Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. METHODS: All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. RESULTS: Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p < 0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. CONCLUSIONS: ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF

Plasma copeptin as biomarker of disease progression and prognosis in cirrhosis

BACKGROUND & AIMS: Research on vasopressin (AVP) in cirrhosis and its role in the assessment of prognosis has been hindered by the difficulty of measuring AVP levels accurately. Copeptin, a 39-aminoacid glycopeptide, is released from the neurohypophysis together with AVP. Copeptin could have a role as biomarker of prognosis in cirrhosis as it may reflect circulatory dysfunction. The aim of this study is to investigate the role of copeptin as biomarker of disease progression and prognosis in cirrhosis. METHODS: This prospective study is divided in 2 study protocols including 321 consecutive patients. Plasma copeptin levels were measured in all patients at study inclusion. Protocol 1: to investigate the relationship of copeptin with kidney and circulatory function (56 patients). Protocol 2: to investigate the relationship between copeptin and prognosis, as assessed by the development of complications of cirrhosis or mortality at 3months (265 patients admitted to hospital for complications of cirrhosis). RESULTS: Patients with decompensated cirrhosis showed significantly higher plasma copeptin levels compared to those of patients with compensated cirrhosis. Copeptin levels had a significant positive correlation with model for end-satge liver disease (MELD) score, AVP, endogenous vasoconstrictor systems, and kidney function parameters. Patients developing complications of cirrhosis or mortality had significantly higher plasma copeptin levels compared to those of the remaining patients. Plasma copeptin levels were an independent predictive factor of both the development of complications and mortality at 3months. This was confirmed in a validation series of 120 patients. CONCLUSIONS: Copeptin is a novel biomarker of disease progression and prognosis in cirrhosis. LAY SUMMARY: Copeptin is a fragment of the vasopressin precursor, a hormone that is known to be increased in patients with cirrhosis and that plays a role in the development of complications of the disease. Vasopressin is difficult to measure, but copeptin is a more stable molecule and is easier to measure in blood. Solà and Kerbert and colleagues have shown in a series of 361 patients that copeptin is markedly increased in patients with cirrhosis who develop complications during the following 3months, compared to those patients who do not develop complications. Moreover, copeptin correlates with prognosis

Copeptin in acute decompensation of liver cirrhosis: relationship with acute-on-chronic liver failure and short-term survival.

BACKGROUND: Acute-on-chronic liver failure (ACLF) is characterized by the presence of acute decompensation (AD) of cirrhosis, organ failure, and high short-term mortality rates. Hemodynamic dysfunction and activation of endogenous vasoconstrictor systems are thought to contribute to the pathogenesis of ACLF. We explored whether copeptin, a surrogate marker of arginine vasopressin, is a potential marker of outcome in patients admitted for AD or ACLF and whether it might be of additional value to conventional prognostic scoring systems in these patients. METHODS: All 779 patients hospitalized for AD of cirrhosis from the CANONIC database with at least one serum sample available for copeptin measurement were included. Presence of ACLF was defined according to the CLIF-consortium organ failure (CLIF-C OF) score. Serum copeptin was measured in samples collected at days 0-2, 3-7, 8-14, 15-21, and 22-28 when available. Competing-risk regression analysis was applied to evaluate the impact of serum copeptin and laboratory and clinical data on short-term survival. RESULTS: Serum copeptin concentration was found to be significantly higher in patients with ACLF compared with those without ACLF at days 0-2 (33 (14-64) vs. 11 (4-26) pmol/L; p < 0.001). Serum copeptin at admission was shown to be a predictor of mortality independently of MELD and CLIF-C OF scores. Moreover, baseline serum copeptin was found to be predictive of ACLF development within 28 days of follow-up. CONCLUSIONS: ACLF is associated with significantly higher serum copeptin concentrations at hospital admission compared with those with traditional AD. Copeptin is independently associated with short-term survival and ACLF development in patients admitted for AD or ACLF

Impact of hepatic encephalopathy on liver transplant waiting list mortality in regions with different transplantation rates.

Overt hepatic encephalopathy (OHE) negatively impacts the prognosis of liver transplant candidates. However, it is not taken into account in most prioritizing organ allocation systems. We aimed to assess the impact of OHE on waitlist mortality in 3 cohorts of cirrhotic patients awaiting liver transplantation, with differences in the composition of patient population, transplantation policy, and transplantation rates. These cohorts were derived from two centers in the Netherlands (reference and validation cohort, n = 246 and n = 205, respectively) and one in Spain (validation cohort, n = 253). Competing-risk regression analysis was applied to assess the association of OHE with 1-year waitlist mortality. OHE was found to be associated with mortality, independently of MELD score, other cirrhosis-related complications and hepatocellular carcinoma (HCC; sHR = 4.19, 95% CI = 1.9-9.5, P = 0.001). The addition of extra MELD points for OHE counteracted its negative impact on survival. These findings were confirmed in the Dutch validation cohort, whereas in the Spanish cohort, containing a significantly greater proportion of HCC and with higher transplantation rates, OHE was not associated with mortality. In conclusion, OHE is an independent risk factor for 1-year waitlist mortality and might be a prioritization rule for organ allocation. However, its impact seems to be attenuated in settings with significantly higher transplantation rates

Clinical and hemodynamic characteristics of cirrhotic rats and control rats at 18 weeks.

<p><i>MAP</i>, <i>mean arterial blood pressure; MBF</i>, <i>mesenteric blood flow</i>.</p><p>Clinical and hemodynamic characteristics of cirrhotic rats and control rats at 18 weeks.</p

Association of serum copeptin concentration with transplant-free survival.

<p>Kaplan Meier survival analysis at 6 months of follow-up of 61 cirrhotic patients registered at the waiting list for liver transplantation, stratified according to serum copeptin concentration (pmol/L) at time of registration.</p

Parameters associated with survival time.

<p><i>LT</i>, <i>liver transplantation; HR</i>, <i>hazard ratio; 95% CI</i>, <i>95% confidence interval; high</i>, <i>exceeding the optimal cut-off point; low</i>, <i>equal to or below the optimal cut-off point; MELD</i>, <i>Model for End-Stage Liver Disease; MELD-Na</i>, <i>sodium MELD</i></p><p>^§,† “Low” and “high” refers to values below and above the optimal cut-off point as defined using the Youden index, respectively. The reference groups were patients with low serum copeptin and ^§low MELD score or ^†low MELD-Na score.</p><p>Optimal cut-off points and results of univariate (A) and multivariate (B) Cox proportional hazard regression analysis assessing factors associated with liver transplantation or death awaiting liver transplantation in relation to time of follow-up in cirrhotic patients registered at the waiting list for liver transplantation (n = 61).</p

Demographic and clinical characteristics of 61 cirrhotic patients at time of registration at the waiting list for liver transplantation.

<p><i>HBV</i>, <i>hepatitis B virus; HCV</i>, <i>hepatitis C virus; PSC</i>, <i>primary sclerosing cholangitis; PBC</i>, <i>primary biliary cirrhosis; AIH</i>, <i>autoimmune hepatitis; NASH</i>, <i>non-alcoholic steatohepatitis; HCC</i>, <i>hepatocellular carcinoma; MELD</i>, <i>Model for End-Stage Liver Disease; MELD-Na</i>, <i>sodium MELD; INR</i>, <i>International Normalized Ratio; MAP</i>, <i>mean arterial blood pressure</i></p><p>Data are shown as counts (percentage) or as median (interquartile range).</p><p>^§ Median (interquartile range) doses of diuretics used at baseline: spironolactone 100.0 (50.0–187.5) mg/day, furosemide 40.0 (40.0–70.0) mg/day.</p><p>^† MAP was determined in 55 patients.</p><p>Demographic and clinical characteristics of 61 cirrhotic patients at time of registration at the waiting list for liver transplantation.</p