Liver steatosis is a major predictor of poor outcomes in chronic hepatitis C patients with sustained virological response.

Sustained virological response (SVR) results in reduced incidence of hepatocellular carcinoma (HCC) and mortality among chronic hepatitis C (CHC) patients with advanced fibrosis. Since both advanced fibrosis and liver steatosis (LS) may coexist in CHC patients, we evaluated their individual effects on a composite outcome of all-cause mortality and HCC in CHC patients with SVR following direct-acting antivirals (DAA) treatment. We retrospectively evaluated inception cohort of 515 CHC patients who achieved SVR following treatment with DAA, with a mean follow-up of 24 months. Baseline liver fibrosis was assessed by transient elastography, and LS was validated by at least three independent ultrasonographic examinations. 211 of 515 patients (41%) had baseline LS. Patients with LS had a higher cumulative rate of all-cause mortality and HCC at 2 years of follow-up compared to patients without LS (15.75% and 2.79%, respectively, P < 0.001), although they did not have increased incidence of advanced fibrosis or cirrhosis. Consistently, multivariate analysis showed that LS was associated with a significant 7.5-fold increased risk of all-cause mortality and HCC (HR 7.51, 95% C.I 3.61-13.36, P < 0.001) even upon adjustment to components of the metabolic syndrome, whereas advanced fibrosis showed only a trend towards statistical significance (HR 2.32, 95% C.I 0.97-6.59, P = 0.06). In conclusion, LS is a major predictor of all-cause mortality and HCC in patients who achieved SVR following DAA treatment regardless of fibrosis stage. These patients should be rigorously screened for HCC.

Telomere shortening in liver transplant recipients is not influenced by underlying disease or metabolic derangements.

BACKGROUND: Telomeres are non-coding regions of DNA that cap the ends of chromosomes. Their length is considered a marker of human replicative senescence and premature aging. Given the high association of liver transplantation with the metabolic syndrome, we hypothesized that liver transplant recipients may exhibit premature and accelerated aging. MATERIAL AND METHODS: Telomere length in peripheral blood lymphocytes was measured by polymerase chain reaction in 62 consecutive liver-transplant recipients and 59 healthy control subjects aged 20-76 years. Clinical and laboratory parameters were collected from the medical files. RESULTS: The liver transplant recipients were significantly older than the control subjects (p=0.012), with significantly higher rates of obesity (BMI >30 kg/m(2)), dyslipidemia, hypertension, diabetes, and fatty liver. Mean telomere length was significantly shorter in the transplant group (0.59±0.6 vs. 1.91±1.78 in the controls, p<0.0001). Within the transplant group, there was no significant association between mean telomere length and underlying liver disease or presence of the metabolic syndrome or its constituents. On multivariate analysis, telomere length was negatively associated with patient age (p=0.0001), male sex (p=0.04), acute rejection (p=0.005), and fatty liver (p=0.009), and was positively associated with time from transplantation (p=0.006). CONCLUSIONS: Liver transplantation is associated with shortened telomere length in peripheral blood lymphocytes, suggesting accelerated senescence.

Serum adipocyte fatty acid binding protein in liver transplant recipients and the metabolic syndrome.

BACKGROUND: Liver transplantation is often associated with metabolic derangements. Adipocyte fatty-acid-binding protein 4 (AFABP4) integrates inflammatory and metabolic responses. It has also been associated with metabolic syndrome in animal models and clinical studies in the general population. AIM: To determine the role of AFABP4 in post-transplant metabolic syndrome. MATERIAL AND METHODS: Consecutive patients followed for at least 6 months after liver transplantation were tested for insulin resistance by homeostasis model assessment (HOMA). Serum levels of AFABP4 were tested by an enzyme-linked immunosorbent assay. RESULTS: The study group included 76 patients (64.5% male, mean age 56.3 ± 12.4 years). Hypertension was present in 56.5%, hyperlipidemia in 69.7%, diabetes mellitus in 23.6%. Half of the patients met at least 3 criteria for metabolic syndrome. Serum AFABP4 levels (p < 0.0001), HOMA index ≥ 2.5 vs. < 2.5 (p < 0.0002) and BMI ≥ 30 vs. < 30 (p < 0.0006) were significantly higher in patients with metabolic syndrome. Within the metabolic syndrome subgroup, AFABP4 levels significantly correlated with age, aspartate aminotransaminase level, waist circumference, and HOMA index. High AFABP4 significantly increased the odds of acquiring metabolic syndrome (OR 1.04, 95% CI 1.007-1.074, p = 0.017). On multiple logistic regression analysis, independent predictors of high AFABP4 were cryptogenic liver disease, steroid administration, high HOMA index, and a high degree of fatty infiltration. CONCLUSION: Prevalence of metabolic syndrome is significantly higher in liver transplant recipients than in the general population. AFABP4 may serve as a circulating biomarker in the clinical prediction/diagnosis of metabolic syndrome in patients post-liver transplantation.

Metabolic syndrome in liver transplant recipients: prevalence, risk factors, and association with cardiovascular events.

Features of metabolic syndrome are not uncommon in patients after liver transplantation. To examine the prevalence and risk factors of posttransplantation metabolic syndrome (PTMS), the files of 252 transplant recipients (mean age, 54.5 ± 2.8 years, 57.9% male) were reviewed for pretransplant and posttransplant clinical and laboratory parameters (mean follow-up, 6.2 ± 4.4 years). Rates of obesity (body mass index >30 kg/m(2) ), hypertriglyceridemia (>150 mg/dL), high-density lipoprotein cholesterol <40 mg/dL (men) or <50 mg/dL (women), hypertension, and diabetes were significantly higher after transplantation than before. Metabolic syndrome was diagnosed in 5.4% of patients before transplantation and 51.9% after. Besides significantly higher rates of the typical metabolic derangements (P < 0.0001), the patients with PTMS were older and heavier than those without PTMS, and they had a higher rate of pretransplant hepatitis C virus infection (P < 0.03) and more posttransplant major vascular and cardiac events (20 events in 15.2% of patients with PTMS versus 6 events in 4.9% of patients without PTMS; P < 0.007). There was no between-group difference in mortality or causes of death (mainly related to recurrent disease, graft failure, and sepsis). Significant independent predictors of PTMS on logistic regression analysis were age (odds ratio [OR] = 1.04), pretransplant nonalcoholic fatty liver disease (OR = 3.4), body mass index (OR = 1.13), diabetes (OR = 5.95), and triglycerides (OR = 1.01). The rate of metabolic syndrome in liver transplant recipients is more than twice that reported for the general population. PTMS is associated with cardiovascular morbidity but not mortality, and it may be predicted by pretransplantation conditions. Prospective studies are required to determine the significance and management of PTMS.