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PubMed2005

Apoptosis and fibrosis in non-alcoholic fatty liver disease.

Nonalcoholic fatty liver disease is becoming an increasingly common medical problem in the developed countries which, unfortunately, still is associated with the lack of any effective treatment. However, recent data favor a model in which a pathologically increased rate of hepatocytic apoptosis and the subsequent induction and upregulation of inflammation and fibrosis in the liver provide both a rationale for the pathogenesis of nonalcoholic fatty liver disease, as well as a clue for designing first effective therapeutic strategies. In order to illuminate this context, this article focuses on the pathogenesis and possible new therapeutic options in nonalcoholic fatty liver disease.

Animals↗
PubMedDate not supplied

Nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease is a clinicopathologic syndrome that encompasses several clinical entities. The spectrum of conditions ranges from simple steatosis to steatohepatitis, fibrosis and end stage liver disease. The condition was originally described in obese, diabetic, middle-aged females without a history of significant alcohol use with liver histology consistent with alcoholic hepatitis. It is known that this entity occurs without any particular sex predilection, in lean individuals, as well as an increasing number of obese children. Other terms have been used to describe this clinical entity such as alcohol-like hepatitis, pseudo-alcoholic hepatitis, diabetic hepatitis and steatonecrosis. Ludwig and colleagues introduced the term nonalcoholic steatohepatitis (NASH) to describe patients fitting the picture of alcoholic hepatitis but without a history of significant alcohol abuse. The term nonalcoholic fatty liver disease (NAFLD) is used more frequently to include the spectrum of conditions that range from steatosis through steatohepatitis, fibrosis and cirrhosis. NASH is reserved for patients with steatohepatitis and fibrosis. NAFLD is now being recognized as the most common cause of elevated liver enzymes in the United States. Although the exact etiology of NAFLD is not known, it may be caused by insulin resistance coupled with increased oxidative stress to the hepatocytes. No specific therapy has been approved for this condition and the mainstay of management is weight loss.

Fatty Liver↗
PubMed2004

Valproate therapy and nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease was defined recently as another symptom of insulin resistance. Continuous therapy with valproate can result in increased body weight and insulin resistance, but no data are yet available on a possible relationship between valproate and nonalcoholic fatty liver disease. We here demonstrate in abdominal ultrasound investigations that characteristics of fatty liver disease were present in 61% of valproate-treated patients as compared with 23% receiving carbamazepine therapy.

Adolescent↗
PubMedDate not supplied

Breath biomarkers for detection of human liver diseases: preliminary study.

Chronic liver disease is initially occult, has multiple aetiologies, involves complex diagnostic questions, and requires follow-up because progression is likely. Blood tests and biopsies are generally used, but have disadvantages. We have developed a new test for liver disease based on abnormal concentrations of metabolic products detected in exhaled breath. This test can be used, in conjunction with other clinically accepted diagnostic protocols, to detect and classify chronic liver diseases. Samples of breath collected from spontaneously breathing human subjects (86 patients presenting with 13 liver diseases and 109 subjects with normal liver function) were concentrated cryogenically and analysed by wide-bore capillary gas chromatography using various detectors. The concentrations of various molecules in exhaled breath were examined for potential use as biomarkers of liver function. Subjects with chronic liver diseases could be differentiated from those with normal liver function by comparing levels of breath carbonyl sulphide, carbon disulphide and isoprene; these differences were confirmed and correlated by comparing the levels with standard clinical blood markers of liver damage. The presence of chronic liver failure can thus be detected with sensitivity and specificity by quantifying sulphur-containing compounds arising from the abnormal metabolism associated with liver disease. The breath test we have developed appears to distinguish between hepatocellular and biliary tract aetiologies, and allows staging for severity. This approach may provide the clinician with a simple, non-invasive technique for use in the screening of large populations and follow-up for patients with chronic liver disease.

Biomarkers↗
PubMed2006

The use of selected nutrition supplements and complementary and alternative medicine in liver disease.

Almost all patients with liver disease, especially advanced liver disease, have some evidence of malnutrition, including mineral/vitamin deficiency. A major health trend in the United States has been the significant growth in the use of complementary and alternative medicine (CAM), including nutrition supplements and herbal agents. In the 1990s, the United States government created the National Center for Complementary and Alternative Medicine (NCCAM), as well as the Office on Dietary Supplements, to extend our knowledge in these areas. CAM users are often highly educated and frequently use CAM therapy for chronic diseases, including chronic liver disease. Indeed, most studies suggest that patients with chronic liver disease frequently use nutrition supplements and CAM agents in addition to their traditional medicines. The purpose of this review is to provide an update on the role of nutrition supplements and herbals in liver disease. This article will focus mainly on 7 selected agents (vitamin E, zinc, magnesium, S-adenosylmethionine, betaine, silymarin, and glycyrrhizin), for which there have been not only in vitro and animal studies but also human clinical trials, and we will review both potential efficacy and safety issues.

Complementary Therapies↗
PubMed2001

Increased serum levels of macrophage migration inhibitory factor in alcoholic liver diseases and their expression in liver tissues.

OBJECTIVES: To study the role of macrophage migration inhibitory factor (MIF) in the pathogenesis of alcoholic liver diseases. DESIGN AND METHODS: The levels of MIF in the sera were estimated by an enzyme-linked immunosorbent assay in 13 patients with alcoholic hepatitis (ALH), 9 patients with alcoholic cirrhosis (ALC) and 26 normal controls. MIF was localized in the liver specimens by immunohistochemistry. RESULTS: The mean levels of MIF in the sera were significantly higher in ALH and ALC compared with the normal controls (p < 0.05). Serial observations revealed a relationship between serum MIF levels and the serum transaminase levels. MIF was expressed by the hepatocytes and by the infiltrating cells around the site of accumulation of neutrophils and ballooned hepatocytes in ALH. CONCLUSIONS: This is the first report on MIF in human alcoholic liver diseases, and the data suggest that MIF may be related to abnormal cytokine homeostasis in ALH.

Case-Control Studies↗
PubMed2003

Liver transplantation for alcoholic liver disease.

In many patients, long-term heavy drinking leads to chronic liver disease, liver failure, and even death. Orthotopic liver transplantation (OLT) is the only definitive treatment for end-stage liver disease, including alcoholic liver disease (ALD). Because of a shortage of donor organs, OLT for ALD patients remains controversial out of concerns that patients may resume drinking, thereby harming the transplanted organ. Therefore, transplant centers conduct careful screening procedures that assess patients' coexisting medical problems and psychosocial status to identify those patients who are medically most suited for the procedure and who are most likely to remain abstinent after OLT. Studies assessing the outcomes of ALD patients after OLT found that the survival rates of the transplanted organ and the patient were comparable to those of patients with nonalcoholic liver disease and that relapse rates among the ALD patients were low. Similarly, ALD patients and patients with other types of liver disease had comparable rates of compliance with complex medication regimens after OLT. Enhanced efforts to identify risk factors for relapse among OLT candidates with ALD and to target interventions specifically to those patients who are at high risk of relapse may further improve patient outcome and enhance the acceptance of OLT for alcoholic patients in the general population.

Humans↗
PubMed1992

Disease recurrence and rejection following liver transplantation for autoimmune chronic active liver disease.

Autoimmune chronic active liver disease (ACALD), a major indication for liver transplantation, is associated strongly with antigenic determinants HLA-B8 and DR3. A retrospective analysis of 43 patients who underwent OLTx for putative ACALD and who, as well as their tissue organ donors, were typed, was performed. Disease recurrence and graft rejection episodes were determined by chart review and histopathological review of all material available. Disease recurrence was histologically documented in 11 (25.6%) of these 43 cases. Graft rejection episodes occurred in 24 (55.8%). All recurrences were in recipients of HLA-DR3-negative grafts. Nine of the recurrences were in HLA-DR3-positive recipients (odds ratio: 6.14, P less than 0.03). Two of 11 cases of disease recurrence were in recipients who were HLA-DR3-negative. Nine of these 11 had received HLA-DR3-negative grafts. Rejection occurred in 13 HLA-B8-positive recipients, 12 of whom received HLA-B8-negative grafts. Eleven HLA-B8-negative recipients experienced at least one rejection episode and 9 of these had received HLA-B8-negative grafts. Based upon these data we conclude: 1) that recurrence of putative ACALD is more likely to occur in HLA-DR3-positive recipients of HLA-DR3-negative grafts; (2) that recurrences were not seen in recipients of HLA-DR3-positive grafts; (3) that HLA-B8 status does not affect disease recurrence; and (4) that neither the HLA-B8 nor the DR3 status of the graft or recipient has an effect on the observed frequency of rejection.

Adult↗
PubMed2002

Insulin-like growth factors and insulin-like growth factor binding proteins in adult patients with severe liver disease before and after orthotopic liver transplantation.

INTRODUCTION: The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. METHODS: In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. RESULTS: Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 +/- 7 vs. 256 +/- 30 ng/ml, p < 0.001; free IGF-I: 1.3 +/- 0.3 vs. 3.5 +/- 0.6 ng/ml, p < 0.01; IGF-II: 177 +/- 28 vs. 618 +/- 30 ng/ml, p < 0.001; IGFBP-3: 1,230 +/- 136 vs. 3,665 +/- 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 +/- 40 vs. 90 +/- 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 +/- 296 vs. 1,303 +/- 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). CONCLUSION: Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.

Adult↗
PubMed1982

[Progress in the diagnosis of chronic liver disease: diagnostic activity in liver fibrosis and cirrhosis].

The incidence of chronic liver disease has increased due to more wide-spread alcoholism. Unfortunately practically no success has been achieved as yet in treating the final stage--decompensated cirrhosis of the liver. A decisive factor for progression of this disease is connective tissue formation, that is to say fibrosis in the liver. Up to now fibrosis of the liver can be diagnosed only by biopsy, but there is no method available to estimate the degree of its activity and progression, which would allow a more precise prognosis in the individual case. Some studies done in recent years on this problem of assessing the degree of activity of fibrosis of the liver are reviewed; these studies deal with enzymes and metabolites of collagen metabolism in the serum, glycoproteins and proteoglycans derived from the connective tissue matrix. According to various studies the best indicator of the degree of activity of liver fibrosis seems to be N-acetyl-beta-glucosaminidase and procollagen-peptide type III in the serum.

Acetylglucosaminidase↗
PubMed2002

Therapeutic Options in Nonalcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease, an entity that includes nonalcoholic steatohepatitis, is typically a benign, indolent condition. However, in a subset of patients, the clinical course may progress to advanced cirrhosis, end-stage liver disease, or hepatocellular carcinoma. Unfortunately, the pathogenesis, natural history, and potential therapies for these disorders remain poorly understood. Identifying patients who should be targeted for potential treatment remains difficult. Liver biopsy should be considered to assess the degree of hepatic inflammation and fibrosis, because physical examination findings, biochemical parameters, and the results of radiographic studies have been shown to correlate poorly with the severity of steatohepatitis and fibrosis. Although there is some evidence suggesting that obesity, diabetes mellitus, older age, and perhaps an aspartate transaminase:alanine aminotransaminase ratio higher than 1 may be predictors of more advanced fibrosis, histology remains the gold standard. Most patients with simple hepatic steatosis appear to follow a benign course and probably do not require aggressive therapy. Conversely, patients with steatohepatitis with extensive inflammation and fibrosis are the patients who are most likely to benefit from effective therapies. The most commonly recommended treatment is weight loss. Existing data suggest that rapid weight loss may promote hepatic inflammation and fibrosis; therefore, gradual weight loss should be recommended. Large, randomized, controlled trials evaluating the long-term histologic impact and clinical outcomes of weight loss strategies are lacking. Potentially promising pharmacologic therapies include insulin-sensitizing oral hypoglycemic agents such as metformin and the thiazolidenediols, antihyperlipidemic agents such as gemfibrozil or 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, vitamin E and other antioxidants, ursodeoxycholic acid, and betaine. As with weight loss, data regarding the efficacy of these pharmacologic options are limited. In addition, there are no widely accepted guidelines to help direct the clinician in the optimal use of these agents in patients with nonalcoholic fatty liver diseases.

Journal Article↗
PubMedDate not supplied

Severe cholestatic liver disease secondary to liver fluke (Platynosomum concinnum) infection in three cats.

Three middle-aged domestic cats were presented for vomiting, lethargy, anorexia, and jaundice. Complete blood counts, serum biochemical profiles, and abdominal ultrasounds were suggestive of extrahepatic biliary obstruction in all of the cats. Infection with the liver fluke Platynosomum concinnum was confirmed by intraoperative bile cytology in three cases and by histopathology in two cases. All three cats were euthanized in the postoperative period because of complications. These cases illustrate the severity of signs and complications that can occur with liver fluke infection in cats.

Animals↗
PubMed1992

Encephalopathy and neuropathy in end-stage liver disease before and after liver transplantation.

The nervous system involvement of 8 patients with end-stage liver disease was evaluated by means of clinical neurological, neuropsychological, neurophysiological and neuroradiological investigation before and 6-12 months after a successful liver transplantation. Preoperatively, all subjects (7 women, 1 man; mean age 40 years, range 30-54 years) exhibited decreased muscle strength and 2 patients manifested clinical signs of polyneuropathy. In neuropsychological tests, slight visuoconstructive apraxia, and disturbances of verbal memory and cognitive function were observed. Magnetic resonance imaging (MRI) revealed cerebral lesions in two patients. After transplantation, muscle strength reverted to normal in all patients, polyneuropathy improved and in all but 2 patients recovery of neuropsychological functioning was observed. Clinical signs of encephalopathy had disappeared. All patients were emotionally better adjusted after transplantation. Four subjects showed new, albeit mild changes in neurophysiological and neuropsychological tests postoperatively. We conclude that the majority of neurological impairment disappeared after liver transplantation. We want to stress that evaluation of neurological sequelae of liver transplantation needs to be based on assessments both before and after liver transplantation.

Adult↗
PubMed1994

[Study on decision support system for the interpretation of laboratory data by an artificial neural network--with a special reference to estimation for histological diagnosis of liver diseases with laboratory data on liver function].

An artificial neural network (ANN) was trained on laboratory data of liver function tests to estimate for histological diagnosis in patients with liver diseases such as chronic hepatitis, liver cirrhosis and fatty liver. ANN diagnosed accurately 95.3% of the cases for training and 50% of the test cases. Elimination of ZTT, GOT or A/G ratio from the data set for input reduced the ability of accurate diagnosis, whereas elimination of TBA raised this ability to 66.7%. On the other hand, accuracy of physician in diagnosing the test cases ranged from 20.8 to 62.5%. From our results it is expected that ANN may support a physician's decision on the interpretation of laboratory data.

Algorithms↗
PubMed2001

Physician specialty and the outcomes and cost of admissions for end-stage liver disease.

OBJECTIVES: Chronic liver disease is a frequent cause of morbidity and mortality. The aim of this study was to characterize the effects of physician specialty on length of stay, mortality, and costs during hospitalizations for end-stage liver disease. METHODS: We used data from the HBS International EXPLORE database. Patients hospitalized for treatment of variceal hemorrhage, spontaneous bacterial peritonitis, or hepatic encephalopathy were identified from primary discharge diagnoses. Patients were characterized by the specialty of the attending physician and by whether a gastroenterology consultation was obtained. Procedures performed were identified using ICD-9CM procedure codes. Costs were computed using proprietary HBS International Standard Transaction Codes. Linear and logistic regression analyses were used to examine the effect of physician specialty and consultation on length of stay, in-hospital mortality, and costs. RESULTS: Attending gastroenterologist care was associated with a shorter length of stay compared to nongastroenterologist attending care (median 4 vs 5 days, p = 0.01), which persisted after adjustment for differences in patient age, comorbidity, and number of procedures performed. There was a strong trend toward greater in-hospital mortality for patients without a gastroenterology attending or consultant (adjusted OR 1.72; 95% CI = 0.99, 2.98) compared to patients with a gastroenterology attending. Costs of hospital care were not significantly different between physician groups. CONCLUSIONS: Gastroenterologist involvement in inpatient care for end-stage liver disease was associated with shorter length of stay and a strong trend toward improved survival. Hospital costs were similar for patients cared for by the different physician groups.

Gastroenterology↗