| BackgroundChina has the heaviest burden of liver disease in the world and the number of patients with liver disease has exceeded 300 million.Among them,the number of patients with liver cirrhosis has exceeded 7 million.Hyponatremia is the most common electrolyte disturbance in liver cirrhosis,which significantly associated with a poor outcome.Therefore,to explore the prevalence of hyponatremia and the prognostic factors of hyponatremia is critical for formulate the managing strategies of hyponatremia,improve the patient’s quality of life,and decrease the burden.However,it should be noted that the effective and safe treatment of hyponatremia in liver cirrhosis remain lacking.Recent studies suggested that human albumin(HA)might be effective for the treatment of hyponatremia.However,the use of HA on the management of patients with liver cirrhosis and hyponatremia remains controversial among the current practice guidelines due to the poor evidence.Additionally,the results of previous studies regarding the HA managing hyponatremia also are heterogeneous.Taken together,the effects of HA on the management of hyponatremia in liver cirrhosis should be further explored.AimsCurrent work focuses on the management of hyponatremia in liver cirrhosis.First,to explore the prevalence of hyponatremia in patients with liver cirrhosis in China.Second,to explore the risk factors for the death of hyponatremia and develop prediction models.Third,to explore the effect of HA on the prevention and treatment of hyponatremia in cirrhosis.Finally,to explore the role of HA in the prognosis of patients with liver cirrhosis and to identify the factors which might influence the effects of HA infusion.Methods1.PubMed,CNKI,VIP,and Wanfang databases were searched.Studies regarding the patients with liver cirrhosis and hyponatremia were included.The prevalence of hyponatremia was pooled.Subgroup analyses were performed by location,publication year,and patients with ascites.2.Retrospectively included patients with liver cirrhosis and hyponatremia.To explore the risk factors for the death of hyponatremia in patients with liver cirrhosis.To develop the artificial neural network(ANN)model and predict the death of cirrhotic patients with hyponatremia.3.PubMed,EMBASE,and Cochrane Library databases were searched.Studies regarding the HA prevent and treat hyponatremia in patients with liver cirrhosis was included.Incidence of hyponatremia,improvement rate of hyponatremia,and serum sodium level were compared between cirrhotic patients received HA infusion or not.4.Retrospectively included patients with liver cirrhosis.Patients were divided into Hospitalization Outcome cohort and Long-term Outcome cohort based on the length of followup.The development and improvement of hyponatremia were compared between patients who received HA infusion and did not.Propensity score matching(PSM)analyses were performed.Logistic regression analyses were performed to explore the role of development and improvement of hyponatremia during hospitalizations in patients’ in-hospital outcome.Cox regression analyses were performed to explore the role of development and improvement of hyponatremia during hospitalizations in the patients’ long-term outcome.5.EMBASE,PubMed,and Cochrane Library databases were searched.Randomized controlled trials(RCTs)regarding the use of HA infusion in cirrhotic patients were included.The mortality of patients with liver cirrhosis was pooled.Subgroup analyses based on indications,severity of liver cirrhosis,baseline albumin level,and duration and dosage of HA.Results1.Seventy-six studies were included.The pooled prevalence of hyponatremia was 38.1%(95%CI:37.5%-38.8%)in patients with liver cirrhosis.As for the location,Zhejiang(70.7%,95%CI:66.2%-75.20),Shanghai(63.9%,95%CI:58.5%-69.2%),and Yunnan(67.5%,95%CI:60.2%-74.8%)had high prevalence of hyponatremia.As for publication year,the prevalence of hyponatremia has been gradually decreased in the past 30 years.As for the patients with ascites,the prevalence of hyponatremia was 46.8%(95%CI:44.4%-49.2%).2.Overall,943 cirrhotic patients with hyponatremia were included.Among them,100 patients died during hospitalizations.Patients were randomly assigned to the training cohort(n=472)and the validation cohort(n=471).Multivariate analysis showed that HCC,white blood cell(WBC),TBIL,Scr,and international normalized ratio(INR)were independent associated with the death of hyponatremia in the training cohort.Among the training cohort,the ANN model for predict the death of hyponatremia was developed and the AUC was 0.865(95%CI:0.831-0.894,P<0.0001).This ANN model remains had a good performance in the validation cohort and the AUC was 0.810(95%CI:0.772-0.845,P<0.0001).3.Thirty studies were included.Among them,18 studies explored the incidence of hyponatremia after HA infusion.Meta-analysis showed that the HA group had a significantly lower incidence of hyponatremia(OR=0.55,95%CI:0.38-0.80,P=0.001)than the control group.Nineteen studies explored the change of serum sodium level after HA infusion.Metaanalysis showed that the HA group had a significantly higher serum sodium level(MD=0.95,95%CI:0.47-1.43,P=0.0001)than the control group.Two studies explored the role of HA in the treatment of hyponatremia.Meta-analysis showed that the HA group had a significantly higher rate of resolution of hyponatremia(OR=1.50,95%CI:1.17-1.92,P=0.001)than the control group.4.In the Hospitalization Outcome cohort,1796 patients were included to explore the prevention of hyponatremia.Among them,621 patients received HA infusion and 1175 did not.After PSM,602 patients were included.The results showed that the HA group had a significant lower incidence of hyponatremia(16.30%vs.41.90%,P<0.001)than the control group.1004 patients were included to explore the treatment of hyponatremia.Among them,545 patients received HA infusion and 459 did not.After PSM,394 patients were included.The results showed that the HA group had a significant higher improvement rate of hyponatremia(82.70%vs.54.80%,P<0.001)than the control group.The development of hyponatremia during hospitalizations was significantly increased the in-hospital mortality(OR=2.493,P<0.001),and the improvement of hyponatremia during hospitalizations was significantly decreased the in-hospital mortality(OR=0.599,P=0.014).In the Long-term Outcome cohort,291 patients were included to explore the prevention of hyponatremia.Among them,93 patients received HA infusion and 198 did not.After PSM,78 patients were included.The results showed that the HA group had a significant lower incidence of hyponatremia(7.70%vs.30.80%,P=0.010)than the control group.88 patients were included to explore the treatment of hyponatremia.Among them,42 patients received HA infusion and 46 did not.After PSM,16 patients were included.The results showed that the HA group had a significant higher improvement rate of hyponatremia(87.50%vs.37.50%,P=0.039)than the control group.The development of hyponatremia during hospitalizations was significantly decreased the long-term survival(HR=0.400,P<0.001),and the improvement of hyponatremia during hospitalizations was not significantly associated with the long-term survival(HR=1.085,P=0.813).5.Forty-two RCTs were included.Meta-analysis showed that HA infusion could significantly decrease the mortality of patients with liver cirrhosis(OR=0.81,95%CI:0.670.98,P=0.03).Subgroup analyses showed that HA infusion could significantly decrease the mortality of cirrhotic patients with spontaneous bacterial peritonitis(SBP)(OR=0.36,95%CI:0.20-0.64,P=0.0005)or hepatic encephalopathy(OR=0.43,95%CI:0.22-0.85,P=0.02),but not those with ascites,non-SBP infection,or underwent LVP.Short-term HA infusion could significantly decrease short-term mortality(OR=0.67,95%CI:0.50-0.89,P=0.005),but not long-term mortality.Long-term HA infusion could not significantly decrease long-term mortality(OR=0.72,95%CI:0.48-1,08,P=0.11).HA infusion could significantly decrease the mortality of patients with serum albumin level>25 g/L(OR=0.73,95%CI:0.58-0.91,P=0.004),but not those with serum albumin level<25 g/L(OR=1.01,95%CI:0.74-1.39,P=0.93).HA infusion could significantly decrease the mortality of patients with non-severe liver cirrhosis(OR=0.72,95%CI:0.53-0.98,P=0.04),but not those with severe liver cirrhosis(OR=0.79,95%CI:0.59-1.07,P=0.13).Conclusions1.The prevalence of hyponatremia was 38.1%in patients with liver cirrhosis and 46.8%in patients with liver cirrhosis and ascites in China.2.Based on the risk factors for the death of hyponatremia in patients with liver cirrhosis,the ANN models were developed.3.HA infusion can effectively prevent the development of hyponatremia and improve hyponatremia in patients with liver cirrhosis.HA should be considered to manage the hyponatremia in patients with liver cirrhosis in the future.Additionally,the development and improvement of hyponatremia could significantly influence the survival of patients with liver cirrhosis.4.HA infusion could decrease the mortality of patients with liver cirrhosis.Additionally,the effects of HA could be influent by indications,baseline serum albumin level,severity of liver cirrhosis,and the infusion strategy. |
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