Is moderate alcohol use in nonalcoholic fatty liver disease good or bad? A critical review

Moderate alcohol consumption in patients with nonalcoholic fatty liver disease (NAFLD) is common, yet the effects on cardiovascular and liver health are unclear. Moderate alcohol use is associated with improved insulin sensitivity and decreased cardiovascular mortality in the general population, but whether similar benefits would be observed in persons with NAFLD remains largely unstudied. There is significant overlap in the pathogenesis of alcoholic liver disease (ALD) and NAFLD, although studies of ALD have focused on pathological alcohol intake and few mechanistic studies of moderate alcohol use in NAFLD exist. We undertook a critical review of the effect of moderate alcohol use on cardiovascular and liver disease in patients with NAFLD. A total of seven observational studies met the criteria for inclusion (one for cardiovascular endpoints and six for liver endpoints). Insufficient studies have assessed the association of moderate alcohol use with cardiovascular outcomes. There was a positive association between moderate alcohol use and decreased NASH and fibrosis; however, heavy episodic drinking may accelerate fibrosis progression and moderate alcohol use may increase the risk of hepatocellular carcinoma in patients with advanced fibrosis. Significant methodological limitations were present, including incomplete adjustment for confounding factors and failure to measure lifetime use or the pattern of alcohol intake. Thus, a strong recommendation of benefit of moderate alcohol use in NAFLD cannot be made. There remains a need for additional high-quality longitudinal studies that evaluate both cardiovascular and liver outcomes among NAFLD patients with moderate or lesser degrees of alcohol use. (Hepatology 2017;65:2090-2099)

Gestational Diabetes Mellitus Is Strongly Associated With Non-Alcoholic Fatty Liver Disease

ObjectivesInsulin resistance is central to the development of non-alcoholic fatty liver disease (NAFLD), and gestational diabetes mellitus (GDM) is an early marker of insulin resistance. We hypothesized that a history of GDM would identify women at higher risk of NAFLD in middle age.MethodsWomen from the multicenter Coronary Artery Risk Development in Young Adults (CARDIA) cohort study who delivered ≥1 birth, were free of diabetes prior to pregnancy(ies), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n=1,115). History of GDM by self-report, validated in a subsample by review of antenatal glucose testing, and metabolic risk factors were assessed prospectively. NAFLD was defined by liver attenuation (LA)≤40 Hounsfield Units on CT scan after exclusion of other causes of hepatic steatosis.ResultsOf 1,115 women meeting selection criteria (57% black, 43% white, median age 25 years at baseline), 124 (11%) reported a history of GDM and 75 (7%) met the CT definition for NAFLD at year 25. The crude risk of NAFLD at the 25-year visit was significantly higher in women with GDM compared to those without (14 vs. 5.8%, OR: 2.56, 95% CI: 1.44-4.55, P<0.01). History of GDM remained associated with NAFLD (OR: 2.29, 95% CI: 1.23-4.27, P=0.01) after adjustment for covariates in multivariable logistic regression. Addition of incident diabetes mellitus (DM) into the final model attenuated the association between GDM and NAFLD (OR: 1.48, 95% CI: 0.73-3.02, P=0.28).ConclusionGDM is a risk marker for NAFLD and represents an opportunity to identify women at risk for NAFLD at a young age and may be mediated by the development of incident DM

Longer lactation duration is associated with decreased prevalence of non-alcoholic fatty liver disease in women

Background & aimsLactation lowers blood glucose and triglycerides, and increases insulin sensitivity. We hypothesized that a longer duration of lactation would be associated with lower prevalence of non-alcoholic fatty liver disease (NAFLD), which is the leading cause of chronic liver disease in the United States.MethodsParticipants from the Coronary Artery Risk Development in Young Adults cohort study who delivered ≥ 1 child post-baseline (Y0: 1985-1986), and underwent CT quantification of hepatic steatosis 25 years following cohort entry (Y25: 2010-2011) were included (n = 844). The duration of lactation was summed for all post-baseline births, and NAFLD at Y25 was assessed by central review of CT images and defined by liver attenuation ≤ 40 Hounsfield Units after exclusion of other causes of hepatic steatosis. Unadjusted and multivariable logistic regression analyses were performed using an a priori set of confounding variables; age, race, education, and baseline body mass index.ResultsOf 844 women who delivered after baseline (48% black, 52% white, mean age 49 years at Y25 exam), 32% reported lactation duration of 0 to 1 month, 25% reported >1 to 6 months, 43% reported more than 6 months, while 54 (6%) had NAFLD. Longer lactation duration was inversely associated with NAFLD in unadjusted logistic regression. For women who reported >6 months lactation compared to those reporting 0-1 month, the odds ratio for NAFLD was 0.48 (95% CI 0.25-0.94; p = 0.03) and the association remained after adjustment for confounders (adjusted odds ratio 0.46; 95% CI 0.22-0.97; p = 0.04).ConclusionsA longer duration of lactation, particularly greater than 6 months, is associated with lower odds of NAFLD in mid-life and may represent a modifiable risk factor for NAFLD.Lay summaryA longer duration of breastfeeding has been associated with multiple potential health benefits for the mother including reduction in heart disease, diabetes and certain cancers. In this study we found that breastfeeding for longer than 6 months was associated with a lower risk of non-alcoholic fatty liver disease in mid-life

Liver Stiffness Severity is Associated With Increased Cardiovascular Risk in Patients With Type 2 Diabetes.

Cardiovascular disease (CVD) is the leading cause of death among patients with nonalcoholic fatty liver disease (NAFLD) and is strongly associated with type 2 diabetes mellitus (DM2).1 Accurately assessing CVD risk in NAFLD patients is critical to improving clinical outcomes.1 Use of liver stiffness measurements to noninvasively assess for liver fibrosis is broadening, and magnetic resonance elastography (MRE) is the most accurate modality in NAFLD.2 However, the association between fibrosis severity on MRE and the degree of CVD risk is unknown. The aim of this study was to determine whether MRE-assessed liver fibrosis stage is associated with CVD risk determined by Framingham risk score (FRS) and coronary artery calcium (CAC)

Rescue liver re-transplantation after graft loss due to severe rejection in the setting of pre-transplant nivolumab therapy

Immune checkpoint inhibitors (ICI) have been used to treat hepatocellular carcinoma (HCC) since 2017. The safety of ICIs in the setting of solid organ transplantation remains controversial. When used in the post-transplant setting, ICIs have been associated with high allograft rejection rates, but there are few published reports on the use of ICIs prior to transplant. We present the first reported case of rescue liver re-transplantation after loss of the first allograft due to severe acute rejection with extensive hepatic necrosis in the setting of pre-transplant ICI therapy with the PD-1 inhibitor nivolumab. It is likely that the durable immune response triggered by nivolumab contributes to graft rejection, therefore extreme caution should be taken when using ICIs before transplant until further investigation has been conducted on their safety in the pre-transplant setting

Optimal Threshold of Controlled Attenuation Parameter for Detection of HIV-Associated NAFLD With Magnetic Resonance Imaging as the Reference Standard.

BackgroundControlled attenuation parameter (CAP) is an ultrasound-based point-of-care method to quantify liver fat; however, the optimal threshold for CAP to detect pathologic liver fat among persons living with human immunodeficiency virus (HIV; PLWH) is unknown. Therefore, we aimed to identify the diagnostic accuracy and optimal threshold of CAP for the detection of liver-fat among PLWH with magnetic resonance imaging proton-density fat fraction (MRI-PDFF) as the reference standard.MethodsPatients from a prospective single-center cohort of PLWH at risk for HIV-associated nonalcoholic fatty liver disease (NAFLD) who underwent contemporaneous MRI-PDFF and CAP assessment were included. Subjects with other forms of liver disease including viral hepatitis and excessive alcohol intake were excluded. Receiver operatic characteristic (ROC) curve analysis were performed to identify the optimal threshold for the detection of HIV-associated NAFLD (liver fat ≥ 5%).ResultsSeventy PLWH (90% men) at risk for NAFLD were included. The mean (± standard deviation) age and body mass index were 48.6 (±10.2) years and 30 (± 5.3) kg/m2, respectively. The prevalence of HIV-associated NAFLD (MRI-PDFF ≥ 5%) was 80%. The M and XL probes were used for 56% and 44% of patients, respectively. The area under the ROC curve of CAP for the detection of MRI-PDFF ≥ 5% was 0.82 (0.69-0.95) at the cut-point of 285 dB/m. The positive predictive value of CAP ≥ 285 dB/m was 93.2% in this cohort with sensitivity of 73% and specificity of 78.6%.ConclusionsThe optimal cut-point of CAP to correctly identify HIV-associated NAFLD was 285 dB/m, is similar to previously published cut-point for primary NAFLD and may be incorporated into routine care to identify patients at risk of HIV-associated NAFLD