U/ml, and 1.25 (0.92, 3.75) U/ml, respectively. The difference was not statistically significant ( P>0.05) when the neutralizing antibody positivity rates in hepatitis B virus (HBV) DNA-negative and positive patients and HBeAg-negative and positive patients at different time points were compared. The overall incidence of adverse reactions following vaccination was 18.30%. Pain at the site of inoculation and fatigue were the main presentations, and no serious adverse reactions occurred. Conclusion:CHB patients, when inoculated with an inactivated novel coronavirus vaccine, can produce neutralizing antibodies, which can stay at certain levels for 3, 4, and 5 months. However, the neutralizing antibody level gradually decreases over time, and the decrease is remarkable at 6 months. So, it is recommended to boost vaccinations at an appropriate time. Additionally, the results of the study suggest that HBV replication status has little effect on the production of neutralizing antibodies in CHB patients with relatively stable liver function, which means the inactivated novel coronavirus vaccine has a good safety profile.

Objective:To explore the epidemic characteristics, clinical features and therapeutic effects of Kala-azar in Yangquan City, Shanxi Province in recent years, and to improve the cognition of Kala-azar.Methods:The clinical data of 17 adult cases of Kala-azar in Yangquan City, Shanxi Province in 2018 and 2019 were collected by retrospective analysis method, the epidemiological characteristics, clinical diagnosis and first diagnosis, clinical manifestations, laboratory and imaging examination, treatment and prognosis of the patients were sorted and analyzed.Results:All 17 patients were from Yangquan City, Shanxi Province, including 15 males and 2 females. The main clinical manifestations were long-term irregular fever (17 cases), anemia (13 cases) and splenomegaly (16 cases). The main manifestations of blood routine included decreased white blood cell count (14 cases), anemia (13 cases), and decreased platelet count (10 cases). The positive rate of rk39 immunochromatographic strip test was 100.00% (14/14). Nine patients underwent bone marrow puncture smear examination, 7 patients were positive for Leishman-Donovan bodies. All patients were treated with sodium pentavalent antimony gluconate (hereinafter referred to as antimonials) for 10 days, the cure rate was 88.24% (15/17), and recurrence rate was 11.76% (2/17).Conclusions:The clinical manifestations of Kala-azar are not typical, and it is easy to be misdiagnosed. Early examination of bone marrow puncture smear and serum antibody should be carried out for suspected patients. Antimonials is still a safe and effective drug for treating Kala-azar.

Fungal infection complicated in patients with severe liver disease is not only an important predisposing factor bringing liver failure in patients, but also one of the important causes for the aggravation of the disease and even death. However, its clinical manifestations are not specific, and thereby easily leading to be undiagnosed. Therefore, early screening, and standardized treatment are very important to improve the prognosis.

Chronic hepatitis B (CHB) is a serious disease threatening the health and even life of people, at present antiviral therapy is the key approach to alter the disease outcome.The treatment objectives are to maximize the long-term inhibition of viral replication ; to reduce the inflammatory necrosis of hepatocytes and hepatic fibrosis ; to decompensate the cirrhosis ; to avoid the occurrence of liver failure , hepatocellular carcinoma and other complications ; thereby to improve the quality of life and prolong the survival of patients.The clinical cure should be pursued as far as possible ; however, most of CHB patients can not meet the standard of drug withdrawal and achieve clinical cure.This article reviews the current hot spots and difficult issues in the treatment of CHB.

Objective To evaluate the efficacy of precision therapy with direct-acting antiviral drugs (DAAs) for patients with chronic HCV gene type 1b infection.Methods One hundred and thirteen patients with chronic HCV genotype 1b infection admitted in the Department of Infectious Diseases of First Hospital of Shanxi Medical University from January 2018 to July 2019 were enrolled,including 89 patients with chronic hepatitis and 24 patients with cirrhosis.Different DAAs therapeutic schedule were taken based on liver function, kidney function, complication and treatment costs.Seventy-two patients were treated with pan-genotype drugs, including 43 patients treated with Sofosbuvir and Velpatasvir (SOF+VEL), 13 treated with Sofosbuvir and Ribavirin ( SOF +RBV), and 16 treated with Sofosbuvir and Daclatasvir ( SOF +DCV).Forty one patients were treated with specific genotype DAAs , including 15 treated with Ombitasvir and Dasabuvir (OBV+DSV), and 26 treated with Elbasvir and Grazoprevir tablets (EBR+GZR).Pair t test and Chi-square test were used to compare virological response rate , the liver function and the adverse reactions were observed.Results The super-rapid virological response (SRVR) rate with DAAs treatment at 1 week was 88.5%(100／113),and the rapid virological response ( RVR) at 4 weeks of treatment was 98.2%(111／113).There was no significant differences in SRVR and RVR among the patients treated with five treatment regimens (χ2 ＝5.95 and 1.04,P＞0.05), all the patients obtained complete early virological response (CEVR) at 12 weeks and sustained virological response ( SVR12) at 12 weeks after treatment. Besides, there were no significant differences in SRVR and RVR between pan-genotype and gene-specific drugs (χ2 ＝0.03 and 0.17, P＞0.05),both CEVR and SVR12 reached 100% in all patients.The liver transaminase levels were improved in patients undergoing pan-genotype or gene-specific drugs treatment. Mild adverse reactions were observed in 5 cases, hemolysis occurred in 1 patient and it was cured after replacement of drugs.Conclusion Both pan-genotype and specific genotypes of DAAs can achieve high virological response rates.Genotypic testing should be performed before antiviral therapy , in order to accurately select treatment options and to save costs.

Intrahepatic cholangiocarcinoma is an uncommon malignant tumor,and its incidence has been increasing in the recent 30 years. Since patients have no specific clinical manifestations in early stage,the diagnosis of this disease is often very difficult,with a low rate of radical resection in late stage and poor prognosis.Therefore,as for patients with intrahepatic cholangiocarcinoma,early screening and diag-nosis is of vital importance.Imaging examination is an important method for the diagnosis of intrahepatic cholangiocarcinoma,and when com-bined with laboratory markers and pathological examination,it can increase diagnostic rate and reduce the rate of missed diagnosis.It is im-portant in clinical practice to select reasonable methods based on the patient′s actual condition.