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Background & Aims: The predictors of progression from steatosis to more advanced stages of metabolic dysfunction-associated steatotic liver disease (MASLD) remain unclear. We evaluated the association between the quantity of hepatic steatosis and longitudinal changes in liver stiffness measurements (LSMs) using magnetic resonance elastography (MRE) in patients with MASLD., Methods: We retrospectively analysed patients with MASLD who underwent at least two serial MRE and magnetic resonance imaging-based proton density fat fraction (MRI-PDFF) examinations at least 1 year apart. Fine-Gray competitive proportional hazard regression was used to identify LSM progression and regression factors., Results: A total of 471 patients were enrolled. Factors linked to LSM progression were steatosis grade 3 (MRI-PDFF ≥17.1%, adjusted hazard ratio [aHR] 2.597; 95% confidence interval [CI] 1.483-4.547) and albumin-bilirubin grade 2 or 3 (aHR 2.790; 95% CI 1.284-6.091), while the only factor linked to LSM regression was % decrease rate of MRI-PDFF ≥5% (aHR 2.781; 95% CI 1.584-4.883). Steatosis grade 3 correlated with a higher incidence rate of LSM progression than steatosis grade 1 (MRI-PDFF <11.3%) in patients with LSM stage 0 (<2.5 kilopascal [kPa]), and a % annual decrease rate of MRI-PDFF ≥5% correlated with a higher incidence rate of LSM regression than that of MRI-PDFF >-5% and <5% in patients with LSM stage 1 or 2-4 (≥2.5 kPa)., Conclusions: Severe hepatic steatosis was linked to significant LSM progression in patients with MASLD and low LSM (<2.5 kPa)., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Several preliminary reports have suggested the utility of ultrasound attenuation coefficient measurements based on B-mode ultrasound, such as iATT, for diagnosing steatotic liver disease. Nonetheless, evidence supporting such utility is lacking. This prospective study aimed to investigate whether iATT is highly concordant with magnetic resonance imaging (MRI)-based proton density fat fraction (MRI-PDFF) and could well distinguish between steatosis grades., Methods: A cohort of 846 individuals underwent both iATT and MRI-PDFF assessments. Steatosis grade was defined as grade 0 with MRI-PDFF < 5.2%, grade 1 with 5.2% MRI-PDFF < 11.3%, grade 2 with 11.3% MRI-PDFF < 17.1%, and grade 3 with MRI-PDFF of 17.1%. The reproducibility of iATT and MRI-PDFF was evaluated using the Bland-Altman analysis and intraclass correlation coefficients, whereas the diagnostic performance of each steatosis grade was examined using receiver operating characteristic analysis., Results: The Bland-Altman analysis indicated excellent reproducibility with minimal fixed bias between iATT and MRI-PDFF. The area under the curve for distinguishing steatosis grades 1, 2, and 3 were 0.887, 0.882, and 0.867, respectively. A skin-to-capsula distance of ≥ 25 mm was identified as the only significant factor causing the discrepancy. No interaction between MRI-logPDFF and MRE-LSM on iATT values was observed., Conclusions: Compared to MRI-PDFF, iATT showed excellent diagnostic accuracy in grading steatosis. iATT could be used as a diagnostic tool instead of MRI in clinical practice and trials. Trial registration This study was registered in the UMIN Clinical Trials Registry (UMIN000047411)., (© 2024. The Author(s).)

Introduction: Liver fibrosis stage is one of the most important factors in stratifying the risk of developing hepatocellular carcinoma (HCC). We evaluated the usefulness of liver stiffness measured by magnetic resonance elastography (MRE) to stratify the risk of developing HCC in patients who underwent MRE before receiving direct-acting antivirals (DAAs) and subsequently achieved sustained virological response (SVR)., Methods: A total of 537 consecutive patients with persistent hepatitis C virus who underwent initial MRE before DAA therapy and achieved SVR were enrolled. Factors associated with HCC development were analyzed by univariate and multivariate Cox proportional hazards models., Results: Albumin-bilirubin score ≥ -2.60 (adjusted hazard ratio [aHR] 6.303), fibrosis-4 (FIB-4) score >3.25 (aHR 7.676), and MRE value ≥4.5 kPa (aHR 13.190) were associated with HCC development according to a univariate Cox proportional hazards model. A multivariate Cox proportional hazards model showed that an MRE value ≥4.5 kPa (aHR 7.301) was the only factor independently associated with HCC development. Even in patients with an FIB-4 score >3.25, the cumulative incidence rate of HCC development in those with an MRE value <4.5 kPa was significantly lower than that in patients with an MRE value ≥4.5 kPa., Discussion: Liver stiffness measured by MRE before DAA therapy was an excellent marker for predicting subsequent HCC development in patients with hepatitis C virus infection who achieved SVR. The same results were observed in patients with high FIB-4 scores., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Corticotropin-releasing factor (CRF) in the brain acts on physiological and pathophysiological modulation of the hepatobiliary system. Central CRF administration aggravates experimental acute liver injury by decreasing hepatic blood flow. Conversely, minimal evidence is available regarding the effect of centrally acting CRF on hepatic lipid metabolism and inflammation. We examined whether central CRF affects hepatic lipid metabolism and inflammation-related gene expression in rats. Male Long Evans rats were intracisternally injected with CRF (10 μg) or saline. Rats were sacrificed 2 h, 6 h, and 24 h after the CRF injection, the liver was isolated, and mRNA was extracted. Next, hepatic lipid metabolism and inflammation-related gene expression were examined. Hepatic SREBF1 (sterol regulatory element-binding transcription factor 1) mRNA levels were significantly increased 6 h and 24 h after intracisternal CRF administration when compared with those in the control group. Hepatic TNFα and IL1β mRNA levels increased significantly 6 h after intracisternal CRF administration. Hepatic sympathectomy or guanethidine treatment, not hepatic branch vagotomy or atropine treatment, inhibited central CRF-induced increase in hepatic SREBF1, TNFα and IL1β mRNA levels. These results indicated that central CRF affects hepatic de novo lipogenesis and inflammation-related gene expression through the sympathetic-noradrenergic nervous system in rats.

The autonomic nervous system, consisting of sympathetic and parasympathetic branches, plays an important role in regulating metabolic homeostasis. The sympathetic nervous system (SNS) regulates hepatic lipid metabolism by regulating adrenergic receptor activation, resulting in the stimulation of hepatic very-low-density lipoprotein-triglyceride (TG) production in vivo. However, only a few studies on the relationship between SNS and hepatic steatosis have been reported. Here, we investigate the effect of adrenergic receptor agonists on hepatic steatosis in mice fed a high-fat diet (HFD). The α-adrenergic receptor agonist phenylephrine (10 mg/kg/d) or the β-adrenergic receptor agonist isoproterenol (30 mg/kg/d) was coadministered with HFD to male mice. After five weeks, hepatic steatosis, TG levels, and hepatic fat metabolism-related biomarkers were examined. HFD treatment induced hepatic steatosis, and cotreatment with phenylephrine, but not isoproterenol, attenuated this effect. Phenylephrine administration upregulated the mRNA levels of hepatic peroxisome proliferator-activated receptor alpha and its target genes (such as carnitine palmitoyltransferase 1) and increased hepatic β-hydroxybutyrate levels. Additionally, phenylephrine treatment increased the expression of the autophagosomal marker LC3-II but decreased that of p62, which is selectively degraded during autophagy. These results indicate that phenylephrine inhibits hepatic steatosis through stimulation of β-oxidation and autophagy in the liver.

Background & Aims: Noninvasive methods have been evaluated for the assessment of liver fibrosis and steatosis in patients with nonalcoholic fatty liver disease (NAFLD). We compared the ability of transient elastography (TE) with the M-probe, and magnetic resonance elastography (MRE) to assess liver fibrosis. Findings from magnetic resonance imaging (MRI)-based proton density fat fraction (PDFF) measurements were compared with those from TE-based controlled attenuation parameter (CAP) measurements to assess steatosis., Methods: We performed a cross-sectional study of 142 patients with NAFLD (identified by liver biopsy; mean body mass index, 28.1 kg/m(2)) in Japan from July 2013 through April 2015. Our study also included 10 comparable subjects without NAFLD (controls). All study subjects were evaluated by TE (including CAP measurements), MRI using the MRE and PDFF techniques., Results: TE identified patients with fibrosis stage ≥2 with an area under the receiver operating characteristic (AUROC) curve value of 0.82 (95% confidence interval [CI]: 0.74-0.89), whereas MRE identified these patients with an AUROC curve value of 0.91 (95% CI: 0.86-0.96; P = .001). TE-based CAP measurements identified patients with hepatic steatosis grade ≥2 with an AUROC curve value of 0.73 (95% CI: 0.64-0.81) and PDFF methods identified them with an AUROC curve value of 0.90 (95% CI: 0.82-0.97; P < .001). Measurement of serum keratin 18 fragments or alanine aminotransferase did not add value to TE or MRI for identifying nonalcoholic steatohepatitis., Conclusions: MRE and PDFF methods have higher diagnostic performance in noninvasive detection of liver fibrosis and steatosis in patients with NAFLD than TE and CAP methods. MRI-based noninvasive assessment of liver fibrosis and steatosis is a potential alternative to liver biopsy in clinical practice. UMIN Clinical Trials Registry No. UMIN000012757., (Copyright © 2016 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Objective: The aim of this study was to assess the significance and degree of correlation between the intake of fish oil, magnesium (Mg), and zinc (Zn) and metabolic parameters., Methods: Correlation coefficients among nutrient intake and physical and laboratory parameters were determined using Spearman's rho (ρ) test or a multiple regression model among Japanese individuals (male:female, 37:66; median age, 55 y) who completed a semiquantitative food questionnaire and underwent testing for diabetes. Individuals with diabetes were excluded., Results: Spearman's test revealed several weak but significant correlations between intake of fish oil including ω-3 polyunsaturated fatty acids (PUFAs) and various metabolic parameters. The test showed that Zn intake in women significantly correlated with reduced systolic blood pressure (SBP), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (γ-GPT), and homeostasis model assessment-insulin resistance (HOMA-IR). Multivariate analysis revealed that intake of fish oil, eicosapentaenoic acid (EPA), and Zn was significantly associated with increased serum levels of high-density lipoprotein cholesterol (HDL-C; fish oil versus HDL-C, P = 0.0438; 95% confidence interval [CI], 0.0055-0.3724; EPA versus HDL-C, P = 0.0439; 95% CI, 0.0053-0.3724; Zn versus HDL-C, P = 0.0041; 95% CI, 0.0890-0.4609). Multivariate analysis revealed that ω-3 PUFAs were associated with decreased serum ALT levels (P = 0.0240; 95% CI, -5.000 to -0.0367) and that Zn correlated with SBP (P = 0.0239; 95% CI, -0.5149 to -0.0377) in women., Conclusion: Intake of fish oil, Mg, and Zn was associated with some metabolic parameters. Abundant intake of fish oil including ω-3 PUFAs and Zn can exert antiarteriosclerotic effects through increasing serum levels of HDL-C. ω-3 PUFAs can reduce liver inflammation and Zn can reduce SBP in women., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Aim: To investigate the relationship between the iron-metabolism-related gene expression profiles and efficacy of antiviral therapy in chronic hepatitis C patients., Methods: The hepatic expression profile of iron-metabolism-related genes was analyzed and its association with virological response to pegylated-interferon plus ribavirin combination therapy was evaluated. A hundred patients with chronic hepatitis C (genotype1b, n = 50; genotype 2, n = 50) were enrolled and retrospectively analyzed. Liver biopsy samples were subjected to quantitative polymerase chain reaction for iron-metabolism-related genes and protein expression (Western blotting analysis) for ferroportin. As a control, normal liver tissue was obtained from 18 living donors of liver transplantation. Serum hepcidin level was measured by sensitive liquid chromatography/electrospray ionization tandem mass spectrometry., Results: Iron overload is associated with liver damage by increasing oxidative stress and hepatitis C virus (HCV) is reported to induce iron accumulation in hepatocytes in vivo. Conversely, iron administration suppresses HCV replication in vitro. Therefore, the association between HCV infection and iron metabolism remains unclear. Compared with controls, patients had significantly higher gene expression for transferrin, iron-regulatory proteins 1 and 2, divalent metal transporter 1, and ferroportin, but similar for transferrin receptors 1 and 2, and hepcidin. When the expression profiles were compared between sustained virological response (SVR) and non-SVR patients, the former showed significantly lower transcription and protein expression of hepcidin and ferroportin. Expression of hepcidin-regulating genes, BMPR1, BMPR2, and hemojuvelin, was significantly increased, whereas BMP2 was decreased in HCV-infected liver. BMPR2 and hemojuvelin expression was significantly lower in the SVR than non-SVR group. HCV infection affects the expression of iron-metabolism-related genes, leading to iron accumulation in hepatocytes., Conclusion: Decreased expression of hepcidin and ferroportin in SVR patients indicates the importance of hepatocytic iron retention for viral response during pegylated-interferon plus ribavirin treatment.

It is estimated that 30% of the adult population in Japan is affected by nonalcoholic fatty liver disease (NAFLD). Fatty changes of the liver are generally diagnosed using imaging methods such as abdominal ultrasonography (US) and computed tomography (CT), but the sensitivity of these imaging techniques is low in cases of mild steatosis. Alanine aminotransferase levels may be normal in some of these patients, warranting the necessity to establish a set of parameters useful for detecting NAFLD, and the more severe form of the disease, nonalcoholic steatohepatitis (NASH). Although liver biopsy is currently the gold standard for diagnosing progressive NASH, it has many drawbacks, such as sampling error, cost, and risk of complications. Furthermore, it is not realistic to perform liver biopsies on all NAFLD patients. Diagnosis of NASH using various biomarkers, scoring systems and imaging methods, such as elastography, has recently been attempted. The NAFIC score, calculated from the levels of ferritin, fasting insulin, and type IV collagen 7S, is useful for the diagnosis of NASH, while the NAFLD fibrosis score and the FIB-4 index are useful for excluding NASH in cases of advanced fibrosis. This article reviews the limitations and merits of liver biopsy and noninvasive diagnostic tests in the diagnosis of NAFLD/NASH.

Background: To identify predictors of changes in functional hepatic volumes after portal vein embolization (PVE) before hepatectomy, we examined the relationship between hepatic functional parameters and changes in functional volume of the embolized and non-embolized liver based on a previous volumetric analysis., Material and Methods: Subjects were 24 patients who underwent PVE, which was performed through the trans-ileocolic vein (n = 4) or by percutaneous transhepatic puncture (n = 20). The RI liver volume parameter was measured by liver scintigraphy with technetium-(99m) galactosyl human serum albumin ((99m)Tc-GSA). Computed tomography (CT) volume parameter was also measured., Results: Significant atrophy of the embolized liver and hypertrophy of the non-embolized liver (change of 72 ± 108 cm(3) and 111 ± 91 cm(3), respectively) (change of 7.8%) was observed after PVE. The change in these RI volume parameters (change of 173 ± 175 cm(3) and 145 ± 137 cm(3) , respectively) (16.5%) was significantly greater than CT volume parameters (P < 0.01). CT vol and RI vol in the embolized and non-embolized liver were well correlated (r = 0.75 and 0.69, respectively). However, the correlation between CT and RI volume parameters in the embolized and non-embolized liver after PVE was very weak (r = 0.17 and 0.03, respectively). Only alkaline phosphatase level correlated negatively with atrophic CT volume parameter of the embolized liver (r = -0.455, P < 0.05). When compared with CT volume parameter, more parameters were significantly correlated with changes of RI volume parameter in the embolized liver: pre-PVE pressure; ICGR15; and serum levels of hyaluronate, total bilirubin, albumin, and alkaline phosphatase. Only platelet count was significantly correlated with hypertrophy of the non-embolized liver., Conclusion: RI volume parameter might more accurately reflect functional changes in the embolized liver and non-embolized liver than CT volume parameter. Correlated parameters might allow us to predict the functional effect of PVE., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Background: To achieve complete anatomic hepatectomy, hepatic transection by an anterior approach is useful. The liver hanging maneuver is a useful procedure for transection of adequate cut plane in anatomical liver resections and may reduce intraoperative bleeding and transection time., Methods: We examined the records of 71 patients who underwent anatomic hepatic resection with (n = 24, between 2001 and September 2007) or without liver hanging maneuver (LHM) (n = 47, between 2000 and 2003). Groups were historically compared in terms of patient demographics, preoperative hepatic function, surgical records, and outcome. LHM was conducted according to the Belghiti's original method., Results: LHM could be performed not only in hemihepatectomy but also in right and left trisectionectomy. Demographics and preoperative hepatic function tests were not significantly different between the LHM and non-LHM groups. Although intraoperative bleeding, blood transfusion, and operating time were not significantly different between groups, the time required for liver parenchymal transection was significantly shorter in the LHM group (36.5 +/- 9.9 vs. 48.1 +/- 12.7 min, P = 0.004). Postoperative liver function, morbidity, and mortality were not significantly different between the groups. In other hepatectomy with cut plane along the right hepatic vein, the transection time tended to be shorter in the LHM group (n = 5, 32.4 +/- 6.1 min) than in the non-LHM group (n = 5, 44.4 +/- 8.3 min), albeit insignificantly (P = 0.06)., Conclusion: LHM can reduce the transection time at the cut plane in hepatic resections. Our results emphasized the advantages and usefulness of LHM in anatomical liver resections.

Anatomic resection is theoretically effective in eradicating intrahepatic metastasis of hepatocellular carcinoma (HCC). In patients who undergo a larger volume of hepatectomy or who have hepatic dysfunction, the extent of hepatectomy is limited to avoid postoperative hepatic failure. In the present case, a limited anatomic resection according to Couinaud's segment was performed because of the large volume of the right hemi-liver. A 62-year-old male was found to have a 12-cm HCC in segments 5, 6 and 7, with alcoholic liver disease. The total liver function was Child-Pugh grade A, as indocyanine green retention rate at 15 minutes (ICGR15) was 12%. The resected liver volume of right hemihepatectomy estimated by CT volumetry was 72% and the permitted resected volume based on Takasaki's formula applying ICGR15 was 65%. As the portal branches of segment 8 was free from HCC involvement and the estimated volume of segments 5, 6 and 7 was 51%, we scheduled anatomic resection of these segments to secure remnant liver function. Under Pringle's maneuver, hepatic transection on the border between right and left liver was performed and the right paramedian Glisson's pedicle was exposed in the first step. Branches of segment 5 were divided and the border between segments 5 and 8 was confirmed. Then, the right lateral sector was resected and the right hepatic vein draining segment 8 was secured. Postoperative course was satisfactory and the patient was free from tumor relapse for 16 months after hepatectomy. Under a balance between tumor location and hepatic functional reserve, anatomic resection would be necessary for the treatment of HCC patients.

A 47-year man was hospitalized to our hospital because of consciousness disturbance. He had been abnormally fond of soy bean products since childhood. His plasma levels of ammonia and citrulline were elevated, and we suspected of adult-onset type II citrullinemia (CTLN2). Gene examination demonstrated abnormality in the SLC25A13 gene, confirming CTLN2. Serum levels of hepatobiliary enzymes were increased and his liver biopsy revealed nonalcoholic steatohepatitis. Although we considered that living donor liver transplantation was suitable for the treatment, unfortunately, there was no appropriate donor candidate in his family. He has received conservative treatments, showing a symptom-free course.

Background: To identify predictors of changes in hepatic volumes after portal vein embolization (PVE) before hepatectomy, we examined the relationship between clinicopathological parameters and changes in volume of embolized and nonembolized liver and regeneration of remnant liver after hepatectomy., Materials and Methods: The subjects were 25 patients who underwent laparotomy. PVE was performed through transileocolic vein (n = 15) and percutaneous transhepatic puncture (n = 10)., Results: Significant atrophy and hypertrophy of the embolized and nonembolized liver were observed after PVE, respectively, and further increase of remnant liver volume was observed after hepatectomy. Background liver disease did not seem to influence the results. Alkaline phosphatase (ALP) level correlated negatively with atrophy of embolized lobe (r = -0.433). Platelet count correlated positively with hypertrophy of nonembolized lobe (r = 0.412, P < 0.05) and percent increase between lobes and (r = 0.515, P < 0.05). Seven (32%) patients developed postoperative complications, such as long-term ascites or cholestasis. Changes in embolized liver and percent increase between lobes in patients with postoperative cholestasis (-94 +/- 97 cm(3) and 9.6 +/- 5.1% gain) were significantly lower than those in patients without cholestasis (17 +/- 54 cm(3) and 6.6 +/- 1.3% gain, P < 0.05)., Conclusion: ALP and platelet counts might be able to predict PVE effect and were related to postoperative course. Identification of more specific predictors is desirable.

Liver biopsy interpretation remains the gold standard for diagnosis of NASH. It also permits determination of disease severity and may provide insight into prognosis. The histopathologic criteria for NASH generally include the presence of hepatic steatosis, lobular inflammation, and hepatocyte ballooning degeneration. The system proposed by Brunt remains the best known and most frequently used method for the grading and staging of NASH. Recently a histologic scoring system (NAFLD activity score (NAS)) has been proposed that can assist in diagnosis of NAFLD and may be useful for assessing the response to therapy. In our hospital, informed consent about liver biopsy was obtained from 65(56%) of 116 consecutive NAFLD patients with elevated ALT levels: 35% (23/65) had NASH, 59% (38/65) had simple steatosis, and 6% (4/65) had normal liver histology. Sampling variability continues to be a limitation of liver biopsy in staging NASH.

Background/aims: Long-term follow-up study was performed to identify the candidates for antiviral therapy for hepatitis C virus (HCV) infection among carriers with persistently normal aminotransferase (ALT< or = 30 U/L) levels (PNAL)., Methods: One hundred and twenty-nine HCV carriers with PNAL who underwent liver biopsy and had platelet count over 150,000/microl were entered and 69 were followed for over 5 years. Thirty-five patients underwent serial liver biopsies. Serum ferritin and thioredoxin levels were also determined., Results: Seventeen patients had normal liver histology, 10 had moderate chronic hepatitis and the remainder 102 had mild hepatitis. Serum ferritin and thioredoxin levels were normal. The mean follow-up period for the 69 patients was 8.5 years. Of these 69 patients, 10 had persistently normal ALT levels (group A), 39 had transient elevation of ALT (group B), and 20 changed to symptomatic chronic hepatitis (group C). The rate of progression of fibrosis for groups A, B, and C were 0.05, 0.04, and 0.08, respectively. Hepatocellular carcinoma was not diagnosed in any of the patients., Conclusions: Around 90% of HCV carriers with PNAL have normal to mild liver histology. This long-term follow-up study demonstrated that 30% of such carriers became candidates for antiviral therapy within 5 years.

Nitric oxide (NO) formation in the liver and blood of the mouse following intraperitoneal treatment with nitroglycerin (glycerol trinitrate, GTN) was determined using electron spin resonance (ESR) spectroscopy. ESR signals of heme-NO complexes were detected at maximum levels within 5 min in the liver, but increased to a maximum level about 15-30 min later in the blood. GTN is not metabolized to release NO in vitro in the blood of the mouse. The hepatic microsomes which showed the heme-NO complexes ESR signals were incubated with mouse erythrocytes, with the result that a hemoglobin-NO signal was obtained from the erythrocytes. The activities of microsomal cytochrome P-450, the hepatic level of glutathione, and the reduction rate of nitroxide radicals in the in vivo liver, measured using L-band ESR spectroscopy, were temporarily decreased following GTN administration. In conclusion, NO in the liver could be scavenged by circulating erythrocytes, which might minimize NO-induced liver damage.

The therapeutic efficacy of ursodeoxycholic acid (UDCA) has been widely demonstrated in various liver diseases, suggesting that UDCA might protect hepatocytes against common mechanisms of liver damage. A candidate for such protection is oxidative injury induced by reactive oxygen species. This study was designed to assess the effects of UDCA on oxidative injury and antioxidative systems in cultured rat hepatocytes. The viability of the hepatocytes dose-dependently decreased after hydrogen peroxide or cadmium administration. Pretreatment with UDCA significantly prevented this decrease in viability. The amounts of glutathione (GSH) and protein thiol increased significantly, but the activities of antioxidative enzymes such as superoxide dismutase, glutathione peroxidase and catalase were unchanged in UDCA-treated hepatocytes. The mRNA levels of gamma-glutamylcysteine synthetase and metallothionein (MT) were significantly higher in UDCA-treated hepatocytes than in controls. In conclusion, UDCA increased hepatocyte levels of GSH and thiol-containing proteins such as MT, thereby protecting hepatocytes against oxidative injury. Our results provide a new perspective on the hepatoprotective effect of UDCA., (Copyright 1999 Academic Press.)