Hepatobiliary and pancreatic disorders in celiac disease

A variety of hepatic and biliary tract disorders may complicate the clinical course of celiac disease. Some of these have been hypothesized to share common genetic factors or have a common immunopathogenesis, such as primary biliary cirrhosis, primary sclerosing cholangitis and autoimmune forms of hepatitis or cholangitis. Other hepatic changes in celiac disease may be associated with malnutrition resulting from impaired nutrient absorption, including hepatic steatosis. In addition, celiac disease may be associated with rare hepatic complications, such as hepatic T-cell lymphoma. Finally, pancreatic exocrine function may be impaired in celiac disease and represent a cause of treatment failure.     

Risk factors for hepatic steatosis in adults with cystic fibrosis: Similarities to non-alcoholic fatty liver disease

AIM To investigate the clinical, biochemical and imaging characteristics of adult cystic fibrosis(CF) patients with hepatic steatosis as compared to normal CF controls.METHODS We performed a retrospective review of adult CF patients in an academic outpatient setting during 2016. Baseline characteristics, genetic mutation analysis as well as laboratory values were collected. Abdominal imaging(ultrasound, computed tomography, magnetic resonance) was used to determine presence of hepatic steatosis. We compare patients with hepatic steatosis to normal controls.RESULTS Data was collected on 114 patients meeting inclusion criteria. Seventeen patients(14.9%) were found to have hepatic steatosis on imaging. Being overweight(BMI 25)(P = 0.019) and having a higher pp FEV1(75 vs 53, P = 0.037) were significantly associated with hepatic steatosis. Patients with hepatic steatosis had a significantly higher median alanine aminotransferase level(27 vs 19, P = 0.048). None of the hepatic steatosis patients had frank CF liver disease, cirrhosis or portal hypertension. We found no significant association with pancreatic insufficiency or CF related diabetes.CONCLUSION Hepatic steatosis appears to be a clinically and phenotypically distinct entity from CF liver disease. The lack of association with malnourishment and the significant association with higher BMI and higher pp FEV1 demonstrate similarities with non-alcoholic fatty liver disease. Long term prospective studies are needed to ascertain whether CF hepatic steatosis progresses to fibrosis and cirrhosis.     

Celiac disease in patients with severe liver disease: gluten-free diet may reverse hepatic failure

BACKGROUND & AIMS: Mild liver abnormalities are common in patients with celiac disease and usually resolve with a gluten-free diet. We investigated the occurrence of celiac disease in patients with severe liver failure. METHODS: Four patients with untreated celiac disease and severe liver disease are described. Further, the occurrence of celiac disease was studied in 185 adults with previous liver transplantation using serum immunoglobulin A endomysial and tissue transglutaminase antibodies in screening. RESULTS: Of the 4 patients with severe liver disease and celiac disease, 1 had congenital liver fibrosis, 1 had massive hepatic steatosis, and 2 had progressive hepatitis without apparent origin. Three were even remitted for consideration of liver transplantation. Hepatic dysfunction reversed in all cases when a gluten-free diet was adopted. In the transplantation group, 8 patients (4.3%) had celiac disease. Six cases were detected before the operation: 3 had primary biliary cirrhosis, 1 had autoimmune hepatitis, 1 had primary sclerosing cholangitis, and 1 had congenital liver fibrosis. Only 1 patient had maintained a long-term strict gluten-free diet. Screening found 2 cases of celiac disease, 1 with autoimmune hepatitis and 1 with secondary sclerosing cholangitis. CONCLUSIONS: The possible presence of celiac disease should be investigated in patients with severe liver disease. Dietary treatment may prevent progression to hepatic failure, even in cases in which liver transplantation is considered.     

675例肝脏穿刺活检的肝细胞脂肪变性分析

目的通过对675例肝脏穿刺病理结果的回顾性研究,分析各种肝脏疾病的肝细胞脂肪变性情况。方法收集西京医院2008年7月-2011年9月进行的675例肝脏穿刺活检的病理结果,分析其病理诊断及脂肪变性的构成比,肝细胞脂肪变性的发生率,以及肝细胞脂肪变性与血清甘油三酯的相关性。结果 72.6%(490/675)的肝脏穿刺患者为肝肿瘤或瘤样变、自身免疫性肝病、慢性病毒性肝炎及肝硬化。15.7%(106/675)患者存在不同程度的肝细胞脂肪变性,其中49.1%(52/106)的患者为肝硬化、病毒性肝炎及肝损害,33.0%(35/106)患者为酒精性/非酒精性脂肪肝。肝硬化患者发生肝细胞脂肪变性的比率高达30.7%。结论肝细胞脂肪变性普遍存在于各种慢性肝脏损害性疾病,尤其是肝硬化合并肝细胞脂肪变性的比率高达30.7%,需要在临床诊治过程中高度重视。     

Liver involvement in patients with erythropoietic protoporphyria

BackgroundIn erythropoietic protoporphyria (EPP), which presents with severe painful phototoxicity, progressive deposition of protoporphyrins in hepatocytes and bile canaliculi may result in liver disease. Clinically EPP related liver disease ranges from mildly elevated liver enzymes to cirrhosis and acute cholestatic hepatic failure. The prevalence of liver disease in EPP, and factors predicting the risk of developing liver disease, have not been defined in a large series of unselected EPP patients.AimTo determine the prevalence of liver disease in EPP-patients.MethodsA single-center prospective unselected cohort study of 114 adult EPP patients, who underwent routine laboratory testing, abdominal ultrasonography and transient elastography to assess the presence of steatosis (controlled attenuation parameter,dB/m) and liver stiffness (kPa).Results114 adult EPP patients were included. Elevated liver enzymes were found in 6.2% of the patients. Liver steatosis was detected in 29.0%, and significant fibrosis as assessed with liver stiffness measurements was present in 9.6% of patients. BMI positively predicted CAP-values (p = 0.026); and protoporphyrin IX levels (p = 0.043) positively predicted liver stiffness.ConclusionsThis study demonstrates a prevalence of hepatic steatosis and fibrosis in adult EPP-patients comparable to that found in the general population. Protoporphyrin IX levels correlate with increased liver stiffness in EPP.     

Serum lipid profile and hepatic steatosis of adult beta-thalassaemia patients with chronic HCV infection

OBJECTIVES: The aim of this study was to evaluate the serum lipid profile and to assess the prevalence of hepatic steatosis in adult beta-thalassaemic patients with chronic hepatitis C virus (HCV) infection. METHODS: Thirty-five adult HCV infected, multi-transfused, beta-thalassaemia patients (beta-HCV patients), 63 otherwise normal patients with chronic HCV infection (HCV patients) and 54 beta-thalassaemia patients without chronic viral hepatitis (beta patients) were studied. Total cholesterol, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides, viral markers and liver histology were evaluated. RESULTS: Serum total cholesterol, HDL-C and LDL-C were found at significantly lower levels in beta-HCV and beta patients than in HCV patients. Triglyceride levels were significantly lower in the HCV group compared with the beta group. Nine (25.7%) of the 35 beta-HCV patients had mild hepatic steatosis. Thirteen (23.6%) of 55 HCV patients presented mild and 4/55 (7.3%) moderate hepatic steatosis. None of the beta group presented steatosis. When we compared beta-HCV and HCV patients with steatosis, we found that beta-HCV patients had a lower degree of steatosis (11.1+/-7% vs 22.9+/-17.2%, P=0.021). Multivariate logistic regression analysis showed that the only independent predictor associated with hepatic steatosis in beta-HCV and HCV patients was genotype 3a (OR, 3.61; 95% CI, 1.22-10.71, P=0.021). CONCLUSIONS: Adult beta-thalassaemia patients, compared to other patients with chronic HCV infection, present lower cholesterol levels (total cholesterol, HDL, LDL) and similar frequency but a lower degree of hepatic steatosis. This difference in the degree of steatosis is most likely due to the higher prevalence of genotype 3a in the non-beta-thalassaemia group.     

The impact of visceral fat in nonalcoholic fatty liver disease: cross-sectional and longitudinal studies

Background Nonalcoholic fatty liver disease is increasing worldwide, and attention is being paid to its association with obesity and metabolic syndrome. The aim of this study was to elucidate the role of visceral fat accumulation in hepatic steatosis by cross-sectional and longitudinal studies. Methods We enrolled 125 patients in a cross-sectional study and 28 patients in a longitudinal study and examined visceral and subcutaneous fat thickness, hepatic steatosis score, and biochemical parameters. In the longitudinal study, the influence of weight change on fat distribution and hepatic steatosis was investigated. Results In the cross-sectional study, the severity of hepatic steatosis showed a significant positive correlation with body mass index, visceral fat thickness, serum albumin, alanine aminotransferase (ALT), cholinesterase, fasting insulin, and the homeostasis model assessment of insulin resistance. ALT, visceral fat thickness, and serum albumin were independent factors for hepatic steatosis. In the longitudinal study, visceral fat thickness fluctuated closely with changes in body weight, and had the strongest relationship with the change of hepatic steatosis by multivariate analysis. Conclusions Visceral fat was the most important factor for the development of hepatic steatosis. Visceral fat thickness can be measured by sonography easily, noninvasively, and repeatedly for assessment of central obesity and monitoring of the efficacy of treatment of nonalcoholic fatty liver disease.     

Hepatic steatosis and metabolic risk factors among patients with chronic hepatitis B: The multicentre,prospective CAP-Asia study

We aimed to compare the severity of liver disease, metabolic profile and cardiovascular disease (CVD) risk of chronic hepatitis B (CHB) patients with and without hepatic steatosis and patients with non-alcoholic fatty liver disease (NAFLD). Patients with NAFLD and CHB were prospectively enrolled from 10 Asian centres. Fibroscan was performed for all patients and hepatic steatosis was defined based on controlled attenuation parameter >248 dB/m. CVD risk was assessed using the Framingham risk score. The data for 1080 patients were analysed (67% NAFLD, 33% CHB). A high proportion (59%) of CHB patients had hepatic steatosis. There was a significant stepwise increase in alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transpeptidase, controlled attenuation parameter and liver stiffness measurement, from CHB patients without hepatic steatosis to CHB patients with hepatic steatosis to NAFLD patients (p < 0.001 for all comparisons). There was a significant stepwise increase in the proportion of patients with metabolic syndrome and in CVD risk, with very high or extreme CVD risk seen in 20%, 48% and 61%, across the groups (p < 0.001 between CHB patients with and without hepatic steatosis and p < 0.05 between CHB patients with hepatic steatosis and NAFLD patients). In conclusion, there was a high proportion of CHB patients with hepatic steatosis, which should be diagnosed, as they may have more severe liver disease, so that this and their metabolic risk factors can be assessed and managed accordingly for a better long-term outcome     

Prevalence of hepatic steatosis in an urban population in the United States: impact of ethnicity

Despite the increasing prevalence of nonalcoholic fatty liver disease (NAFLD), its pathogenesis and clinical significance remain poorly defined. In this study, we examined and compared the distribution of hepatic triglyceride content (HTGC) in 2,287 subjects from a multiethnic, population-based sample (32.1% white, 48.3% black, and 17.5% Hispanic) using proton magnetic resonance spectroscopy. HTGC varied over a wide range (0.0%-41.7%; median, 3.6%) in the population. Almost one third of the population had hepatic steatosis, and most subjects with hepatic steatosis had normal levels of serum alanine aminotransferase (79%). The frequency of hepatic steatosis varied significantly with ethnicity (45% in Hispanics; 33% in whites; 24% in blacks) and sex (42% in white men; 24% in white women). The higher prevalence of hepatic steatosis in Hispanics was due to the higher prevalence of obesity and insulin resistance in this ethnic group. However, the lower frequency of hepatic steatosis in blacks was not explained by ethnic differences in body mass index, insulin resistance, ethanol ingestion, or medication use. The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics. The ethnic differences in the frequency of hepatic steatosis in this study mirror those observed previously for NAFLD-related cirrhosis (Hispanics > whites > blacks). In conclusion, the significant ethnic and sex differences in the prevalence of hepatic steatosis documented in this study may have a profound impact on susceptibility to steatosis-related liver disease.     

Relationship among histologic, radiologic, and biochemical assessments of hepatic steatosis: a study of human liver samples

BACKGROUND AND AIMS: In patients with nonalcoholic fatty liver disease, there is not a consistent relationship between severity of steatosis and the presence of steatohepatitis. This leads to the possibility that severity of steatosis is not an important factor in the pathogenesis of nonalcoholic steatohepatitis. Alternatively, it is possible that currently used method to quantify hepatic steatosis (histologic grading) may not accurately reflect hepatic lipid content. Therefore, we examined the relationship between hepatic triglyceride (TG) content and nonbiochemical assessment of steatosis in 38 human liver samples. METHODS: Hepatic steatosis was histologically graded by the 3 hepatopathologists and hepatic TG levels were determined from liver homogenate. Additionally, we characterized the relationship between (a) hepatic steatosis quantified by magnetic resonance spectroscopy (MRS) and histologic grading and hepatic TG content and (b) hepatic long-chain polyunsaturated fatty acid n-6/n-3 ratio and the severity of steatosis. RESULTS: Twenty-two samples had <5% steatosis, 9 had 5% to 33% steatosis and 7 had >33% steatosis. The mean (+/-SD) hepatic TG was 1.8+/-1.3 mg/mg of protein and MRS fat score was 6.4+/-6.0. There was a significant correlation between histologic grading and hepatic TG content (r=0.64, P<0.001). A significant correlation existed between MRS fat score and histologic grading (r=0.61, P=0.006), and hepatic TG (r=0.63, P=0.004). Severity of steatosis as graded histologically had significant correlation with n-6/n-3 ratio (r=0.61, P<0.001). CONCLUSIONS: Hepatic steatosis quantified by histologic grading or by MRS is significantly reflective of hepatic TG content. Further research is needed to investigate the relationship we observed between n-6/n-3 ratio and the severity of steatosis.     

Non-invasive means of measuring hepatic fat content

Hepatic steatosis affects 20% to 30% of the general adult population in the western world. Currently, the technique of choice for determining hepatic fat deposition and the stage of fibrosis is liver biopsy. However, it is an invasive procedure and its use is limited, particularly in children. It may also be subject to sampling error. Non-invasive techniques such as ultrasound, computerised tomography （CT）, magnetic resonance imaging （MRI） and proton magnetic resonance spectroscopy （^1H MRS） can detect hepatic steatosis, but currently cannot distinguish between simple steatosis and steatohepatitis, or stage the degree of fibrosis accurately. Ultrasound is widely used to detect hepatic steatosis, but its sensitivity is reduced in the morbidly obese and also in those with small amounts of fatty infiltration. It has been used to grade hepatic fat content, but this is subjective. CT can detect hepatic steatosis, but exposes subjects to ionising radiation, thus limiting its use in longitudinal studies and in children. Recently, magnetic resonance （MR） techniques using chemical shift imaging have provided a quantitative assessment of the degree of hepatic fatty infiltration, which correlates well with liver biopsy results in the same patients. Similarly, in vivo ^1H MRS is a fast, safe, non-invasive method for the quantification of intrahepatocellular lipid （IHCL） levels. Both techniques will be useful tools in future longitudinal clinical studies, either in examining the natural history of conditions causing hepatic steatosis （e.g. non-alcoholic fatty liver disease）, or in testing new treatments for these conditions.     

Statins and hepatic steatosis: perspectives from the Dallas Heart Study

Non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease are independently associated. Due to the efficacy of 3-hydroxy 3-methylglutaryl-coenzyme A reductase inhibitors (statins) in the prevention of cardiovascular disease, increasing interest has been shown in establishing the safety of these drugs in NAFLD. In this study, the relationship between statin use, hepatic triglyceride content (HTGC), and serum alanine aminotransferase (ALT) levels was examined in 2,264 Dallas Heart Study participants who were using no lipid-lowering agent (n = 2,124) or using only a statin for lipid management (n = 140). Statin use was not associated with a greater frequency of hepatic steatosis (38% vs. 34%) or elevated serum ALT (15% vs. 13%) by a pair-matched analysis. Statin use was also not associated with a greater prevalence of elevated serum ALT among subjects with hepatic steatosis (n = 638). This finding persisted when controlling for possible sample bias as a result of current prescribing practices for statins. Among subjects with serum lipid abnormalities who were not using a statin, hepatic steatosis was present in 60% of those with mixed hyperlipidemia and 83% of those with both mixed hyperlipidemia and an elevated serum ALT. In conclusion, statin use was not associated with a higher frequency of hepatic steatosis or serum ALT abnormalities, even among those with hepatic steatosis. Individuals meeting criteria for statin therapy are likely to have coexistent hepatic steatosis.     

Evaluation of hepatosteatosis in patients with chronic hepatitis B virus infection

Background and study aimsThe current study aimed to investigate the frequency of hepatic steatosis in chronic hepatitis B (CHB) patients and determine the possible risk factors associated with its presence.Patients and methodsThis cross-sectional study retrospectively evaluated the medical records of 255 adult CHB patients visiting an infectious disease outpatient clinic. Patients with hepatitis B surface antigen positivity for >6 months and those who did not receive antiviral therapy were included in the study. The presence and stage of hepatic steatosis were determined through hepatobiliary ultrasonography.ResultsThe mean age of the patients was 40.6 ± 12.7 years. Hepatic steatosis was detected in 44.4 % of the patients through ultrasound imaging. Our findings showed that the detected steatosis prevalence in our patients with CHB was significantly higher compared to the highest prevalence of non-alcoholic steatohepatitis found in the general Turkish population (19.9 %) [RR 2.23 (1.75–2.86), p < 0.001]. CHB patients with steatosis had significantly higher age, triglyceride, and gamma-glutamyl transferase levels than those without steatosis (p < 0.05). No significant association was found between the presence of steatosis, sex, liver function test results, and platelet, alkaline phosphatase, cholesterol, alpha fetoprotein, or HBV-DNA levels. No significant relationship was found between aspartate aminotransferase (AST)/platelet ratio index (APRI) and steatosis was examined (p > 0.05). Post-hoc analysis showed a significant relationship between HBV-DNA levels and ALT, AST, and APRI scores.ConclusionOur data showed that hepatic steatosis is more common in CHB patients than in the general population. Older age and high triglyceride levels increased the risk of hepatic steatosis in CHB patients, consequently increasing GGT levels, which are indicative of liver damage, in these patients.     

Evaluation of hepatosteatosis in patients with chronic hepatitis B virus infection

Background and study aimsThe current study aimed to investigate the frequency of hepatic steatosis in chronic hepatitis B (CHB) patients and determine the possible risk factors associated with its presence.Patients and methodsThis cross-sectional study retrospectively evaluated the medical records of 255 adult CHB patients visiting an infectious disease outpatient clinic. Patients with hepatitis B surface antigen positivity for >6 months and those who did not receive antiviral therapy were included in the study. The presence and stage of hepatic steatosis were determined through hepatobiliary ultrasonography.ResultsThe mean age of the patients was 40.6 ± 12.7 years. Hepatic steatosis was detected in 44.4 % of the patients through ultrasound imaging. Our findings showed that the detected steatosis prevalence in our patients with CHB was significantly higher compared to the highest prevalence of non-alcoholic steatohepatitis found in the general Turkish population (19.9 %) [RR 2.23 (1.75–2.86), p < 0.001]. CHB patients with steatosis had significantly higher age, triglyceride, and gamma-glutamyl transferase levels than those without steatosis (p < 0.05). No significant association was found between the presence of steatosis, sex, liver function test results, and platelet, alkaline phosphatase, cholesterol, alpha fetoprotein, or HBV-DNA levels. No significant relationship was found between aspartate aminotransferase (AST)/platelet ratio index (APRI) and steatosis was examined (p > 0.05). Post-hoc analysis showed a significant relationship between HBV-DNA levels and ALT, AST, and APRI scores.ConclusionOur data showed that hepatic steatosis is more common in CHB patients than in the general population. Older age and high triglyceride levels increased the risk of hepatic steatosis in CHB patients, consequently increasing GGT levels, which are indicative of liver damage, in these patients.     

Copper overload in the developing guinea pig liver: a histological, histochemical and biochemical study

The copper profile in Wilson's disease resembles that of human and guinea pig neonates. Microvesicular steatosis is characteristic of early histological damage in Wilson's disease. The aim of this study was to relate the histological, histochemical and ultrastructural changes seen in developing guinea pig liver to the developmental pattern of liver copper in these animals. Copper-stressed and control guinea pigs were studied. Liver biopsies were stained with haematoxylin and eosin, rhodanine (for copper), orcein (for copper-associated protein) and oil Red 0 (for fat). Selected specimens were examined by electron microscopy. Liver and serum copper levels and copper oxidase activity were also determined. Fetal liver copper increased during the last trimester of pregnancy, reaching five times the adult level in the perinatal period and falling rapidly in the 4 days after birth. Marked steatosis developed in both control and copper-stressed guinea pig liver. The fat score correlated strongly with liver copper concentration (r: 0.60; p less than 0.001). Orcein and rhodanine staining correlated with liver copper concentration (r: 0.52 and r: 0.40 respectively, p less than 0.01). Marked prenatal hepatic steatosis and its postnatal clearance correlates with changes in liver copper concentration. This experimental model provides an opportunity to study the pathogenesis of hepatic steatosis and the relationship between copper retention and steatosis.     

Impact of obesity,hepatic steatosis,and insulin resistance on hepatitis C treatment outcomes

Hepatitis C virus (HCV) infection is commonly associated with hepatic steatosis, an important factor predicting disease severity in all genotypes. There appears to be a strong association between the presence of steatosis and insulin resistance (IR) in HCV infection, especially in genotype 1 infection. Obesity, hepatic steatosis, and IR all appear to negatively influence response to antiviral therapy. IR is important not only in the development of hepatic steatosis, but also in fibrosis severity. Recent studies also suggest that IR is a significant independent predictor of sustained virologic response to antiviral therapy, not only in genotype 1 infection but also in hepatitis C genotypes 2 and 3. It remains to be seen whether interventions such as weight loss, hepatic steatosis reduction, and improvement in IR will increase the response to antiviral therapy and/or delay disease progression in chronic hepatitis C.     

Metabolic Dysfunction-Associated Fatty Liver Disease Better Predicts Incident Cardiovascular Disease

Background/AimsMetabolic dysfunction (MD)-associated fatty liver disease is a new positive diagnostic criterion based on hepatic steatosis and MD. However, a comprehensive evaluation on the association of MD and hepatic steatosis with incident cardiovascular disease (CVD) has yet to be performed.MethodsThis retrospective cohort study included 333,389 participants from the Korean National Health Insurance Service database who received a health examination between 2009 and 2010. Hepatic steatosis was defined using the Korean National Health and Nutrition Examination Survey-derived nonalcoholic fatty liver disease scoring system. Cox proportional hazards regression was adopted to determine the adjusted hazard ratio (aHR) with 95% confidence interval (CI) for CVD according to the presence of hepatic steatosis and MD, as well as the composite term.ResultsThis study included 179,437 men and 153,952 women with a median age of 57 years. Hepatic steatosis with MD (aHR, 2.00; 95% CI, 1.89 to 2.13) and without MD (aHR, 1.30; 95% CI, 1.10 to 1.54) significantly increased the risk of CVD compared to no steatosis without MD (reference). However, steatosis revealed no significant difference in the risk of CVD compared to no steatosis among participants with one MD (aHR, 1.09; 95% CI, 0.91 to 1.30). In participants with steatosis, the presence of one and ≥2 MDs had aHR values of 1.25 (95% CI, 0.87 to 1.79) and 1.71 (95% CI, 1.22 to 2.41), respectively, compared to no MD.ConclusionsCombined consideration of hepatic steatosis and MD was significantly associated with increased CVD risk and showed better predictive performance for CVD than hepatic steatosis or MD alone.     

Oxidative stress in experimental liver microvesicular steatosis: role of mitochondria and peroxisomes

BACKGROUND: Hepatic microvesicular steatosis is a clinical manifestation seen in a number of liver diseases. Although the role of mitochondrial beta-oxidation in the development of the disease has been well studied, information on lipid peroxidative damage in liver subcellular organelles is scarce. The present study looked at oxidative stress in hepatic peroxisomes and microsomes in microvesicular steatosis, using an animal model of the disease. METHODS: Rats were given i.p. injections of sodium valproate (700 mg/kg bodyweight) to induce microvesicular steatosis, which was confirmed by histology. RESULTS: Oxidative stress was evident in liver in steatosis, accompanied by structural and functional alterations in hepatic mitochondria. Alterations in lipid composition, with decreased phosphatidyl choline and ethanolamine and increased lysophosphatidyl choline and ethanolamine, were seen. An increase in triglyceride content was also seen. In addition, increased lipid peroxidation was also evident in peroxisomes and microsomes from steatotic rats. Pretreatment with clofibrate results in partial reversal of changes produced by valproate. CONCLUSIONS: These results suggest that in addition to impaired mitochondrial beta-oxidation, oxidative stress is also seen in the hepatic peroxisomes and microsomes during microvesicular steatosis.     

Mechanisms of intrahepatic triglyceride accumulation

Hepatic steatosis defined as lipid accumulation in hepatocytes is very frequently found in adults and obese adolescents in the Western World. Etiologically, obesity and associated insulin resistance or excess alcohol intake are the most frequent causes of hepatic steatosis. However, steatosis also often occurs with chronic hepatitis C virus(HCV) infection and is also found in rare but potentially life-threatening liver diseases of pregnancy. Clinical significance and outcome of hepatic triglyceride accumulation are highly dependent on etiology and histological pattern of steatosis. This review summarizes current concepts of pathophysiology of common causes of hepatic steatosis, including non-alcoholic fatty liver disease(NAFLD), alcoholic fatty liver disease, chronic HCV infections, drug-induced forms of hepatic steatosis, and acute fatty liver of pregnancy. Regarding the pathophysiology of NAFLD, this work focuses on the close correlation between insulin resistance and hepatic triglyceride accumulation, highlighting the potential harmful effects of systemic insulin resistance on hepatic metabolism of fatty acids on the one side and the role of lipid intermediates on insulin signalling on the other side. Current studies on lipid droplet morphogenesis have identified novel candidate proteins and enzymes in NAFLD.     

Hepatitis C and nonalcoholic fatty liver disease

Hepatitis C virus (HCV) and nonalcoholic fatty liver disease (NAFLD) are the two most common causes of chronic liver disease in North America. NAFLD represents a spectrum of liver lesions that occur in individuals who either do not consume any alcohol or only consume alcohol in quantities generally considered not to be harmful to the liver. This spectrum consists of isolated hepatic macrovesicular steatosis at one end and nonalcoholic steatohepatitis (NASH) at the other. Hepatic steatosis is present in approximately 50% of the subjects with HCV. Genotype 3 is independently associated with hepatic steatosis. In those with genotype 1 infection, steatosis is associated with features of the metabolic syndrome. The presence of hepatic steatosis correlates with the stage of hepatic fibrosis in patients with HCV. This has been related to the presence of insulin resistance. Hepatic steatosis also adversely affects the virologic response rates to anti-HCV therapy. In this article, we will review the epidemiology of HCV and NAFLD, their impact on each other, and the course of the liver disease in individuals afflicted with both conditions.