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Background and Aim: New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD)., Methods: Japanese individuals who received annual health checkups including abdominal ultrasonography (n = 15 788, men/women: 10 250/5538, mean age: 49 years) were recruited., Results: The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t-distributed stochastic neighbor embedding and K-means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning-based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides, was selected as a useful feature for SLDs., Conclusions: The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs., (© 2024 The Authors. Journal of Gastroenterology and Hepatology published by Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

In Japan, liver biopsies were previously crucial in evaluating the severity of hepatitis caused by the hepatitis C virus (HCV) and diagnosing HCV-related hepatocellular carcinoma (HCC). However, due to the development of effective antiviral treatments and advanced imaging, the necessity for biopsies has significantly decreased. This change has resulted in fewer chances for diagnosing liver disease, causing many general pathologists to feel less confident in making liver biopsy diagnoses. This article provides a comprehensive overview of the challenges and potential solutions related to liver biopsies in Japan. First, it highlights the importance of considering steatotic liver diseases as independent conditions that can coexist with other liver diseases due to their increasing prevalence. Second, it emphasizes the need to avoid hasty assumptions of HCC in nodular lesions, because clinically diagnosable HCCs are not targets for biopsy. Third, the importance of diagnosing hepatic immune-related adverse events caused by immune checkpoint inhibitors is increasing due to the anticipated widespread use of these drugs. In conclusion, pathologists should be attuned to the changing landscape of liver diseases and approach liver biopsies with care and attention to detail., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflicts of interest related to this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Aim: Fatty liver and the liver fibrosis are known risk factors for cardiovascular disease (CVD). The severity of fatty liver can be assessed by determining the fatty liver index (FLI), and the severity of liver fibrosis can be assessed by determining the fibrosis-4 (FIB-4) score. We examined the differences in the associations of these two liver scoring systems with the pathophysiological abnormalities associated with the risk of development of CVD., Methods: The FLI and FIB-4 score were calculated in 2,437 Japanese men without any history of CVD. The serum NT-pro-BNP levels and brachial-ankle pulse wave velocity (baPWV) were also measured at the start of the study and the end of three years' follow-up., Results: The FLI was significantly correlated with the baPWV (p＜0.01) and the FIB-4 score was significantly correlated with the serum NT-pro-BNP level (p＜0.01). Furthermore, the delta change of the FLI was significantly correlated with the delta change of the baPWV during the study period (p=0.01), and the delta change of the FIB-4 score was significantly correlated with the delta change of the serum NT-pro-BNP level during the study period (p＜0.01)., Conclusions: While the FIB-4 score may serve as a marker of the risk of development of heart failure, the FLI may be a marker of arterial stiffness in Japanese men without any history of CVD.

Patients with primary aldosteronism (PA) are complicated by metabolic syndrome more frequently than those without PA. Hyperaldosteronism has been reported to be associated with a higher prevalence of non-alcoholic fatty liver disease (NAFLD). We aimed to clarify the risk factors for hepatic steatosis in the two subtypes of PA, comparing the status of hepatic steatosis in each of these subtypes. This was a retrospective observational study. We enrolled patients with an aldosterone producing adenoma (APA) (n = 33) or idiopathic hyperaldosteronism (IHA) (n = 56). Hepatic fat content was evaluated using the ratio of liver to spleen (L/S) X-ray attenuation on unenhanced computed tomography. L/S ratio <1.0 was utilized for assessing as hepatic steatosis. Age, sex distribution, visceral fat percentage (VF%), and visceral fat area (VFA) did not differ between patients with the two PA subtypes. The percentages of patients with L/S ratio <1.0 was not different between the two subtypes (APA: 21.2 % (7/33) vs. IHA: 19.6 % (11/56), p = 1.00). In both subtypes, the L/S ratio negatively correlated with VF% (APA: r = -0.66, p < 0.001; IHA: r = -0.66, p < 0.001) and with VFA (APA: r = -0.44, p < 0.01; IHA: r = -0.37, p < 0.01). The status of hepatic steatosis, evaluated using L/S ratio, did not differ between patients with APA or IHA. Hepatic steatosis was affected by the amount of visceral fat.

Aim: To evaluate effects of dietary supplementation of sulforaphane (SF)-rich broccoli sprout (BS) extract on hepatic abnormalities in Japanese male participants., Methods: In a randomized, placebo-controlled, double blind trial, male participants with fatty liver received either BS capsules containing glucoraphanin [GR; a precursor of SF (n = 24)] or placebo (n = 28) for 2 mo. Liver function markers, serum levels of aspartate and alanine aminotransferases (AST and ALT, respectively) and γ-glutamyl transpeptidase (γ-GTP) and an oxidative stress marker, urinary levels of 8-hydroxydeoxyguanosine (8-OHdG), were measured and compared in participants before and after the trial period. In an animal model, chronic liver failure was induced in Sprague-Dawley rats by successive intraperitoneal injection with N-nitrosodimethylamine (NDMA) for 4 wk. Concomitantly, rats received AIN-76 diets supplemented with or without BS extract. Thereafter, rats were sacrificed, and their sera and livers were collected to measure serum liver function markers and hepatic levels of thiobarbituric acid reactive substances (TBARS) levels and hepatic glutathione S-transferase (GST) activity, a prototypical phase 2 antioxidant enzyme., Results: Dietary supplementation with BS extract containing SF precursor GR for 2 mo significantly decreased serum levels of liver function markers, ALT [median (interquartile range), before: 54.0 (34.5-79.0) vs after supplementation: 48.5 (33.3-65.3) IU/L, P < 0.05] and γ-GTP [before: 51.5 (40.8-91.3) vs after: 50.0 (37.8-85.3) IU/L, P < 0.05], as well as the alkali phosphatase activity. Placebo showed no significant effects on the markers. The urinary level of 8-OHdG, an established oxidative stress marker, was significantly reduced in participants who had received BS capsules but not the placebo [before: 6.66 (5.51-9.03) vs after: 5.49 (4.89-6.66) ng/mg-creatinine, P < 0.05]. The reduction of urinary 8-OHdG was significantly correlated with decreased levels of both ALT and γ-GTP [∆8-OHdG and ∆ALT: Spearman r (r) 0.514 and P = 0.012, ∆8-OHdG and ∆γ-GTP: r = 0.496 and P = 0.016]. Intake of BS extract prevented NDMA-induced chronic liver failure in rats, which was attributable to the suppression of the increase in TBARS through induction of hepatic phase 2 antioxidant enzymes including hepatic GST (86.6 ± 95.2 vs 107.8 ± 7.7 IU/g, P < 0.01)., Conclusion: Dietary supplementation with BS extract containing the SF precursor GR is likely to be highly effective in improving liver function through reduction of oxidative stress.

Objectives: To evaluate the incidence of hepatic steatosis after pancreatectomy and whether pancrelipase improves steatosis more effectively than other conventional digestive enzymes., Methods: Patients who underwent distal pancreatectomy, pancreaticoduodenectomy (PD), or total pancreatectomy (TP) from August 2008 to July 2013 were included. Incidence of newly developed hepatic steatosis recognized by computed tomography and outcomes by treatment with pancrealipase or other enzymes were evaluated., Results: A total of 473 patients were evaluated. Among 366 patients who did not take any digestive enzymes until the recognition of steatosis or the last follow-up date, hepatic steatosis was recognized in 3% (4/130), 17% (38/229), and 45% (3/7) of patients after distal pancreatectomy, PD, and TP, respectively, during the median follow-up of 641 days. Seventy patients including 25 patients taking digestive enzymes showed hepatic steatosis and were treated with pancrelipase (20 patients), other enzymes (19 patients), or no enzyme (31 patients). Cumulative improvement rate after 1 year of treatment in the 3 groups was 92%, 51%, and 56%, respectively, and that of the pancrelipase group was significantly better than the other 2 groups., Conclusion: The risk of hepatic steatosis should be a concern after PD and TP. Treatment with pancrelipase was more effective compared to other enzymes.

Non-alcoholic fatty liver disease (NAFLD) is considered to be a hepatic manifestation of metabolic syndrome. NAFLD has become an important public health issue because of its high prevalence. NAFLD consists of two clinicopathological entities: simple steatosis, which generally follows a benign non-progressive clinical course, and non-alcoholic steatohepatitis (NASH), which may progress to cirrhosis and hepatocellular carcinoma. The diagnosis of NAFLD is based on the following three criteria: non-alcoholic, detection of steatosis either by imaging or by histology, and appropriate exclusion of other liver diseases. Alcoholic liver disease can occur when daily alcohol consumption exceeds 20 g in women or 30 g in men. Thus, non-alcoholic indicates lower levels of these alcohol consumptions. However, there is still no clear consensus regarding the threshold alcohol consumption for defining non-alcoholic liver disease. Then, there is the strong recommendation for a change in the nomenclature, such as use of the term metabolic fatty liver and metabolic steatohepatitis. NASH has emerged as a clinicopathological entity, and even now, a liver biopsy remains the gold standard for making a definitive diagnosis. However, liver biopsy has several drawbacks. In general practice, NAFLD is a convenient-to-use term for the diagnosis and management of these patients, and serum biomarkers that indicate the severity of fibrosis serve as clinically useful tools for the identification of NAFLD in patients with bridging fibrosis or cirrhosis. In the future, improved understanding of the pathogenesis of NASH and new technologies may contribute to the diagnostic process and provide reliable, non-invasive alternatives to liver biopsy., (© 2013 Journal of Gastroenterology and Hepatology Foundation and Wiley Publishing Asia Pty Ltd.)

Background: Nonalcoholic fatty liver disease (NAFLD) can progress to advanced liver disease and non-liver-related diseases. To prevent NAFLD onset, clinicians must be able to easily identify high-risk NAFLD patients so that intervention can begin at an earlier stage. We sought to identify the predictive factors for NAFLD onset., Methods: In a community-based, longitudinal design, the records of 6,403 Japanese subjects were reviewed to identify those meeting the criteria for NAFLD onset. Univariate and multivariate logistic regression analyses were used to identify predictive factors for NAFLD onset. The accuracy of different models was evaluated according to their areas under the receiver operating characteristic curves. Comparative risk analysis was performed using the Kaplan-Meier method., Results: Multivariate analysis of 400 subjects who met the criteria for the onset of NAFLD during the observation period confirmed that body mass index (BMI) at baseline was the most useful predictive factor for NAFLD onset in both sexes. Cutoff levels of BMI for NAFLD onset were estimated at 23 kg/m2 for men and 22.2 kg/m2 for women. The cumulative onset rate of NAFLD was significantly higher in the high BMI group than in the low BMI group in both sexes (P < 0.001)., Conclusion: BMI was confirmed as the most useful predictive factor for NAFLD onset in both sexes; its cutoff levels were similar to those recommended by the World Health Organization for helping to prevent metabolic disease. An accurate BMI cutoff level will enable clinicians to identify subjects at risk for NAFLD onset.

Background: Sex hormone-binding globulin (SHBG) levels and sex hormones have been implicated in the pathogenesis of type 2 diabetes and cardiovascular diseases. As fatty liver has been suggested to be a major determinant of SHBG levels, we examined whether the associations of SHBG and testosterone with diabetes were independent of fatty liver., Methods: We conducted a case-control study that included 300 diabetes cases (215 men and 85 women) and 300 matched controls from the Saku cohort study. Diabetes was defined by either fasting plasma glucose levels ≥126 mg/dL, 2-h post-load glucose levels ≥200 mg/dL after a 75 g oral glucose tolerance test, or diabetes diagnosed by physicians. We fitted conditional logistic regression models to examine the associations between SHBG and total testosterone levels with diabetes by sex. To evaluate the impact of fatty liver, we used the fatty liver index (FLI), a validated measure derived from serum triglyceride levels, body mass index (BMI), waist circumference, and γ-glutamyltransferase levels., Results: After adjusting for age, family history of diabetes, smoking, physical activity, BMI, and FLI, SHBG levels were inversely associated with diabetes among women (odds ratio [OR] comparing the highest with the lowest quartiles, 0.13 [95% confidence interval {CI}, 0.02-0.96]), but not among men. Similar patterns were observed in a subgroup analysis restricted to postmenopausal women"(OR, 0.12 [95% CI, 0.01-1.17]). In contrast, testosterone levels were inversely associated with diabetes among men (OR, 0.45 [95% CI, 0.23-0.89]), but not among women., Conclusions: Our findings suggest that SHBG in women and testosterone in men may be inversely associated with diabetes.

Maturity-onset diabetes of the young type 3 (MODY3) is caused by heterozygous mutation in the HNF1A gene. Liver adenomatosis has been reported in MODY3 patients. The patient reported in this paper is a Japanese girl who first developed hepatomegaly, fatty liver, and hepatic dysfunction at age 5 years. Liver biopsy demonstrated steatosis and degeneration of hepatocytes. At that time, blood glucose and HbA1c levels were within normal ranges. Elevated HbA1c was noticed 4 years later, but islet cell and glutamic acid decarboxylase antibodies were not detected in the serum. Therefore, MODY3 was suspected and subsequent analysis of the HNF1A gene identified a heterozygous germline splice donor-site mutation in intron 9. MODY3 patients should be screened by non-invasive liver imaging, and careful follow-up of liver disease should be performed.

Background/aims: The degree of hepatic fibrosis is an important factor for prognosis and management of patients with chronic liver disease; however, liver biopsy is an invasive method of measuring fibrosis. Here, we investigated the diagnostic utility of liver stiffness, as measured by transient elastography in assessing hepatic fibrosis of viral chronic liver disease and nonalcoholic fatty liver disease (NAFLD)., Methodology: Four hundred and nine eligible patients underwent transient elastography to measure liver stiffness. Liver biopsy for histopathological assessment of fibrosis (F0-F4) was performed in 71 of these patients. Serum levels of hyaluronic acid were determined in 110 patients. We assessed liver stiffness in several chronic liver diseases and compared correlations among liver stiffness, hepatic fibrosis stage and serum hyaluronic acid levels., Results: A steady stepwise increase in liver stiffness was observed with progressing severity of hepatic fibrosis (p<0.0001) in 71 patients who underwent liver biopsy. In 32 chronic viral hepatitis patients, measuring liver stiffness was useful for differentiating between F1, or F2, or F3 and F4, while in 32 NAFLD liver stiffness can differentiate between F0 and F1, F2, or F3, F1 and F3 or F4 and F2 and F4. There was no significant correlation between liver fibrotic stages and serum hyaluronic levels., Conclusions: The present data advocates measuring liver stiffness for assessing hepatic fibrosis is more sensitive in NAFLD than viral chronic diseases, and liver stiffness is useful compared to serum hyaluronic acid level in estimating hepatic fibrosis.

Background: A reliable and inexpensive noninvasive marker of hepatic fibrosis is required in patients with nonalcoholic fatty liver disease (NAFLD). FIB4 index (based on age, aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels, and platelet counts) is expected to be useful for evaluating hepatic fibrosis. We validated the performance of FIB4 index in a Japanese cohort with NAFLD., Methods: The areas under the receiver operating characteristic curves (AUROC) for FIB4 and six other markers were compared, based on data from 576 biopsy-proven NAFLD patients. Advanced fibrosis was defined as stage 3-4 fibrosis. FIB4 index was assessed as: age (yr) × AST (IU/L)/(platelet count (10(9)/L) × √ALT (IU/L)) RESULTS: Advanced fibrosis was found in 64 (11%) patients. The AUROC for FIB4 index was superior to those for the other scoring systems for differentiating between advanced and mild fibrosis. Only 6 of 308 patients with a FIB4 index below the proposed low cut-off point (< 1.45) were under-staged, giving a high negative predictive value of 98%. Twenty-eight of 59 patients with a FIB4 index above the high cut-off point (> 3.25) were over-staged, giving a low positive predictive value of 53%. Using these cutoffs, 91% of the 395 patients with FIB-4 values outside 1.45-3.25 would be correctly classified. Implementation of the FIB4 index in the Japanese population would avoid 58% of liver biopsies., Conclusion: The FIB4 index was superior to other tested noninvasive markers of fibrosis in Japanese patients with NAFLD, with a high negative predictive value for excluding advanced fibrosis. The small number of cases of advanced fibrosis in this cohort meant that this study had limited power for validating the high cut-off point.

Background: The severity of liver fibrosis is known to be a good indicator for surveillance, and for determining the prognosis and optimal treatment of nonalcoholic fatty liver disease (NAFLD). However, it is virtually impossible to carry out liver biopsies in all NAFLD patients. The purpose of this study was to investigate the clinical usefulness of measuring the platelet count for predicting the severity of liver fibrosis in a large retrospective cohort of Japanese patients with NAFLD., Methods: A total of 1,048 patients with liver-biopsy-confirmed NAFLD seen between 2002 and 2008 were enrolled from nine hepatology centers in Japan. Laboratory evaluations were performed for all patients., Results: A linear decrease of the platelet count with increasing histological severity of hepatic fibrosis was revealed. The area under the receiver operating characteristic curve estimating the diagnostic performance of the platelet count for hepatic fibrosis Stage 3 was 0.774 (optimal cutoff value, 19.2 × 10(4)/μl; sensitivity, 62.7%; specificity, 76.3%), and that for Stage 4 was 0.918 (optimal cutoff value, 15.3 × 10(4)/μl; sensitivity, 80.5%; specificity, 88.8%)., Conclusions: The platelet count may be an ideal biomarker of the severity of fibrosis in NAFLD patients, because it is simple, easy to measure and handle, cost-effective, and accurate for predicting the severity of fibrosis. Furthermore, by using the platelet count cutoff value validated in our multiple large trials, efficient recruitment of NAFLD patients may be facilitated.

Background and Aim: The hepatitis C virus (HCV) core protein induces hepatic steatosis and glucose intolerance in transgenic mice. The aim of this study was to clarify the impact of mutations in the HCV core region on hepatic steatosis and glucose tolerance in patients with chronic hepatitis C., Methods: Seventy-four Japanese patients (27 men, 47 women; mean age, 61.9 years) infected with HCV 1b with high viral load (>5 log IU/ml), without cirrhosis and overt diabetes, were enrolled. Substitutions in amino acids 70 and 91 of the HCV genotype 1b core region, the percentage of hepatic steatosis by liver histology, and glucose tolerance evaluated by the oral glucose tolerance test were investigated in all patients., Results: Steatosis was observed in 40 patients (54%). Transaminase activities, γ-glutamyl-transpeptidase, serum ferritin levels, homeostasis model assessment of insulin resistance index, and substitutions of amino acid 70 were significantly associated with the presence of steatosis, upon univariate analysis. Glucose intolerance was more prevalent in patients with steatosis (63%) than in those without steatosis (32%, P = 0.012). Multivariate analysis showed that substitution of amino acid 70 (odds ratio: 4.924; 95% confidence interval: 1.442-16.815; P = 0.014) and glucose intolerance (odds ratio: 3.369; 95% confidence interval: 1.076-10.544; P = 0.040) were independent factors related to liver steatosis. Levels of plasma glucose and serum insulin after glucose load were similar between patients with and without substitutions of amino acids 70 and 91., Conclusions: Amino acid substitutions in the HCV genotype 1b core region are associated with hepatic steatosis in patients with chronic hepatitis C, independent of glucose intolerance., (© 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.)

Background: Liver histology is the gold standard for the diagnosis of nonalcoholic steatohepatitis (NASH). Noninvasive, simple, reproducible, and reliable biomarkers are greatly needed to differentiate NASH from nonalcoholic fatty liver disease (NAFLD)., Methods: To construct a scoring system for predicting NASH, 177 Japanese patients with biopsy-proven NAFLD were enrolled. To validate the scoring system, 442 biopsy-proven NAFLD patients from eight hepatology centers in Japan were also enrolled., Results: In the estimation group, 98 (55%) patients had NASH. Serum ferritin [≥200 ng/ml (female) or ≥300 ng/ml (male)], fasting insulin (≥10 μU/ml), and type IV collagen 7S (≥5.0 ng/ml) were selected as independent variables associated with NASH, by multilogistic regression analysis. These three variables were combined in a weighted sum [serum ferritin ≥200 ng/ml (female) or ≥300 ng/ml (male) = 1 point, fasting insulin ≥10 μU/ml = 1 point, and type IV collagen 7S ≥5.0 ng/ml = 2 points] to form an easily calculated composite score for predicting NASH, called the NAFIC score. The area under the receiver operating characteristic (AUROC) curve for predicting NASH was 0.851 in the estimation group and 0.782 in the validation group. The NAFIC AUROC was the greatest among several previously established scoring systems for detecting NASH, but also for predicting severe fibrosis., Conclusions: NAFIC score can predict NASH in Japanese NAFLD patients with sufficient accuracy and simplicity to be considered for clinical use.

Background: The number of patients with morbid obesity is increasing worldwide. However, the prevalence of morbid obesity is still low in Japan, and therefore few systematic investigations of liver dysfunction in this population have so far been carried out. This study aimed to investigate the clinical characteristics in severe obese Japanese patients undergoing laparoscopic Roux-en-Y gastric bypass surgery (LRYGB)., Methods: Eighty-four patients with severe obesity, including 61 Japanese and 23 non-Japanese patients, were analyzed., Results: The mean body mass index (BMI) was 43.7 +/- 7.8 kg/m(2), and there was no difference between Japanese and non-Japanese patients. Nonalcoholic fatty liver disease (NAFLD) was observed in 45/59 (76.2%) of the Japanese patients. Although there were no differences in the BMI and body weight, serum ALT was higher in Japanese patients in comparison to non-Japanese patients (P < 0.05). The indices for insulin resistance were significantly higher in the Japanese patients in comparison to non-Japanese patients (P < 0.01). The liver/spleen computed tomography (CT) ratios were lower in Japanese patients (P < 0.05). The laboratory data and BMI significantly improved at 1 year after LRYGB in both groups., Conclusions: Racial difference may exist difference may exist in NAFLD in patients with severe obesity. When the BMI is similar, liver dysfunction among Japanese patients with severe obesity tends to be higher than in non-Japanese patients. Japanese patients with severe obesity must therefore reduce their body weight to a greater degree in comparison to non-Japanese patients with the same BMI. LRYGB can achieve effective weight control and lower ALT levels in Japanese patients with severe obesity.

Background: In 2003, we encountered the first donor death for living donor liver transplantation in Japan, which was related to nonalcoholic steatohepatitis (NASH). The aim of this study was to retrospectively investigate the prevalence of NASH among a living donor liver transplantation donor population and to analyze the postoperative course for both donors and recipients of NASH grafts to minimize risk for donors., Methods: The study population comprised 263 donors who donated the right lobe of the liver between February 1998 and April 2003. Their zero-hour biopsy specimens were screened retrospectively. Regarding severe steatosis or NASH, long-term follow-up results for laboratory data from donors were investigated along with changes in graft histologic findings in recipients., Results: NASH was diagnosed histopathologically in three cases (1.1%). Pathologic examination showed that a donor who died in 2003 had the most severe NASH among the three cases. The remaining two NASH donors had uneventful postoperative courses without complications. All grafts showed improvement with respect to the steatosis and histologic findings of NASH., Conclusions: Donor safety is a top priority in living donor liver transplantation. To exclude patients with NASH from potential donor lists, careful evaluation, including selective preoperative liver biopsy, should be carried out.

Background and Aim: Nonalcoholic fatty liver disease (NAFLD) represents a spectrum of liver disease from simple steatosis to cirrhosis. Therefore, markers for predicting NAFLD with advanced fibrosis are needed. The aim of this study was to establish non-invasive predictive markers of liver fibrosis in NAFLD., Methods: One hundred and forty-eight patients were diagnosed as having biopsy-proven NAFLD. In order to separately identify severe fibrosis (bridging fibrosis plus cirrhosis) and cirrhosis, the patients were analyzed twice: first, as mild fibrosis versus severe fibrosis; and second, as non-cirrhosis versus cirrhosis. Univariate and multivariate analyses were conducted. The diagnostic ability to detect severe fibrosis and cirrhosis was assessed by the area under the receiver operating characteristic curve. The cut-off values of serum markers to detect severe fibrosis and cirrhosis were determined., Results: Hyaluronic acid was selected as a predictive marker for severe fibrosis. A cut-off value of 42 ng/mL of hyaluronic acid had a 100% predictive value for patients free of severe fibrosis and was associated with an optimal combination of sensitivity (100%, 95% confidence interval [CI] 90-100%) and specificity (89%, 95%CI 80-94%). The platelet count was found to be an independent predictor of cirrhosis. A cut-off value of 16 x 10(4)/microL for the platelet count was associated with an optimal combination of sensitivity (100%, 95%CI 82-100%) and specificity (95%, 95%CI 90-98%)., Conclusions: Hyaluronic acid levels can accurately identify NAFLD patients with severe fibrosis, and the platelet count can identify NAFLD patients with cirrhosis. Thus, these markers offer a good guideline for the assessment of hepatic fibrosis in the many patients with NAFLD.

Background/aims: The aims of the present study were to determine the prevalence of patients with cryptogenic liver cirrhosis, and to clarify the clinical characteristics of these patients, with special focus on obesity and type 2 diabetes mellitus., Methodology: For the case-control study, we selected age- and sex-matched control patients with cirrhosis of known etiology., Results: Of 404 patients with liver cirrhosis, 40 (9.9%) were diagnosed as having cryptogenic cirrhosis. Of these 40 patients, 29 (73%) were female. The mean age was 66.1 +/- 8.9 (range 40-87 years old), and was significantly higher than that of either virus, or alcohol-related liver cirrhosis patients. Both obesity and type 2 diabetes mellitus were more common in patients with cryptogenic cirrhosis (53% and 40%, respectively) compared with the case-controls (20%, 18%, respectively)., Conclusions: Cryptogenic liver cirrhosis accounted for approximately 10% of liver cirrhosis, and was associated with both obesity and type 2 diabetes mellitus. Nonalcoholic steatohepatitis sequelae may be the most important etiological factor in patients with cryptogenic liver cirrhosis in Okinawa, Japan, where virus-etiology is more predominant in liver cirrhosis compared with Western countries.

We describe a 12-year-old patient with focal fatty liver change (FFLC). The lesion was incidentally detected by ultrasonography which showed a circumscribed hyperechoic lesion measuring approximately 6 x 4 cm. The lesion was also examined by CT and MRI. Histologically, the lesion corresponded to a focal area of lipid-laden hepatocytes. FFLC has been delineated as a disease entity in adults. As shown by this report, it may also occur in children. There was no associated clinical morbidity and the lesion was incidentally detected by modern imaging techniques. The aetiology and pathogenesis are unknown. The significance of focal fatty lesions is their differentiation from other focal lesions such as hepatic cell carcinomas, metastatic tumours, abscess and benign tumours including lipoma, haemangioma and angiomyolipoma.

A total of 2,574 residents in Yaeyama District of Okinawa, Japan, were investigated using real time ultrasonography to determine the real prevalence of fatty liver in the general population and to define its associated factors. Overall prevalence of fatty liver was 14.0%. Prevalence of fatty liver in persons under 19 years old was only 1.2%, and increased with age to a maximum in persons 40-49 years of age and then decreased. For persons over 20 years old, obesity index and serum levels of triglyceride and total cholesterol were measured, and alcohol consumption was asked. Prevalence of fatty liver was significantly higher in drinkers than non-drinkers (p less than 0.01), and increased with alcohol consumption. Furthermore, in persons not suffering from obesity prevalence of fatty liver was significantly higher in drinkers than in non-drinkers (p less than 0.001). The results of logistic regression analysis indicated that obesity and elevated serum triglyceride level in both sexes, and alcohol in males were significant predictors of fatty liver. In conclusion, prevalence of fatty liver increased with age to a maximum in persons 40-49 years of age and overall was 14.0%. Obesity was the strongest associated factor in both sexes and in males alcohol was also a strong factor.

Recently, fatty liver of unknown etiology has been increasing in number among relatively younger persons in Japan. The tendency is very likely related to drastic reformation of the standard of living with the height of economic prosperity due to industrial advances in Japan at present. On the basis of our own 392 patients with fatty liver of unknown etiology, in whom fatty liver could be confirmed laparoscopically and bioptically, clinical and pathophysiological aspects of fatty liver of unknown etiology have been into consideration. The clinical outline of the disease was stated in this paper.