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ObjectiveTo investigate the differences in abnormal liver biochemical parameters in pregnant patients during the epidemic or non-epidemic period of coronavirus disease 2019 (COVID-19). MethodsA retrospective analysis was performed for 539 pregnant women who were discharged from Department of Obstetrics, Peking University First Hospital, from October 2017 to March 2022 and had at least one abnormal liver biochemical parameter among alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma-glutamyl transpeptidase (GGT), total bilirubin (TBil), and total bile acid. The patients in the epidemic period of COVID-19 and those in the non-epidemic period of COVID-19 were compared in terms of etiology, coagulation parameters, aminotransferases, bile acid, and renal function. The independent samples t-test was used for comparison of continuous data between two groups, and the chi-square test was used for comparison of categorical data between two groups. ResultsAmong the patients discharged from Department of Obstetrics during the non-epidemic period of COVID-19, 262 had abnormal liver biochemical parameters, accounting for 1.46%, while 277 patients had abnormal liver biochemical parameters during the epidemic period of COVID-19, accounting for 1.73% among the patients discharged from Department of Obstetrics during the same period of time, and there was a significant difference between these two groups (χ2=3.947, P=0.047). The etiological analysis of the patients with abnormal liver biochemical parameters during the two periods showed that there was no difference in the proportion of patients with four pregnancy-specific liver diseases (hyperemesis gravidarum, preeclampsia and eclampsia, intrahepatic cholestasis of pregnancy, and acute fatty liver of pregnancy). As for the patients with abnormal liver biochemical parameters in pregnancy, there was no significant difference in the proportion of patients with normal creatinine and stimated glomerular filtration rate (eGFR) between the epidemic period and the non-epidemic period (86.78% vs 87.90%, χ2=0.141, P=0.708). The patients with ALT≥5×upper limit of normal accounted for 7.94% in the epidemic period of COVID-19 and 9.54% in the non-epidemic period (χ2=0.433, P=0.511), and the patients with severe cholestasis accounted for 7.75% in the epidemic period of COVID-19 and 9.27% in the non-epidemic period (χ2=0.392, P=0.531). The proportion of patients with obstetric bleeding during the epidemic period of COVID-19 was significantly lower than that during the non-epidemic period (14.61% vs 24.19%, χ2=489.334, P<0.001). ConclusionThere is no difference in the proportion of patients with pregnancy-specific liver diseases among the patients with abnormal liver biochemical parameters in pregnancy between the epidemic period and the non-epidemic period of COVID-19, and there is no change in the proportion of patients with normal creatinine and eGFR among these patients in the epidemic period of COVID-19.
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Objective To investigate the serum levels of soluble programmed death-1 (sPD-1) and soluble programmed death-ligand 1 (sPD-L1) in chronic hepatitis B (CHB) patients with clinical cure, the correlation between programmed death-1 (PD-1) and lymphocytes by flow cytometry, and the recovery of hepatitis B virus (HBV)-specific immunity. Methods A total of 26 CHB patients with clinical cure, 26 treatment-naïve CHB patients, and 26 healthy controls who were diagnosed at the outpatient service of Peking University First Hospital from January to May of 2022 were enrolled, and related clinical data and peripheral blood samples were collected. ELISA was used to measure the serum levels of sPD-1 and sPD-L1, and flow cytometry was used to measure the expression of PD-1 in peripheral blood lymphocytes. CHB patients with clinical cure were compared with the treatment-naïve CHB patients and the healthy controls. The Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between three groups, and the chi-square test was used for comparison of categorical data between groups. The Pearson correlation analysis or the Spearman correlation analysis was used to investigate the correlation between two continuous variables. Results For the 26 CHB patients with clinical cure, the mean time of antiviral therapy was 8.33 years, with entecavir as the antiviral drug. The CHB patients with clinical cure had significantly higher levels of sPD-1 and sPD-L1 than the healthy controls ( P 0.05). Conclusion The serum levels of sPD-1 and sPD-L1 in treatment-naïve CHB patients are mainly associated with exhausted CD8 + T cells in peripheral blood, while there is no significant correlation between serum sPD-1/sPD-L1 and exhausted CD8 + T cells in peripheral blood in CHB patients with clinical cure.
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Combined immunotherapy for hepatocellular carcinoma (HCC) based on immune checkpoint inhibitors (ICIs), especially programmed death receptor-1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors, has achieved a remarkable clinical effect in clinical research and practice. Hepatitis B virus (HBV) infection is considered a major risk factor in the process of HCC. Studies are being conducted to investigate the efficacy and safety of PD-1/PD-L1 ICIs used alone or in combination in the treatment of patients with HBV-associated HCC, and some studies have shown that the patients with HBV-associated HCC receiving PD-1/PD-L1 inhibitors have achieved a similar treatment outcome to those without HBV infection; however, no consensus has been reached on the safety issues related to HBV activation. This article reviews the clinical trials of PD-1/PD-L1 blockade immunotherapy for HCC, so as to clarify the safety and efficacy of this new treatment regimen in the particular circumstances of HBV infection.
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Objective To investigate the impact of the change in anti-hepatitis B virus (HBV) therapy indication on treatment rate and the features of the population requiring treatment. Methods The treatment-naïve patients with chronic hepatitis B (CHB) in the China Registry of Hepatitis B (CR-HepB) database were selected as subjects, and related demographic, virological, hematological, and biochemical data were collected. 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; the chi-square test or the Fisher's exact test was used for comparison of categorical data between groups. Results A total of 3640 treatment-naïve CHB patients were included in this study, among whom 64.4% were male, 68.7% had an age of 30-59 years, and 46.8% had an indeterminate clinical stage. According to the 2015 and 2019 editions of Guidelines for the prevention and treatment of chronic hepatitis B and the 2022 edition of expert consensus, the number of patients who had the indication for antiviral therapy was 625(17.2%), 1333(36.6%), and 2890(79.4%), respectively. The number of patients requiring treatment was increased by 1557 according to the 2022 edition of expert consensus, among whom 1424(91.5%) met the treatment threshold of alanine aminotransferase (ALT) > 30 U/L for male patients or ALT > 19 U/L for female patients. The additional patients requiring treatment according to the 2022 edition of expert consensus had significantly higher levels of ALT and HBV DNA and significantly lower scores of APRI and FIB-4 than the additional patients requiring treatment according to the 2019 edition of Guidelines (all P < 0.05). Conclusion The expansion of antiviral therapy indications for CHB may significantly increase the proportion of CHB patients receiving antiviral treatment and help mild CHB patients at the risk of disease progression to receive timely treatment and achieve the improvement in long-term prognosis.
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Objective To investigate the influencing factors for direct-acting antiviral agent (DAA) therapy failure in the treatment of hepatitis C by comparing baseline clinical data and resistance-associated substitution (RAS) in sequencing data between the patients with HCV RNA reactivation after DAA therapy and the patients with successful DAA treatment. Methods A total of 13 patients from multiple centers who failed DAA therapy from November 2019 to October 2021 were enrolled as treatment failure group, and sequencing was performed for their positive serum samples. A total of 51 patients with successful DAA treatment were enrolled as control group, and baseline clinical data and sequencing results were compared between the treatment failure group and the control group. The Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups, and the chi-square test was used for comparison of categorical data between groups; univariate and multivariate logistic regression analyses were performed to calculate odds ratio ( OR ) and investigate the influencing factors for treatment failure. Results All 12 patients with complete treatment data experienced recurrence within 1 year after the end of medication. The male patients with treatment failure had significantly higher baseline total bilirubin, direct bilirubin, and creatinine than their female counterparts ( Z =-2.517, -2.440, and -2.132, P =0.010, 0.010, and 0.038), and the patients with an age of ≤55 years ( OR =5.152, 95% confidence interval [ CI ]: 1.116-23.790, P =0.036) or genotype 3b ( OR =9.726, 95% CI : 1.325-71.398, P =0.025) had a higher probability of treatment failure. There were differences in the incidence rates of major RAS mutations on three gene fragments between the treatment failure group and the treatment success group, and the common RAS mutations detected in the treatment failure group were not detected in the treatment success group. Conclusion Age, genotype, and RAS in serum virus gene sequence are influencing factors for DAA treatment failure.
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ObjectiveTo investigate the virologic response to direct-acting antiviral (DAA) therapy and the changes in liver stiffness measurement (LSM), fibrosis-4 (FIB-4), and aspartate aminotransferase-to-platelet ratio index (APRI) after treatment in chronic hepatitis C (CHC) patients with different alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels at baseline in a real-world setting. MethodsCHC patients who attended the outpatient service of Department of Infectious Diseases, Peking University First Hospital, from December 2017 to May 2020 were enrolled, and virologic response rate was calculated. The Wilcoxon rank-sum test was used to compare LSM, FIB-4, and APRI between groups at baseline and at 12 weeks after treatment, and the chi-square test was used for comparison of categorical data between groups. ResultsA total of 48 CHC patients were enrolled, among whom 33.3% had abnormal ALT or AST at baseline. Among these patients, the virologic response rate was 85.4% at week 4 of treatment and 100% at the end of treatment and at 12, 24, and 48 weeks after treatment, and there were significant changes from baseline to 12 weeks after treatment in LSM [6.1 (51-12.4) kPa vs 8.6 (5.7-16.9) kPa, Z=-1.676, P=0.043] and APRI [0.24(0.19-0.48) vs 0.42(0.23-1.17), Z=-2.050, P=0027]. From baseline to 12 weeks after treatment, the patients with abnormal ALT or AST at baseline had significant changes in LSM [89(5.6-13.1) kPa vs 14.4(8.0-28.2) kPa, Z=-1.679, P=0.047] and APRI [0.44(0.25-0.50) vs 1.29(0.99-2.09), Z=-3.427, P=0.001]. ConclusionCHC patients achieve a high sustained virologic response rate after DAA therapy, and the patients with abnormal ALT or AST at baseline tend to have more significant improvements in LSM and APRI than those without such abnormality.
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Objective:To study the effects of resistant dextrin (RD) on liver fat deposition in high-fat diet-fed (HFD) mice, and to further explore whether it can regulate the AMPK signaling pathway.Methods:Thirty-six 4-week-old male C57BL/6 mice were randomly divided into three groups: normal control group (chow), high-fat diet group (HFD), and high-fat diet+ resistant dextrin group (HFD+ RD, 10 g·kg -1·d -1). After 12 weeks of intervention, the liver tissues and serum samples were collected. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine transaminase (ALT) levels and liver TG were measured. Liver tissue HE and oil red O staining were performed to observe hepatocyte steatosis and liver fat deposition. Quantitative real-time PCR was performed to detect the relative expression of fatty acid synthesis related genes SREBP1, ACC, SCD1 in the liver tissue, and Western blot was performed to detect relative protein levels of pAMPK, SREBP1, Fasn, and ACC in the liver. Results:Compared with chow group, the body weight gain, fasting blood glucose (FBG), serum TC, LDL-C, HDL-C, and ALT levels were increased in HFD group ( P<0.01), and serum AST level was also increased ( P<0.05). Moreover, liver oil red O staining revealed that liver fat deposition was much more obvious in HFD group than that in chow group, and liver TG was also increased in HFD group ( P<0.01). The mRNA levels of SREBP1 and ACC were increased in HFD group compared with that in chow group, and the protein level of pAMPK was reduced in HFD group ( P<0.05). As compared with HFD group, the body weight gain, serum TG, TC, LDL-C, HDL-C and ALT levels were significantly reduced in RD group ( P<0.01), and FBG level was also reduced ( P<0.05). Moreover, RD treatment alleviated liver fat deposition and TG accumulation ( P<0.01). The mRNA levels of SREBP1, ACC, and SCD1 were all reduced in RD group compared with HFD group. The protein level of pAMPK was increased, and the expression of Fasn was reduced with RD treatment ( P<0.01). Conclusion:Resistant dextrin improves liver fat deposition and activates the AMPK signaling pathway in HFD-fed mice.
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Objective:To investigate the mechanisms of effects of high fat and high fructose diet on rat aging.Methods:Adult male SD rats were divided into normal diet(ND) group and high fat and high fructose diet(HFHFD) group. After treatment for 48 weeks, these rats were sacrificed and the blood, liver, and brain tissues were collected. Serum triglyceride(TG), total cholesterol(TC), low density lipoprotein-cholesterol(LDL-C), high density lipoprotein-cholesterol(HDL-C) levels were determined by automatic biochemical analyzer. The serum levels of interluekin-2(IL-2), IL-6, and advanced glycation end products(AGEs) were measured using enzyme linked immunosorbent assay. The expressions of p16, p21, and p53 genes in the liver and brain tissues were detected by real-time quantitative PCR and western blot.Results:After 48 weeks treatment, there were significant differences in body weight and fasting plasma glucose between two groups. Serum TG, TC, and LDL-C in HFHFD group were significantly higher than those in the ND group( P<0.05), with an increase trend in HDL-C but without statistical difference. Compared with ND group, the level of IL-2 in HFHFD group was significantly decreased while the levels of IL-6 and AGEs were significantly increased(all P<0.05). The levels of p16 and p21 mRNA expressions as well as p53 and p21 protein expressions in liver and brain in HFHFD group were markedly increased compared with ND group(all P<0.05). Conclusion:Long-term high fat and high fructose diets accelerate the aging process of rats, which may be related to the damage of the immune system and the changes of cell senescence related gene expressions in liver and brain tissues.
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The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.
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The ability of prevention, treatment and management of infectious diseases is a basic requirement for general practitioners. This article introduces our experience in the infectious disease rotation for general practice residency training, focusing on the rotation management at different stages of training to explore how to improve teaching quality and the ability of trainers in a short period of the rotation.
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Objective@#To study the effects of resistant dextrin (RD) on liver fat deposition in high-fat diet-fed (HFD) mice, and to further explore whether it can regulate the AMPK signaling pathway.@*Methods@#Thirty-six 4-week-old male C57BL/6 mice were randomly divided into three groups: normal control group (chow), high-fat diet group (HFD), and high-fat diet+ resistant dextrin group (HFD+ RD, 10 g·kg-1·d-1). After 12 weeks of intervention, the liver tissues and serum samples were collected. Serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), aspartate aminotransferase (AST), alanine transaminase (ALT) levels and liver TG were measured. Liver tissue HE and oil red O staining were performed to observe hepatocyte steatosis and liver fat deposition. Quantitative real-time PCR was performed to detect the relative expression of fatty acid synthesis related genes SREBP1, ACC, SCD1 in the liver tissue, and Western blot was performed to detect relative protein levels of pAMPK, SREBP1, Fasn, and ACC in the liver.@*Results@#Compared with chow group, the body weight gain, fasting blood glucose (FBG), serum TC, LDL-C, HDL-C, and ALT levels were increased in HFD group (P<0.01), and serum AST level was also increased (P<0.05). Moreover, liver oil red O staining revealed that liver fat deposition was much more obvious in HFD group than that in chow group, and liver TG was also increased in HFD group (P<0.01). The mRNA levels of SREBP1 and ACC were increased in HFD group compared with that in chow group, and the protein level of pAMPK was reduced in HFD group (P<0.05). As compared with HFD group, the body weight gain, serum TG, TC, LDL-C, HDL-C and ALT levels were significantly reduced in RD group (P<0.01), and FBG level was also reduced (P<0.05). Moreover, RD treatment alleviated liver fat deposition and TG accumulation (P<0.01). The mRNA levels of SREBP1, ACC, and SCD1 were all reduced in RD group compared with HFD group. The protein level of pAMPK was increased, and the expression of Fasn was reduced with RD treatment (P<0.01).@*Conclusion@#Resistant dextrin improves liver fat deposition and activates the AMPK signaling pathway in HFD-fed mice.
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With the improvement in clinical treatment and the increase in life expectancy, the incidence rate of osteoporosis is gradually increasing in patients with hepatitis B. However, the specific mechanism of different stages of hepatitis B on osteoporosis is still complex and remains unclear, and there are few studies on the prevention and treatment of osteoporosis in patients with hepatitis B. This article reviews the pathogenesis and clinical prevention and treatment of osteoporosis in patients with hepatitis B, in order to provide better guidance for clinical management and treatment.
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Since the development of direct-acting antivirals (DAAs) for hepatitis C virus(HCV), more than 95% of the patients with hepatitis C can be cured, but a very small proportion of patients still face treatment failure. There are many reasons for treatment failure, among which HCV genotype and resistance-associated substitutions (RASs) in virus genes show a certain impact. This article mainly introduces the RASs associated with the NS5B and NS5A gene fragments in genotype 2/3 HCV, summarizes the distribution of RASs, and compares the difference in the distribution of RASs between previously untreated chronic hepatitis C patients and patients with treatment failure.
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Liver cirrhosis is the end stage of a variety of chronic liver diseases. In recent years, a number of clinical studies related to cirrhosis have provided new evidence for natural history of cirrhosis, etiologic treatment and management of complications. The present article evaluates the cirrhosis-related articles in this issue and summarizes the advances of cirrhosis staging, antiviral therapy in patients with decompensated hepatitis C cirrhosis, drug treatment of portal hypertension, terlipressin in the treatment of cirrhotic ascites, and the management of portal vein thrombosis. The unmet needs in cirrhosis-related clinical studies are also discussed.
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The World Health Organization (WHO) has put forward the strategic goal of eliminating viral hepatitis as a major public health threat by 2030, and the research and development of new treatment for chronic hepatitis B (CHB) patients is an important part of this. In recent years, functional or clinical cure marked by HBsAg clearance and continuous undetectable HBV DNA has gradually become an ideal treatment endpoint recommended by clinical guidelines at home and abroad. Studies have shown that CHB patients who achieved long-term viral suppression after nucleoside analogues (NAs), adding or switching to interferons may have the potential to improve the clearance rate of HBsAg. However, the HBsAg conversion rate of patients in each treatment group in these studies was still low, and a reasonable combined therapy strategy and suitable patient population need to be further explored. In addition, some new drugs are being developed in pursuit of a CHB cure, though many clinical trials of new drugs are still based from a long-term treatment of NAs. Therefore, NAs antiviral therapy remains the cornerstone at this stage for CHB.
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Objective To establish clinical pharmacists' competency behavior questionnaire and confirm the validity of the competency model of clinical pharmacists. Methods On the basis of previous model research, clinical pharmacists' behavior questionnaire combining the Likert scaling and literature retrieval method was established,and the competency model was verified by method of exploring factor analysis and " construct validity" and confirmatory factor analysis. Results Questionnaire included 47 characteristic projects and ten basic information projects.Exploratory factor analysis extracted 5 factors,whose content was in accordance with the model of competency characteristics.Cronbach 's alpha coefficients of each factor project were (0.510-0.961).Discrimination validity of the behavior questionnaire was good.T-test results showed good statistical difference between the outstanding group and the normal group, and the empirical validity of the model was better. Confirmatory factor analysis of structural equation model was acceptable,and the CIF was 0. 825. Conclusion The competency model is valid and can distinguish clinical pharmacists with excellent performance.
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Objective To explore the possible associations between EBV capsid antigen-immunoglobulin M antibody (EBV-VCA-IgM ) ,serum EBV DNA load and clinical severity ,laboratory results in adolescent and adult patients with infectious mononucleosis (IM ).Methods Clinical data of 250 adolescent and adult IM patients were retrospectively analyzed .Patients were divided into two groups by EBV-VCA-IgM titer (>160 U/mL or≤160 U/mL) and serum EBV DNA level (>3 .38 lg copies/mL or <3.38 lg copies/mL) ,respectively . Clinical data were compared between the two groups ,respectively .The t test was used for intergroup comparison and the Mann-Whitney U test was used for non-normally distributed data .Results Compared with those with lower VCA-IgM antibody titer (≤160 U/mL) ,sore throat (83.0%[122/147] vs 67.2%[43/64] ,χ2= 6.534 ,P=0 .011) ,pharynx secretion (59 .9%[88/147] vs 40 .6%[26/64] ,χ2=6.645 , P=0 .010) ,and swollen tonsils (78 .9%[116/147] vs 59.4%[38/64] ,χ2=8.631 , P=0.003) were more common in those with higher VCA-IgM antibody titer (>160 U/mL).ALT level was higher as well in those with higher VCA-IgM antibody titer (290 .5 [168.0 ,460.5] U/L vs 221 .0[113 .0 ,440.5] U/L ,Z= -2.251 ,P=0.024).The peak body temperature ([39.2 ± 0.7]°C vs [38.7 ± 0 .7]°C ,t= -3 .150 ,P=0.002) ,maximum WBC counts (16 .2 [12 .2 ,20.4]×109/L vs 13.4[11 .1 ,17.3]×109/L ,Z= -2 .098 , P=0.036) ,maximum percentage of lymphocyte ([72.0 ± 7.8]% vs [68.2 ± 7 .0]%,t= -2.238 ,P=0.028) ,and lymphocyte EBV DNA load ([5 .5 ± 0.9] lg copies/mL vs [4 .8 ± 1 .0] lg copies/mL ,t= -2 .602 ,P=0.012)in those with higher serum EBV DNA load >3 .38 lg copies/mL were higher than those with serum EBV DNA load <3.38 lg copies/mL . Regression analysis showed that serum EBV DNA load was associated with the peak body temperature (regression coefficient 0.368 , P=0.003) and lymphocyte EBV DNA load (regression coefficient 0.389 , P=0.002).Conclusions In adolescents and adults ,EBV-VCA-IgM antibody titer and serum EBV DNA load are associated with severity of patients with infectious mononucleosis .
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Hepatitis B virus (HBV) pregenomic RNA (pgRNA) is the direct transcription product of HBV covalently closed circular DNA (cccDNA) and can reflect the transcriptional activity of HBV cccDNA and the progression of chronic hepatitis B, which provides guidance for clinical treatment and prognostic prediction. Compared with other common serological markers for HBV infection, HBV pgRNA is more sensitive in reflecting HBV replication and the effect of antiviral therapy has a certain predictive value for endpoints in the stages of antiviral therapy. This article elaborates on the significance of HBV pgRNA in reflecting the changes in disease conditions with reference to the correlation of HBV pgRNA with HBcrAg and HBV cccDNA.
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The incidence of hepatitis C virus infection is commonly seen in patients with renal dysfunction (RD),especially those with end-stage renal disease on hemodialysis (HD),among whom the incidence and mortality of liver diseases increase.The development of direct-acting antiviral agents has revolutionized the therapy for chronic hepatitis C (CHC) with a sustained virologic response rate of > 90% and a low rate of adverse events.Grazoprevir/elbasvir,paritaprevir/ritonavir + ombitasvir + dasabuvir,glecaprevir/pibrentasvir,or daclatasvir + asunaprevir regimen is recommended in CHC patients with RD and HD,while the sofosbuvir-based regimen is not recommended.
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Esophageal and gastric varices are common complications of liver cirrhosis and are seen in 50% of patients with liver cirrhosis. The annual incidence rate of esophagogastric variceal bleeding is 5%-15%, and even if the recommended treatment is used, the 6-week mortality rate is still as high as 15%-20%. Spontaneous bacterial peritonitis (SBP) is a common complication of end-stage liver disease and has an incidence rate of 10%-30% in patients with severe liver damage. SBP refers to the bacterial infection of the peritoneum and/or ascites that occurs in the absence of any inflammation in adjacent tissues (e.g., intestinal perforation and intestinal abscess). Hepatic encephalopathy (HE) is the clinical syndrome manifesting as cognitive impairment in patients with chronic liver disease, and its pathogenesis has not yet been fully elucidated and may be associated with ammonia poisoning theory, γ-aminobutyric acid and endogenous benzodiazepine complex receptor theory, and inflammatory pathway theory. This article introduces the advances in the treatment of upper gastrointestinal bleeding in patients with liver cirrhosis, SBP, and HE in 2016.