Watt, Kymberly D.

AbstractBackground & AimsChronic kidney disease (CKD) after liver transplant (LT) is associated with increased long‐term mortality. The impact of gender on CKD before and after LT is unknown. To further define risk factors and analyse gender differences in the incidence and progression of CKD after liver transplant.MethodsFour hundred and fifty‐five consecutive adult primary solitary LT recipients were included. Iothalamate clearance tests performed over time were analysed.ResultsMean age was 51.4 ± 10.4 years with 63% males. A percentage of 29.1% of females and 21.1% of males had a GFR<60 ml/min/1.73 m2 and 10.2% of females and 5.9% of males had GFR<30 ml/min/1.73 m2 prior to transplant. At 1 year, 52.6% of recipients tested (69.6% females, 43.0% males) had GFR<60 ml/min/1.73 m2 and 7.3% (11.6% females, 4.9% males) had GFR<30 ml/min/1.73 m2. Pre‐LT GFR<60 ml/min/1.73 m2 [OR 3.28, (1.76–6.10), P ≤ 0.001], female gender (OR 2.96, (1.72–5.10), P < 0.001) and age [OR 1.09, (1.05–1.12), P < 0.001] were independently predictive of stage ≥3 CKD at 1 year post‐LT. Female gender [OR 2.52, (1.25–4.71), P = 0.004], age [OR 1.05, (1.02–1.08), P = 0.003] and NASH [OR 2.95, (1.06–8.21), P = 0.039] were independently predictive of ≥stage 3 CKD at 5 years post‐LT. Pre‐LT diabetes was associated with stage 4 CKD at 5 years [OR 2.91, (1.33–6.36), P = 0.008] post‐LT.ConclusionsIn addition to age and pre‐LT CKD, female gender and NASH are independent predictors of ≥stage 3 CKD post‐LT. Gender‐based approaches to optimize modifiable risk factors are needed to improved post‐transplant renal function.

AbstractBackground and AimsLiver‐related clinical consequences of non‐alcoholic fatty liver disease (NAFLD) are seen only in the minority of patients with advanced fibrosis. The aim of our study was to generate insight into a potential endocrine basis of steatohepatitis with advanced fibrosis in NAFLD.MethodsBiopsy and blood samples were prospectively collected from patients with medically complicated obesity. Patients were categorized, according to liver histology, into: (i) normal, (ii) simple steatosis (SS), (iii) non‐alcoholic steatohepatitis (NASH) with fibrosis stage (FS) 0–1 and (iv) NASH with FS ≥ 2. A broad panel of potential biomarkers included DHEA‐S, growth hormone (GH), homeostasis model assessment‐insulin resistance (HOMA‐IR), leptin, resistin, adiponectin and cytokeratin 18 (CK‐18) fragments.ResultsWe studied 160 patients (mean BMI 46.8 ± 8.2 kg/m2). Liver biopsies demonstrated normal histology in 10%, SS in 45%, NASH with FS 0–1 in 37.5% and NASH with FS ≥ 2 in 7.5%. C‐reactive protein, IL‐6, GH, CK‐18, adiponectin, HOMA‐IR and quantitative insulin sensitivity check index (QUICKI) were significantly associated with NASH in univariate analysis, but overall predictivity of these parameters was low (AUC ROC = 0.62–0.68). In contrast, all patients with NASH with FS ≥ 2 had insulin resistance, as measured by QUICKI, and GH levels <0.45 ng/ml and all but one patient with NASH FS 2–3 had low DHEA levels (<123 μg/dl).ConclusionsLow serum levels of GH and DHEA are very common in patients with NASH with more advanced fibrosis. Other biomarkers, including CK‐18 fragment levels, have predictivity characteristics that would be of low clinical utility for distinguishing patients with normal histology or SS from those with NASH. These findings demonstrate an endocrine profile associated with advanced fibrosis.

Autoimmune hepatitis (AIH) is a chronic inflammatory disorder characterized by periportal inflammation, elevated immunoglobulins, autoantibodies, and a dramatic response to immunosuppression. An environmental agent is hypothesized to trigger an immune-mediated attack directed against liver antigens in genetically predisposed individuals. A plethora of clinical presentations can be seen ranging from chronic indolent disease to fulminant hepatic failure, and diagnosis requires exclusion of other causes of liver disease. Corticosteroid therapy must be instituted early and modified in an individualized fashion. Treatment decisions are often complicated by the diverse clinical manifestations, uncertainty about natural history, evolving ideas about treatment end points, and a multitude of alternative immunosuppressive agents. Achieving normal liver tests and tissue is the ideal treatment end point, but needs to be weighed against the risk of side effects. Decompensated patients may benefit from early liver transplantation. Long-term prognosis is excellent with early and aggressive initiation of therapy. Our paper discusses AIH, giving a detailed overview of its clinical presentation, risk factors, immunopathogenesis, up-to-date diagnostic criteria, current updates in therapy with a brief discussion of AIH in pregnancy, and long-term implications for cirrhosis and hepatocellular carcinoma in AIH patients.