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PubMed2004

Hepatocellular carcinoma with nonalcoholic steatohepatitis.

Nonalcoholic steatohepatitis (NASH) was originally believed to be a benign disease. However, it has been recently revealed that NASH could lead to irreversible liver disease in some patients. We report an unusual case of hepatocellular carcinoma (HCC) in a 76-year-old man with NASH. He had no history of alcohol consumption, drug use, or blood transfusion. He was negative for all serological viral markers and autoantibodies. In addition, he was obese (body mass index [BMI], 30.75 kg/m(2)) and had type 2 diabetes mellitus. A liver biopsy specimen showed moderate steatosis with necroinflammatory changes, ballooning degeneration, Mallory bodies, pericellular fibrosis, and evidence of nodular regeneration. He was diagnosed with NASH with cirrhosis. Simultaneously, a liver tumor, measuring 19 mm in diameter, was detected in segment 6. A tumor biopsy specimen revealed well-differentiated HCC, and imaging modalities confirmed the characteristics of HCC. To our knowledge, ten patients who had HCC with NASH were reported. In all patients with NASH and HCC, cirrhosis was present. Patients with NASH and cirrhosis may progress to HCC, and regular screening, based on tumor markers and imaging modalities, is needed to detect HCC in patients with NASH and cirrhosis.

Aged↗

PubMed2005

Serum iron levels and hepatic iron overload in nonalcoholic steatohepatitis and chronic viral hepatitis.

Our objective was to determine the effect of serum iron levels and hepatic iron overload on hepatocellular damage in nonalcoholic steatohepatitis (NASH) and to compare this with chronic viral hepatitis. Twenty-five patients who had elevated transaminase levels on at least two occasions, without any evidence of viral and autoimmune hepatitis and diabetes, without a history of significant alcohol use, and with a liver biopsy consistent with NASH were enrolled in the study. Twenty-five patients with chronic viral hepatitis (13 patients with chronic hepatitis C and 12 with chronic hepatitis B) who were not under any antiviral treatment were taken as controls. Metabolic factors were studied in the NASH and chronic hepatitis groups. Biopsy specimens were stained with hematoxylin-eosin, and the grade of steatosis and the stage of fibrosis were evaluated as I, II, or III, I being mild and III being severe. Iron overload in the hepatic tissue was studied by Prussian blue staining. Serum ALT, AST, ALP, GGT, globulin, and ferritin levels were comparable in both steatohepatitis and chronic viral hepatitis groups. However, patients with chronic hepatitis had a lower albumin level and a higher serum iron level, with higher transferrin saturation. Among patients with NASH, mild, moderate, and severe steatosis was found in 7, 10, and 8 patients, respectively. Inflammatory infiltration was grade I in 24 patients and grade III in 1 patient. Fibrosis was mild in 12 patients and 13 patients had no fibrosis. Among patients with chronic viral hepatitis, inflammatory infiltration of grade I was seen in 11 patients, grade II in 11 patients, and grade III in 3 patients. Fibrosis was mild in 9 patients, moderate in 13 patients, and severe in 2 patients; 1 patient had no fibrosis. Compared to patients with NASH, those with chronic viral hepatitis cases had more severe inflammatory infiltration and fibrosis (P < 0.01). While five patients with chronic viral hepatitis had mild iron overload, patients with NASH had no hepatic paranchymal iron overload. Neither NASH nor chronic viral hepatitis revealed a relationship between hepatic iron overload and disease activity. This suggests that the iron overload actually may be a result of hemachromatosis gene mutation. The absence of hepatic parenchymal iron overload in the NASH group and only mild iron accumulation in the chronic hepatitis group may be explained by a lower frequency of the gene mutation in our country.

Adult↗

PubMed2005

Symptoms of obstructive sleep apnea in patients with nonalcoholic fatty liver disease.

Nonalcoholic fatty liver disease (NAFLD) is a term often used to describe two related conditions: a relatively benign, nonalcoholic fatty liver (NAFL) and potentially aggressive, nonalcoholic steatohepatitis (NASH). Both conditions (NAFL and NASH) occur in the setting of peripheral insulin resistance. Recently, obstructive sleep apnea (OSA) has been proposed as an independent risk factor for insulin resistance. To date, few studies have documented the prevalence of OSA or symptoms of OSA (SOSA) in NAFLD patients. The objectives of this study were (1) to document the prevalence of SOSA in patients with NAFLD and (2) to determine whether prevalence rates for SOSA differ in NAFL versus NASH patients. One hundred ninety biochemically defined NAFLD patients (116 NAFL and 74 NASH), of whom 50 (18 NAFL and 32 NASH) had undergone liver biopsy, completed a Modified Berlin Sleep Apnea Questionnaire for SOSA. Risk factors for NAFLD were also documented in NAFL and NASH patients. Eighty-seven of the 190 (46%) NAFLD patients met questionnaire criteria for SOSA. The prevalence of SOSA was similar in both biochemically (45% versus 49%, respectively; P = 0.66) and histologically (39% versus 63%, respectively; P = 0.11) defined NAFL and NASH patients. Other risk factors for NAFLD such as body mass index, plasma cholesterol and triglyceride levels, and prevalence of diabetes were also similar in the two groups. Approximately one-half of NAFLD patients, whether NAFL or NASH, have SOSA. Further studies are required to determine whether a causal link exists between NAFLD and OSA.

Adult↗

PubMed2005

Interobserver variation in the histopathological assessment of nonalcoholic steatohepatitis.

Pathological assessment is considered as the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH). However, there is no agreement of histological features required for the diagnosis of NASH. In the present study, eight experienced hepatopathologists read liver biopsy specimen slides of 21 cases of NASH and suspected NASH independently and were asked to assess histopathological features and render a diagnosis. Interobserver variation among pathologists was evaluated by kappa statistics. Significant, good agreement was present in evaluation of the extent of steatosis and grade of fibrosis. Agreement was moderate concerning the localization of steatosis, localization of fibrosis, and glycogen nuclei. Only slight or poor agreement was seen in evaluation of type of steatosis, ballooning, intralobular necroinflammatory change, portal inflammation, and degree of neutrophilic infiltration. Thus the agreement varied for histological variables. Significant, moderate agreement was seen in the diagnosis of NASH but agreement was poor in the diagnosis of suggestive NASH. The agreement for the diagnosis of NASH was not high as for the individual histological findings that were thought to be the basis of the diagnosis. In conclusion, some histological features in NASH might prove useful for the development of a standardized and reliable pathological diagnosis and scoring system.

Journal Article↗

PubMed1999

Mitochondrial abnormalities in non-alcoholic steatohepatitis.

BACKGROUND/AIMS: We assessed mitochondrial morphology by electron microscopy and the prevalence of a mitochondrial gene deletion in patients with non-alcoholic steatohepatitis (NASH), alcohol-related liver disease and non-fatty liver diseases. Respiratory chain function using a cytoplasmic hybrid (cybrid) assay was further studied in NASH patients and healthy controls. METHODS: Electron microscopy was performed in 26 specimens. Fifteen patients were studied by polymerase chain reaction to detect a 520-bp deletion product of the mitochondrial genome (dmtDNA). Cybrids were created by fusion of platelets with anaerobic neuroblastoma cells in six NASH patients and 12 controls. RESULTS: Eight of ten NASH, one of seven alcoholics and two of nine other patients had linear crystalline inclusions in megamitochondria (p<0.05). Three of five patients with alcohol-related liver disease had dmtDNA compared to one of five NASH patients and one of five non-steatohepatitis controls. Cybrid respiratory chain function in platelets was not different from that of controls. CONCLUSIONS: Respiratory chain dysfunction, if present in NASH, is not expressed in platelet-derived mitochondria. In contrast to alcohol-related liver disease with active drinking, NASH patients do not commonly express the 5-kb mitochondrial DNA gene deletion in liver tissue. As previously described in early alcohol-related liver disease, crystalline inclusions of unknown composition are seen in hepatic mitochondria in NASH. Their presence suggests either an adaptive process or mitochondrial injury.

Adult↗

PubMed2006

Histologic spectrum of nonalcoholic fatty liver disease in morbidly obese adolescents.

BACKGROUND & AIMS: To characterize the spectrum of nonalcoholic fatty liver disease (NAFLD) in morbidly obese adolescents, we correlated liver histology with clinical features and compared findings with reported adult data. We hypothesized that NAFLD would be less severe as a result of younger age and shorter duration of obesity, but portal inflammation and fibrosis would be more prevalent. METHODS: Cross-sectional study was made of 41 adolescent subjects, 13-19 years old (mean, 16 years), 61% female, 83% non-Hispanic white, mean body mass index 59 kg/m(2), undergoing gastric bypass with liver biopsy. Liver biopsies were graded and staged as proposed by the NASH Clinical Research Network. Data were analyzed by using descriptive statistics, analysis of variance, and Fisher exact tests. RESULTS: Eighty-three percent had NAFLD: 24% steatosis alone, 7% isolated fibrosis with steatosis, 32% nonspecific inflammation and steatosis, and 20% nonalcoholic steatohepatitis (NASH). Twenty-nine percent had fibrosis; none had cirrhosis. Abnormal ALT (P = .05) and AST (P = .01) were more prevalent in NASH. Mean fasting glucose was significantly higher in NASH (P = .05), but prevalence of the metabolic syndrome was not significantly different. CONCLUSIONS: NAFLD was very prevalent in morbidly obese adolescents, but severe NASH was uncommon. In contrast to morbidly obese adults, lobular inflammation, significant ballooning, and perisinusoidal fibrosis were rare, whereas portal inflammation and portal fibrosis were more prevalent, even in those who did not meet criteria for NASH. These findings might support use of a modified scoring system for pediatric NASH. Presence of the metabolic syndrome in morbidly obese adolescents did not distinguish NASH from steatosis alone.

Adolescent↗

PubMed2003

Nonalcoholic steatohepatitis: summary of an AASLD Single Topic Conference.

Fatty liver disease that develops in the absence of alcohol abuse is recognized increasingly as a major health burden. This report summarizes the presentations and discussions at a Single Topic Conference held September 20-22, 2002, and sponsored by the American Association for the Study of Liver Diseases. The conference focused on fatty liver disorders. Estimates based on imaging and autopsy studies suggest that about 20% to 30% of adults in the United States and other Western countries have excess fat accumulation in the liver. About 10% of these individuals, or fully 2% to 3% of adults, are estimated to meet current diagnostic criteria for nonalcoholic steatohepatitis (NASH). Sustained liver injury leads to progressive fibrosis and cirrhosis in a fraction, possibly up to one third, of those with NASH, and NASH may be a cause of cryptogenic cirrhosis. NASH is now a significant health issue for obese children as well, leading to cirrhosis in some. The diagnostic criteria for NASH continue to evolve and rely on the histologic findings of steatosis, hepatocellular injury (ballooning, Mallory bodies), and the pattern of fibrosis. Generally recognized indications for biopsy include establishing the diagnosis and staging of the injury, but strict guidelines do not exist. Liver enzymes are insensitive and cannot be used reliably to confirm the diagnosis or stage the extent of fibrosis. Older age, obesity, and diabetes are predictive of fibrosis. The pathogenesis of NASH is multifactorial. Insulin resistance may be an important factor in the accumulation of hepatocellular fat, whereas excess intracellular fatty acids, oxidant stress, adenosine triphosphate (ATP) depletion, and mitochondrial dysfunction may be important causes of hepatocellular injury in the steatotic liver. Efforts are underway to refine the role of insulin resistance in NASH and determine whether improving insulin sensitivity pharmacologically is an effective treatment. An altered lifestyle may be a more effective means of improving insulin sensitivity. The research agenda for the future includes establishing the role of insulin resistance and abnormal lipoprotein metabolism in NASH, determining the pathogenesis of cellular injury, defining predisposing genetic abnormalities, identifying better noninvasive predictors of disease, and defining effective therapy.

Animals↗

PubMed2003

Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone.

Insulin resistance (IR) commonly is associated with nonalcoholic steatohepatitis (NASH). To establish whether IR causes NASH, this study was undertaken to determine if improving IR would improve the histologic features that define NASH. Thirty adults with prior biopsy evidence of NASH were enrolled to receive rosiglitazone, 4 mg twice daily for 48 weeks. All patients were overweight (body mass index [BMI] > 25 kg/m(2)) and 23% were severely obese (BMI > 35 kg/m(2)); 50% had impaired glucose tolerance or diabetes. Liver biopsy specimens were obtained before beginning treatment and at treatment completion. Twenty-six patients had posttreatment biopsies; of these, 22 had initial protocol liver biopsies that met published criteria for NASH on subsequent blinded evaluation. Within this initial NASH group, the mean global necroinflammatory score significantly improved with treatment and biopsies of 10 patients (45%) no longer met published criteria for NASH after treatment. Significant improvement in hepatocellular ballooning and zone 3 perisinusoidal fibrosis also occurred. Five patients withdrew early; the 25 patients completing 48 weeks of treatment had significantly improved insulin sensitivity and mean serum alanine aminotransferase (ALT) levels (104 initially, 42 U/L at the end of treatment). Adverse effects led to withdrawal of 3 patients (10%). Weight gain occurred in 67% of patients and the median weight increase was 7.3%. Within 6 months of completing treatment, liver enzyme levels had increased to near pretreatment levels. In conclusion, improving insulin sensitivity with rosiglitazone resulted in improved histologic markers of NASH, an observation suggesting that insulin resistance contributes to its development and that improving insulin sensitivity may be important in treating this liver disease.

Adult↗

PubMed1996

Recurrence of nonalcoholic steatohepatitis following liver transplantation.

Patients with nonalcoholic steatohepatitis (NASH) may develop progressive liver dysfunction necessitating liver transplantation (OLT). We report the incidence of recurrent disease and outcome in patients undergoing OLT for NASH. Patients transplanted for NASH were identified according to pretransplant and explant liver histology. Patients with significant alcohol consumption were excluded. Medical records were reviewed to extract pre- and posttransplant data, including sequential body weight, biochemistry, and graft histology. Of 622 liver explants, eight patients had features consistent with NASH. All patients were female with a median age of 58. Seven patients were diagnosed with NASH preoperatively, including three who had undergone jejunoileal bypass. One patient was diagnosed as cryptogenic cirrhosis. At a median of 15 months following OLT, all of the eight patients were alive with no graft failure. Six patients developed persistent fatty infiltration in their graft, three of whom had accompanying hepatocellular degeneration, consistent with a diagnosis of recurrent NASH. In two patients, transition from mild steatosis to steatohepatitis and early fibrosis was observed over one to two years. The patients who did not develop recurrent steatosis had significant weight loss following transplantation, although the length of follow-up was relatively short. Patients undergoing OLT for NASH may develop recurrent steatosis shortly after transplantation, with possible progression to steatohepatitis and fibrosis. Although longer follow-up is necessary to determine the eventual prognosis related to the recurrent fat and fibrosis in the graft, patients with endstage liver disease due to NASH should be considered good candidates for OLT.

Adult↗

PubMed2004

Prevalence and significance of autoantibodies in patients with non-alcoholic steatohepatitis.

GOALS: The aim of this study is to evaluate the prevalence and the clinical and histologic correlates of autoantibodies in patients with nonalcoholic steatohepatitis (NASH). BACKGROUND: Antinuclear antibodies (ANA) and anti-smooth muscle antibodies (ASMA) have been identified in patients with NASH. The significance of autoantibodies in NASH is uncertain. STUDY: Clinical data from patients with a histologic diagnosis of NASH at a university hospital in Chicago, Illinois between January 1999 and April 2003 were reviewed retrospectively. Seventy-four patients who were tested for autoantibodies and had no history of alcohol abuse or a systemic autoimmune disease were included. Demographic information and laboratory data were collected. Autoantibody titers > or = 1:40 were considered positive. A single pathologist reviewed all liver biopsies and scored features of NASH and identified characteristics of autoimmune hepatitis. RESULTS: Thirty-four percent of patients with NASH had positive ANA titers and 6% were ASMA positive. Demographic and laboratory parameters did not differ by ANA status, except that women were more frequently ANA positive then men (P = 0.01). The severity of steatosis, inflammation, and fibrosis on liver biopsy were similar in the ANA positive and negative groups. Only 15% of ANA positive patients with NASH had a plasma cell infiltrate on liver biopsy and there was no difference in the frequency of histologic features of autoimmune hepatitis between ANA positive and negative patients. CONCLUSIONS: Antinuclear antibodies are common in patients with NASH and most frequently represent a nonspecific antibody response that is not associated with the pattern or severity of injury on liver biopsy.

Adult↗

PubMed2006

Colloid scintigraphy in non-alcoholic steatohepatitis: a conventional diagnostic method for an emerging disease.

AIM: Non-alcoholic steatohepatitis (NASH) is a progressive liver disease characterized by diffuse fatty infiltration and Kupffer cell dysfunction which contributes to its pathogenesis. Since the liver biopsy, which is considered the 'gold standard' in diagnosing NASH, has some limitations other imaging methods have been explored as alternatives. Colloid scintigraphy is a good method reflecting Kupffer cell activity and we found it worthwhile to evaluate this technique in NASH. We aimed to present the common scintigraphic features and their clinicopathologic correlations in NASH. METHODS: Twenty-two new patients (11 female, mean age 43.7+/-10.8) with biopsy-proven NASH underwent colloid liver scintigraphy. The dynamic, static and SPECT images were performed after intravenous injection of 185 MBq Tc tin colloid. Hepatic perfusion, blood pool clearance time, colloid shift to spleen and bone marrow were assessed and liver right/left lobe ratio was calculated. RESULTS: The values calculated on static and tomographic (SPECT) images showed good correlation. Liver right/left lobe ratio was altered in all patients. Blood pool clearance time was prolonged in seven (32%) but hepatic perfusion was normal in all patients. Colloid shift to the spleen was observed in 55% of patients using SPECT analysis. No correlation between scintigraphy parameters and histological or biochemical findings were observed. CONCLUSION: Altered liver right/left lobe ratio was the universal finding in all our NASH patients. Other common scintigraphic features of NASH include colloid shift to spleen and prolonged blood pool clearance time. Liver scintigraphy might be a promising non-invasive tool in the follow-up of NASH patients in therapeutic trials.

Adult↗

PubMed2006

Laparoscopic findings in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Laparoscopic observation of the liver is important to diagnose liver conditions accurately. However, the laparoscopic findings of nonalcoholic steatohepatitis (NASH) have not been characterized. The aim of this study was to clarify the laparoscopic characteristics of NASH. METHODS: Twenty-four patients were enrolled. The degrees of hepatomegaly, color and irregularity of the liver surface, and the presence of depressions, patches, and vesicles were investigated. These laparoscopic findings were compared among NASH, alcoholic liver disease (ALD), and autoimmune hepatitis (AIH). RESULTS: Mild hepatomegaly, dullness of the liver edge, increased fat accumulation of the round ligament, and whitish markings were found in most of the patients with NASH. Small depressions were observed in approximately 70% of the patients. As fibrosis developed, the liver surface became whiter and more uneven. Compared with patients with ALD and AIH, increased fat accumulation of the round ligament and dullness of the liver edge were observed more frequently in those with NASH. However, coarse and groove-like depressions were rare in NASH patients. CONCLUSIONS: Several findings, including mild hepatomegaly, increased fat accumulation of the round ligament, rounded liver edge, whitish markings, and small depressions were common in patients with NASH. However, coarse and groove-like depressions were rare. These findings may be helpful for confirming a diagnosis of NASH.

Adult↗

PubMed2005

One-year intense nutritional counseling results in histological improvement in patients with non-alcoholic steatohepatitis: a pilot study.

BACKGROUND AND AIM: In individuals with biopsy-proven non-alcoholic steatohepatitis (NASH), short-term weight loss has been shown to improve biochemical abnormalities; however, its effect on liver histology is largely unknown. The aim of the article is to determine if dietary intervention is effective in improving histological features of steatohepatitis in patients with biopsy-proven NASH. METHODS: Twenty-three patients (11M/12F) with BMI >25 kg/m(2) and biopsy-proven NASH received standardized nutritional counseling aimed at reducing insulin resistance (IR) and weight. Blood tests were checked at baseline and every 1-4 months, and liver biopsy was repeated at month 12. IR was assessed by the homeostasis model assessment (HOMA). Liver biopsies were scored according to modified Brunt criteria for NASH. "Histologic response" was defined as a reduction in total NASH score of >/=2 points with at least one point being in the non-steatosis component. RESULTS: Sixteen patients (8M/8F) completed 12 months of dietary intervention, and 15 underwent repeat liver biopsies. At month 12, mean weight decreased from 98.3 to 95.4 kg. Mean waist circumference, visceral fat, fasting glucose, IR, triglycerides, AST, ALT, and histologic score were all reduced but the difference was not significant. Nine patients had a histologic response, six had stable scores, and none had a worsened score. Compared to patients with unchanged histologic scores, patients with improved scores had significantly greater reduction in weight, waist circumference, AST, ALT, steatosis grade, and total NASH score. CONCLUSION: Among patients who successfully completed 1 yr of intense dietary intervention, nine of 15 patients with NASH displayed histologic improvement. This pilot study suggests that dietary intervention can be effective in improving histology in patients with biopsy-proven NASH.

Adipose Tissue↗

PubMed2006

Hepatic histopathology of morbid obesity: concurrence of other forms of chronic liver disease.

BACKGROUND: Obesity is a chronic inflammatory condition, with related steatohepatitis and liver fibrosis. The authors analyzed the hepatic histopathology in morbidly obese patients and predictors of concurrence of clinical and/ or histopathologic findings of steatohepatitis with other forms of chronic liver disease. METHODS: The histopathologic findings in the liver of 160 patients who were undergoing laparoscopic gastric bypass or gastric banding for morbid obesity, were examined. Clinical data (gender, age, BMI and associated diseases) and laboratory evaluation were obtained from the patient records. The degree of steatosis, ballooning degeneration, lobular inflammation and fibrosis were determined and scored. RESULTS: Among the patients, 62.5% (n=100) were females and 37.5% (n=60) were males, age 27 +/- 12 years, with mean BMI 43 +/- 5.8 kg/m(2). 63, 54, 26, 15 and 2 patients were diagnosed as non-nonalcoholic steatohepatitis (non-NASH), NASH, chronic hepatitis B (CHB), alcoholic steatohepatitis and chronic hepatitis C (CHC), respectively. The prevalence of NASH was 33.8%, of which 5 patients (9.2%) had bridging fibrosis, but no cirrhosis was found in the NASH group. The prevalence of CHB was 16.3%, of which 3 patients (11.6%) had bridging fibrosis and/or cirrhosis. Multivariate analysis showed an association between steatosis and AST, ALT, GGT, C-peptide, insulin, HOMA-IR and adiponectin. The predictors of ballooning degeneration were serum sugar and AST, whereas the predictors of lobular inflammation were AST and ALT. There was a trend toward a correlation between abnormal liver function, insulin resistance, steatosis, liver cell injury and Mallory body in the NASH population. BMI, C-peptide, steatosis, ballooning degeneration and portal inflammation were significantly different between NASH and CHB groups, but only steatosis and ballooning degeneration were independent factors of NASH compared with CHB group after multivariate analysis. Overall, AST, AST/ALT ratio, uric acid and portal inflammation were independently associated with advanced fibrosis, while only Mallory body (P=0.033) and portal inflammation (P=0.015) were significantly different between mild-moderate fibrosis and advanced fibrosis in the NASH patients. CONCLUSION: Hepatic steatosis, features of metabolic syndrome and liver cell injuries were common in morbidly obese patients. Abnormal liver function and portal inflammation were related to hepatic fibrosis. The coexistance of clinical and histologic features of steatohepatitis with another chronic liver disease may reflect the biological significance of the chronic inflammatory condition in the obese population, which requires further investigation.

Adult↗

PubMed2006

[Nonalcoholic steatohepatitis in obese children: the prevalence and possible mechanism].

OBJECTIVE: To investigate the prevalence of nonalcoholic steatohepatitis (NASH) in obese children and its possible mechanism. METHODS: Three subgroups were classified according to their body mass index (BMI) in 123 obese children with BMI over 23 aged 7 to 16:34 cases with BMI> or =31 group; 57 cases with 25< or =BMI<30 group; 32 cases with 23< or =BMI<25 group. Ultrasonographic and biochemical parameters including serum alanine aminotransferase (ALT), serum aspartate aminotransferase (AST), serum cholesterol, serum triglyceride, serum uric acid and free glucose to free insulin ratio (FGIR) were assayed. Twenty four children suspected as benign acanthosis nigricans underwent skin biopsy and its association with nonalcoholic steatohepatitis was also discussed. RESULTS: Ninety-nine children (80.49 %) showed abnormal hepatic sonograms and 54 were diagnosed as NASH with the prevalence of 43.90%. Compared with the other two groups, BMI> or =31 group was significantly higher in prevalence of abnormal hepatic sonograms, NASH, decreased FGIR and risk of benign acanthosis nigricans (P<0.01). Fifty-four children diagnosed as NASH showed significantly higher incidence of hyperlipidemia, insulin resistance and higher body mass index as compared with 24 subjects without fatty liver changes. In 54 NASH children, 20(37.04%) had benign acanthosis nigricans. By bivariate analysis, ALT and AST were correlated well with BMI, cholesterol, triglyceride and FGIR (r(s)=0.413, 0.290, 0.379, -0.477, P<0.01; r(s)=0.359, 0.349, 0.348, -0.369, P<0.01). CONCLUSION: There is a high prevalence of nonalcoholic steatohepatitis in simple obese children and high incidence of benign acanthosis nigricans in NASH subjects. BMI> or=30 is a high risk factor of being NASH. Severe disturbance of lipid metabolism and insulin resistance may be involved in the mechanism of NASH.

Acanthosis Nigricans↗

PubMedDate not supplied

[Prevalence of non-alcoholic steatohepatitis. Comparative study with diabetic patients].

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a not very well known disease; it has been described principally in obese and diabetic women without significant alcohol consumption. The women are practically asymptomatic, and the hepatic function test (HFT) shows minimal changes. The liver biopsy findings are identical to those found in alcoholic liver disease. NASH may progress to cirrhosis. OBJECTIVE: To determine the prevalence of NASH in a Mexican community. METHODS: In the City of Pachuca, Mexico, we studied volunteers of both sexes who were between the ages of 17 and 75 years, all with an alcohol consumption of < 20 g/week without any known hepatic disease. A clinical review, laboratory test, and hepatic ultrasound were carried out. Subjects with HFT and ultrasound disorders were invited to continue the study with a hepatic biopsy. RESULTS: Ninety-seven volunteers completed the study, of whom 70 were non-diabetics and 27 were diabetics. Ten patients (10.3%) had NASH confirmed by hepatic biopsy; the prevalence in diabetics was 18.5% and in non-diabetics, 7.1%. In spite of the differences between NASH patients and the control group concerning gender, age, and diabetic status, there was no significant statistical difference except for the gallbladder antecedent. CONCLUSIONS: The prevalence of NASH was 10.3% in the studied group. NASH is more frequent in diabetics and women, but without a significant statistical difference. However, the odds ratio (OR) analysis shows diabetes and female sex to be a risk factor for NASH; therefore it is probable than our sample size is not large enough.

Adolescent↗

PubMedDate not supplied

Chronic liver disease in diabetes mellitus.

BACKGROUND: The association of diabetes with liver disease is well known. AIM: To study the spectrum of liver disease in patients of chronic liver disease (CLD) with diabetics and compare it with age and sex matched patients of CLD without diabetes. METHODS: We studied the patients of chronic liver disease presenting over a period of one year and their diagnosis were established by biochemical studies, imaging, endoscopic examination and liver biopsy when required. They were evaluated for the aetiological causes of liver diseases. RESULTS: A total of 53 patients of CLD with diabetes, M:F 43:8, with an age range of 35-70 years, median age of 51 years were taken as study group. Demographic picture of control group was n = 115, with M:F = 100: 15, age range of 37-68 years, with a median age of 52 years. Spectrum of liver disease in diabetic group were as follows: 56.6% cirrhosis, 15.1% chronic hepatitis, 22.6% fatty liver, 5.7% cirrhosis + hepatocellular carcinoma (HCC). The spectrum in control group was as follows, cirrhosis 46.1%, chronic hepatitis 36.5%, fatty liver 14.8%, cirrhosis and HCC 2.6%. Aetiology of chronic liver disease in diabetic group was as follows: Non-alcoholic steatohepatitis (NASH) with cirrhosis 11.3%, NASH 18.9%, cryptogenic cirrhosis 22.6%, hepatitis B virus (HBV) 17%, hepatitis C virus (HCV) 13.2%, alcohol 17%. Aetiology of chronic liver disease in nondiabetic group was as follows: NASH with cirrhosis 1.7%, NASH 13.0%, cryptogenic cirrhosis 7.8%, HBV 30.43%, HCV 13%, alcohol 29.6% and autoimmune in 4.3%. Incidence of NASH with cirrhosis and cryptogenic cirrhosis were found to be statistically significantly high in diabetic group. Incidence of diabetes in cryptogenic cirrhosis was found to be 57% versus 30% in noncryptogenic cirrhosis. CONCLUSION: NASH, NASH with cirrhosis and cryptogenic cirrhosis are the major causes of chronic liver disease in patients with diabetes mellitus. Alcohol and viral causes are found to be important aetiologies in nondiabetic control group. Diabetes mellitus is an important risk factor for chronic liver disease and progression of NASH to cirrhosis, which may present as cryptogenic cirrhosis.

Case-Control Studies↗

PubMedDate not supplied

Levels of serum hyaluronic acid, TNF-alpha and IL-8 in patients with nonalcoholic steatohepatitis.

BACKGROUND/AIMS: Nonalcoholic steatohepatitis (NASH) is a common cause of liver disease that comprises a wide spectrum of liver damage, ranging from simple steatosis to steatohepatitis. The aim of this study is to investigate serum hyaluronic acid (HA), TNF-alpha, IL-8 levels in patients with non-alcoholic steatohepatitis and to assess their potential value as a noninvasive marker for the severity of histopathology. METHODOLOGY: Twenty-eight patients with biopsy-proven NASH, 14 patients with cirrhosis and 15 healthy controls were studied. Histopathological findings were graded and staged. HA, IL-8, TNF-levels were determined using by ELISA test RESULTS: Serum HA levels in patients with NASH were significantly higher than in the healthy control group (P < 0.05). However, the levels in patients with cirrhosis were markedly higher than in patients with NASH and healthy controls (P < 0.001). Serum TNF-alpha levels were significantly higher in patients with NASH and cirrhosis than in healthy controls (P < 0.05). Serum IL-8 levels in patients with NASH (P < 0.001) and cirrhosis (P < 0.05) were significantly higher than in the healthy control group. There was no correlation between serum HA and IL-8, TNF-alpha, ALT and AST levels. Serum HA level in patients with NASH was 187.26 +/- 139.21 and 143.49 +/- 93.14 in stage in stage 2-3 and in stage 0-1, respectively, but the difference was not significant (P > 0.05). CONCLUSIONS: In conclusion, serum HA, IL-8 and TNF-alpha levels increased in patients with NASH. Their relation with the severity of histopathology is not significant. Serum HA levels may be a useful marker to monitor the conversion from fibrosis to cirrhosis. Further studies are needed on this topic.

Adult↗