Identifying the early predictors of non-response to steroids in patients with flare of autoimmune hepatitis causing acute-on-chronic liver failure.

BACKGROUND AND AIMS: Early identification of non-response to steroids is critical in patients with autoimmune hepatitis (AIH) causing acute-on-chronic liver failure (ACLF). We assessed if this non-response can be accurately identified within first few days of treatment. METHODS: Patients with AIH-ACLF without baseline infection/hepatic encephalopathy were identified from APASL ACLF research consortium (AARC) database. Diagnosis of AIH-ACLF was based mainly on histology. Those treated with steroids were assessed for non-response (defined as death or liver transplant at 90 days for present study). Laboratory parameters, AARC, and model for end-stage liver disease (MELD) scores were assessed at baseline and day 3 to identify early non-response. Utility of dynamic SURFASA score [- 6.80 + 1.92*(D0-INR) + 1.94*(∆%3-INR) + 1.64*(∆%3-bilirubin)] was also evaluated. The performance of early predictors was compared with changes in MELD score at 2 weeks. RESULTS: Fifty-five out of one hundred and sixty-five patients (age-38.2 ± 15.0 years, 67.2% females) with AIH-ACLF [median MELD 24 (IQR: 22-27); median AARC score 7 (6-9)] given oral prednisolone 40 (20-40) mg per day were analyzed. The 90 day transplant-free survival in this cohort was 45.7% with worse outcomes in those with incident infections (56% vs 28.0%, p = 0.03). The AUROC of pre-therapy AARC score [0.842 (95% CI 0.754-0.93)], MELD [0.837 (95% CI 0.733-0.94)] score and SURFASA score [0.795 (95% CI 0.678-0.911)] were as accurate as ∆MELD at 2 weeks [0.770 (95% CI 0.687-0.845), p = 0.526] and better than ∆MELD at 3 days [0.541 (95% CI 0.395, 0.687), p < 0.001] to predict non-response. Combination of AARC score > 6, MELD score > 24 with SURFASA score ≥ - 1.2, could identify non-responders at day 3 (concomitant- 75% vs either - 42%, p < 0.001). CONCLUSION: Baseline AARC score, MELD score, and the dynamic SURFASA score on day 3 can accurately identify early non-response to steroids in AIH-ACLF.

Serum bicarbonate levels and the progression of kidney disease: a cohort study.

BACKGROUND: Animal models of kidney disease have linked metabolic acidosis with renal damage. The role of low serum bicarbonate levels in kidney disease progression in humans has not been studied. STUDY DESIGN: Retrospective cohort study. SETTING & PARTICIPANTS: Adults visiting a medical clinic in the Bronx, NY, from January 1, 2001, to December 31, 2003, were included in the study (n = 5,422) and followed up until June 30, 2007. PREDICTOR: Serum bicarbonate level. OUTCOMES: Kidney disease progression was defined as either a decrease in estimated glomerular filtration rate (eGFR) by 50% or reaching an eGFR less than 15 mL/min/1.73 m(2) (n = 337). MEASUREMENTS: Patients' baseline demographics, comorbid conditions, laboratory data, and socioeconomic status were recorded. Serial outpatient serum creatinine levels were collected (median, 5 measurements/person). RESULTS: Mean age was 52 years, 69% were women, 45% were African American, 31% were Hispanic, 21% had diabetes mellitus, 41% had hypertension, and 9% had a baseline eGFR less than 60 mL/min/1.73 m(2). Kidney disease progressed as defined in 337 patients (6.2%). Compared with the reference group (bicarbonate level, 25 to 26 mEq/L), hazard ratios for progression after adjustment for potential confounders were 1.54 (95% confidence interval [CI], 1.13 to 2.09) for bicarbonate levels of 22 mEq/L or less, 0.97 (95% CI, 0.70 to 1.35) for 23 to 24 mEq/L, and 1.14 (95% CI, 0.84 to 1.55) for 27 mEq/L or greater (global P for inclusion of serum bicarbonate level in the model = 0.01). These results were similar using different definitions of the outcome (eGFR decrease of 30%, 1,288 outcomes [24%]; or doubling of serum creatinine level, 268 outcomes [4.9%]). LIMITATIONS: Data used in the study were collected for clinical, not research, purposes. CONCLUSIONS: Low serum bicarbonate level is associated with progression of kidney disease independent of baseline eGFR and other clinical, demographic, and socioeconomic factors. Prospective studies are needed to confirm this relationship and evaluate the efficacy of alkali supplements for slowing progression.