BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with a...BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.展开更多
Background: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury(DILI). We aimed to develop and validate a new prognostic model to p...Background: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury(DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. Methods: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve(AUC). A high-mortality-risk subgroup was identified according to the score. Results: Three independent DILI cohorts, including one derivation cohort( n = 741) and two validation cohorts( n = 650, n = 617) were recruited. The DILI mortality predictive(DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin(mg/d L) + 0.439 × aspartate aminotransferase/alanine aminotransferase – 1.579 × albumin(g/d L) –0.006 × platelet count(109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941(95% CI: 0.922-0.957), 0.931(0.908-0.949) and 0.960(0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. Conclusions: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.展开更多
BACKGROUND Cytomegalovirus(CMV)infection is common in liver transplant(LT)_recipients,and biliary complications occur in a large number of patients.It has been reported that CMV-DNA is more detectable in bile than in ...BACKGROUND Cytomegalovirus(CMV)infection is common in liver transplant(LT)_recipients,and biliary complications occur in a large number of patients.It has been reported that CMV-DNA is more detectable in bile than in blood.AIM To investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT.METHODS We conducted a retrospective analysis of 57 patients who underwent LT,10 of these patients had no biliary complications and 47 patients had biliary complications.We also compared the levels of CMV-DNA in patients’bile and blood,which were sampled concurrently.We used RNAscope technology to identify CMV in paraffin-embedded liver sections.RESULTS CMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications.In the 47 patients with biliary complications,CMV-DNA was detected in 22 bile samples and 8 blood samples,both bile and blood samples were positive for CMV-DNA in 6 patients.The identification rate of CMV-DNA in blood was 17.0%,and was 46.8%in bile.Moreover,tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining.During the follow-up period,graft failure occurred in 13 patients with biliary complications,8 of whom underwent retransplantation,and 3 died.CMV-DNA in bile was detected in 9 of 13 patients with graft failure.CONCLUSION In patients with biliary complications,the identification rate of CMV-DNA in bile was higher than that in blood.Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases.Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.展开更多
基金Supported by Xinjiang“Tianshan Talents”Medical and Health High-Level Talent Training Program-Young and Middle-Aged Backbone Medical Talents.
文摘BACKGROUND Hepatitis D virus-hepatitis B virus(HDV-HBV)co-infection accelerates liver disease progression and increases the risk of hepatocellular carcinoma,but the immunopathogenic mechanism of its combination with autoimmune hepatitis(AIH)has not been clarified.This study reveals for the first time that HDV may induce AIH through abnormalities in immunoregulation in two specific cases.This is the first report of HDV-HBV co-infected patients who did not receive interferon therapy and achieved serological conversion and histological remission by combining antiviral(entecavir)with immunosuppression(prednisone+azathioprine)therapy,providing new evidence of the mechanism of this complex disease.CASE SUMMARY A 40-year-old female developed malaise and jaundice with an alanine aminotransferase/aspartate aminotransferase>20 upper limit of normal(ULN),total bilirubin:97.20μmol/L,immunoglobulin G(IgG)47.1 g/L(>3×ULN),HDV RNA 1.6×10^(7)copies/mL and liver biopsy showed G3S4.Tenofovir alafenamide combined with prednisone and azathioprine was administered,and three months later the Child-Turcotte-Pugh class C was reduced to class B and IgG decreased to 13.62 g/L.Another 58-year-old male complained of pain in the liver area,antinuclear antibody was 1:320,IgG 22.6 g/L(>1.3×ULN),and liver biopsy showed G2S3.Entecavir was administered in combination with prednisone and azathioprine,and after 3 months,liver function returned to normal,and IgG reduced to 14.22 g/L.CONCLUSION Patients with HDV-HBV co-infection combined with AIH can achieve clinical remission following combination therapy,and the study of immunomodulatory mechanisms should be emphasized.
基金supported by grants from the National Key R&D Program of China (2021ZD0113200)the National Natural Sci-ence Foundation of China (81900526)
文摘Background: Early identification of patients with high mortality risk is critical for optimizing the clinical management of drug-induced liver injury(DILI). We aimed to develop and validate a new prognostic model to predict death within 6 months in DILI patients. Methods: This multicenter study retrospectively reviewed the medical records of DILI patients admitted to three hospitals. A DILI mortality predictive score was developed using multivariate logistic regression and was validated with area under the receiver operating characteristic curve(AUC). A high-mortality-risk subgroup was identified according to the score. Results: Three independent DILI cohorts, including one derivation cohort( n = 741) and two validation cohorts( n = 650, n = 617) were recruited. The DILI mortality predictive(DMP) score was calculated using parameters at disease onset as follows: 1.913 × international normalized ratio + 0.060 × total bilirubin(mg/d L) + 0.439 × aspartate aminotransferase/alanine aminotransferase – 1.579 × albumin(g/d L) –0.006 × platelet count(109/L) + 9.662. The predictive performance for 6-month mortality of DMP score was desirable, with an AUC of 0.941(95% CI: 0.922-0.957), 0.931(0.908-0.949) and 0.960(0.942-0.974) in the derivation, validation cohorts 1 and 2, respectively. DILI patients with a DMP score ≥ 8.5 were stratified into high-risk group, whose mortality rates were 23-, 36-, and 45-fold higher than those of other patients in the three cohorts. Conclusions: The novel model based on common laboratory findings can accurately predict mortality within 6 months in DILI patients, which should serve as an effective guidance for management of DILI in clinical practice.
基金The National Natural Science Foundation of China,No.81570586.
文摘BACKGROUND Cytomegalovirus(CMV)infection is common in liver transplant(LT)_recipients,and biliary complications occur in a large number of patients.It has been reported that CMV-DNA is more detectable in bile than in blood.AIM To investigate the effects of CMV infection on biliary complications by comparing the levels of CMV-DNA in the bile and blood of patients after LT.METHODS We conducted a retrospective analysis of 57 patients who underwent LT,10 of these patients had no biliary complications and 47 patients had biliary complications.We also compared the levels of CMV-DNA in patients’bile and blood,which were sampled concurrently.We used RNAscope technology to identify CMV in paraffin-embedded liver sections.RESULTS CMV-DNA was not detected in bile samples and was detected in 2 blood samples from patients without biliary complications.In the 47 patients with biliary complications,CMV-DNA was detected in 22 bile samples and 8 blood samples,both bile and blood samples were positive for CMV-DNA in 6 patients.The identification rate of CMV-DNA in blood was 17.0%,and was 46.8%in bile.Moreover,tissue samples from 4 patients with biliary complications tested positive using RNAscope technology but were negative with hematoxylin and eosin staining.During the follow-up period,graft failure occurred in 13 patients with biliary complications,8 of whom underwent retransplantation,and 3 died.CMV-DNA in bile was detected in 9 of 13 patients with graft failure.CONCLUSION In patients with biliary complications,the identification rate of CMV-DNA in bile was higher than that in blood.Blood CMV-DNA negative patients with biliary complications should still be monitored for CMV-related biliary tract diseases.Potential occult CMV infection may also be a contributing etiological factor in the development of graft failure.
