History Of Excessive Alcohol Consumption Research Articles

Clinical classification and characteristics of alcoholic myocardial injury

Objective: To explore the clinical classification and characteristics of patients with alcoholic myocardial injury in the early and late stages, and to improve the understanding of early diagnosis of alcoholic myocardial injury. Methods: From December 2016 to December 2018, a total of 102 patients with long-term history of excessive alcohol consumption, cardiovascular symptoms and evidence of myocardial injury who were admitted to the cardiology outpatient clinic of Hangzhou First People's Hospital, the Third People's Hospital of Yuhang, Dajiangdong Hospital, the Second People's Hospital of Fuyang, and the People's Hospital of Linan were enrolled. According to diagnostic criteria of alcoholic cardiomyopathy (ACM), the patients were divided into ACM group (36 cases) and non-ACM group (66 cases). The baseline data, electrocardiogram and echocardiography characteristics of the two groups were recorded and analyzed. Results: There was no significant difference in the baseline between the two groups (P>0.05), including consumption and duration of alcohol. The left ventricular end-diastolic and right ventricular diameters in ACM group were (59±5) mm and (24±4) mm, respectively, which were significantly higher than those in non-ACM group ((51±4)mm, (22±4) mm, P<0.001 and P=0.044) . The left ventricular ejection fraction in ACM group was 41%±4%, which was significantly lower than that of non-ACM group (63%±8%, P<0.001). The incidence of biatrial enlargement in non-ACM group was 57.58%, which was significantly higher than that of ACM group (36.11%, P=0.038). The incidence of atrial fibrillation in non-ACM group was 54.55%, which was significantly higher than that of ACM group (27.78%, P=0.009). The incidence of diastolic heart failure in non-ACM group was significantly higher than that of ACM group (P=0.005). Conclusions: ACM is characterized by ventricular enlargement, decreased ejection fraction and heart failure, while non-ACM may belong to the early stage of alcoholic myocardial injury, characterized by biatrial expansion, atrial fibrillation and diastolic insufficiency. Due to the lack of understanding and no clinical diagnostic criteria, non-ACM is prone to be missed diagnosed and misdiagnosed.

Regulatory Non-coding RNAs Network in Non-alcoholic Fatty Liver Disease.

Non-alcoholic fatty liver disease (NAFLD) spectrum comprises simple steatosis and non-alcoholic steatohepatitis (NASH) that can lead to fibrosis and cirrhosis. The patients usually have no history of excessive alcohol consumption and other etiologies that can cause fatty liver. Understanding of the pathophysiology of NAFLD has revealed that non-coding RNAs (ncRNAs) play significant roles in modulating the disease susceptibility, pathogenesis and progression. Currently, the ncRNAs are grouped according to their sizes and their regulatory or housekeeping functions. Each of these ncRNAs has a wide range of involvement in the regulation of the genes and biological pathways. Here, we briefly review the current literature the regulatory ncRNAs in NAFLD pathogenesis and progression, mainly the microRNAs, long non-coding RNAs and circular RNAs. We also discuss the co-regulatory functions and interactions between these ncRNAs in modulating the disease pathogenesis. Elucidation of ncRNAs in NAFLD may facilitate the identification of early diagnostic biomarkers and development of therapeutic strategies for NAFLD.

Pouch Wall Thickness and Floppy Pouch Complex

Introduction: Floppy pouch complex (FPC) consists of disease phenotypes in patients with ileal pouches, including pouch prolapse, afferent limb syndrome, enterocele, redundant loop, and pouch folding (Figure 1). The main symptoms of patients with FPC are dyschezia, incomplete evacuation, and bloating. Our recent study demonstrated that lower body weight, lower peripouch fat, family history of IBD, female gender, and dyschezia are risk factors for FPC patients with inflammatory bowel disease (IBD). The aim of the study was to investigate the relationship between FPC and pouch wall thickness.691_A Figure 1. Categorical analysis of FPC and pouch wall thickness.Methods: This case-control study included all eligible patients with FPC from our prospectively maintained, IRB-approved Pouchitis Registry from 2011 to 2017. We measured pouch wall thickness on fully distended pouches on cross-sectional imaging. Patients with stoma or non-distended pouches were excluded. Categorical analysis was performed to explore risk factors of FPC. Results: A total of 140 out of 451 patients from our Pouch Database found to have fully distended pouches on imaging. Of the 140, 32 (22.9%) patients had diagnoses of FPC. Out of 32 patients in study group, 14 (43.8%) were female and 11 (34.4%) had smoking history. Eight (25.0%) patients had history of excessive alcohol consumption. Three (9.4%) patients had extra-intestinal manifestations (EIM) of IBD. Thirteen (40.6%) patients had family history of IBD. Twenty eight (87.5%) patients had j-pouch and 1 (3.1%) had an s pouch. Seven (21.9%) patients underwent 1-stage pouch surgery, 16 (50.0%) had 2- stage pouch surgery, 9 (28.1%) had 3-stage pouch surgery. Patients were further categorized based on pouch wall thickness: 21 (65.6%) patients had 1-1.9 mm pouch wall thickness; 8 (25.0%) had 2-2.9mm; and 3 (9.4%) had 3-3.9mm thick pouch wall. The control group of 106 patients without FPC was also divided into 3 subgroups based on the pouch wall thickness: 47 (44.3%) had 1-1.9 mm; 50 (47.2%) had 2-2.9mm; and 9 (8.5%) 3-3.9mm. Statistical analysis showed that patients with a pouch wall thickness of 1-1.9 mm and 2-2.9 mm were shown to have a higher incidence of FPC (65.6% vs. 44.3%, p = 0.04; 25.0% vs. 47.3%, p = 0.03) than controls (Table 1). Conclusion: This study showed that patients with thin pouch wall tend to have a higher risk of FPC. These findings will have implications in both diagnosis and investigation of etiopathogenesis of this group of challenging disorders.

Aggressive non-alcoholic steatohepatitis following rapid weight loss and/or malnutrition

While non-alcoholic steatohepatitis is a slowly progressive disease, patients may rarely present in acute liver failure. We describe six patients who developed severe hepatic dysfunction following rapid weight loss or malnutrition. Rapid weight loss (18 to 91 kg) occurred after Roux-en-Y gastric bypass in four patients and starvation-like dieting or hypoalbuminemia was noted in two patients. Four patients either died or received an urgent liver transplant. Pathologic findings were characterized by advanced alcoholic steatohepatitis-like features, including extensive/circumferential centrizonal pericellular fibrosis, central scar with perivenular sclerosis/veno-occlusion with superimposed hepatocellular dropout, abundant/prominent hepatocellular balloons, and numerous Mallory–Denk bodies, but there was no history of excess alcohol consumption. This study characterizes clinicopathologic features of aggressive non-alcoholic steatohepatitis following rapid weight loss or malnutrition, which should be included in the differential diagnosis with alcohol when a patient is considered for liver transplantation. The mechanism of liver injury in aggressive steatohepatitis is unknown, but rapid fat mobilization in obese patients may potentially cause oxidative stress to the liver and further study is needed to determine if there is a genetic predisposition to this form of injury and if antioxidants may protect the liver during rapid weight loss/malnutrition.

Appeals against detention in excessive security (outcomes of appeals against detention in conditions of excessive security in Scotland).

The Mental Health (Care and Treatment) (Scotland) Act 2003 introduced the right for patients in high-security psychiatric care to appeal against detention in conditions of excessive security. A previous study examined the first 100 patients to appeal under this provision. In this study we compare them with the next cohort of 110 patients to lodge an appeal, finding, contrary to expectations, no change in patient characteristics or the outcome of their appeals. The clinical, legal and demographic features of successful and unsuccessful appellants, who made up 38% and 27% of the 110 patients, respectively, were also compared. Those patients with the support of their responsible medical officer and those already included on a transfer list had a significantly better chance of success (p = 0.00). It was also found that a history of excessive alcohol consumption was associated with successful appeals (p = 0.002). A diagnosis of learning disability was associated with unsuccessful appeals (p = 0.018), though the sub-sample was very small. These findings are important given the forthcoming extension of this right of appeal to other levels of security.

Prevalence of Non-alcoholic Fatty Liver Disease and Steatohepatitis Risk Factors in Patients Undergoing Bariatric Surgery.

Non-alcoholic fatty liver disease (NAFLD) associated with obesity comprises pathological changes ranging from steatosis to steatohepatitis; these can evolve to cirrhosis and hepatocellular carcinoma. The objectives of this study are to assess the prevalence of and predictive markers for steatohepatitis in obese patients undergoing bariatric surgery. A prospective study of 184 morbidly obese patients undergoing bariatric surgery formed the study cohort. Patients taking potentially hepatotoxic medications and those with viral diseases and a history of excessive alcohol consumption were excluded. Liver biopsies were performed during surgery with a "Trucut" needle. Patients were classified into the following groups according to the histopathological findings: normal, steatosis, mild steatohepatitis, and moderate-severe steatohepatitis. Factors associated with steatohepatitis were evaluated using logistic regression. p values <0.05 were considered significant. The prevalence of NAFLD was 84 % (steatosis, 22.0 %; mild steatohepatitis, 30.8 %; moderate-severe steatohepatitis, 32.0 %). Independent predictive factors for steatohepatitis were age (odds ratio (OR), 1.05; 95 % confidence interval (CI), 1.01-1.09; p = 0.011), waist circumference (OR, 1.03; 95 % CI, 1.00-1.06; p = 0.021), serum alanine aminotransferase (ALT) levels (OR, 1.04; 95 % CI, 1.01-1.08; p = 0.005), and serum triglyceride levels (OR, 1.01; 95 % CI, 1.00-1.01; p = 0.042). Score values for each predictor were derived from regression coefficients and odds ratio, and a total (risk) score was obtained from the sum of the points to evaluate the probability of having steatohepatitis. Age, waist circumference, serum ALT levels, and serum triglyceride levels are efficient and non-invasive predictive markers for the diagnosis and management of steatohepatitis in morbidly obese patients.

Thyroid function is associated with non-alcoholic fatty liver disease in euthyroid subjects

Objectives: This study was designed to test the hypothesis that normal thyroid function is associated with non-alcoholic fatty liver disease (NAFLD) in euthyroid general subjects. Methods: A total of 739 euthyroid subjects were enrolled in this cross-sectional study. Using ultrasound, a diagnosis of NAFLD was made in subjects without a history of excessive alcohol consumption or liver diseases. Fasting serum samples were collected for determining thyroid function [thyroid-stimulating hormone (TSH), free thyroxine (FT4), and free triiodothyronine (FT3) levels] and other biochemical parameters. Results: Among the enrolled subjects, 196 (26.5%) satisfied the diagnostic criteria for NAFLD. Subjects with NAFLD had significantly higher TSH levels and lower FT4 levels than those without NAFLD (p < 0.01 for both). NAFLD prevalence increased gradually with increasing quartiles of TSH levels and decreasing quartiles of FT4 levels. After adjustment for gender and age, TSH levels were found to correlate positively with body mass index (BMI), waist circumference (WC), and LDL-cholesterol levels (p < 0.05 for all) and negatively with HDL-cholesterol levels (p < 0.01). FT4 levels correlated negatively with both BMI and WC (p < 0.05 for both). Multiple logistic regression analysis showed that TSH and FT4 levels were independent risk factors for NAFLD [odds ratio (OR): 2.21, 95% confidence interval (CI): 1.21–4.02, p = 0.01, for TSH levels; OR: 0.39, 95% CI: 0.17–0.87, p = 0.02, for FT4 levels]. Conclusion: Our findings suggest that serum FT4 and TSH levels, even those within the reference range, are associated with NAFLD in the general population, independent of known metabolic risk factors.

Hip fractures and chronic alcohol excess: a series of 7,023 cases.

We aim to compare trends in characteristics and outcomes for 131 patients with evidence of excess alcohol intake at the time of admission with a hip fracture against 6,892 hip fracture patients with no evidence of alcohol excess. Alcohol excess was determined by a finding of abnormal liver function tests in association with a history of excessive alcohol consumption. Patients who consumed excess alcohol were younger (64 versus 80 years mean age), more likely to be male (47% versus 22%), smoke cigarettes (54% versus 11%), be more mobile and less likely to use a walking aid (28% versus 46%). They were also more likely to sustain an extracapsular fracture (53% versus 39%) and to be living in their own homes at the time of injury (85% versus 66%). Hypertension and cardiac disease were less common in those with alcohol excess. Postoperatively those with alcohol abuse had a shorter hospital stay (mean nine days versus 16 days) but were at a greater risk of developing deep wound infections (2.3% versus 0.6%). For those patients who sustained intracapsular fractures treated by internal fixation there was an increased risk of fracture non-union occurring (29% versus 16%) but there were no other differences in operative complications.

Giant Cell Myocarditis and Endomyocardial Calcification in a 2.5-Month-Old Infant Triggered by Excessive Maternal Alcohol Abuse: Case Study of an Unusual Association

This report describes an unusual case of a 2.5-month-old infant's sudden death secondary to giant cell myocarditis and endomyocardial calcification, both unusual entities in pediatric patients. The mother had a history of excessive alcohol consumption during pregnancy and the postnatal period. No infectious etiologies, hypersensivity, or autoimmune disorders were identified. Therefore, the authors assume that alcohol exposure might be responsible for the inflammatory giant cell process complicated with endomyocardial calcification in susceptible infants. This report is the first to describe the rare form of noninfectious myocarditis complicated with endomyocardial calcification possibly triggered by a toxic agent. The authors discuss the possible interaction between these processes that led to the infant's sudden death.

Murine Models of Nonalcoholic Fatty Liver Disease and Steatohepatitis

In 1980, Ludwig et al. first reported patients of steatohepatitis who lacked a history of excessive alcohol consumption but showed liver histology resembling alcoholic hepatitis and progression to cirrhosis of the liver accompanied by inflammation and fibrosis. The development of nonalcoholic steatohepatitis (NASH) is associated with obesity, diabetes mellitus, insulin resistance, and hyperlipidemia. However, the pathogenesis of NASH remains incomplete. A “multiple-hit” hypothesis for the pathogenesis of NASH based on an animal model has been proposed and remains a foundation for research in this field. We review the important dietary and genetic animal models and discuss the pathogenesis of NASH.

Excessive alcohol consumption after liver transplantation impacts on long-term survival, whatever the primary indication

Beyond 5 years, poorer survival, related to alcohol relapse, is observed in patients with liver transplant for alcohol-related liver disease (ALD). However, alcohol consumption has been significantly understudied in non-ALD transplant recipients. We aimed at analyzing the impact of alcohol consumption on long-term survival irrespective of the indication for transplantation. This observational study included consecutive adult recipients of a primary liver graft between 1991 and 2007 in our hospital, who survived >6 months. Patients without ALD as primary indication, but with a history of excessive alcohol consumption before transplantation, were classified as secondary indication ALD. We studied the impact on survival of excessive consumption of alcohol after transplantation and several other variables. The 441 patients had mean follow-up of 81.7 months. Among the 281 patients with excessive alcohol consumption before transplantation, 206 had ALD as primary indication. After transplantation, alcohol consumption was reported by 32.3% of the study population, 43.7% in primary indication ALD, and 24.3% in non-ALD patients. Survival was 82% at 5 years and 49% at 10 years for patients with excessive alcohol relapse, compared with 86% and 75%, respectively, for patients without persistent excessive alcohol relapse. By multivariable analysis, the independent risk factors of death were: excessive alcohol relapse, age >51 years, post-transplantation diabetes mellitus, cyclosporine-based immunosuppression, and non-hepatic cancer. Excessive alcohol consumption has a negative impact on long-term survival after liver transplant, irrespective of the primary indication. Death is mainly due to recurrence of liver disease and non-hepatic cancer.

Increased prevalence of chronic kidney disease in patients with Type 1 diabetes and non‐alcoholic fatty liver

We determined whether non-alcoholic fatty liver is associated with an increased prevalence of chronic kidney disease in Type 1 diabetes. We studied 343 patients with Type 1 diabetes, who had no history of excessive alcohol consumption or other secondary causes of chronic liver disease. Non-alcoholic fatty liver was diagnosed by ultrasonography. Chronic kidney disease was defined as presence of either abnormal albuminuria (i.e., urinary albumin/creatinine ratio ≥ 30 mg/g) or estimated glomerular filtration rate of less than 60 ml min(-1) 1.73 m(-2) . Compared with those without steatosis, patients with non-alcoholic fatty liver (n = 182) had significantly lower estimated GFR (83.0 ± 27 vs. 93.3 ± 29 ml min(-1) 1.73 m(-2) , P < 0.001) and a greater prevalence of abnormal albuminuria (50.0 vs. 20.5%, P < 0.0001) and chronic kidney disease (54.4 vs. 24.2%, P < 0.0001). Multivariable logistic regression analysis revealed that non-alcoholic fatty liver was associated with an increased risk of either abnormal albuminuria (adjusted odds ratio 2.21, 95% CI 1.2-4.1, P = 0.01) or chronic kidney disease (adjusted odds ratio 1.93, 95% CI 1.1-3.6, P = 0.02), independently of age, gender, smoking status, physical activity, diabetes duration, HbA(1c) , BMI, systolic blood pressure, plasma lipids and use of anti-hypertensive and lipid-lowering medications. Our findings demonstrate that ultrasound-diagnosed non-alcoholic fatty liver is associated with a higher prevalence of chronic kidney disease in patients with Type 1 diabetes, independently of several risk factors, including the components of the metabolic syndrome.

Assessment of NAFLD cases and its correlation to BMI and metabolic syndrome in healthy blood donors in Kerman.

The aim of this study was to review cases of non-alcoholic fatty liver disease cases and to determine the prevalence of non-alcoholic fatty liver disease as a cause of elevated alanine aminotransferase in healthy blood donors in the Permian area and also assess risk factors of NAFLD such as BMI and correlation with metabolic syndrome in these subjects. Non-alcoholic fatty liver disease has been increasingly recognized as the most common pathological conditions affecting the liver. Non-alcoholic fatty liver disease is now recognized as the hepatic component of the metabolic syndrome, which includes hyperlipidemia, glucose intolerance, obesity, and systemic hypertension. 2002 randomly selected blood donors were recruited for this study. Subjects with elevated serum ALT level (greater than two times the upper limit of normal) were chosen for further follow up. Subjects with a persistently elevated ALT level, evidence of steatosis on computerized tomography and a negative cirrhosis screen (viral hepatitis B and C serology, autoimmune hepatitis, transferrin saturation <45% and a no history of excess alcohol consumption or hepatotoxic medication) were presumed to have non-alcoholic fatty liver disease. 378 donors (20.5% of all subjects recruited) had elevated ALT levels at first measurement. 35 cases had persistently elevated serum ALT level. In 22 of these 35 cases (62.9%) non-alcoholic fatty liver disease was the diagnosis. The mean body mass index of the 22 cases was 31.18 ±5.7 and non-alcoholic fatty liver disease was associated with the metabolic syndrome in these subjects. Non-alcoholic fatty liver disease is the most common diagnosis for subjects with elevated serum ALT level in healthy blood donors in Kerman, Iran.

Relative Etiological Role of Prior Hepatitis B Virus Infection and Nonalcoholic Fatty Liver Disease in the Development of Non-B Non-C Hepatocellular Carcinoma in a Hepatitis B-Endemic Area

Background and Aims: We investigated the relative etiological role of prior hepatitis B virus (HBV) infection and nonalcoholic fatty liver disease (NAFLD) in the development of non-B non-C, non-alcohol or specific cause-related hepatocellular carcinoma (NBNC-NA-NS HCC) in an HBV-endemic area of Korea. Methods: A total of 329 patients with NBNC-NA-NS HCC were enrolled in this study. Prior HBV infection was defined as the presence of isolated IgG hepatitis B core antibody (anti-HBc), and NAFLD was diagnosed by the findings from the imaging in the absence of a history of excessive alcohol consumption. Results: Prior HBV infection was the most common cause of underlying liver disease (76.6%). Only 8.2% of the patients had NAFLD as the only risk factor and the same proportion of patients had evidence of both prior HBV infection and NAFLD. Patients without definitive causes accounted for 7.0% of the cases. During the past 10 years, the relative proportion of isolated IgG anti-HBc-positive HCC decreased significantly from 86.6% in 2001–2005 to 67.4% in 2006–2010 (p < 0.0001) and that of NAFLD-related HCC increased from 3.8% to 12.2% in the same period, respectively (p = 0.008). The mean age of NAFLD-related HCC patients (67.3 years) was significantly older than that of HCC patients related to prior HBV infection (61.2 years, p < 0.001). Conclusions: NAFLD-related HCC increased significantly while HCC related to prior HBV infection decreased during the past 10 years in an HBV-endemic area of Korea; however, the relative etiological role of prior HBV infection was still greater than that of NAFLD in the development of NBNC-NA-NS HCC.

Ruptured duodenal varices arising from the main portal vein successfully treated with endoscopic injection sclerotherapy: a case report

Duodenal varices result from retroperitoneal portosystemic shunts that usually come from the pancreaticoduodenal vein and drain into the inferior vena cava. Because they are a rare but fatal cause of gastrointestinal bleeding, a prompt hemostatic intervention is mandatory. A 62-year-old man who had a history of excessive alcohol consumption presented with massive hematemesis and melena. Emergent endoscopy revealed ruptured varices with an adhering whitish fibrin clot on the postbulbar portion of the duodenum. Abdominal computed tomography demonstrated a cirrhotic liver with venous collaterals around the duodenum and extravasated contrast in the second and third portions. The collaterals originated from the main portal vein and drained via the right renal vein into the inferior vena cava. Endoscopic injection sclerotherapy with cyanoacrylate was successful in achieving hemostasis, and resulted in the near eradication of duodenal varices at a 6-month follow-up.

Prevalence of psychiatric and physical morbidity in an urban geriatric population

Background:With a rapidly increasing population of older aged people, epidemiological data regarding the prevalence of mental and physical illnesses are urgently required for proper health planning. However, there is a scarcity of such data from India.Aims:To study the frequency and pattern of psychiatric morbidity present and the association of physical illness with psychiatric morbidity in an elderly urban population.Settings and Design:Cross-sectional, epidemiological study.Materials and Methods:All the consenting elderly persons in a municipal ward division (n=202) were enrolled after surveying a total adult population of 7239 people. A door to door survey was undertaken where the participants were interviewed and physically examined. General Health Questionnaire-12, Mini Mental State Examination, CAGE Questionnaire and Geriatric Depression Scale were used in the interview apart from consulting the available documents. Other family members were also interviewed to verify the information.Statistical Analysis:Chi-square test with Yates correction.Results:Psychiatric illnesses were detected in 26.7% while physical illnesses were present in 69.8% of the population surveyed. Predominant psychiatric diagnoses were depressive disorders, dementia, generalized anxiety disorder, alcohol dependence and bipolar disorder. The most common physical illness was visual impairment, followed by cardiovascular disease, rheumatic illnesses, pulmonary illnesses, hearing impairment, genitourinary diseases and neurological disorders. Presence of dementia was associated with increased age, single/widowed/separated status, nuclear family, economic dependence, low education, cardiovascular disorders, rheumatic disorders and neurological disorders. Depression was associated with female sex, single/widowed/separated status, staying in nuclear families, economic dependence on others and co-morbid physical illnesses, specifically cardiovascular disorders and visual impairment.Conclusions:This study presented a higher rate of dementia and old age depression. The interesting association with several sociodemographic factors as well as physical illnesses may have important implications for health planning.

Severe anemia by rectal prolapse

A 57 year old woman, with no known allergies, a history of excessive alcohol consumption and a previous diagnosis of compensated alcoholic cirrhosis of the liver, was admitted because of intermittent rectal bleeding and severe anaemia ( Hb: 5 gr/dl). Physical examination showed a large rectal prolapse (Fig 1). After reducing the prolapse, a colonoscopy was performed and no other abnormalities were found. We also performed an anal endosonography that showed sphincter changes secondary to longstanding complete rectal prolapse, without disruption at any level. A surgical treatment was decided and it consisted in rectal wall section 1.5 cm. above the dentate line, opening of the anterior pelvic peritoneum and circumferential section of the meso with ligature and haemostatic suture. After separating the vaginal wall, the redundant peritoneum was excised and was fixed to the colon. Furthermore, a four sutures levator muscle anterior plasty and a manual coloanal anastomosis were performed.

Animal models of nonalcoholic fatty liver disease

In 1980, Ludwig and colleagues described a series of patients with liver histology characterized by the accumulation of fat and the presence of hepatic necroinflammation in the absence of a history of excessive alcohol consumption. They coined the term nonalcoholic steatohepatitis (NASH), which today is regarded as one of the most common causes of liver disease in affluent countries. NASH is a subset of a larger spectrum of diseases termed fatty liver disease (including alcoholic and nonalcoholic fatty liver disease; AFLD and NAFLD, respectively). NAFLD and NASH are linked to visceral adiposity, insulin resistance, dyslipidemia and type 2 diabetes, and are increasing due to the prevalence of the metabolic syndrome. In this context, research has been undertaken using animals to model human steatosis and NAFLD to NASH disease progression. This Review discusses the prevalent dietary and inflammation-based genetic animal models described in recent years.

Role for mammalian target of rapamycin complex 1 signaling in neuroadaptations underlying alcohol-related disorders

Alcohol addiction is a chronically relapsing disorder that includes certain maladaptive learning and memory. The serine and threonine kinase complex, mammalian target of rapamycin complex 1 (mTORC1), has been implicated in synaptic plasticity, learning, and memory by controlling protein translation. Here we show that administration of alcohol and excessive voluntary consumption of alcohol induce the activation of the mTORC1-mediated signaling pathway in the nucleus accumbens (NAc) of rodents. We further show that the protein expression levels of GluR1 and Homer, two synaptic proteins whose translation has been shown to be modulated by mTORC1, are up-regulated in the NAc of rodents with a history of excessive alcohol consumption. In addition, our results document that the Food and Drug Administration-approved inhibitor of mTORC1, rapamycin, decreases expression of alcohol-induced locomotor sensitization and place preference, as well as excessive alcohol intake and seeking in preclinical rodent models of alcohol abuse. Together, our results suggest that mTORC1 within the NAc is a contributor to molecular mechanisms underlying alcohol-drinking behaviors. Furthermore, despite its massive health and socioeconomic impact worldwide, pharmacotherapies for alcohol abuse and addiction remain limited. Our data therefore put forward the possibility that targeting the mTORC1 signaling cascade is an innovative and valuable strategy for the treatment of alcohol use and abuse disorders.

Alcoholic steatohepatitis

Severe alcoholic steatohepatitis has a poor prognosis and is characterized by jaundice and signs of liver failure. Its incidence is unknown, but prevalence is around 20% in cohorts of alcoholics undergoing liver biopsy. Diagnosis is established with elevated liver transaminases, neutrophil counts, serum bilirubin, and impaired coagulation and a history of excessive alcohol consumption, and exclusion of other etiologies. Histology is helpful but not mandatory. Prognostic scores include the Maddrey's discriminant function, the model of end-stage liver disease, and the Glasgow Alcoholic Hepatitis Score. Pathophysiology involves hepatic fat storage, increased hepatic uptake of gut-derived endotoxins triggering Kupffer cell activation and release of proinflammatory triggers, induction of cytochrome P4502E1 producing toxic acetaldehyde and reactive oxygen species, and ethanol-mediated hyperhomocysteinemia causing endoplasmic reticulum stress. Treatment includes abstinence, enteral nutrition, corticosteroids, and possibly pentoxifylline. A debate is ongoing whether certain patients with severe alcoholic steatohepatitis could be eligible for liver transplantation.