Does taurolidine have any effect on liver regeneration and oxidation in the experimental hepatectomy model?

Objectives: Taurolidine is a bicyclic molecule produced by the natural amino acid taurine. Antibacterial, antiendotoxic and cytoprotective effects of taurolidine have been shown experimentally. Data on the effects of taurolidine on oxidative stress and hepatic regeneration are limited. The aim of the study was to evaluate the effect of taurolidine on hepatic regeneration and oxidative stress in rats undergoing partial hepatectomy. Material and Methods: Forty adult, male Wistar Albino rats were randomly divided into four equal groups: sham (S) group (n= 10), post-sham opera- tion taurolidine administered (ST) group (n= 10), partial hepatectomy (H) group (n= 10) and post-partial hepatectomy taurolidine administered (HT) group (n= 10). 100 mg/kg/day taurolidine was administered for seven days. Blood and liver tissue samples were collected on postoperative day seven. Liver tissue malondialdehyde, glutathione and Cu-Zn superoxide dismutase activity (SOD) were measured to assess oxidative stress. Binuclear hepato- cyte and Ki-67 antigen levels were measured to evaluate hepatic regeneration. Results: There was no difference between the groups for malondialdehyde, Cu-Zn superoxide dismutase and glutathione levels (p> 0.05). Binuclear nuclei levels were comparable between the H and HT groups (p= 0.06), while taurolidine decreased binuclear hepatocyte levels in the sham operated groups (p= 0.02). Taurolidine application decreased Ki-67 levels after partial hepatectomy (p= 0.001). Conclusion: Taurolidine may cause anti-regenerative effects after partial hepatectomy without causing oxidative damage.

Hepatic apoptotic markers are not predictors for the virological response to interferon-based therapy in chronic hepatitis C patients.

INTRODUCTION: Chronic hepatitis C virus (HCV) infection is a major health problem worldwide. The majority of cases involving HCV infection develop into chronic hepatitis because of a failure to develop an effective immune response. Apoptosis of the hepatocytes plays a significant role in the pathogenesis of HCV infection: the interaction between the Fas antigen on hepatocytes and the Fas ligand on T cells corresponds to the main mechanism for hepatocyte damage. Interferon (IFN)-α has antiviral, immunoregulatory, and antiproliferative properties, and apoptosis seems to be a critical event in the action mechanisms of both IFNs. In this study, we aimed to detect any relationship between apoptotic markers in the liver and the response to the treatment. MATERIALS AND METHODS: The study included 180 chronic HCV patients treated with IFN and ribavirin in four centers. Apoptotic markers (Fas, Fas ligand, Fas-associated death domain, caspases 3, 8, and 9, and in-situ apoptosis) were studied in the liver. The age, sex of the patients, response to therapy, ALT level, viral load, and genotype were recorded. RESULTS: The results of the study showed that the histological activity index and fibrosis correlated with CD95 staining density, caspase-8 intensiveness, and portal and parenchymal Fas ligand scores. The apoptotic parameters of the responsive cases were not significantly different from those of the unresponsive cases. CONCLUSION: The apoptotic parameters studied in liver tissue are associated with inflammation and fibrosis; however, these parameters may not predict response to treatment.

Shear wave elastography in the evaluation of liver fibrosis in children.

BACKGROUND: Shear-wave elastography (SWE) is a novel noninvasive method that involves application of local mechanical compression on soft tissue using focused ultrasonography and acquiring strain images that show tissue response. In this study, our goal was to assess the performance of SWE in the staging of liver fibrosis in children with chronic liver disease. METHODS: The study involved measuring SWE values in the right lobe of the liver in a patient group of 76 children with chronic liver disease and a control group of 50 healthy subjects. In the patient group, the shear elastic modulus values were correlated with biopsy results according to the Brunt scoring system (F0: portal fibrosis, F1: perisinusoidal or portal/periportal fibrosis, F2: both perisinusoidal and portal/periportal fibrosis, F3: bridging fibrosis, and F4: cirrhosis). Performance of SWE in estimating liver fibrosis in children was determined based on a receiver-operating characteristics (ROC) analysis. RESULTS: Mean SWE values of the control group and F0 group were not statistically significantly different (P = 0.106). The mean SWE values of the F1, F2, F3, and F4 groups were higher than that of the control group (all P < 0.001). Based on kiloPascal measurement values, the area under the ROC curve was 95.2% (95% confidence interval [CI] 92.1-99.5), with a sensitivity for diagnosing liver fibrosis of 91.5%, a specificity of 94.0%, a positive predictive value of 93.1%, and a negative predictive value of 92.6%. Based on meter-per-second measurement values, the area under the ROC curve was 96.3% (95% CI 92.7-99.8), with a sensitivity for diagnosing liver fibrosis of 93.2%, a specificity of 94.0%, a positive predictive value of 93.2%, and a negative predictive value of 94.0%. Mean SWE values for patients with nonalcoholic steatohepatitis were higher than those in the remainder of the study group. CONCLUSIONS: Although liver fibrosis can be detected using SWE, differentiation of fibrosis stages could not be achieved. The presence of steatosis significantly increased the mean SWE values on elastography and so care should be taken when assessing children with nonalcoholic steatohepatitis.

Mixed hepatocellular carcinoma and hepatoblastoma: cytohistopathologic findings and differential diagnosis.

BACKGROUND: Hepatocellular carcinoma (HCC) accounts for approximately 80% of all the primary malignant tumors of the liver. Hepatoblastoma (HBL) is the most common primary malignant neoplasm of the liver in childhood, and extremely rare in adults. To the best of our knowledge, this is the first report of an adult case with cytopathologic description of a combined HCC and HBL, occurring in a noncirrhotic liver. CASE: A 24-year-old male was admitted to the hospital with right-sided abdominal pain. Masses in the liver were detected radiologically. Fine-needle aspiration biopsy and core-needle biopsy revealed a malignant hepatocellular tumor with features of both HCC and HBL. CONCLUSION: In the present case among the distinct HCC cell groups, areas of smaller and more primitive cells consistent with embryonal type HBL and some other groups of cells with intermediate morphology were observed. These findings suggested the probable single stem cell origin of the tumor with differentiation to both cell groups rather than a combination of two different tumors. Therefore, the term 'malignant hepatocellular tumor' could also be considered to define this particular tumor. This case provides support to the previous reports in which HBL areas are described in HCC.

Long-term effect of interferon therapy in patients with HBeAg positive chronic hepatitis B infection.

INTRODUCTION: Several studies have reported that interferon therapy increases elimination rate of HBeAg and anti-HBe seroconversion in chronic hepatitis B (CHB) patients. We aimed to evaluate long-term results of interferon-α treatment in HBeAg positive CHB patients in a country with exclusively D genotype. METHODS: Seventy-one naive CHB patients (M/F 61/10, mean age 29±12 years, range 16-62) treated with 6 months of interferon-α 2b, 10 MU tiw and had a consequent untreated follow-up period of at least 10 years with positive response were identified and their data were reviewed. The therapy response was defined as HBeAg seroconversion with undetectable HBV-DNA. The responders were followed-up at 3-6-month intervals. RESULTS: Twenty-eight (39%) patients achieved HBeAg seroconversion (25 within the therapy, 3 within the consequent 12 months off-treatment follow-up). The responders were followed-up with a mean period of 152 months (range 123-181). In the follow-up period, 21/25 (84%) initial responders relapsed. On the other hand, 3 patients who did not respond at the end of therapy sustained the response during follow-up. Hence 21/28 total responders relapsed (75%), either with HBeAg reversion (3, 14.3%) or HBV-DNA elevation over 2000 IU/ml (or its equivalent in other types of definitions) and ALT elevation (18, 85.7%). The sustained response was present in 7 patients (9.8%). Serious side effects precluding completion of treatment occurred in three patients (4.2%). In multivariate analysis none of the pre-treatment parameters appeared to be significant in predicting response. CONCLUSION: Sustained response to interferon treatment is low in HBeAg positive CHB patients with genotype D.

Validation of biochemical markers for the prediction of liver fibrosis and necroinflammatory activity in hemodialysis patients with chronic hepatitis C.

BACKGROUND: Liver biopsy is an imperfect gold standard for assessing the disease severity in hemodialysis patients with chronic hepatitis C. Our purpose was to compare the accuracy of the FibroTest (FT) and ActiTest (AT) with liver biopsy and the AST-to-platelet ratio index (APRI) in determining hepatic fibrosis and necroinflammatory activity in hemodialysis patients with hepatitis C virus (HCV). METHODS: The FT-AT index combining 6 biochemical markers was assessed in 33 hemodialysis patients with HCV. Liver fibrosis and necroinflammatory activity was staged and graded according to the METAVIR scoring system. RESULTS: The accuracy of FT-AT versus biopsy was 0.46 for significant fibrosis and 0.36 for severe necroinflammatory activity. The FT index had a positive predictive value of 20% for scores greater than 0.6 and a negative predictive value of 45% for scores less than 0.2. Eleven of the 33 patients had scores ≤0.2, 6 had significant fibrosis on biopsy. Four out of 5 patients with FT scores >0.6 had mild fibrosis. APRI correlated well with the biopsy. CONCLUSION: The FT-AT test does not seem to be a reliable noninvasive marker for the prediction of necroinflammatory activity and fibrosis in hemodialysis patients with HCV and cannot be used as an alternative to either liver biopsy or APRI.

Effects of clinoptilolite treatment on oxidative stress after partial hepatectomy in rats.

BACKGROUND/OBJECTIVE: Clinoptilolite is a natural zeolite crystal. Cytoprotective effects of clinoptilolite have been reported. However, so far there are no data about the effects of clinoptilolite treatment on oxidative stress after partial hepatectomy. In this experimental study, the effects of clinoptilolite treatment after partial hepatectomy on oxidative stress were evaluated. METHODS: There were four experimental groups (n=8): Group S, the sham group; Group H, the hepatectomy group; Group HC, the clinoptilolite treatment after partial hepatectomy group; and Group CS, the clinoptilolite-treated sham group. A 70% partial hepatectomy was performed for Group H and HC. Clinoptilolite (5mg/kg) was given to the rats orally (via gavage tube) twice a day for 10 days after hepatectomy. Malondialdehyde (MDA), Cu-Zn super oxide dismutase (SOD), and glutathione (GSH) levels were assessed to evaluate oxidative stress. RESULTS: Plasma and liver tissue MDA levels of Group HC were significantly lower than the H group (p=0.018 and p=0.000, respectively). Liver tissue Cu-Zn SOD activity and GSH levels of Group HC were significantly higher than Group H (p=0.003, p=0.007, respectively). CONCLUSION: Clinoptilolite administration reduces oxidant activity and supports antioxidant response after partial hepatectomy.

Adult Langerhans cell histiocytosis and sclerosing cholangitis: a case report and review of the literature.

BACKGROUND/AIMS: Sclerosing cholangitis is a rare complication of Langerhans cell histiocytosis in children which can result in liver failure. This combination is even rarer in adults. CASE REPORT: We report a 65-year-old female who developed sclerosing cholangitis 4 years after the diagnosis of Langerhans cell histiocytosis. CONCLUSION: Sclerosing cholangitis caused by Langerhans cell histiocytosis is a rare condition in the adult population, but it has a high mortality. There is no definitive therapy other than liver transplantation. The long-term efficacy of liver transplantation remains unknown.

Is alanine aminotransferase level a surrogate biomarker of hepatic apoptosis in nonalcoholic fatty liver disease?

AIM: To evaluate the serum alanine aminotransferase (ALT) variabilities in nonalcoholic fatty liver disease (NAFLD) and correlate it with hepatocyte apoptosis and oxidative stress parameters. METHODS: 24 patients with NAFLD and normal ALT were compared with 26 subjects with NAFLD and elevated ALT. Liver oxidative stress was estimated on the basis of malondialdehyde, superoxide dismutase and glutathione. Immunohistochemistry was performed for activated caspase 3 and 8, nuclear factor-kappaB, antiapoptotic Bcl-2 protein and serum TNF receptor levels were measured. RESULTS: The mean caspase 3 and 8 activity scores, oxidative stress parameters, necroinflammatory grade and prevalence of severe fibrosis were comparable across the groups with normal versus elevated ALT. Patients with nonalcoholic steatohepatitis had significantly higher caspase 3 and 8 activity (percentage of cells with positive staining per high power field), and serum malondialdehyde (mmol/l) levels than those with simple steatosis. ALT elevation was not a risk factor for advanced necroinflammatory grade and fibrosis. A receiver operating characteristic curve did not demonstrate sensitivity and specificity for discriminative power of ALT. CONCLUSION: Apoptosis and oxidative stress are the main processes contributing to disease progression in NAFLD. ALT values do not correlate with the parameters of apoptosis and oxidative stress. The disease severity can only be determined by liver biopsy.

Serum neopterin levels in children with hepatitis-B-related chronic liver disease and its relationship to disease severity.

AIM: To evaluate serum neopterin levels and their correlations with liver function tests and histological grade in children with hepatitis-B-related chronic liver disease. METHODS: The study population comprised 48 patients with chronic active hepatitis B, 32 patients with hepatitis-B-related active liver cirrhosis and 40 normal controls. Serum neopterin was measured using an enzyme-linked immunosorbent assay. RESULTS: The mean +/- SD serum neopterin levels were 14.2 +/- 5.6 nmol/L in patients with chronic hepatitis, 20.3 +/- 7.9 nmol/L in patients with liver cirrhosis and 5.2 +/- 1.4 nmol/L in control group. Serum neopterin levels were significantly higher in patients with chronic hepatitis (P = 0.005) and cirrhosis patients (P = 0.008), than in control subjects. Cirrhotic patients had significantly higher serum neopterin levels than patients with chronic hepatitis (P = 0.004). There was a positive correlation between serum neopterin levels and alanine aminotransferase levels in patients with chronic hepatitis (r = 0.41, P = 0.004) and cirrhotic patients (r = 0.39, P = 0.005). Positive correlations were detected between serum neopterin levels and inflammatory score in patients with chronic hepatitis (r = 0.51, P = 0.003) and cirrhotic patients (r = 0.49, P = 0.001). CONCLUSION: Our results suggest that serum neopterin levels can be considered as a marker of inflammatory activity and severity of disease in children with hepatitis-B-related chronic liver disease.

Serum gamma-glutamyltranspeptidase distinguishes non-alcoholic fatty liver disease at high risk.

BACKGROUND/AIMS: Hepatocyte apoptosis is an important and invasive predictor of liver injury and fibrosis in non-alcoholic fatty liver disease (NAFLD). Increased gamma-glutamyltranspeptidase (GGT) level is frequently observed in NAFLD. Hepatocyte growth factor (HGF) stimulates fibrogenesis and is correlated with GGT. The study aimed to determine whether GGT can distinguish NAFLD patients at high risk. METHODOLOGY: Fifty biopsy-proven NAFLD patients (M/F: 24/26) were divided as the normal GGT group (n = 25) and the high GGT group (n = 25) (each patients' GGT > two fold of upper-limit of normal). Liver histology was graded according to Brunt et al. TNF-sRp55, caspase-3 and 8, NFkappaB and Bcl-2 were measured by immunohistochemical methods. For statistical analysis, Student's t test, chi-square test, multivariate regression analysis and the area under receiver operating characteristic (ROC) curve were used. RESULTS: The high GGT group had significantly higher NFkappaB, caspase-3 and 8, and Bcl-2 levels (54.52 +/- 26.02, p = 0.002; 55.95 +/- 27.18, p = 0.002; 47.85 +/- 28.04, p = 0.001; 11.19 +/- 12.33, p = 0.016, respectively). Serum TNF-sRp55 levels of both groups were similar (2922.93 +/- 307.26, and 2885 +/- 194.47; p = 0.78). Differences in reference to histological steatosis grade and inflammation were not significant. However, fibrosis stage was higher in the high GGT group (p = 0.048). CONCLUSION: Multinominal logistic regression analysis showed that increased GGT level was a risk factor for advanced fibrosis in NAFLD (OR: 1.0, CI: 0.98-1.01; p =0.032). Using serum GGT levels the area under the ROC curve for the prediction of advanced fibrosis was 0.74 (95% CI: 0.54-0.94). The serum GGT cut-off value for the prediction of advanced fibrosis was 96.5 U/L; with 83% sensitivity and 69% specificity.

Leptin in nonalcoholic fatty liver disease.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is a prevalent condition associated with obesity and insulin resistance (IR). Leptin plays a key role in the control of energy balance, and insulin sensitivity. In this study, we aimed to examine whether serum leptin levels correlate with insulin resistance, oxidative stress parameters and the severity of histological changes in NAFLD. METHODS: Fifty-two patients (M/F: 28/24) with no alcohol intake and biopsy-proven diagnosis of NAFLD were studied. Serum leptin levels were measured by radioimmunoassay. HOMA (homeostasis model assessment) IR index was calculated. Comparisons between the patients with NAFLD and non-alcoholic steatohepatitis (NASH) were performed using the Student's t test. Multivariate regression analysis and the area under the receiver operating characteristic (ROC) curve were used to identify the independent predictors for NASH. RESULTS: We found no association between serum leptin, fasting insulin levels, and oxidative stress parameters. ROC curve and multiple regression analysis revealed no association between the severity of histological changes and serum leptin levels. During six months followed-up period only NASH group with elevated leptin levels had significant reductions of ALT and AST values (p = 0.03, and 0.005, respectively). CONCLUSION: Our findings show a preventive effect of leptin against progressive liver injury in NAFLD.

Clinicopathologic features of dual chronic hepatitis B and C infection: a comparison with single hepatitis B, C and delta infections.

UNLABELLED: There is controversial data in the literature about the characteristics or features of dual hepatitis B and C infection. Several studies have reported that the dual infection has a more severe histological picture; faster progression leading to cirrhosis and a higher risk for hepatocellular carcinoma compared with the single infections. These findings have not yet been supported. We assessed the patients with dual hepatitis B and C infection with respect to their different features in our country. METHOD: the chronic hepatitis patients of our clinics were tested, and both HBsAg and anti-HCV positive patients with chronic hepatitis were enrolled to the study. All patients were tested for the biochemical parameters and the presence of HBV-DNA and HCV-RNA. RESULTS: Of the 1950 patients, 51 (2.6%) were both HBsAg and anti-HCV positive and 67 were anti-delta positive. Patients were followed up for 5.4+/-2.1 years. Of the 51 dual hepatitis patients, 6 had no HBV-DNA and HCV-RNA detectable by PCR, 36 were only HCV-RNA positive, 9 were only HBV-DNA positive and 3 were both HBV-DNA and HCV-RNA positive. Dominant infection in (3/4) of the patients was hepatitis C. Clinical and histological properties of the cases with dual Hepatitis B and C infection showed no significant differences compared to the single infections. In conclusion, regarding the prognosis, no significant differences were found between such dual and single infections. Dual infection with hepatitis B virus and delta virus is a significantly more severe condition than the dual infection with hepatitis B and C viruses.

Acute renal failure in a patient with severe hemolysis.

Paroxysmal nocturnal hemoglobinuria (PNH) is a clonal disorder of bone marrow. It is characterized by blood cells lacking membrane proteins that are normally attached by the glycosylphosphatidylinositol (GPI) anchor. The cellular defect arises in a hematopoetic stem cell and is due to somatic mutation of the Phosphatidylinositol-glycan protein-A gene (PIG-A gene), encoding a protein needed for the biosynthesis of the anchor GPI. Paroxysmal nocturnal hemoglobinuria is presented by intravascular hemolysis, cytopenias, frequent infections, bone marrow hypoplasia, and a high incidence of life threatening venous thrombosis. Kidney involvement is usually benign and secondary to chronic tubular deposition of hemosiderin. Acute renal failure may occur in association with a hemolytic crisis. Here we report a case of 40-year-old woman with hematuria, pancytopenia, and acute renal failure due to PNH.

Liver steatosis in hepatitis C positive hemodialysis patients and factors affecting IFN-2a treatment.

OBJECTIVE: Hepatitis C virus (HCV) infection is endemic among hemodialysis (HD) patients. It is well known that HCV causes approximately 50% of hepatosteatosis in patients with normal renal function and that this rate is higher in patients infected with genotype 3. The aim of this study was to investigate the rate of steatosis, the regression in steatosis with interferon (IFN) treatment and factors affecting IFN treatment in hemodialysis patients with chronic hepatitis C (CHC). MATERIAL AND METHODS: Thirty-seven HD patients with CHC were included in the study. All patients received hemodialysis treatment three times a week during the follow-up period. Patients were treated with 3 million units (MU) of IFN-alpha 2a monotherapy for at least 6 months. All patients were evaluated by liver biopsy before therapy and 16 were evaluated at 12-month follow-up. RESULTS: Mean age of the 37 patients (23 M, 14 F) was 44+/-11.6 years and body mass index was 21.8+/-1.8 kg/m2. Twenty-eight of the patients included in the study (75.7%) were of genotype 1b. RNA response after treatment was 78.4% and sustained response after the follow-up period of 14.9+/-8 months was 54%. Total cholesterol values were directly proportional to RNA response (p<0.003) and inversely correlated with resistance to treatment (p<0.008). Triglyceride values were inversely correlated with resistance to treatment (p<0.041). At evaluation of steatosis scores in baseline liver biopsy, severe and mild to moderate steatosis was found in 3 (8.1%) and 16 (43.2%) patients, respectively. In 18 patients (48.7%) there was no steatosis. The rate of steatosis was found to be 44% in control biopsies. While there was no regression in the rates of steatosis (p=0.499), it was found that steatosis regressed after IFN treatment in two patients infected with genotype 3. No correlations were observed between HCV genotype, sustained response and liver steatosis. CONCLUSIONS: Response and sustained response rates of HD patients with HCV in a Turkish population were found to be high after IFN monotherapy. With the exception of two patients infected with genotype 3a, the rate of liver steatosis was found to be high and did not change after IFN treatment in HD patients with CHC.

Efficacy of interferon alpha-2b and lamivudine combination treatment in comparison to interferon alpha-2b alone in chronic delta hepatitis: a randomized trial.

BACKGROUND AND AIM: Delta hepatitis is characterized by rapidly progressive liver disease with adverse prognosis in most patients. Patients benefit from high doses and prolonged courses of interferon (IFN) therapy; however, lamivudine as a single agent has been disappointing. Data relating to the efficacy of IFN and lamivudine in combination is limited. The aim of this study was to test the efficacy of IFN-alpha 2b and lamivudine combination treatment in comparison to IFN-alpha 2b alone in patients with chronic delta hepatitis. METHODS: Twenty-six patients with chronic delta hepatitis were randomized into two groups. Twelve patients received IFN-alpha 2b alone (eight men, four women; mean +/- SD age: 43.83 +/- 8.57 years), and 14 patients received IFN-alpha 2b plus lamivudine combination (seven men, seven women; mean +/- SD age: 42.5 +/- 11.02 years). The dose of IFN-alpha 2b was 10 MU t.i.w. and of lamivudine was 100 mg/day. The groups were comparable in reference to serum alanine aminotransferase (ALT), aspartate aminotransferase, bilirubin, albumin levels, histological activity and stage. Four patients (33.3%) in the IFN group and two (14.3%) in the combination group had cirrhosis (P = 0.2). The duration of treatment was 48 weeks with an untreated follow-up period of at least 96 weeks (mean +/- SD, 3.1 +/- 1.9 years). A liver biopsy was performed at the end of treatment. RESULTS: Eight patients from the IFN group and 11 from the combination group completed treatment. Serum ALT values became normal in 8/14 patients (57.1%) treated with IFN plus lamivudine and in 5/12 patients (41.7%) treated with IFN alone (P = 0.43). Serum hepatitis delta virus RNA was no longer detectable in nine of 14 (64.3%) patients treated with IFN plus lamivudine as compared to five of 12 (41.6%) patients treated with IFN alone (P = 0.024). In both groups female patients had significantly better virological response rate (P = 0.007). There was a significant improvement in histological activity in the combination group (mean decrease 5.27 +/- 1.08 score, P = 0.001), but not in the IFN group (mean decrease 1.44 +/- 1.59 score, P = 0.39). No significant improvement was observed in regards to fibrosis. Four of the 14 patients (28.6%) treated with combination therapy as compared to two of 12 patients treated with IFN (16.7%) were sustained virological responders (P = 0.47). The 5-year survival rate was 65% in the IFN group and 85% in the combination group (P > 0.05). CONCLUSION: Interferon and lamivudine in combination is an encouraging treatment method and may be superior to IFN alone in chronic delta hepatitis.

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.