Chronic kidney disease in patients with non-alcoholic fatty liver disease: What the Hepatologist should know?

The association of non-alcoholic fatty liver disease (NAFLD) with several other diseases has gained increased interest during the recent years. Among them, the association with chronic kidney disease (CKD) has emerged as an important one regarding both its prevalence and significance. The early recognition of this association is important for the prognosis of patients with NAFLD and CKD. Apart from early diagnosis, the accurate assessment of renal function is also crucial in the clinical practice of hepatologists. Several methods have been used in the literature for the evaluation of kidney function in patients with NAFLD up to now. In this respect, calculators (or formulas) for the estimation of Glomerular Filtration Rate (eGFR) and Albumin to Creatinine Ratio (ACR) are simple, practical and easily available methods for this purpose. The aim of this review is to report on the epidemiology and pathophysiology of the relationship between NAFLD and CKD and to describe the different methods of kidney function assessment in patients with NAFLD. The collection of all relevant data regarding this association will provide hepatologists with pertinent knowledge on this topic and allow them to use the most accurate methods for the assessment of kidney function in these patients in their clinical practice.

Aspartate aminotransferase-to-platelet ratio index can predict the outcome in patients with stable decompensated cirrhosis.

Background: Platelet (PLT)-based biomarkers have been studied for the evaluation of liver fibrosis and cirrhosis. There are no data regarding their prognostic significance in decompensated cirrhosis. Methods: We studied 525 stable decompensated patients from the 2 Greek transplant centers. We measured PLT values, mean PLT volume (MPV), red cell distribution width, γ-globulins, and calculated PLT-based scores: aspartate aminotransferase-to-PLT ratio index (APRI), γ-globulin-to-PLT model, and γ-glutamyl transpeptidase-to-PLT ratio (GPR). Results: We followed our cohort for 12 (range: 1-84) months. Baseline mean model for end-stage liver disease (MELD) and Child-Turcotte-Pugh (CTP) scores were 15±6 and 8±2, respectively. On univariate analysis, MPV/PLT (hazard ratio [HR] 3.75, 95% confidence interval [CI] 1-14.5; P=0.05), APRI (HR 1.03, 95%CI 1.006-1.06; P=0.016), GPR (HR 1.096, 95%CI 1.016-1.182; P=0.017) were significantly associated with our patients' outcome (survival vs. death or liver transplantation). In a multivariate model without MELD and CTP scores, APRI was the only significant factor associated with the outcome (HR 1.054, 95%CI 1.009-1.101; P=0.018). APRI had good discriminative ability for the outcome (area under the curve 0.723 vs. 0.675 and 0.656 for MELD and CTP scores, respectively). The optimal cutoff point was 1.3 (sensitivity 71%, specificity 65%). There were 200 patients (38%) with APRI scores <1.3 who had better survival than patients with APRI >1.3 (log rank 22.4, P<0.001). Conclusions: This study found a prognostic role for APRI in stable decompensated cirrhosis, regardless of the underlying etiology of chronic liver disease. This suggests new perspectives for PLT-based noninvasive scores to discriminate patients' outcomes.

The significance of C-reactive protein to albumin ratio in patients with decompensated cirrhosis.

BACKGROUND: Prognostic indicators in patients with decompensated cirrhosis are vital for the estimation of death risk. The ratio of C-reactive protein to albumin (CAR) has been verified as a prognostic marker in patients with hepatocellular carcinoma and decompensated cirrhosis related to hepatitis B virus. Neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-monocyte ratio (LMR), and gamma globulins have been separately studied in cirrhosis. We evaluated the predictive role of CAR and other inflammatory markers in decompensated patients. METHODS: We prospectively studied 159 patients with stable decompensated cirrhosis, calculating the following indexes: CAR, NLR, LMR, Child-Turcotte-Pugh (CTP), and model for end-stage liver disease (MELD). RESULTS: MELD (area under the curve [AUC] 0.814) and CTP score (AUC 0.752) were superior to the other markers above in predicting patients' mortality (P<0.05). Patients with CAR<2.17 (median value) presented better times of survival: 20 months (12-27) vs. 14 months (10-17) (log rank P=0.015). NLR and LMR barely discriminated patients' prognosis. In multivariate analysis, only MELD and CTP scores were significant risk factors, whether using the proposed cutoff of 1.3 (hazard ratio [HR] 1.17 [1.106-2.44], P<0.001) or the median 2.17 CAR categorical variable (HR 1.17 [1.104-1.243], P<0.001). When patients who underwent liver transplantation were excluded, apart from the MELD and CTP scores CAR 2.17 was the only significant factor associated with the outcome (HR 3.61 [0.96-13.6], P=0.05) and detected different survival times: 10 (1-48) vs. 11 (2-38) months, log rank P=0.003. Patients with LMR≥1.9 presented significantly better renal function, in terms of true glomerular filtration rate (80±34 vs. 64±33 mL/min, P=0.004) and creatinine levels: 0.84 (0.1-1.8) vs. 0.98 (0.59-3.3) mg/dL (P=0.001). CONCLUSION: Our findings demonstrate the significance of CAR and LMR in the outcome and renal function of decompensated patients.

Nucleos(t)ide analogues for the prevention of hepatitis B recurrence after liver transplantation do not affect serum phosphorus levels.

BACKGROUND: Nucleos(t)ide analogues (NAs) constitute the backbone of treatment for the prevention of hepatitis B virus recurrence after liver transplantation (LT). Decline in serum phosphorus levels is a common side effect of nucleotide therapy. Our aim was to assess the impact of nucleotide treatment on the occurrence of hypophosphatemia after LT and determine possible predictors. METHODS: We retrospectively analyzed data from liver transplant recipients who had been transplanted for various indications. All patients were evaluated every 3 months. Each patient was considered to be having hypophosphatemia when at least one value of serum phosphorus ≤2.5 mg/dL was detected. RESULTS: In total, 109 patients [83 males (76%)] with a mean age of 55±10 years were included. 46/67 (67%) patients with hepatitis B received a nucleotide. The rate of hypophosphatemia (55%) was not different between patients with hepatitis B and those transplanted for other indications (62%). Patients receiving a nucleotide did not run a greater risk of hypophosphatemia than patients receiving only nucleosides (59% vs. 48%, P=0.39). Male gender and everolimus use were associated with the occurrence of hypophosphatemia in patients with hepatitis B. In multivariate analysis only gender was associated with hypophosphatemia (odds ratio 11.43, 95%CI -2.11 to -0.49; P=0.0025). CONCLUSIONS: Hypophosphatemia occurs in more than half of liver transplant recipients regardless of the indication for LT. Male gender and everolimus use seem to predispose to hypophosphatemia, whereas the type of antiviral agent does not.