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PubMed1998

Social factors and mortality from NASH in Canada.

The NASH categories (Natural, Accident, Suicide, Homicide) used on death certificates are known to obscure many of the psychological dimensions of death. Although there are many studies of death certificates of the extent to which suicide may be misclassified as accidental or natural deaths, and a few studies comparing individuals who commit suicides to accidental death victims, this topic is often neglected at a sociological level. This analysis of the NASH modes of death examines if these deaths differ from a sociological perspective. Specifically, rates of divorce, marriage, birth, and unemployment were correlated with deaths of natural causes (stomach cancer, cirrhosis of the liver), accidents (motor vehicle accident), suicide, and homicide. The results suggest that the sociological associations with some causes of death (i.e., cirrhosis of the liver, suicide and, homicide) have a similar social pattern but are different from others (i.e., motor vehicle accidents and stomach cancer). Although there are problems of interpretation at a sociological level, it is suggested that the social epidemiology of death may be obscured by the NASH classification. Recent suggestions on terminology and taxonomy by the International Academy for Suicide Research (IASR) are offered as one step towards addressing this issue.

Accidents, Traffic↗

PubMed2003

[NASH -- nonalcoholic steatohepatitis].

Nonalcoholic steatohepatitis describes a hepatic disorder with the typical characteristics of an alcoholic pathogenesis without alcohol consumption. It was first described in 1962 and named NASH by Ludwig et al. 1980. Many researchers worked on this disease since this time. It represents the hepatic manifestation of the syndrome X. The pathogenesis is a two-hit phenomenon. The first hit leads to steatosis hepatis and makes the liver vulnerable to the second hit. Central factors of the second hit are oxygen-radicals, oxidative stress, lipid-peroxidation and cytokines. The exact pathogenic mechanisms are still unknown. NASH is a hepatic disease which can end up in liver cirrhosis and liver failure. Up to now a curative drug therapy does not exist. The poor prognosis in some cases, the increasing incidence in western populations and the lack of therapeutic options renders NASH to a serious problem. The aim of this article is to show the actual knowledge of this disease, especially focussed on the pathogenesis, by review of the literature from 1979 up to the present time.

Biopsy↗

PubMed1998

Cooperation and self-interest: Pareto-inefficiency of Nash equilibria in finite random games.

The relative merits of cooperation and self-interest in an ensemble of strategic interactions can be investigated by using finite random games. In finite random games, finitely many players have finite numbers of actions and independently and identically distributed (iid) random payoffs with continuous distribution functions. In each realization, players are shown the values of all payoffs and then choose their strategies simultaneously. Noncooperative self-interest is modeled by Nash equilibrium (NE). Cooperation is advantageous when a NE is Pareto-inefficient. In ordinal games, the numerical value of the payoff function gives each player's ordinal ranking of payoffs. For a fixed number of players, as the number of actions of any player increases, the conditional probability that a pure strategic profile is not pure Pareto-optimal, given that it is a pure NE, apparently increases, but is bounded above strictly below 1. In games with transferable utility, the numerical payoff values may be averaged across actions (so that mixed NEs are meaningful) and added across players. In simulations of two-player games when both players have small, equal numbers of actions, as the number of actions increases, the probability that a NE (pure and mixed) attains the cooperative maximum declines rapidly; the gain from cooperation relative to the Nash high value decreases; and the gain from cooperation relative to the Nash low value rises dramatically. In the cases studied here, with an increasing number of actions, cooperation is increasingly likely to become advantageous compared with pure self-interest, but self-interest can achieve all that cooperation could achieve in a nonnegligible fraction of cases. These results can be interpreted in terms of cooperation in societies and mutualism in biology.

Journal Article↗

PubMed2005

Non-alcoholic steatohepatitis (NASH) and hepatocellular carcinoma.

Non-alcoholic fatty liver disease (NAFLD) is characterized by an excessive accumulation of fatty acids and triglycerides within the cytoplasm of the hepatocytes of non-alcohol users. The natural history varies according to the initial histological diagnosis. A current consideration is that cryptogenic cirrhosis may be representative of a late stage of non-alcoholic steatohepatitis (NASH), which has lost its features of necroinflammatory activity and steatosis in up to 80% of patients. Since NASH is able to progress to cirrhosis, hepatocellular carcinoma (HCC) development may be an end-stage of this disease. We report below two clinical cases of patients diagnosed with NASH who developed HCC. The relationship between NAFLD and HCC is reviewed.

Aged↗

PubMed2006

Roux-en-Y gastric bypass improves the nonalcoholic steatohepatitis (NASH) of morbid obesity.

BACKGROUND: Hepatic steatosis and nonalcoholic steatohepatitis (NASH) have been increasingly implicated in the genesis of hepatic fibrosis and cirrhosis. However, no consensus exists about whether weight reduction may reverse this process. METHODS: To assess the effect of Roux-en-Y gastric bypass (RYGBP) on the histological evolution of NASH diagnosed in 64 patients by routine liver biopsy ("first" biopsy) performed during surgery, we performed a "second" biopsy after 23.5 +/- 8.4 months in 16 patients (14 female, 2 male). RESULTS: From the first to the second biopsy, BMI decreased from 53.4 +/- 8.8 kg/m2 to 31.1 +/- 4.7 kg/m2, arterial hypertension decreased from 75% to 43.8%, and type 2 diabetes decreased from 43.8% to zero. On the first biopsy, nonalcoholic fatty liver disease (NAFLD) type 3 was observed in 12 patients (75%) and type 4 in 4 (25%). The second biopsy revealed complete regression of NAFLD in 15 patients (93.7%) and only 1 (6.3%) had NAFLD type 1 (mild steatosis without inflammation). Complete regression of necroinflammatory activity was observed in all patients. Among the 4 patients presenting fibrosis in the first biopsy, complete remission was observed in 1 and improvement in 1. Two continued to show the same degree of fibrosis without evidence of disease activity. No worsening of steatosis, necroinflammatory activity or fibrosis was observed in any of the patients, and none progressed to cirrhosis. CONCLUSION: RYGBP improves steatosis, necroinflammatory activity and hepatic fibrosis in patients with morbid obesity and NASH.

Adult↗

PubMed2000

Toremifene-induced fatty liver and NASH in breast cancer patients with breast-conservation treatment.

We have described fatty liver, diagnosed by computed tomography scanning (CT) in more than 30% of patients with breast cancer who received tamoxifen. Therefore, it is urgent to elucidate the frequency and the degree of fatty liver induced by toremifene, an analogue of tamoxifen, which is also used in breast cancer. We enrolled 52 breast cancer patients who were treated with breast-conservation treatment and administered oral toremifene for 3-5 years as adjuvant endocrine therapy. We evaluated the degree of fatty liver by abdominal CT performed annually. CT demonstrated toremifene-induced fatty liver in four (7.7%) of 52 breast cancer patients. Toremifene-induced fatty liver did not correlate with abnormal levels of AST, ALT, GGT or total cholesterol. One patient who demonstrated moderate fatty liver by CT was histologically diagnosed as non-alcoholic steatohepatitis (NASH) by liver biopsy. The incidence of toremifene-induced fatty liver was significantly lower than that induced by tamoxifen. Accordingly, in terms of fatty liver and NASH, toremifene is considered to be more appropriate agent than tamoxifen. Though toremifene is less likely to induce fatty liver, the possibility remains that toremifene-induced steatohepatitis occurs. Because the diagnosis of fatty liver or NASH can be easily missed if only a blood test is performed, it is necessary to screen fatty liver by annual CT examination for patients who receive an antiestrogen agent.

Alanine Transaminase↗

PubMedDate not supplied

[Treatment of non-alcoholic steatohepatitis (NASH). A comparative study of ursodeoxycholic acid and alpha-tocopherol. A preliminary report].

BACKGROUND: At the present time, there is no accepted treatment for non-alcoholic steatohepatitis (NASH); nevertheles, there are some reports of non-controlled studies with apparently good answer with ursodeoxycholic acid (UDCA) as much with alpha-tocopherol (aTP). OBJECTIVE: To value the clinical, biochemical and hepatic ultrasound (US) response in patients with NASH in treatment for 1 year with UDCA or aTP, as well as to establish tolerance, undesirable effects and fulfillment. METHOD: Three patients received UDCA (250 mg TID) and six aTP (100 mg TID). Changes in hepatic function test and US were analyzed. All patients were women with an average age of 52 years, body mass index of 27, five with diabetes mellitus (DM) type II. RESULTS: Fulfillment of treatment was 95%; undesirable effects were not reported; clinical course was asymptomatic and clinically we did not observe important changes; US showed favorable changes in four patients (44%), two in each group. Alkaline phosphatase was normalized in patient who initially registered it as high. ALT and AST average diminished by 40% and normalization was obtained in five of six patients in treatment with aTP (83%) and in one of the UDCA group (33%). No statistically significant difference was obtained. CONCLUSIONS: The group is small and requires more persons and to be compared with a control group. It is possible that both drugs can be useful in the treatment of NASH; they are well tolerated and allow good fulfillment.

Adult↗

PubMed2005

[Tumor suppressor gene PTEN and non-alcoholic steatohepatitis (NASH)].

Although hepatic steatosis had been considered to be a benign condition that does not deteriorate to either liver cirrhosis or hepatocellular carcinoma (HCC). Non-alcoholic steatohepatitis (NASH) is notable disease that has similar pathological features to alcoholic liver injury and progresses to liver cirrhosis and HCC. But the molecular mechanism for the onset of NASH, and for the transformation from steatosis to carcinogenesis are still unclear. Hepatocyte-specific PTEN deficient mice, we generated, have similar histological features to the patients of human NASH. These hepatocytes showed enhanced lipid accumulation, inflammatory change, and hyperoxidation. Moreover, they developed into HCC. Thus, impairment of PI3K/PTEN signaling may possibly be involved in a part of NASH/HCC cases in human.

Animals↗

PubMedDate not supplied

Nateglinide is useful for nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes.

BACKGROUND/AIMS: In the present study we administered nateglinide to nonalcoholic steatohepatitis (NASH) patients with type 2 diabetes who had failed to respond adequately to diet and exercise therapy, and we compared the resulting changes in insulin kinetics and improvements in blood glucose levels, as well as the concomitant changes in hepatic function, diagnostic liver images and liver histology, with the results from a non-treated control group. METHODOLOGY: Subjects for this study consisted of 10 patients with NASH. They all suffered from diabetes and they were all diagnosed with fatty liver by abdominal ultrasonography (US) and computed tomography (CT). Nonalcoholic steatohepatitis was diagnosed as the result of liver biopsy. The subjects were randomly divided into two groups, the nateglinide-treated group and the non-treated control group. Each group contained five patients. The members of the nateglinide-treated group were administered nateglinide every day (270mg/day) before each meal for a period of 20 weeks. Both groups continued to receive diet and exercise therapy. Body mass index (BMI), blood chemistry, plasma glucose and HbAlc, abdominal US and CT were measured before treatment, and every four weeks thereafter. Liver biopsy was performed over again at 16 weeks af terinitiating treatment. RESULTS: The results were compared. Postprandial blood glucose, HbA1c, a 75-g oral glucose tolerance test, liver function, abdominal US and CT imaging tests and liver histological findings were all improved after treatment with nateglinide. CONCLUSIONS: From these results we concluded that nateglinide is useful in the treatment of NASH in patients with type 2 diabetes.

Adult↗

PubMed2006

[Treatment of NASH: nutritional counseling and physical exercise].

Nonalcoholic fatty liver disease(NAFLD) is recognized as a cause of potentially progressive liver damage. NAFLD is often associated with metabolic syndrome that comprises central obesity, insulin resistance, and hyperlipidemia. Among these, severer forms with histopathological features of increasing ballooned hepatocytes and fibrosis are defined as nonalcoholic steatohepatitis (NASH). The natural history of NASH is only partly known, the disease is slowly progressive and therapeutic outcomes are difficult to define. Since central obesity and insulin resistance are most likely involved in the pathogenesis, justification of life style including physical exercise and nutritional counseling is essential for the treatment of NASH.

Carbohydrate Metabolism↗

PubMed2006

[NASH in children].

It has long been recognized that hepatic steatosis (fatty liver) occurs in obese children as in adults. Steatosis of any etiology can be associated with the development of necro-inflammation and fibrosis, so called steatohepatitis, and even cirrhosis. Nonalcoholic steatohepatitis (NASH) has been proposed as a component of insulin resistant syndrome and exists in pediatric population. The other etiology of NASH in children has not been clearly understood. In addition to obesity, adipose tissue distribution also appears to influence metabolic complications. Subjects with visceral fat adiposity appear to be at risk for fatty liver because of their ability to transport free fatty acids directly into the portal vein for conversion to triglycerides within the liver. A stronger relationship of serum ALT to visceral adiposity than BMI was demonstrated. Many metabolic diseases such as Wilson's disease, NICCD, OTC deficiency, carnitine deficiency have steatohepatitis and cirrhosis. It may play the important role to reveal the mechanism of progress to NASH.

Child↗

PubMed2006

[Natural history of Japanese patients with non-alcoholic fatty liver disease (NAFLD), especially non-alcoholic steatohepatitis (NASH) patients with hepatocellular carcinoma (HCC)].

Our current knowledge of the natural history of NAFLD can be summarized as follows: 1) simple steatosis can progress to steatohepatitis, fibrosis, cirrhosis, and even liver-related death but progression occurs in less than 5% of patients, 2) patients with NASH can progress to cirrhosis, 3) once cirrhosis develops in patients with NAFLD the prognosis appears to be poor with several studies reporting that some patients develop HCC and up to a third of patients develop liver-related morbidity or mortality, 4) older age and advanced fibrosis are risk factors for HCC in NASH. Changes in lifestyle have resulted in a dramatic increase in the prevalence of NAFLD. It is extremely important that we diagnose NASH definitely and perform appropriate treatment.

Asian People↗

PubMed2005

Hepatitis C as a metabolic disease: Implication for the pathogenesis of NASH.

In addition to the link with development of hepatocellular carcinoma (HCC), hepatitis C virus (HCV) infection is associated with several extrahepatic manifestations such as essential mixed cryoglobulinemia, porphyria cutanea tarda or Sjögren's syndrome. A role of hepatic steatosis in the pathogenesis of chronic hepatitis C has also been known, implying hepatitis C as a metabolic disease. In addition, recent epidemiological studies have suggested a linkage between type 2 diabetes and chronic HCV infection. However, the presence of additional factors in patients, such as obesity, aging or cirrhosis, prevents the establishment of a definite relationship between HCV infection and these two conditions, lipid metabolism disturbance and diabetes. In addition to the data indicating the presence of dyslipidemia and diabetes or insulin resistance in our cohort of chronic hepatitis C patients, we found a series of evidence showing the association between the conditions and HCV infection in mouse models that are transgenic for the HCV genes. In patients with chronic hepatitis C, a significant decrease in the serum levels of total cholesterol and apolipoproteins C2 and C3 was observed compared to those with chronic hepatitis B that were comparable in liver function. In an animal model, C18:1 mono-unsaturated fatty acids were significantly increased in the liver from HCV core gene transgenic mice, which was similarly observed in the liver from human hepatitis C patients. Thus, a disturbance in lipid metabolism was observed in both humans and an HCV mouse model, supporting that it is a specific event in HCV infection. A significant increase in the value of an indicator for homeostasis model assessment of insulin resistance (HOMA-IR), was observed in patients with chronic hepatitis C, even at the very early stage of chronic hepatitis. In the animal model, a marked insulin resistance was exhibited from a very young age in HCV core gene transgenic mice. Insulin resistance observed in the core gene transgenic mice was chiefly due to the shortage of insulin action on the suppression of glucose production in the liver. Thus, the ability of insulin to lower the plasma glucose level in the HCV transgenic mice was impaired, as observed in chronic hepatitis C patients. These results provide a direct experimental evidence for the contribution of HCV in the development of insulin resistance in human HCV infection, which finally leads to the development of type 2 diabetes. Insulin resistance may be a critical factor in the pathogenesis of chronic hepatitis C as recently suggested in non-alcoholic steatohepatitis (NASH), along with impairment in lipid metabolism. Our results would provide a clue for further understanding of pathobiology of HCV infection, and may provide an implication for the pathogenesis of NASH.

Journal Article↗

PubMed2001

Adam Nash: legally speaking, a happy ending or slippery slope?

The birth of Adam Nash, following IVF and then preimplantation genetic diagnosis (PGD) on the resulting 15 embryos to find which would be a potential bone marrow match for his older sibling, suffering from Fanconi's anaemia, is the first reported case of genetic selection of an embryo to save the life of an existing person. The case has stirred debates worldwide over the appropriateness and implications of using the technique for this and related purposes. Legally, it is suggested that embryos are indeed entitled to special respect because of their potential for life, but certain principles must not be overlooked, and the Nash case was wholly within acceptable legal principles. The legal perspective offered here concludes: (i) while embryos are entitled to certain protections, the mere fact that they are extracorporeal raises the danger that the rights and protections assigned to them will be wrongly elevated over the legally protected procreation rights of the adults who create them; (ii) divorce litigation involving "custody" of embryos is not a direct parallel and legal analogies must be distinguished; (iii) the status of embryos must be carefully defined; and (iv) a national or international, multi-disciplinary body should be created to grapple with the developing issues and uses that are sure to follow.

Journal Article↗

PubMed2002

Liver regeneration is not altered in patients with nonalcoholic steatohepatitis (NASH) when compared to chronic hepatitis C infection with similar grade of inflammation.

Fatty infiltration is associated with an increased incidence of complications and mortality after liver resection and transplantation. The aim of this study was to document the regenerative response in patients with hepatic steatosis and mild inflammatory activity (NASH) and to identify potential levels of impaired regeneration. Ki-67 immunostaining was similar in patients with NASH (ages 44.6 +/- 15 years, labeling index, 0.4 +/- 0.3%) when compared to patients with chronic hepatitis C infection (ages 50.7 +/- 17 years, labeling index; 0.4 +/- 0.7%). The labeling index was not increased in patients with a higher level of inflammation, a higher level of fibrosis, and a higher level of fat in either study group. In conclusion, liver regeneration is not altered in patients with nonalcoholic steatohepatitis, suggesting that the delayed postoperative liver failure seen in these patients may be related to another mechanism.

Adult↗

PubMed1988

Artifacts in the determination of microsomal xenobiotic N-demethylation in the presence of ascorbic acid tris buffer and Nash reagent.

1. During investigation of microsomal xenobiotic N-demethylation in the presence of ascorbic acid, large increases in apparent enzymic activity were observed. 2. Examination of incubation components indicated that a non-enzymic interaction between ascorbic acid and Tris buffer, in the presence of acetylacetone and ammonium acetate (Nash reagent), was occurring. 3. The resulting chromophore had an absorption maximum at 412 nm that coincided with the absorption for the chromophore resulting from the interaction of the Nash reagent with the product (formaldehyde) of the enzymic reaction. 4. Strict controls of ascorbic acid potential chemical interaction with incubation components are required in enzymic studies.

Acetates↗

PubMed2004

[Case of NASH exacerbated after testectomy due to seminoma].

A 41-year-old Japanese male was admitted to our hospital because of the increased levels of serum AST, ALT, and gamma-GTP on December 18, 2002. He was diagnosed with right testis seminoma in 1994 and had received right high orchiectomy and radiation therapy. At that time, liver dysfunction was not pointed out. As weight was increased in 2001, liver dysfunction was pointed out. He was diagnosed as left testis seminoma in June, 2002, left high orchiectomy and chemotherapy was performed. Abdominal ultrasonography showed the moderate fatty liver, and hepatic histopathology revealed a typical and remarkable steatohepatitis with lymphocyte infiltration. He had no life history of alcohol-consumption, and he was diagnosed as non-alcoholic steatohepatitis (NASH). He was treated with a low-calorie diet, which showed favorable effects on his serum levels of AST, ALT, gamma-GTP, and LDH. This case suggests that the altered sex hormone balance might exacerbate NASH because liver dysfunction was particularly worsened after bilateral high orchiectomy.

Adult↗

PubMed2006

[Rabbit model for the study of human NASH].

Although non-alcoholic steatohepatitis (NASH) has become a worldwide common disease, pathogenesis of this disease remains unsolved. Establishment of a proper animal model is one of urgent issues to analyze the molecular mechanisms. We have developed a NASH model by using Japanese White rabbits fed by high fat diet. These rabbits exhibited prominent fatty change in the liver and the increased serum and hepatic levels of lipid peroxide. Pericellular matrix deposition was seen around hepatocytes and fibrosis radically extended from portal area. Many TUNEL-positive cells were seen in the liver of high fat rabbits. We discuss the usefulness of this model for the molecular analysis of human

Animals↗