Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

As of this writing, the most common cause of hepatic fibrosis is chronic hepatitis C virus infection (HCV), the characteristic feature of which is hepatic steatosis. Hepatic steatosis leads to an increase in lipid peroxidation in hepatocytes, which in turn activates hepatic stellate cells (HSCs). HSCs are also thought to be the primary target cells for inflammatory stimuli, and produce extracellular matrix components. Based on available clinical information, chronic hepatitis C appears to progress more rapidly in men than in women, and cirrhosis is predominately a disease of men and postmenopausal women. It should be noted that estradiol (E2) is a potent endogenous antioxidant. A recent study has shown that hepatic steatosis became evident in an aromatase-deficient mouse and was diminished in animals, after treatment with E2. Our studies showed that E2 suppressed hepatic fibrosis in hepatic fibrosis models, inhibited the activation of activator protein 1 and nuclear factor-kappa B in cultured hepatocytes undergoing oxidative stress, and attenuated HSC activation in primary culture. Recently, variant oestrogen receptors (ERs) were found to be expressed to a greater extent in male patients with chronic liver disease than in female subjects. We also demonstrated decreased levels of ERs in postmenopausal women and cirrhotic patients of both genders. The actions of E2 are mediated through ER alpha and beta. HSCs have also been found to possess functional ER beta but not ER alpha. A better understanding the basic mechanisms underlying the gender-associated differences observed in the development of hepatic fibrosis would provide valuable information relative to the search for effective antifibrogenic therapies.
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PMID:Impact of oestrogens on the progression of liver disease. 1264 Jul 29

The aim of this study was to determine if body mass index (BMI) was an independent predictor of response to antiviral treatment in patients with chronic hepatitis C. A retrospective review was performed of all patients at a single center with chronic hepatitis C treated with antiviral medication from 1989 to 2000. A sustained response was defined as either negative hepatitis C virus (HCV) RNA by polymerase chain reaction and/or normal alanine aminotransferase (ALT) level (only in those treated before availability of HCV RNA testing) 6 months following completion of therapy. All patients were classified into one of 3 groups according to BMI (normal, <25 kg/m(2); overweight, 25-30 kg/m(2); obese, >30 kg/m(2)). A total of 253 patients were treated with either interferon (IFN) monotherapy or IFN in combination with ribavirin. Patients were excluded if predetermined clinical characteristics were unavailable. Using logistic regression, and after adjusting for the examined variables (age, sex, history of alcohol consumption >50 g/d, cirrhosis on pretreatment biopsy, and BMI), likelihood ratio tests showed significant differences in response to treatment according to BMI group (P =.01), genotype (P <.01), and cirrhosis (P <.01). Those with genotypes 2 or 3 had an odds ratio (OR) for success of 11.7 compared with those with genotype 1, cirrhotic patients had an OR of 0.15 compared with noncirrhotic patients, and obese patients had an OR of 0.23 compared with normal and overweight patients. Hepatic steatosis was not an independent risk factor for response to antiviral treatment. In conclusion, obesity, only when defined as a BMI greater than 30 kg/m(2), is an independent (of genotype and cirrhosis) negative predictor of response to hepatitis C treatment.
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PMID:High body mass index is an independent risk factor for nonresponse to antiviral treatment in chronic hepatitis C. 1293 81

Heavy iron overload, in both primary and secondary hemochromatosis, may cause fibrosis of parenchymal organs, especially the liver. The toxicity of iron is believed to involve increased oxidative stress, with iron-catalyzed production of reactive oxygen species causing oxidative damage to lipids, proteins, and nucleic acids. Lesser degrees of hepatic iron deposition are also associated with, and seem to be risk factors for, certain nonhemochromatotic liver diseases. Porphyria cutanea tarda is associated with hepatic iron overload and responds to iron-reduction therapy. Results of recent studies have demonstrated high prevalences (about 60%-80%) of HFE gene mutations in patients with porphyria cutanea tarda. Chronic hepatitis C is another risk factor for porphyria cutanea tarda. Other recent evidence indicates that the prevalence of HFE gene mutations is increased in chronic viral hepatitis and that patients with chronic hepatitis C harboring especially the C282Y mutation are more likely to suffer from advanced hepatic fibrosis or cirrhosis and to do so at younger ages. A role for modest iron overload in increasing severity of alcohol-induced liver disease has been well established from results of experimental studies. However, it is currently unresolved whether mild-to-moderate hepatic iron deposition or heterozygosity for the C282Y mutation plays a role in human alcoholic liver disease or in nonalcoholic fatty liver disease or nonalcoholic steatohepatitis. There is persuasive evidence that iron reduction decreases insulin resistance, and it likely also decreases oxidative stress, two key pathogenic features of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis. Iron loading has also been described after portosystemic shunts and in end-stage liver disease.
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PMID:Iron as a co-morbid factor in nonhemochromatotic liver disease. 1295 98

Elevation of transaminase levels in asymptomatic subjects could be due to a common benign condition such as fatty liver or a more serious disease such as chronic hepatitis due to various causes; in some subjects a liver biopsy is indicated. Heterozygous apolipoprotein B deficiency is an uncommon cause of transaminase elevation, as indicated by low levels of cholesterol and low density lipoprotein-cholesterol. This should be noted to avoid unnecessary investigations (including liver biopsy) in asymptomatic subjects with persistent elevation of transminase levels in the serum.
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PMID:Fatty liver with elevated transaminase levels due to heterozygous apolipoprotein B deficiency. 1297 15

We report a case of 19-year-old male with an underlying case of chronic hepatitis C infection who suffered from two types of benign liver tumor: focal nodular hyperplasia (FNH) and pseudotumor due to focal fatty spared area in a fatty liver. These two kinds of lesions rarely occur simultaneously. The spectral Doppler ultrasound (US) images of these lesions were also provided. We suggest that spectral Doppler US provides an alternative diagnostic tool for the differentiation of liver tumors regarding their vascular pattern, which might help ensure a correct diagnosis.
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PMID:Coexistence of focal nodular hyperplasia and pseudotumor caused by focal spared lesion in the liver of a young man. 1453 93

The mechanism by which the hepatitis C virus (HCV) causes chronic, progressive liver damage is unknown. Factors other than the virus itself have been implicated. The role of liver steatosis has been recently studied. Hepatic steatosis is a common histological finding occurring in more 50% of patients with chronic hepatitis C. Both host and viral factors have been demonstrated to play an important role in its development. In those patients infected with genotype 1, steatosis appears to be due to the co-existence of Non-Alchoholic SteatoHepatitis (NASH) with HCV and associated with an increased body mass index (BMI). Some recent observations suggest that steatosis may be of viral origin and related to genotype 3. This fact raises the possibility of a direct effect of specific viral sequences on the pathogenesis of lipid accumulation. Furthermore, hepatic steatosis attributed to genotype 3 correlates directly with serum and intrahepatic titters of HCV RNA. The resolution of steatosis after successful antiviral therapy as well as steatosis being a sign of recurrent HCV infection in patients with genotype 3 add convincing evidence that steatosis is viral related. The pathogenic mechanism induced by genotype 3 is speculative. A correlation between steatosis, intrahepatic HCV RNA and core protein expression suggest a direct effect. Further support is provided by the finding that HCV core protein induces steatosis in transgenic mice. Another possibility relates to interaction with hepatic triglyceride turnover. In conclusion, for patients infected with genotype 1, BMI has a role in the pathogenesis of steatosis while in those infected with genotype 3, steatosis may be due to a virus-specific cytopathic effect. Regardless of etiology, the contribution of both to liver fibrosis progression seems accepted.
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PMID:Hepatitis C virus infection and liver steatosis. 1463 8

It is increasingly recognized that host factors can modulate the fibrogenic response in patients with chronic hepatitis C. Obesity, because of its prevalence, and diabetes, which seems to occur more frequently in patients infected by the hepatitis C virus (HCV), are often present in patients with chronic hepatitis C. Both conditions result in fatty liver, which in turn is associated with more severe liver damage, especially fibrosis or inflammation. Steatosis can either originate from associated metabolic alterations (insulin resistance resulting in metabolic steatosis) or from a direct cytopathic effect of the virus (genotype 3, resulting in viral steatosis). Metabolic steatosis seems to be a factor in resistance to antiviral therapy, whereas viral steatosis is reduced in sustained responders. Whether metabolic steatosis has a direct role in liver fibrosis progression or is only a surrogate marker of an underlying defect triggering fibrogenesis, such as insulin resistance, is a subject of debate. High serum glucose levels and diabetes have a strong and independent profibrogenic impact. Exciting new data are expanding our understanding of the mechanisms of steatogenesis in HCV infection and providing potential links between insulin resistance or hyperglycemic states and liver fibrogenesis.
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PMID:Fat, diabetes, and liver injury in chronic hepatitis C. 1472 Apr 50

Liver biopsy continues to have a central role in the evaluation of patients with suspected liver disease. The procedure is often indicated to evaluate otherwise unexplained liver biochemical test abnormalities, but the precise degree of serum aminotransferase elevations that should prompt a liver biopsy is controversial, as is the need for liver biopsy in all patients with suspected nonalcoholic fatty liver disease and chronic hepatitis C. Standard liver biopsy is contraindicated in patients with severe coagulopathy and ascites, although the degree of coagulopathy that contraindicates a liver biopsy is controversial. A transjugular approach is an alternative in patients with coagulopathy or ascites. Controversy surrounds all the technical aspects of liver biopsy, particularly the choice of needle (cutting vs suction) and the use of ultrasound to mark or guide the biopsy site. Bleeding is the major complication of liver biopsy, with a risk of 0.3%; cutting needles are more likely to cause hemorrhage than are suction needles. Traditionally, liver biopsy has been the province of the hepatologist/ gastroenterologist. However, an increasing number of liver biopsies are performed by radiologists. The implications of this trend with respect to patient outcome, safety, and training of fellows is unclear.
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PMID:Controversies in liver biopsy: who, where, when, how, why? 1472 Apr 51

Steatosis is increasingly recognized as a cofactor influencing the progression of fibrosis in chronic hepatitis C; however, the mechanisms by which it contributes to liver injury remain uncertain. We studied 125 patients with chronic hepatitis C to assess the effect of steatosis on liver cell apoptosis and the expression of Bcl-2, Bcl-x(L), Bax, and tumor necrosis factor alpha (TNF-alpha) and the relationship between liver cell apoptosis and disease severity. A significant increase in liver cell apoptosis was seen in liver sections with increasing grade of steatosis (r = 0.42; P <.0001). Hepatic steatosis and previous heavy alcohol consumption were the only two variables independently associated with the apoptotic index. Increasing steatosis was associated with decreased Bcl-2 mRNA levels and an increase in the proapoptotic Bax/Bcl-2 ratio (r = -0.32, P =.007; and r = 0.27, P =.02, respectively). In the absence of steatosis, increased liver cell apoptosis was not associated with stellate cell activation or fibrosis (r = 0.26, P =.11; r = 0.06, P =.71, respectively). In contrast, in the presence of steatosis, increasing apoptosis was associated with activation of stellate cells and increased stage of fibrosis (r = 0.35, P =.047; r = 0.33, P =.03, respectively), supporting the premise that the steatotic liver is more vulnerable to liver injury. In patients with hepatitis C virus genotype 3, there was a significant correlation between TNF-alpha mRNA levels and active caspase-3 (r = 0.54, P =.007). In conclusion, these observations suggest a mechanism whereby steatosis contributes to the progression of liver injury in chronic hepatitis C. Further investigation will be required to determine the molecular pathways responsible for the proapoptotic effect of steatosis and whether this increase in apoptosis contributes directly to fibrogenesis.
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PMID:Steatosis and liver cell apoptosis in chronic hepatitis C: a mechanism for increased liver injury. 1512 51

There has been a remarkable rise in incidence of hepatocellular carcinoma (HCC) in the United States and the developed Western world over the last few decades (1). This has been attributed largely to the emergence of hepatitis C over the same period of time. Other possible factors operative in the United States contributing to this rise in incidence include chronic hepatitis B virus (HBV) infection among immigrants from countries with a high prevalence of HBV and a rise in prevalence of nonalcoholic fatty liver disease (NAFLD). Thus, specialized liver centers have to deal with larger number of patients with HCC.
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PMID:Screening for hepatocellular carcinoma: being old is not all bad. 1530 62


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