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Statin Therapy Does Not Reduce Liver Fat Scores in Patients Receiving Antiretroviral Therapy for HIV Infection.
El Kamari, V, Hileman, CO, Gholam, PM, Kulkarni, M, Funderburg, N, McComsey, GA
Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association. 2019;(3):536-542.e1
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Abstract
BACKGROUND & AIMS Therapies are needed to limit progression of fatty liver diseases in patients with human immunodeficiency virus (HIV) infection. We analyzed data from a prospective study of the effects of rosuvastatin (a statin) on hepatic steatosis in HIV-positive adults. METHODS We performed a secondary analysis of data from a double-blind trial of adult patients with HIV infection (78% male; 68% African American; mean age, 46 y; body mass index, 29 kg/m2; HIV1 RNA < 1000 copies/mL; low-density lipoprotein cholesterol, <130 mg/dL) receiving antiretroviral therapy. The patients were randomly assigned to groups given 10 mg daily rosuvastatin (n = 72) or placebo (n = 75). Demographic and clinical data were collected, and blood samples were analyzed. Changes in liver fat score (LFS, a composite score calculated from metabolic and liver function parameters) and markers of systemic inflammation and immune activation were assessed through 96 weeks of drug or placebo administration. We performed multivariable linear and logistic regressions to study relationships among variables. RESULTS The placebo and rosuvastatin groups each had significant increases in LFS, compared with baseline, at 96 weeks (P = .01 and P < .01; P = .49 for difference increase between groups). Baseline LFS was independently associated with blood level of C-X-C motif chemokine ligand 10 (P = .04) and the soluble CD163 molecule (P = .01). After we adjusted for baseline characteristics, an increase in LFS over time was significantly associated with the blood level of C-X-C motif chemokine ligand 10 (P = .04), insulin resistance (P < .01), and viral load (P = .02), but not rosuvastatin use (P = .06). CONCLUSIONS In a secondary analysis of data from a trial of patients receiving treatment for HIV infection, hepatic steatosis increased over time, regardless of statin treatment, and was independently associated with markers of immune activation. Patients who received rosuvastatin appeared to have a nonsignificant increase in hepatic steatosis over 96 weeks. Despite their ability to reduce the risk of cardiovascular disease, statins do not appear to reduce hepatic steatosis. Clinicaltrials.gov no: NCT01218802.
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Non-alcoholic steatohepatitis in morbidly obese patients.
Tran, A, Gual, P
Clinics and research in hepatology and gastroenterology. 2013;(1):17-29
Abstract
The hepatic complications of morbid obesity range from steatosis to steatohepatitis (Non-alcoholic steatohepatitis [NASH]), fibrosis, cirrhosis and finally hepatocellular carcinoma. The pathophysiological mechanisms of the progression of a normal liver to a liver showing steatosis and then steatohepatitis are complex, including, per se, insulin-resistance, iron accumulation, oxidative stress and hepatocyte death. An imbalance in anti- and pro-inflammatory factors may be the trigger. These factors can originate from intra- or extrahepatic sites, particularly the adipose tissue and the gut. This review will provide insight into the current diagnosis and understanding of hepatic inflammation including non-invasive markers of NASH (markers of hepatocyte death), intrahepatic mechanisms (regulation of the immune and inflammatory response, hepatocellular iron deposition, hepatocyte death) and extrahepatic factors (from adipose tissue and gut) in morbidly obese patients.
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Liver steatosis in celiac disease: the open door.
Abenavoli, L, Luigiano, C, Larussa, T, Milic, N, De Lorenzo, A, Stelitano, L, Morace, C, Consolo, P, Miraglia, S, Fagoonee, S, et al
Minerva gastroenterologica e dietologica. 2013;(1):89-95
Abstract
Non-alcoholic fatty liver disease (NAFLD) is a common disease of unknown origin characterized by histological features similar to alcoholic-like liver injury but in the absence of significant alcohol intake. Non-alcoholic fatty liver disease refers to a spectrum of diseases of the liver ranging from simple steatosis (i.e., fatty infiltration of the liver) to nonalcoholic steatohepatitis (i.e., steatosis with inflammation and hepatocyte necrosis) to cirrhosis. Non-alcoholic fatty liver disease is frequently associated with disorders such as insulin resistance, obesity, type 2 diabetes mellitus, hyperlipidemia and protein-calorie malnutrition. However, in a subgroup of NAFLD patients, the true relevant cause remains undetermined. Celiac disease (CD) is a common immune-mediated disorder and develops in genetically susceptible subjects after the ingestion of gluten proteins. Celiac disease has been found in about 10% of patients with unexplained abnormal liver tests, and in about 3.5% of patients with NAFLD as the only manifestation of the disease. The frequency of subclinical or silent presentations in older children and adults highlights the importance of CD screening in patients with unexplained chronic abnormal liver function tests and NAFLD without any specific etiology. The pathogenesis of liver steatosis in CD is uncertain. The aims of this review are to describe the possible mechanisms involved in the occurrence and progression of liver steatosis in CD patients.
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Angiotensin-receptor blockers as therapy for mild-to-moderate hypertension-associated non-alcoholic steatohepatitis.
Georgescu, EF, Ionescu, R, Niculescu, M, Mogoanta, L, Vancica, L
World journal of gastroenterology. 2009;(8):942-54
Abstract
AIM: To evaluate insulin resistance, cytolysis and non-alcoholic steatohepatitis (NASH) score (NAS) using the Kleiner and Brunt criteria in 54 patients with NASH and mild-to-moderate hypertension, treated with telmisartan vs valsartan for 20 mo. METHODS All patients met the NCEP-ATP III criteria for metabolic syndrome. Histology confirmed steatohepatitis, defined as a NAS greater than five up to 3 wk prior inclusion, using the current criteria. Patients with viral hepatitis, chronic alcohol intake, drug abuse or other significant immune or metabolic hepatic pathology were excluded. Subjects were randomly assigned either to the valsartan (V) group (standard dose 80 mg o.d., n = 26), or to the telmisartan (T) group (standard dose 20 mg o.d., n = 28). Treatment had to be taken daily at the same hour with no concomitant medication or alcohol consumption allowed. Neither the patient nor the medical staff was aware of treatment group allocation. Paired liver biopsies obtained at inclusion (visit 1) and end of treatment (EOT) were assessed by a single blinded pathologist, not aware of patient or treatment group. Blood pressure, BMI, ALT, AST, HOMA-IR, plasma triglycerides (TG) and total cholesterol (TC) were evaluated at inclusion and every 4 mo until EOT (visit 6). RESULTS At EOT we noticed a significant decrease in ALT levels vs inclusion in all patients and this decrease did not differ significantly in group T vs group V. HOMA-IR significantly decreased at EOT vs inclusion in all patients but in group T, the mean HOMA-IR decrease per month was higher than in group V. NAS significantly diminished at EOT in all patients with a higher decrease in group T vs group V. CONCLUSION Angiotensin receptor blockers seem to be efficient in hypertension-associated NASH. Telmisartan showed a higher efficacy regarding insulin resistance and histology, perhaps because of its specific PPAR-gamma ligand effect.
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Genetics of alcoholic liver disease and nonalcoholic fatty liver disease.
Wilfred de Alwis, NM, Day, CP
Seminars in liver disease. 2007;(1):44-54
Abstract
Although the vast majority of heavy drinkers and individuals with obesity, insulin resistance, and the metabolic syndrome have steatosis, only a minority ever develop steatohepatitis, fibrosis, and cirrhosis. Genetic and environmental risk factors for advanced alcoholic liver disease (ALD) and nonalcoholic fatty liver disease (NAFLD) seem likely to include factors that influence the severity of steatosis and oxidative stress, the cytokine milieu, the magnitude of the immune response, and/or the severity of liver fibrosis. For ALD, the dose and pattern of alcohol intake, coffee intake, and dietary and other lifestyle factors leading to obesity are the most important environmental determinants of disease risk. For NAFLD, dietary saturated fat and antioxidant intake, small bowel bacterial overgrowth, and obstructive sleep apnea syndrome may play a role. Family studies and interethnic variations in susceptibility suggest that genetic factors are important in determining disease risk. For ALD, functional polymorphisms in the ADH and ALDH alcohol metabolizing genes play a role in determining susceptibility in Oriental populations. No genetic associations with advanced NAFLD have been replicated in large studies. Preliminary data suggest that polymorphisms in the genes encoding microsomal triglyceride transfer protein, superoxide dismutase 2, the CD14 endotoxin receptor, tumor necrosis factor alpha, transforming growth factor beta, and angiotensinogen may be associated with steatohepatitis or hepatic fibrosis or both.