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Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study
(2012)
Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far.
Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications.
Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P <0.001). Elevated levels of IL-22 were associated with ascites (P = 0.006), hepatorenal syndrome (P <0.0001), and spontaneous bacterial peritonitis (P = 0.001). Patients with elevated IL-22 (>18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)).
Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis.
Background and Aims: In patients with advanced liver cirrhosis due to chronic hepatitis C virus (HCV) infection antiviral therapy with peginterferon and ribavirin is feasible in selected cases only due to potentially life-threatening side effects. However, predictive factors associated with hepatic decompensation during antiviral therapy are poorly defined.
Methods: In a retrospective cohort study, 68 patients with HCV-associated liver cirrhosis (mean MELD score 9.18±2.72) were treated with peginterferon and ribavirin. Clinical events indicating hepatic decompensation (onset of ascites, hepatic encephalopathy, upper gastrointestinal bleeding, hospitalization) as well as laboratory data were recorded at baseline and during a follow up period of 72 weeks after initiation of antiviral therapy. To monitor long term sequelae of end stage liver disease an extended follow up for HCC development, transplantation and death was applied (240weeks, ±SD 136weeks).
Results: Eighteen patients (26.5%) achieved a sustained virologic response. During the observational period a hepatic decompensation was observed in 36.8%. Patients with hepatic decompensation had higher MELD scores (10.84 vs. 8.23, p<0.001) and higher mean bilirubin levels (26.74 vs. 14.63 µmol/l, p<0.001), as well as lower serum albumin levels (38.2 vs. 41.1 g/l, p = 0.015), mean platelets (102.64 vs. 138.95/nl, p = 0.014) and mean leukocytes (4.02 vs. 5.68/nl, p = 0.002) at baseline as compared to those without decompensation. In the multivariate analysis the MELD score remained independently associated with hepatic decompensation (OR 1.56, 1.18–2.07; p = 0.002). When the patients were grouped according to their baseline MELD scores, hepatic decompensation occurred in 22%, 59%, and 83% of patients with MELD scores of 6–9, 10–13, and >14, respectively. Baseline MELD score was significantly associated with the risk for transplantation/death (p<0.001).
Conclusions: Our data suggest that the baseline MELD score predicts the risk of hepatic decompensation during antiviral therapy and thus contributes to decision making when antiviral therapy is discussed in HCV patients with advanced liver cirrhosis.
Intrahepatic cholangiocarcinoma (iCCA) is the most frequent subtype of cholangiocarcinoma (CCA), and the incidence has globally increased in recent years. In contrast to surgically treated iCCA, data on the impact of fibrosis on survival in patients undergoing palliative chemotherapy are missing. We retrospectively analyzed the cases of 70 patients diagnosed with iCCA between 2007 and 2020 in our tertiary hospital. Histopathological assessment of fibrosis was performed by an expert hepatobiliary pathologist. Additionally, the fibrosis-4 score (FIB-4) was calculated as a non-invasive surrogate marker for liver fibrosis. For overall survival (OS) and progression-free survival (PFS), Kaplan–Meier curves and Cox-regression analyses were performed. Subgroup analyses revealed a median OS of 21 months (95% CI = 16.7–25.2 months) and 16 months (95% CI = 7.6–24.4 months) for low and high fibrosis, respectively (p = 0.152). In non-cirrhotic patients, the median OS was 21.8 months (95% CI = 17.1–26.4 months), compared with 9.5 months (95% CI = 4.6–14.3 months) in cirrhotic patients (p = 0.007). In conclusion, patients with iCCA and cirrhosis receiving palliative chemotherapy have decreased OS rates, while fibrosis has no significant impact on OS or PFS. These patients should not be prevented from state-of-the-art first-line chemotherapy.
Standard monitoring of heart rate, blood pressure and arterial oxygen saturation during endoscopy is recommended by current guidelines on procedural sedation. A number of studies indicated a reduction of hypoxic (art. oxygenation < 90% for > 15 s) and severe hypoxic events (art. oxygenation < 85%) by additional use of capnography. Therefore, U.S. and the European guidelines comment that additional capnography monitoring can be considered in long or deep sedation. Integrated Pulmonary Index® (IPI) is an algorithm-based monitoring parameter that combines oxygenation measured by pulse oximetry (art. oxygenation, heart rate) and ventilation measured by capnography (respiratory rate, apnea > 10 s, partial pressure of end-tidal carbon dioxide [PetCO2]). The aim of this paper was to analyze the value of IPI as parameter to monitor the respiratory status in patients receiving propofol sedation during PEG-procedure. Patients reporting for PEG-placement under sedation were randomized 1:1 in either standard monitoring group (SM) or capnography monitoring group including IPI (IM). Heart rate, blood pressure and arterial oxygen saturation were monitored in SM. In IM additional monitoring was performed measuring PetCO2, respiratory rate and IPI. Capnography and IPI values were recorded for all patients but were only visible to the endoscopic team for the IM-group. IPI values range between 1 and 10 (10 = normal; 8–9 = within normal range; 7 = close to normal range, requires attention; 5–6 = requires attention and may require intervention; 3–4 = requires intervention; 1–2 requires immediate intervention). Results on capnography versus standard monitoring of the same study population was published previously. A total of 147 patients (74 in SM and 73 in IM) were included in the present study. Hypoxic events occurred in 62 patients (42%) and severe hypoxic events in 44 patients (29%), respectively. Baseline characteristics were equally distributed in both groups. IPI = 1, IPI < 7 as well as the parameters PetCO2 = 0 mmHg and apnea > 10 s had a high sensitivity for hypoxic and severe hypoxic events, respectively (IPI = 1: 81%/81% [hypoxic/severe hypoxic event], IPI < 7: 82%/88%, PetCO2: 69%/68%, apnea > 10 s: 84%/84%). All four parameters had a low specificity for both hypoxic and severe hypoxic events (IPI = 1: 13%/12%, IPI < 7: 7%/7%, PetCO2: 29%/27%, apnea > 10 s: 7%/7%). In multivariate analysis, only SM and PetCO2 = 0 mmHg were independent risk factors for hypoxia. IPI (IPI = 1 and IPI < 7) as well as the individual parameters PetCO2 = 0 mmHg and apnea > 10 s allow a fast and convenient conclusion on patients’ respiratory status in a morbid patient population. Sensitivity is good for most parameters, but specificity is poor. In conclusion, IPI can be a useful metric to assess respiratory status during propofol-sedation in PEG-placement. However, IPI was not superior to PetCO2 and apnea > 10 s.