Development of a new Cox model for predicting long-term survival in hepatitis cirrhosis patients underwent transjugular intrahepatic portosystemic shunts

BACKGROUND Transjugular intrahepatic portosystemic shunt(TIPS)placement is a procedure that can effectively treat complications of portal hypertension,such as variceal bleeding and refractory ascites.However,there have been no specific studies on predicting long-term survival after TIPS placement.AIM To establish a model to predict long-term survival in patients with hepatitis cirrhosis after TIPS.METHODS A retrospective analysis was conducted on a cohort of 224 patients who un-derwent TIPS implantation.Through univariate and multivariate Cox regression analyses,various factors were examined for their ability to predict survival at 6 years after TIPS.Consequently,a composite score was formulated,encompassing the indication,shunt reasonability,portal venous pressure gradient(PPG)after TIPS,percentage decrease in portal venous pressure(PVP),indocyanine green retention rate at 15 min(ICGR15)and total bilirubin(Tbil)level.Furthermore,the performance of the newly developed Cox(NDC)model was evaluated in an in-ternal validation cohort and compared with that of a series of existing models.RESULTS The indication(variceal bleeding or ascites),shunt reasonability(reasonable or unreasonable),ICGR15,post-operative PPG,percentage of PVP decrease and Tbil were found to be independent factors affecting long-term survival after TIPS placement.The NDC model incorporated these parameters and successfully identified patients at high risk,exhibiting a notably elevated mortality rate following the TIPS procedure,as observed in both the training and validation cohorts.Additionally,in terms of predicting the long-term survival rate,the performance of the NDC model was significantly better than that of the other four models[Child-Pugh,model for end-stage liver disease(MELD),MELD-sodium and the Freiburg index of post-TIPS survival].CONCLUSION The NDC model can accurately predict long-term survival after the TIPS procedure in patients with hepatitis cirrhosis,help identify high-risk patients and guide follow-up management after TIPS implantation.

Novel ATP8B1 mutation in an adult male with progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis type 1 is a rare disease that is characterized by low serum γ-glutamyltransferase levels due to mutation inATP8B1.We present a 23-year-old male who experienced persistent marked pruritus for eighteen years and recurrent jaundice for thirteen years,in addition to cholestasis that eventually became fatal.Genetic sequencing studies of the entire coding(exon) sequences of ATP8B1 and ABCB11 uncovered a novel heterozygous missense 3035G>T mutation(S1012I) and a synonymous 696T>C mutation in ATP8B1.The patient's progression was associated with not only impaired familial intrahepatic cholestasis 1(FIC1) function but also impaired bile salt export pump expression due to the impaired FIC1 function.Our findings show that patients with intermittent cholestasis can develop progressive liver disease even after several decades and require regular follow up.

Prednisolone therapy accelerates recovery of severe drug-induced liver injury: A prospective, randomized controlled study

Background and aims:Drug-induced liver injury(DILI)is one of the most serious adverse drug reactions and its incidence has been increasing rapidly.Accumulating evidence suggests that immune activation and systemic inflammatory responses are very important in the progression of DILI.Corticosteroids are often used in DILI,but their clinical usefulness remains controversial.We therefore conducted a prospective,randomized controlled study to investigate whether corticosteroid therapy can accelerate recovery and reduce mortality in severe DILI(SDILI).Methods:SDILI patients with total bilirubin?171μmol/L who presented to the Fifth Medical Center of Chinese PLA General Hospital,Beijing from 2016 to 2019 were randomly allocated to prednisolone and control groups.The endpoints were resolution of SDILI,defined as a decrease in total bilirubin of at least 35μmol/L to<171μmol/L,and overall survival at 6 months.Patients in the prednisolone group received prednisolone 60 mg/day therapy for the first 7 days.Patients with a decrease in total bilirubin of more than 35μmol/L on day 8 continued on tapering doses of prednisolone;otherwise,prednisolone was discontinued.Results:On day 8,50.75%(34/67)and 26.47%(18/68)of the participants in the prednisolone and control groups,respectively,achieved the primary endpoint(p¼0.002).However,there was no significant difference in overall survival at 6 months:95.52%(64/67)vs.91.18%(62/68)in the prednisolone and control groups,respectively(p¼0.3).All deaths in both groups occurred in patients who failed to achieve SDILI resolution on day 8.Conclusion:Prednisolone therapy may accelerate the recovery of SDILI.