Ablation for Benign Liver Tumors: Current Concepts and Limitations.

Percutaneous ablation under imaging guidance is a curative treatment that can induce complete tumor necrosis with advantages of minimal invasiveness and a low risk of complications. Thermal ablation, which includes radiofrequency ablation and microwave ablation, is a representative technique that has sufficient antitumor effects in cases of hepatocellular carcinoma with ≤3 lesions measuring ≤3 cm and preserved liver function. The short- and long-term outcomes of patients are comparable with those achieved with surgical resection. Despite their nonmalignant nature, some benign liver tumors require treatment for symptoms caused by the presence of the tumor and/or continuous enlargement. Ablation may be the treatment of choice because it has lower burden on patients than surgical treatment. This review describes the recent concepts, progress, and limitations of ablation-based treatment for benign liver tumors.

Contrast-enhanced ultrasonography for the management of portal hypertension in cirrhosis.

Portal hypertension is a major pathophysiological condition in patients with cirrhosis. This accounts for the occurrence and severity of the various manifestations. The degree is determined by the portal pressure or hepatic venous pressure gradients, both of which are obtained by invasive interventional radiological procedures. Ultrasound (US) is a simple and minimally invasive imaging modality for the diagnosis of liver diseases. Owing to the availability of microbubble-based contrast agents and the development of imaging modes corresponding to contrast effects, contrast-enhanced US (CEUS) has become popular worldwide for the detailed evaluation of hepatic hemodynamics, diffuse liver disease, and focal hepatic lesions. Recent advancements in digital technology have enabled contrast-based demonstrations with improved resolution, leading to a wider range of applications. This review article describes the current role, benefits, and limitations of CEUS in the management of portal hypertension.

A novel noninvasive formula for predicting cirrhosis in patients with chronic hepatitis C.

Evaluating liver fibrosis is crucial for disease severity assessment, treatment decisions, and hepatocarcinogenic risk prediction among patients with chronic hepatitis C. In this retrospective multicenter study, we aimed to construct a novel model formula to predict cirrhosis. A total of 749 patients were randomly allocated to training and validation sets at a ratio of 2:1. Liver stiffness measurement (LSM) was made via transient elastography using FibroScan. Patients with LSM ≥12.5 kPa were regarded as having cirrhosis. The best model formula for predicting cirrhosis was constructed based on factors significantly and independently associated with LSM (≥12.5 kPa) using multivariate regression analysis. Among the 749 patients, 198 (26.4%) had LSM ≥12.5 kPa. In the training set, multivariate analysis identified logarithm natural (ln) type IV collagen 7S, ln hyaluronic acid, and ln Wisteria floribunda agglutinin positive Mac-2-binding protein (WFA+-Mac-2 BP) as the factors that were significantly and independently associated with LSM ≥12.5 kPa. Thus, the formula was constructed as follows: score = -6.154 + 1.166 × ln type IV collagen 7S + 0.526 × ln hyaluronic acid + 1.069 × WFA+-Mac-2 BP. The novel formula yielded the highest area under the curve (0.882; optimal cutoff, -0.381), specificity (81.5%), positive predictive values (62.6%), and predictive accuracy (81.6%) for predicting LSM ≥12.5 kPa among fibrosis markers and indices. These results were almost similar to those in the validated set, indicating the reproducibility and validity of the novel formula. The novel formula scores were significantly, strongly, and positively correlated with LSM values in both the training and validation data sets (correlation coefficient, 0.721 and 0.762; p = 2.67 × 10-81 and 1.88 × 10-48, respectively). In conclusion, the novel formula was highly capable of diagnosing cirrhosis in patients with chronic hepatitis C and exhibited better diagnostic performance compared to conventional fibrosis markers and indices.

Hepatocellular carcinoma in young morbid obese patients with non-alcoholic fatty liver disease.

We report the two youngest cases of hepatocellular carcinoma (HCC) in non-alcoholic fatty liver disease (NAFLD) among our 119 NAFLD-HCC patients. A 36-year-old man was referred to our hospital due to a 5 cm in diameter liver tumor with elevation of α-fetoprotein and des-γ-carboxy prothrombin found at his annual health check. He had no symptoms other than 20 kg weight loss. He has been morbidly obese since he was a child. At the time of the diagnosis of NAFLD-HCC, blood chemistry showed FIB4-index 0.52, α-fetoprotein 11.1 ng/mL and des-γ-carboxy prothrombin 361 mAU/mL. He underwent curative operation. The non-cancerous lesion showed steatohepatitis with mild fibrosis. A 41-year-old man was diagnosed as having a huge liver tumor (15 cm in diameter) during medical examination for 10 kg weight loss. He had no clinical symptoms except weight loss. He has been morbidly obese since childhood. NAFLD was diagnosed at age 20. At the time of the HCC diagnosis, blood chemistry showed FIB4-index 1.42, α-fetoprotein 1974 ng/mL, and des-γ-carboxy prothrombin 82,602 mAU/mL. He underwent curative operation. We have to be aware that HCC can develop in young NAFLD patients without advanced fibrosis. Concerning tumor markers, elevation of des-γ-carboxy prothrombin was more sensitive than α-fetoprotein.

Characteristic Features of Nonalcoholic Fatty Liver Disease in Japan with a Focus on the Roles of Age, Sex and Body Mass Index.

This review provides an update on the characteristics of nonalcoholic fatty liver disease (NAFLD), with a focus on the effects of age, sex, and body mass index. Age is a risk factor for NAFLD progression; however, extremely old patients have unique features, namely, the associations between metabolic comorbidities and NAFLD are weaker and NAFLD is not a risk factor for mortality. The prevalence of NAFLD is higher in men than in premenopausal women, whereas the reverse is true after menopause. Thus, before menopause, estrogen may have protective effects against NAFLD. Our hospital data showed that over 25% of male patients with NAFLD and almost 40% of female patients with NAFLD, especially elderly patients, were nonobese. Although histological steatosis and activity were associated with body mass index, the prevalence of nonalcoholic steatohepatitis was not. The prevalence of advanced fibrosis showed a significant sex difference. Advanced fibrosis was significantly more frequent among severely obese men but the prevalence was lower among severely obese women. This difference could be because a substantial proportion of severely obese women were premenopausal; thus, estrogen may have much stronger effects on the development of fibrosis than on obesity. Further studies are required to develop tailored management strategies.

The characteristics and risk factors of hepatocellular carcinoma in nonalcoholic fatty liver disease without cirrhosis.

BACKGROUND AND AIM: We evaluated the characteristics of hepatocellular carcinoma (HCC) in patients who had non-alcoholic fatty liver disease (NAFLD) without cirrhosis. METHODS: We prospectively followed NAFLD patients at our University hospital. NAFLD was diagnosed from detection of steatosis by histology or imaging, no alcohol intake, and exclusion of other liver diseases. Cirrhosis was defined by histological features, imaging data, and symptoms. We compared NAFLD-related HCC with or without cirrhosis and non-cirrhotic NAFLD with or without HCC. RESULTS: There were 48 non-cirrhotic HCC patients and 71 cirrhotic HCC patients. Multiple logistic regression analysis revealed that other than liver function factors, male gender (OR: 5.603, 95%CI: 1.577-19.900), light drinker (OR: 2.797, 95%CI: 1.031-7.589), and tumor size (OR: 1.031, 95%CI 1.009-1.055) differ significantly between these two groups. The recurrence rate was significantly lower in the non-cirrhotic HCC group than the cirrhotic HCC group, with risk factors being des-γ-carboxy prothrombin and the number of HCCs. The non-cirrhotic HCC group showed significantly better survival because of absence of non-cancerous liver failure. Comparison between non-cirrhotic NAFLD patients with or without HCC (n = 612) revealed the following risk factors for HCC: male gender (OR: 7.774, 95%CI: 2.176-27.775), light drinker (OR: 4.893, 95%CI: 1.923-12.449), and high FIB4 index (OR 2.634, 95%CI: 1.787-3.884). CONCLUSION: In patients with non-cirrhotic NAFLD, important risk factors for HCC were male gender, alcohol consumption, and the FIB4 index. HCC recurrence and survival were only influenced by the tumor stage. We should be aware of alcohol consumption as a modifiable risk factor for HCC.

Diffusion kurtosis imaging in the assessment of liver function: Its potential as an effective predictor of liver function.

OBJECTIVES:: We aimed to determine whether diffusion kurtosis imaging (DKI) analysis with the breath-hold technique can replace liver function results obtained from laboratory tests. METHODS:: Patients (n = 79) suspected of having a hepatobiliary disease, and control group without liver diseases (n = 15) were examined with non-Gaussian diffusion-weighted imaging using a 3.0 T magnetic resonance imaging unit. Based on the findings of DKI, various blood serum parameters, including the indocyanine green (ICG) retention rate 15 min after an intravenous injection of ICG (ICG-R15) and mean kurtosis values and Child-Pugh and albumin-bilirubin (ALBI) scores, were calculated. In total, 17 patients were tested using ICG-R15. For evaluating liver function, correlations between the mean kurtosis value and the Child-Pugh score, ALBI score, and ICG-R15 value as indicators of liver function obtained from blood data were assessed using Spearman's rank correlation. In apparent diffusion coefficient as well, we assessed correlations with these indicators. RESULTS:: The mean kurtosis value correlated with the Child-Pugh score (Spearman's rank-correlation coefficient, ρ = 0.3992; p < 0.0001). Moreover, the mean kurtosis value revealed a correlation with the ICG-R15 value (Spearman's rank-correlation coefficient, ρ = 0.5972; p = 0.00114). The correlation between the mean kurtosis value and the ALBI score was the poorest among these (Spearman's rank-correlation coefficient, ρ = 0.3395; p = 0.0008). CONCLUSION:: Liver function correlating with the Child-Pugh score and ICG-R15 value can be quantitatively estimated using the mean kurtosis value obtained from DKI analysis. DKI analysis with the breath-hold technique can be used to determine liver function instead of performing laboratory tests. ADVANCES IN KNOWLEDGE:: Previous studies have not evaluated liver function in vivo using DKI.

Characteristics of non-alcoholic steatohepatitis among lean patients in Japan: Not uncommon and not always benign.

BACKGROUND AND AIM: To elucidate features of nonobese non-alcoholic fatty liver disease (NAFLD), we assessed Japanese patients with NAFLD stratified by body mass index (BMI) and by sex. METHODS: Biopsy-proven 762 NAFLD patients (404 men) were classified into three groups by the Japanese criteria: nonobese group (BMI < 25 kg/m2 ), obese group (25 to 30), and severely obese group (≥ 30). Clinicopathological features and single nucleotide polymorphism of patatin-like phospholipase 3 (PNPLA3) rs738409 were investigated, and body composition analysis was performed by bioelectrical impedance analysis and computed tomography. RESULTS: Over 25% of men and almost 40% of women were nonobese, but most of them had visceral fat obesity and/or insulin resistance. The median age (years) of the nonobese, obese, and severely obese men was 49.9, 46.8, and 40.5 (P < 0.01), respectively, while those of women was 60.2, 59.6, and 48.5 (P < 0.01), respectively. The prevalence of metabolic comorbidities and PNPLA3 risk alleles did not differ among these groups in both sexes. Also, the prevalence of non-alcoholic steatohepatitis was not significantly different in both sexes, although nonobese patients had a higher prevalence of mild steatosis. Advanced fibrosis showed a marked difference between men and women. Advanced fibrosis was significantly more frequent among severely obese men (nonobese: 31.0%, obese: 41.6%, severely obese: 60.9%; P < 0.01), but it was lower among severely obese women (51.4%, 62.9%, 33.7%; P < 0.01). Skeletal muscle mass was significantly lower in nonobese patients. CONCLUSIONS: Non-alcoholic fatty liver disease was not milder in nonobese patients. Histological steatosis was associated with BMI, but advanced fibrosis was not and showed a significant sex difference.

Clinicopathological investigation of steatohepatitic hepatocellular carcinoma: A multicenter study using immunohistochemical analysis of adenoma-related markers.

AIMS: Steatohepatitic hepatocellular carcinoma (SH-HCC) is a newly proposed concept, which shows histological features of steatohepatitis in HCC lesions, and it is strongly associated with metabolic syndrome (MS) and steatosis/steatohepatitis in non-cancerous lesions. Recently, a substantial number of HCC associated with MS were reported to have developed from pre-existing inflammatory hepatocellular adenoma (HCA). To elucidate the characteristic features of SH-HCC, we clinicopathologically investigated strictly diagnosed SH-HCC and non-SH-HCC (standard HCC). METHODS: This was a retrospective multicenter study. A clinicopathological investigation was undertaken to compare 62 cases with SH-HCC features to 31 age- and sex-matched standard HCC cases, including an immunohistochemical study using markers for classification of HCA and diagnosis of HCC. RESULTS: The characteristic features of SH-HCC compared with standard HCC include a higher rate of complications of MS, more frequent non-alcoholic fatty liver disease as an underlying liver disease, and HCC development in non-cirrhotic liver. The rate of solitary tumors showed no difference between the two groups, but the median diameter of the main tumor was greater in SH-HCCs (45 mm/20 mm, P = 0.01). The HCCs were mostly moderately differentiated, and the patterns were mainly trabecular in both groups. Positive findings for serum amyloid A and C-reactive proteins, classification markers of inflammatory HCA, were significantly higher in cancerous lesions of SH-HCC cases (50%/13%, P < 0.01 and 42%/16%, respectively; P = 0.01). CONCLUSIONS: We confirmed that SH-HCC was strongly associated with MS and NAFLD, and found that classification markers of inflammatory HCA were significantly higher in SH-HCC. Further studies are needed to elucidate the relationship between SH-CCC and HCA for understanding the carcinogenic pathways in these diseases.

Diffusion kurtosis imaging with the breath-hold technique for staging hepatic fibrosis: A preliminary study.

PURPOSE: To evaluate the potential of diffusion kurtosis imaging (DKI) analysis with the breath-hold technique to assess the stage or classify hepatic fibrosis. MATERIALS AND METHODS: Patients (n=67) suspected of having a disease of the hepatobiliary system examined by diffusion-weighted imaging (DWI) using a 3.0-T magnetic resonance imaging unit were enrolled in this study. To evaluate hepatic fibrosis, mean kurtosis, Mean apparent diffusion (MD) and apparent diffusion coefficient (ADC) values were compared between groups with varying fibrosis; F0-F1, F2-F3, and F4. The Steel-Dwass test was used for overall comparisons. Correlations between the fibrosis stage and mean kurtosis, MD or ADC values were assessed using Spearman's rank correlation. Discriminative capacities of DKI were evaluated using receiver operating characteristic (ROC) analysis. RESULTS: There were significant differences in ADC, MD and mean kurtosis values between non-cirrhosis and cirrhosis groups. Moreover, the mean kurtosis value was statistically different between the F0-F1 and F2-F3, F0-F1 and F4, and F2-F3 and F4 groups (all P<0.05). MD value was statistically different between the F0-F1 and F4 groups, and F2-F3 and F4 groups (all P<0.05). However, there was no significant difference in ADC values for all groups (all P>0.05). In addition, mean kurtosis and MD values significantly correlated with the extent of hepatic fibrosis staging (Spearman's rank correlation coefficient, ρ=0.851 and -0.672; P<0.0001). However, ADC values did not reveal a correlation with the extent of hepatic fibrosis staging (ρ=-0.227; P=0.078). According to the ROC analysis for the assessment of no fibrosis (F0), fibrosis (≥F1), and advanced fibrosis (≥F2) and liver cirrhosis, the DKI cut-off values were 0.923, 0.955, and 1.11, respectively. CONCLUSION: Using the DKI method with the breath-hold technique in the liver, the stage of hepatic fibrosis can be classified into normal and early hepatic fibrosis, substantial stages, and advanced hepatic fibrosis.

Metachronous early gastric cancer over a period of 13 years after eradication of Helicobacter pylori.

Stomach cancer can occur during chronic inflammation from Helicobacter pylori (HP) infection, and its occurrence can be suppressed by eradication of HP. However, the effects of suppressing stomach cancer by HP eradication are limited, and the cancer is known to recur even after eradication of this infection. Here, we report the case of a 56-year-old male patient with gastric cancer who, although undergoing HP eradication after treatment of early gastric cancer with endoscopy, experienced five metachronous cancer recurrences over a period of 13 years. Whether observation of patients who undergo eradication of HP due to peptic ulcers or chronic gastritis and patients who undergo eradication after endoscopic treatment for early gastric cancer should be performed at the same interval is an issue that must be addressed in the future. The appropriate observation period for each patient must be established while considering the burdens to the patient and from the medical economic perspective.

Investigation of ornithine carbamoyltransferase as a biomarker of liver cirrhosis.

OBJECTIVE: Ornithine carbamoyltransferase (OCT) is a liver-specific mitochondrial matrix enzyme and potential biomarker of liver fibrosis. This study investigated the OCT levels in patients with chronic liver disease with or without cirrhosis in order to assess the usefulness of OCT as a biomarker of cirrhosis. METHODS: The subjects included 440 Japanese patients with chronic liver disease and 80 control subjects. The patients were divided into two groups, those with and without cirrhosis, both of which were further stratified into high-OCT and low-OCT subgroups. RESULTS: In the non-cirrhosis group, the patients with non-alcoholic steatohepatitis (NASH), alcoholic liver disease, primary biliary cirrhosis and primary sclerosing cholangitis (PSC) comprised the high-OCT subgroup, while the patients with hepatitis B, hepatitis C and autoimmune hepatitis formed the low-OCT subgroup. There were significant differences in the OCT levels, OCT/aspartate aminotransferase ratios and OCT/alanine transaminase (ALT) ratios between these two subgroups (p<0.001). The same findings were observed in the cirrhosis group. The OCT levels were markedly higher in the cirrhosis group than in the non-cirrhosis group, particularly among the patients with PSC (p<0.001). The most useful biomarker for predicting cirrhosis was the OCT/ALT ratio in the patients with hepatitis C and NASH and the OCT level in patients with PSC. CONCLUSION: The OCT level differs among patients with different chronic liver diseases. The role of OCT should be further evaluated in order to improve our understanding of the pathogenesis of these diseases. The OCT level is a useful surrogate marker of cirrhosis, particularly in PSC patients.

Serum metabolomic profile and potential biomarkers for severity of fibrosis in nonalcoholic fatty liver disease.

BACKGROUND: Biomarker for usefulness in diagnosing advanced fibrosis in nonalcoholic fatty liver disease (NAFLD) is expected. In order to discover novel biomarkers for NAFLD and its pathogenesis, we performed matabolomics screening. METHODS: (1) The initial cohort was 44 NAFLD patients. (2) This validation cohort was 105 NAFLD patients, 26 primary biliary cirrhosis (PBC) patients, and 48 healthy controls. Using capillary electrophoresis and liquid chromatography with mass spectrometry, we analyzed low molecular weight metabolites in these groups. RESULTS: 1. In the initial cohort, we found 28 metabolites associated with advanced fibrosis. Among them, 4 sulfated steroids showed the greatest difference. A decrease of dehydroepiandrosterone sulfate (DHEA-S) and 5α-androstan-3ß ol-17-one sulfate (etiocholanolone-S) was observed with the progression of fibrosis. Furthermore, 16 hydroxydehydroepiandrosterone sulfate (16-OH-DHEA-S) increased with the progression of fibrosis. 2. In the validation cohort, the decrease of DHEA-S and etiocholanolone-S, as well as the increase of 16-OH-DHEA-S, with the progression of fibrosis was confirmed. The 16-OH-DHEA-S/DHEA-S ratio and 16-OH-DHEA-S/etiocholanolone-S ratio were even more strongly associated with the grade of fibrosis. Among PBC patients, 16-OH-DHEA-S tended to be higher in stages 3 and 4 than in stages 1 and 2. However, levels of DHEA-S, etiocholanolone-S, and the two ratios were not associated with the stage of PBC. CONCLUSION: Several metabolic products were found to be biomarkers of fibrosis in NAFLD and could also be useful for diagnosis of this condition. Our findings suggested disturbance of hormone metabolism in NAFLD and might lead to the development of new therapy.

Prospective study of hepatocellular carcinoma in nonalcoholic steatohepatitis in comparison with hepatocellular carcinoma caused by chronic hepatitis C.

BACKGROUND: This study was performed to clarify the outcomes and recurrence of hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) in comparison with the data for HCC caused by hepatitis C virus (HCV) infection. METHODS: Data for 34 NASH patients with HCC (NASH-HCC) were analyzed prospectively, and data for 56 age- and sex-matched patients with HCC due to HCV chronic liver disease (HCV-HCC) were collected retrospectively. After the initial treatment for HCC, patients were followed regularly at least every 4 months by performing clinical examinations, serum liver function tests, monitoring alpha-fetoprotein and des-gamma-carboxy prothrombin, and utilizing various imaging modalities. RESULTS: The five-year survival rate was 55.2% and the cumulative recurrence of HCC at 5 years was 69.8% in treated cases of NASH-HCC. The NASH-HCC and HCV-HCC groups showed similar survival and recurrence rates. Of the 16 NASH-HCC patients curatively treated, recurrence was detected more than 2 years after the initial treatment in 9. Three patients showed intrahepatic recurrences away from the initial HCC, and 3 patients showed a change in tumor marker production after treatment of the initial HCC. The size of the HCC and the stage of fibrosis were significant risk factors for HCC recurrence in NASH-HCC. CONCLUSIONS: HCC recurrence was very high in NASH, and the HCC may be of multicentric origin, similar to HCC based on viral hepatitis. Regular screening for HCC is extremely important for NASH patients with HCC, even after curative treatment. This study confirmed that NASH-HCC has a similar course to that of HCV-HCC.

Clinical significance of serum ornithine carbamoyltransferase in patients with non-alcoholic steatohepatitis.

AIM: Ornithine carbamoyltransferase (OCT) is reported to be a liver-specific marker for the evaluation of hapatocellular damage. In this study, we investigated its clinical significance in non-alcoholic steatohepatitis (NASH). METHODS: Serum OCT levels were measured by the ELISA (enzyme-linked immunosorbent assay) method. One hundred and twenty patients with NASH (18 liver cirrhosis induced by NASH and 9 NASH combined with hepatocellular carcinoma) were measured. RESULTS: The serum levels of OCT and the ratios of OCT : alanine amino transferase (ALT) and OCT : aspartate amino transferase (AST) were increased in parallel with the progression of NASH. Especially, OCT and both ratios were markedly increased in hepatocellular carcinoma. As for the relationship between fibrosis grade and OCT, the serum OCT levels and the ratio of OCT : ALT levels were increased in parallel with liver fibrosis. In NASH patients with ALT within normal range, about 30% showed elevation of OCT. CONCLUSION: Serum OCT levels and the ratios of OCT : ALT and OCT : AST increase in parallel with the progression of NASH. It was suggested that OCT is a useful marker in the progression of NASH.

Treatment of nonalcoholic steatohepatitis with colestimide.

AIM: To clarify the usefulness of colestimide in patients with nonalcoholic steatohepatitis (NASH) with hyperlipidemia. METHODS: In an open-label randomized controlled trial, 17 NASH patients with hyperlipidemia received colestimide (3 g/day) for 24 weeks. There were 21 control patients. All patients received lifestyle modification therapy. Efficacy was assessed based on metabolic profile, insulin resistance, transaminases, serum hepatic fibrosis markers, adipokine levels, visceral fat on computed tomography (CT), and the fatty liver grade on CT. NASH patients with moderate to severe steatosis by histology were also evaluated separately. RESULTS: Baseline clinical characteristics of the two groups were similar. Both groups experienced a significant decrease of BMI with no difference between them. However, visceral fat decreased significantly more in the colestimide group (P = 0.046). Aspartate aminotransferase (AST) showed a significantly greater decrease in the colestimide group compared with the control group (P = 0.042). In patients with moderate to severe histological steatosis, there were significant differences between the two groups regard to HbA(1c), transaminases, and hyaluronic acid (P = 0.018 for HbA(1c), P = 0.003 for AST, P = 0.042 for alanine aminotransferase, and P = 0.042 for hyaluronic acid). Steatosis significantly improved in patients in the colestimide group who had fatty liver on CT (P = 0.049). In the colestimide group, abdominal distension and/or constipation were seen, but mostly tolerable, no other clinical or laboratory adverse events associated with the use of this medicine were not observed. CONCLUSIONS: Colestimide seems to increase the efficacy of lifestyle modification in NASH patients with hyperlipidemia. Its beneficial effects were more prominent in NASH patients with moderate to severe histological steatosis.

Imaging of nonalcoholic steatohepatitis: advantages and pitfalls of ultrasonography and computed tomography.

OBJECTIVE: The present study was performed to clarify the ability of ultrasonography (US) and computed tomography (CT) to detect steatosis and advanced fibrosis in nonalcoholic steatohepatitis (NASH) patients, and to assess the influence of steatosis, fibrosis, and obesity on the radiological detection of steatosis and advanced fibrosis. METHODS: One hundred and eighteen biopsy proven NASH patients underwent US and CT within 6 months before or after biopsy. The ability of US and CT to detect histological steatosis and advanced fibrosis was assessed. To evaluate whether fibrosis and obesity interfered with the detection of moderate to severe histological steatosis by US and CT, we analyzed 88 NASH patients with moderate to severe steatosis. To evaluate interference with the detection of advanced fibrosis by steatosis and obesity, we analyzed 59 NASH patients with advanced fibrosis. RESULTS: The sensitivity of US for detecting moderate to severe histological steatosis in patients with mild histological fibrosis was 100%, but this was reduced to 77.8% in patients with advanced histological fibrosis (p=0.001). The sensitivity of CT was 69.8% in patients with mild histological fibrosis and 48.9% in those with advanced histological fibrosis (p=0.047). The sensitivity of US and CT for moderate to severe histological steatosis was similar in each body mass index group. The sensitivity for detecting advanced fibrosis was markedly decreased by severe steatosis and obesity in the case of both US and CT. CONCLUSION: If we are aware of these disadvantages of US and CT, it is useful for diagnosing steatosis and fibrosis in NAFLD patients.

Hepatocellular carcinoma in patients with nonalcoholic steatohepatitis.

BACKGROUND: There have been few reports on hepatocellular carcinoma (HCC) in nonalcoholic steatohepatitis (NASH) and the natural history of NASH. Accordingly, we assessed the clinical features of HCC in NASH, the risk factors for HCC, and natural history of NASH with advanced fibrosis. PATIENTS AND METHODS: There were 34 NASH patients with HCC and 348 NASH patients without HCC. To clarify the clinical features of NASH patients with HCC and to determine the risk factors for HCC, we compared NASH patients with HCC with those without HCC. Univariate and multivariate logistic regression models were used for statistical analysis. A prospective cohort study of the outcomes of 137 NASH with advanced fibrosis was started in 1990. The impact of baseline risk factors on the development of HCC and survival was evaluated by Cox regression analysis. RESULTS: In total, 88% of patients with HCC had advanced fibrosis, with a median age of 70 years. Older age, low level of AST, low grade of histological activity, and advanced stage of fibrosis were risk factors for HCC. A prospective cohort study showed that the 5-year cumulative incidence of HCC was 7.6%, and the 5-year survival rate was 82.8%. HCC was the leading cause of death. CONCLUSIONS: The present study confirmed that older age and advanced fibrosis were important risk factors for HCC, and that HCC was the major cause of mortality in NASH patients with advanced fibrosis. Regular screening for HCC is thus extremely important for NASH patients with advanced fibrosis.

Clinical features and outcomes of cirrhosis due to non-alcoholic steatohepatitis compared with cirrhosis caused by chronic hepatitis C.

BACKGROUND AND AIM: Ethnic differences in non-alcoholic steatohepatitis (NASH) are well-documented, but there has been no study on the prognosis of Japanese NASH patients with cirrhosis. Accordingly, we compared cirrhotic NASH with liver cirrhosis caused by chronic hepatitis C (LC-C) to clarify its clinical features and define the risk factors for death. METHODS: A prospective evaluation of the outcomes of NASH patients with severe fibrosis was started in 1990. Data on age- and sex-matched patients with biopsy-proven LC-C were collected retrospectively and used as the control. RESULTS: There were 68 patients with cirrhotic NASH and 69 with LC-C. The Child-Turcotte-Pugh (CTP) class was similar in these two groups. Although the outcome of the NASH group was better than that of the LC-C group, cirrhotic NASH followed a similar course to that of LC-C; that is, complications of cirrhosis developed, including hepatocellular carcinoma (HCC; the 5-year HCC rate was 11.3% for NASH and 30.5% for HCV) and death (the 5-year survival rates were 75.2% and 73.8%, respectively). HCC was the leading cause of death in both groups (NASH, 47%; HCV, 68%). The occurrence of HCC and the CTP class were significant risk factors for mortality in NASH patients according to a multivariate analysis (HCC: hazard ratio [HR] 7.96, 95% confidence interval [CI] 2.45-25.88, CTP class A: HR 0.17, 95% CI 0.06-0.50). CONCLUSION: In conclusion, the present study confirmed that cirrhotic NASH has a similar course to LC-C. The occurrence of HCC was the strongest predictor of mortality in the NASH groups. These findings may be helpful when deciding on therapeutic interventions for NASH and also for the daily management of these patients.