One-year survival in cirrhosis ranges from 1 to 57% depending on the clinical stage. Accurate sub-classification has important prognostic implications but there is no stage beyond cirrhosis using current qualitative histological systems. We compared the performance of all histological semi-quantitative and quantitative methods specifically developed for sub-classifying cirrhosis that have been described to date, with collagen proportionate area (CPA), to evaluate how well they distinguish patients with and without hepatic clinical decompensation at presentation, and in predicting future decompensating events. We included consecutive patients with a histological diagnosis of cirrhosis that had a suitable liver biopsy between 2003 and 2007. We used semi-quantitative histological scoring systems proposed by Laennec, Kumar, and Nagula. We also measured quantitatively nodule size, septal width and fibrous tissue expressed in CPA. Sixty-nine patients, mean age 52.3±11years, mean MELD 11.8±5.8, median follow-up 56months. Main aetiologies were alcohol (38%) and hepatitis C (27.5%). Twenty-four patients (34.8%) had had a previous episode of clinical decompensation. Amongst the 45 patients who were compensated, 11 (24%) decompensated on follow-up. In Cox regression, amongst all histological parameters, CPA was the only variable independently associated with clinical decompensation up to the time of biopsy, with an odds ratio that ranged from 1.245 to 1.292. Furthermore, only CPA was significantly associated with future decompensation (OR: 1.117, 95% CI 1.020-1.223; p=0.017). Cirrhosis can be accurately sub-classified using quantification of fibrosis with CPA, and furthermore CPA is the only independent predictor of clinical decompensation amongst all other histological sub-classification systems described to date.

The best predictors of short- and medium-term mortality of cirrhotic patients receiving intensive care support are unknown. We conducted meta-analyses from 13 studies (2523 cirrhotics) after selection of original articles and response to a standardized questionnaire by the corresponding authors. End-points were in-ICU, in-hospital, and 6-month mortality in ICU survivors. A total of 301 pooled analyses, including 95 analyses restricted to 6-month mortality among ICU survivors, were conducted considering 249 variables (including reason for admission, organ replacement therapy, and composite prognostic scores). In-ICU, in-hospital, and 6-month mortality was 42.7, 54.1, and 75.1%, respectively. Forty-eight patients (3.8%) underwent liver transplantation during follow-up. In-ICU mortality was lower in patients admitted for variceal bleeding (OR 0.46; 95% CI 0.36–0.59; p < 0.001) and higher in patients with SOFA > 19 at baseline (OR 8.54; 95% CI 2.09–34.91; p < 0.001; PPV = 0.93). High SOFA no longer predicted mortality at 6 months in ICU survivors. Twelve variables related to infection were predictors of in-ICU mortality, including SIRS (OR 2.44; 95% CI 1.64–3.65; p < 0.001; PPV = 0.57), pneumonia (OR 2.18; 95% CI 1.47–3.22; p < 0.001; PPV = 0.69), sepsis-associated refractory oliguria (OR 10.61; 95% CI 4.07–27.63; p < 0.001; PPV = 0.76), and fungal infection (OR 4.38; 95% CI 1.11–17.24; p < 0.001; PPV = 0.85). Among therapeutics, only dopamine (OR 5.57; 95% CI 3.02–10.27; p < 0.001; PPV = 0.68), dobutamine (OR 8.92; 95% CI 3.32–23.96; p < 0.001; PPV = 0.86), epinephrine (OR 5.03; 95% CI 2.68–9.42; p < 0.001; PPV = 0.77), and MARS (OR 2.07; 95% CI 1.22–3.53; p = 0.007; PPV = 0.58) were associated with in-ICU mortality without heterogeneity. In ICU survivors, eight markers of liver and renal failure predicted 6-month mortality, including Child–Pugh stage C (OR 2.43; 95% CI 1.44–4.10; p < 0.001; PPV = 0.57), baseline MELD > 26 (OR 3.97; 95% CI 1.92–8.22; p < 0.0001; PPV = 0.75), and hepatorenal syndrome (OR 4.67; 95% CI 1.24–17.64; p = 0.022; PPV = 0.88). Prognosis of cirrhotic patients admitted to ICU is poor since only a minority undergo liver transplant. The prognostic performance of general ICU scores decreases over time, unlike the Child–Pugh and MELD scores, even recorded in the context of organ failure. Infection-related parameters had a short-term impact, whereas liver and renal failure had a sustained impact on mortality.

Acetaminophen-induced acute liver failure (ALF) is a complex multiorgan illness. An assessment of the prognosis is essential for the accurate identification of patients for whom survival without liver transplantation (LT) is unlikely. The aims of this study were the comparison of prognostic models [King's College Hospital (KCH), Model for End-Stage Liver Disease, Sequential Organ Failure Assessment (SOFA), and Acute Physiology and Chronic Health Evaluation II (APACHE II)] and the identification of independent prognostic indicators of outcome. We evaluated consecutive patients with severe acetaminophen-induced ALF who were admitted to the intensive care unit. At admission, demographic, clinical, and laboratory parameters were recorded. The discriminative ability of each prognostic score at the baseline was evaluated with the area under the receiver operating characteristic curve (AUC). In addition, using a multiple logistic regression, we assessed independent factors associated with outcome. In all, 125 consecutive patients with acetaminophen-induced ALF were evaluated: 67 patients (54%) survived with conservative medical management (group 1), and 58 patients (46%) either died without LT (28%) or underwent LT (18%; group 2). Group 1 patients had significantly lower median APACHE II (10 versus 14) and SOFA scores (9 versus 12) than group 2 patients (P < 0.001). The independent indicators associated with death or LT were a longer prothrombin time (P = 0.007), the inspiratory oxygen concentration (P = 0.005), and the lactate level at 12 hours (P < 0.001). The KCH criteria had the highest specificity (83%) but the lowest sensitivity (47%), and the SOFA score had the best discriminative ability (AUC = 0.79). In conclusion, for patients with acetaminophen-induced ALF, the SOFA score performed better than the other prognostic scores, and this reflected the presence of multiorgan dysfunction. A further evaluation of SOFA with the KCH criteria is warranted. Liver Transpl 18:405–412, 2012. © 2011 AASLD.

Current expressions based on serum creatinine concentration overestimate kidney function in cirrhosis, leading to significant differences between “true” and calculated glomerular filtration rate (GFR). We compared the performance of the four‐variable and six‐variable Modification of Diet in Renal Disease and chronic kidney disease epidemiology with “true,” or measured, GFR (mGFR) and the impact of this difference on Model for End‐Stage Liver Disease (MELD) calculation. We subsequently developed and validated a GFR equation specifically for cirrhosis and compared the performance of the new derived formula with existing GFR formulae. We included 469 consecutive patients who had a transplant assessment between 2011 and 2014. mGFR was measured using plasma isotope clearance according to a technique validated in patients with ascites. A corrected creatinine was derived from the mGFR after application of the Modification of Diet in Renal Disease formula. Subsequently, a corrected MELD was calculated and compared with the conventionally calculated MELD. Stepwise multiple linear regression was used to derive a GFR equation. This was compared with the mGFR in independent external and internal validation sets of 82 and 174 patients with cirrhosis, respectively. A difference >20 mL/minute/1.73 m²between existing formulae and mGFR was observed in 226 (48.2%) patients. The corrected MELD score was ≥3 points higher in 177 (37.7%) patients. The predicted equation (r²= 74.6%) was GFR = 45.9 × (creatinine^–0·836) × (urea^–0·229) × (international normalized ratio^–0·113) × (age^−0.129[Corrected November 29, 2016: originally written as “age‐129.”]) × (sodium^0·972) × 0.809 (if female) × 0.92 (if moderate/severe ascites). An online calculator is available at http://rfh-cirrhosis-gfr.ucl.ac.uk. The model was a good fit and showed the greatest accuracy compared to that of existing formulae.Conclusion: We developed and validated a new accurate model for GFR assessment in cirrhosis, the Royal Free Hospital cirrhosis GFR, using readily available variables; this remains to be tested and incorporated in prognostic scores in patients with cirrhosis. (Hepatology2017;65:582‐591).