Evaluation of normal or minimally elevated alanine transaminase,age and DNA level in predicting liver histological changes in chronic hepatitis B

Background: Serum alanine transaminase (ALT), hepatitis B virus (HBV) DNA level and age are used in the evaluation of chronic hepatitis B (CHB). Aim: We designed this study to evaluate liver histology with ALT and its relation with age and HBV DNA. Methods: During the period of October 2006 to July 2009, 499 CHB patients were included in this study with detectable HBV DNA at PCR. Of these, 181 had normal ALT, 200 had ALT [>(1 × ULN) <(2 ULN)] and 118 had ALT≥2 ULN and were labelled as Group 1, 2 and 3 respectively. Results: A strong positive correlation was found between ALT and histological activity index (HAI) and fibrosis. However, 29 (52.7%) and five (9.1%) in Group 1 with positive HBeAg status had HAI ≥4 and fibrosis ≥2 respectively. Among those with HBeAg‐negative status, 66 (23.1%) had HAI >4 and 31 (10.8%) had fibrosis ≥2. In Group 2, 14 (15.7%) had moderate‐to‐severe HAI and 19 (21.2%) had fibrosis ≥2 when HBeAg was positive, in those with HBeAg negative 34 (30.6%) had moderate‐to‐severe HAI and 38 (34.2%) had fibrosis ≥2. An ALT value of ≥58.5 U/l had higher sensitivity than that of 80 U/l in predicting significant histological changes. Further, HAI and fibrosis were significantly greater in the age of >30 years. Conclusions: We recommend liver biopsy in HBeAg‐negative CHB over 30 years of age regardless of ALT level and starting treatment at ALT 1.5 × ULN instead of 2 × ULN.     

Larger biopsies evaluation of transient elastography for detecting advanced fibrosis in patients with compensated chronic hepatitis B

Background and Aim: Although larger biopsies sample had been recommended for the study of non‐invasive liver fibrosis assessment, few studies with larger biopsies for transient elastography (TE) detecting liver fibrosis had been reported. The present study tries to re‐evaluate the performance of TE for detecting advanced fibrosis (≥F3) with larger biopsies in patients with compensated chronic hepatitis B. Methods: A total of 375 compensated patients were analyzed, who had undergone liver biopsy, reliable TE and routine blood tests. Results: The area under the receiver operating characteristic curve (AUC) was influenced by liver biopsy sample: 0.873 (95% confidence interval 0.838–0.909) in total patients, 0.880 (0.844–0.917) in length ≥ 15 mm, 0.897 (0.863–0.932) in length ≥ 20 mm and 0.911 (0.874–0.949) in length ≥ 25 mm. In patients with sample length ≥ 20 mm, the cutoffs to exclude and confirm advanced fibrosis were 7.1 kPa and 12.7 kPa, respectively. Stratified by alanine aminotransferase of two times the upper limit of normal (ALT 2 × ULN), transient elastography detecting advanced fibrosis with the most efficiency by 72.5% of patients obviated from liver biopsy. In patients with normal bilirubin and ALT < 2 × ULN, the area was 0.921 (0.860–0.982), and cutoffs for excluding and confirming diagnosis were 7.4 kPa and 10.6 kPa, respectively; 80% of patients could be classified with or without advanced fibrosis (AF). In patients with normal bilirubin and ALT ≥ 2 × ULN, the corresponding numbers were 0.885 (0.824–0.947), 7.5 kPa, 12.7 kPa and 79.2%, respectively. Conclusions: Inadequate sample study would underestimate the efficiency of TE on detecting advanced fibrosis. With ALT 2 × ULN stratified cutoffs, TE determined nearly 80% of patients with normal bilirubin as AF or non‐AF and obviated them from liver biopsies.     

Updated thresholds for alanine aminotransferase do not exclude significant histological disease in chronic hepatitis C

Background and aim: Histological changes in hepatitis C virus (HCV)‐infected patients with persistently normal alanine aminotransferase (PNALT) have not been evaluated for updated upper limits of normal (ULN; ≤19/30U/L for females/males). We assessed significant fibrosis (≥F2, METAVIR) in patients with PNALT and persistently elevated alanine aminotransferase (PEALT). Patients and methods: Nine hundred and twenty consecutive, unselected HCV patients were stratified into four groups: Group I: (n=124) PNALT within the updated ULN [0.5 × ULN (corresponding to ≤19 U/L) for females; 0.75 × ULN (corresponding to ≤30 U/L) for males]; Group II (n=173): PNALT≤1 × ULN but greater than Group I; Group III (n=313): PEALT 1–2 × ULN; and Group IV (n=310): PEALT>2 × ULN. PNALT was defined as ≥3 determinations within the normal range over ≥6 months. Results: Advanced ≥F3 and ≥F2 fibrosis increased incrementally across Groups I; II; III; and IV: 24.2 and 45.2%; 25.4 and 56.1%; 36.1 and 64.2%; and 50 and 77.1% respectively (P<0.0001 for both). Multivariable logistic regression analysis identified age [odds ratio (OR), 1.05; 95% confidence intervals (CI): 1.02–1.08; P<0.0001], alanine aminotransferase (ALT) groups (OR 1.38; 95% CI: 1.03–1.83; P=0.030), presence of moderate–severe steatosis (OR 2.70; 95% CI: 1.19–6.15; P=0.018) and ≥A2 necroinflammation (OR 17.9; 95% CI: 8.88–36.20; P<0.0001) as independent predictors of ≥F2 fibrosis. Updated ULN for ALT were better at excluding ≥F2 fibrosis compared with traditional ULN (90.6 vs. 74.2%, P=0.0041) but less specific (20.8 vs. 44%, P=0.0007) with similar positive/negative predictive values. Conclusions: HCV patients with ‘updated’ normal ALT have the lowest prevalence of significant fibrosis, although utilizing these levels without resorting to biopsy would miss significant fibrosis in almost one‐half of such patients.     

Non invasive evaluation of liver fibrosis in paediatric patients with nonalcoholic steatohepatitis

INTRODUCTION With the current epidemic prevalence of obesity and diabetes mellitus in the general population[1], nonalcoholic fatty liver disease (NAFLD) has become the most common cause of chronic liver disease in many countries[2,3]. The characteristic …     

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.     

Histopathological stages of nonalcoholic fatty liver disease in type 2 diabetes: prevalences and correlated factors

Background/Aims: Nonalcoholic fatty liver disease (NAFLD) is highly prevalent in type 2 diabetes mellitus (T2DM). However, data regarding the prevalence and correlates of its histopathological stages are scarce. The aim was to investigate the prevalence and correlates of the more severe histopathological features of NAFLD, nonalcoholic steatohepatitis (NASH) and advanced fibrosis, in T2DM. Methods: From 125 patients with ultrasonographic evidence of NAFLD, 98 patients underwent liver biopsies, which were examined by two independent pathologists regarding the presence of NASH and graded according to the NASH Clinical Research Network scoring system. Agreement between pathologists was assessed by weighted κ coefficients and independent correlates of NASH and advanced fibrosis (grade ≥2) by multivariate logistic regression. Results: Ninety‐two (94%) patients presented histological NAFLD. Interobserver agreement was substantial to excellent for NASH diagnosis (κ=0.82) and steatosis grading (κ=0.76), and moderate for the NAFLD activity score (κ=0.58) and fibrosis grading (κ=0.52). The prevalence of NASH was 78%, and its independent correlates were hypertriglyceridaemia (P=0.034), high alanine aminotranferase level (P=0.044) and low serum high‐density lipoprotein‐cholesterol (P=0.079). The prevalence of advanced fibrosis ranged from 34% in the best scenario (lowest fibrosis score) to 60% in the worst scenario (highest score). Its independent correlates were a high serum γ‐glutamyl transferase (P=0.002), older age (P=0.022) and male gender (P=0.064). No diabetes‐related clinical characteristic was associated with NASH or advanced liver fibrosis. Conclusions: The prevalence of the severe features of NAFLD is high in T2DM patients. Liver biopsy shall be considered in all diabetic patients with ultrasonographic evidence of NAFLD.     

Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease

OBJECTIVE: The majority of patients with non-alcoholic fatty liver disease (NAFLD) have simple steatosis. A minority, however, present with non-alcoholic steatohepatitis (NASH), a condition that can lead to advanced fibrosis and cirrhosis. The frequencies of NASH and fibrosis among patients with NAFLD and sustained elevation of liver function tests (LFT) are uncertain. Our aim was to estimate these frequencies. We characterize a population with NAFLD, with special emphasis on insulin resistance and the metabolic syndrome, and study possible predictors for different stages of the disease. MATERIAL AND METHODS: All referred patients with sustained elevation of LFT, radiological evidence or clinical suspicion of fatty liver, and absence of other liver disease, were invited to participate in our study in the period June 2002 to December 2004. RESULTS: Of 129 patients who met the inclusion criteria, 88 underwent liver biopsy. NAFLD was verified in 83 of them. Among these patients, 59 (71%) had the metabolic syndrome, 41 (49%) had NASH and 36 (43%) had fibrosis. Abnormal glucose tolerance (T2DM or impaired glucose tolerance) was the only independent risk factor for NASH (OR: 3.14; 95% CI: 1.20-8.23). Independent predictors for fibrosis were abnormal glucose tolerance (OR: 3.83; 95% CI: 1.29-11.40) and body mass index (OR: 1.20; 95% CI: 1.06-1.36) per kg/m2. CONCLUSIONS: Both NASH and fibrosis are frequently present among patients with NAFLD and sustained elevation of LFT. The probability of these potentially progressive stages of NAFLD increases with the presence of abnormal glucose tolerance.     

Fibrosis staging in chronic hepatitis C: analysis of discordance between transient elastography and liver biopsy

Summary. In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir ≥ F2) is variable. Constitutional and liver disease‐related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)‐RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy‐six of 286 (26.6%) had stage ≥F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage <F2 and TE ≥ 7.1 kPa (false positive). No patient with discordant results had cirrhosis. By Dale model, aspartate aminotransferase (AST) was found to be the unique variable significantly related (P = 0.046) with discordance between biopsy and TE. Discordance rate was 43.4% (82 patients) with AST < 1.5 × UNL vs 25.8% (25 patients) with AST ≥ 1.5 × UNL (P = 0.004). False negative rate was 43.4 (82 patients) with AST < 1.5 × UNL vs 17.1% (13 patients) with AST ≥ 1.5 × UNL (P < 0.001). Areas under the receiver operating characteristic (AUROC) for F ≥ 2, according to AST < 1.5 × UNL vs ≥ 1.5 × UNL were 0.738 (95% CI: 0.683–0.812) and 0.854(95% CI: 0.754–0.907). Transient elastography is not adequate on its own to rule out or to rule in significant fibrosis, as it is influenced by major variations in biochemical activity of liver disease. Liver stiffness, at low levels of AST, can underestimate fibrosis.     

A survey of chronic hepatitis B patient management practices in the European Union

Summary. The current study sought to evaluate the characteristics of chronic hepatitis B virus (HBV) infection and current management practices in the European Union by surveying physician and patient records. A detailed survey of physician practices and management of patients with CHB was conducted between July and October 2006 in France, Germany, Italy and Spain. A total of 200 physicians participated in the survey, and data were collected from 2023 patients with chronic HBV infection. Most patients were men (69%), who had hepatitis B e antigen (HBeAg)‐negative disease (64%), and demonstrated evidence of significant disease [53%; moderate fibrosis (35%), compensated cirrhosis (14%), or decompensated cirrhosis (4%)]. Among the 1665 HBV‐monoinfected patients surveyed, 1184 (71%) were currently receiving treatment for chronic HBV infection. At treatment initiation, 70% of HBeAg‐positive patients had both pretreatment serum HBV DNA levels ≤9 log₁₀ copies/mL and alanine aminotransferase (ALT) levels ≥2 × the upper limit of normal (ULN), and 81% of HBeAg‐negative patients had HBV DNA levels of ≤7 log₁₀ copies/mL. Among untreated patients, HBV DNA levels ≤5 log_10, ALT levels <2 × ULN, and mild or no liver fibrosis were present in 48% and 84% of HBeAg‐positive and HBeAg‐negative patients, respectively. In conclusion, the majority of European patients with CHB surveyed were HBeAg negative, Caucasian, men, and presented with significant histologic liver disease. At treatment initiation, most HBeAg‐positive patients had pretreatment serum HBV DNA levels ≤9 log₁₀ copies/mL and ALT levels ≥2 × ULN, while the HBeAg‐negative patients had HBV DNA levels ≤7 log₁₀ copies/mL.     

Serum ferritin is a discriminant marker for both fibrosis and inflammation in histologically proven non‐alcoholic fatty liver disease patients

Introduction: Differentiation between steatosis and non‐alcoholic steatohepatitis (NASH) in non‐alcoholic fatty liver disease (NAFLD) is important as NASH progress to cirrhosis. No specific laboratory/imaging technique exists either to diagnose NASH or to select patients for liver biopsy. Patients and methods: We evaluated serum ferritin and the features of metabolic syndrome with respect to histological inflammation and/or fibrosis in NAFLD patients. The Kleiner scoring system was used to classify NAFLD in consecutive liver biopsies. One hundred and eleven patients: median age 52.6, 64 males, obesity 62, diabetes mellitus (DM) 58, arterial hypertension 26 and hyperlipidaemia 40%. Results: Histologically, 40.7 had fatty liver, 30.6% had borderline NASH, 28.7% had NASH and 11% had cirrhosis. Multivariate regression showed that diabetes, serum ferritin concentrations, body mass index (BMI) and AST were independently associated with NASH: together, the areas under the receiver operating characteristic (AUROC) was 0.91 (95% confidence interval 0.86–0.96); fibrosis was associated with ferritin concentrations and BMI: AUROC 0.87, portal inflammation with ferritin and DM: AUROC 0.82, while lobular inflammation was associated with BMI, DM and ferritin: AUROC 0.85. Conclusion: Serum ferritin concentrations and BMI are strongly associated with fibrosis, portal and lobular inflammation in NAFLD patients. Both ferritin and BMI are potential discriminant markers to select patients for liver biopsy and are associated with inflammation and fibrosis.     

Impact of HIV on liver fibrosis in men with hepatitis C infection and haemophilia

Summary. Hepatitis C virus (HCV) is the major cause of liver disease in haemophilia. Few data exist on the proportion with liver fibrosis in this group after long‐term HCV and HIV co‐infection. We conducted a cross‐sectional multi‐centre study to determine the impact of HIV on the prevalence and risk factors for fibrosis in haemophilic men with chronic hepatitis C. Biopsies were independently scored by Ishak, Metavir and Knodell systems. Variables were tested for associations with fibrosis using logistic regression and receiver operating curves (ROC). Of 220 biopsied HCV(+) men, 23.6% had Metavir ≥F3 fibrosis, with higher mean Metavir fibrosis scores among HIV/HCV co‐infected than HCV mono‐infected, 1.6 vs. 1.3 (P = 0.044). Variables significantly associated with fibrosis included AST, ALT, APRI score (AST/ULN × 100/platelet × 10⁹/L), alpha‐fetoprotein (all P < 0.0001), platelets (P = 0.0003) and ferritin (P = 0.0008). In multiple logistic regression of serum markers, alpha‐fetoprotein, APRI and ALT were significantly associated with ≥F3 fibrosis [AUROC = 0.77 (95% CI 0.69, 0.86)]. Alpha‐fetoprotein, APRI and ferritin were significant in HIV(?) [AUROC = 0.82 (95% CI 0.72, 0.92)], and alpha‐fetoprotein and platelets in HIV(+) [AUROC = 0.77 (95% CI 0.65, 0.88]. In a multivariable model of demographic and clinical variables, transformed (natural logarithm) of alpha‐fetoprotein (P = 0.0003), age (P = 0.006) and HCV treatment (P = 0.027) were significantly associated with fibrosis. Nearly one‐fourth of haemophilic men have Metavir ≥3 fibrosis. The odds for developing fibrosis are increased in those with elevated alpha‐fetoprotein, increasing age and past HCV treatment.     

Non-alcoholic steatohepatitis in type 2 diabetes mellitus

BACKGROUND AND AIMS: Non-alcoholic steatohepatitis (NASH) is commonly associated with type 2 diabetes mellitus (DM). Prevalence of NASH in type 2 DM has not been well studied and there is an epidemic rise in type 2 DM in Asian and Western populations. Its association with chronic liver disease in the form of NASH makes it an important health problem. Hence we have studied its prevalence and correlation of biochemical parameters with histological grades of non-alcoholic fatty liver disease (NAFLD) in otherwise asymptomatic type 2 DM patients. METHODS: One hundred and forty-eight individuals were screened. Forty-eight individuals were excluded due to history of alcohol intake or liver disease as a result of other causes. One hundred non-alcoholic individuals with type 2 DM underwent abdominal ultrasonography (US abdomen). Forty-nine patients had evidence of fatty liver on US abdomen, and 32 of these 49 patients underwent liver biopsy. RESULTS: Four of 32 (12.5%) individuals had steatosis alone. Mild, moderate and severe NASH was present in 21/32 (65.5%), 4/32 (12.5%) and 3/32 (9.35%), respectively. Fibrosis was present in 7/32 (21.8%) patients (four grade 1 and three grade 3). There was no significant difference in body mass index (BMI), transaminase levels, serum cholesterol and triglyceride levels among patients with non-alcoholic fatty liver disease. CONCLUSION: We conclude that the prevalence of NASH is high in type 2 DM patients and liver biopsy is the only investigation to differentiate between non-alcoholic fatty liver and steatohepatitis.     

慢性丙型肝炎患者肝组织学改变及其影响因素分析

目的探讨慢性丙型肝炎患者肝组织学改变及其影响因素。方法选择经皮肝组织活检的慢性丙型肝炎患者102例,记录患者年龄、性别、体质指数(BMI)、感染途径等,检测ALT水平、AST水平、HCV基因分型、病毒载量和肝脏组织学改变。统计学处理采用t检验和Logistic回归分析。结果肝脏炎症活动指数( HAI)≥4的慢性丙型肝炎患者的ALT、AST水平较高,PLT较低,与HAI＜4的患者相比差异有统计学意义(t=2.209、2.298、2.565,均P＜0.05)。纤维化分期评分(F)≥3的患者平均年龄、ALT水平、AST水平以及感染时间均高于F＜3的患者（t=2.340、3.497、2.758、2.570,均P＜0.05）,而PLT则较低(t=2.761,P=0.007)。女性、ALT＞1×正常值上限(ULN)、AST水平、F≥3、HCV RNA≥6 lgIU/mL和PLT计数是HAI≥4的单因素预测因子;经多因素分析后,Ishak纤维化分期评分是HAI≥4的唯一独立预测因子(OR 3.098,95％ Cl1.884～5.092,P＜0.01)。单因素分析F≥3的预测因子为年龄、BMI≥24 kg/m2、ALT＞1×ULN、AST水平、HAI≥4、PLT计数以及感染年限≥15年;多因素回归分析显示,年龄(OR 1.074,95％CI1.006～1.146,P=0.033)、ALT水平(OR 1.035,95％CI 1.015～1.055,P＜0.01)、AST水平(OR0.969,95％CI 0.948～0.990,P=0.005)、感染年限≥15年(OR 37.215,95％CI 5.816～238.127,P＜0.01)和HAI≥4(OR 1.939,95％CI 1.426～2.636,P＜0.01)是F≥3的独立危险因素。结论年龄、ALT水平、AST水平、感染年限≥15年和HAI≥4是肝组织学显著纤维化的独立预测因子。     

ALT低于2倍正常值上限的慢性HBV感染者肝脏病理结果的预测因素分析

目的探索在ALT2倍正常值上限(2×ULN)的慢性HBV感染人群中,一般临床指标对肝脏病理结果的预测作用。方法收集2009年1月至2013年6月新乡医学院第一附属医院收治的122例ALT2×ULN的慢性HBV感染者,在超声引导下行肝穿刺活组织检查术,判断肝组织炎症活动度及纤维化程度,同期化验肝功能、乙型肝炎血清标志物、HBV DNA等指标,应用Logistic回归分析法探索该类患者的一般临床指标对其肝脏病理结果的预测作用。结果 122名患者中有明显炎症或纤维化(G≥2或S≥2)者共94例(77.0%),早期肝硬化者5例(4.1%)。G2组与G≥2组相比,除HBV DNA外,其余各指标间差异均无统计学意义;S2组与S≥2组相比,年龄、HBeAg、HBV DNA、AST、血小板差异均有统计学意义;Logistic回归分析提示,年龄、HBeAg和AST是肝脏明显纤维化(S≥2)的独立预测因子。结论对血清ALT2×ULN的慢性HBV感染者,年龄40岁、HBeAg阴性、AST40U/L者应积极进行肝穿刺活组织检查术,必要时尽早抗病毒治疗。     

Abnormal glucose tolerance is a predictor of steatohepatitis and fibrosis in patients with non-alcoholic fatty liver disease

Objective. The majority of patients with non-alcoholic fatty liver disease (NAFLD) have simple steatosis. A minority, however, present with non-alcoholic steatohepatitis (NASH), a condition that can lead to advanced fibrosis and cirrhosis. The frequencies of NASH and fibrosis among patients with NAFLD and sustained elevation of liver function tests (LFT) are uncertain. Our aim was to estimate these frequencies. We characterize a population with NAFLD, with special emphasis on insulin resistance and the metabolic syndrome, and study possible predictors for different stages of the disease. Material and methods. All referred patients with sustained elevation of LFT, radiological evidence or clinical suspicion of fatty liver, and absence of other liver disease, were invited to participate in our study in the period June 2002 to December 2004. Results. Of 129 patients who met the inclusion criteria, 88 underwent liver biopsy. NAFLD was verified in 83 of them. Among these patients, 59 (71%) had the metabolic syndrome, 41 (49%) had NASH and 36 (43%) had fibrosis. Abnormal glucose tolerance (T2DM or impaired glucose tolerance) was the only independent risk factor for NASH (OR: 3.14; 95% CI: 1.20–8.23). Independent predictors for fibrosis were abnormal glucose tolerance (OR: 3.83; 95% CI: 1.29–11.40) and body mass index (OR: 1.20; 95% CI: 1.06–1.36) per kg/m². Conclusions. Both NASH and fibrosis are frequently present among patients with NAFLD and sustained elevation of LFT. The probability of these potentially progressive stages of NAFLD increases with the presence of abnormal glucose tolerance.     

Serum ferritin is an independent predictor of histologic severity and advanced fibrosis in patients with nonalcoholic fatty liver disease

Serum ferritin (SF) levels are commonly elevated in patients with nonalcoholic fatty liver disease (NAFLD) because of systemic inflammation, increased iron stores, or both. The aim of this study was to examine the relationship between elevated SF and NAFLD severity. Demographic, clinical, histologic, laboratory, and anthropometric data were analyzed in 628 adult patients with NAFLD (age, ≥ 18 years) with biopsy-proven NAFLD and an SF measurement within 6 months of their liver biopsy. A threshold SF >1.5 × upper limit of normal (ULN) (i.e., >300 ng/mL in women and >450 ng/mL in men) was significantly associated with male sex, elevated serum alanine aminotransferase, aspartate aminotransferase, iron, transferrin-iron saturation, iron stain grade, and decreased platelets (P < 0.01). Histologic features of NAFLD were more severe among patients with SF >1.5 × ULN, including steatosis, fibrosis, hepatocellular ballooning, and diagnosis of NASH (P < 0.026). On multiple regression analysis, SF >1.5 × ULN was independently associated with advanced hepatic fibrosis (odds ratio [OR], 1.66; 95% confidence interval [CI], 1.05-2.62; P = 0.028) and increased NAFLD Activity Score (NAS) (OR, 1.99; 95% CI, 1.06-3.75; P = 0.033). CONCLUSIONS: A SF >1.5 × ULN is associated with hepatic iron deposition, a diagnosis of NASH, and worsened histologic activity and is an independent predictor of advanced hepatic fibrosis among patients with NAFLD. Furthermore, elevated SF is independently associated with higher NAS, even among patients without hepatic iron deposition. We conclude that SF is useful to identify NAFLD patients at risk for NASH and advanced fibrosis.     

Association between diabetes, family history of diabetes, and risk of nonalcoholic steatohepatitis and fibrosis

Previous studies have shown familial aggregation of insulin resistance and nonalcoholic fatty liver disease (NAFLD). Therefore, we aimed to examine whether family history of diabetes mellitus (DM) is associated with nonalcoholic steatohepatitis (NASH) and fibrosis in patients with NAFLD. This was a cross-sectional analysis in participants of the NAFLD Database study and PIVENS trial who had available data on family history of DM. One thousand and sixty-nine patients (63% women), with mean age of 49.6 (± 11.8) years and body mass index (BMI) of 34.2 (± 6.4) kg/m(2) , were included. Thirty percent had DM, and 56% had a family history of DM. Both personal history of DM and family history of DM were significantly associated with NASH, with an odds ratio (OR) of 1.93 (95% confidence interval [CI]: 1.37-2.73; P <0.001) and 1.48 (95% CI: 1.11-1.97; P = 0.01) and any fibrosis with an OR of 3.31 (95% CI: 2.26-4.85; P < 0.001) and 1.66 (95% CI: 1.25-2.20; P < 0.001), respectively. When the models were adjusted for age, sex, BMI, ethnicity, and metabolic traits, the association between diabetes and family history of DM with NASH showed an increased adjusted OR of 1.76 (95% CI: 1.13-2.72; P < 0.001) and 1.34 (95% CI: 0.99-1.81; P = 0.06), respectively, and with any fibrosis with a significant adjusted OR of 2.57 (95% CI: 1.61-4.11; P < 0.0001) and 1.38 (95% CI: 1.02-1.87; P = 0.04), respectively. After excluding patients with personal history of diabetes, family history of DM was significantly associated with the presence of NASH and any fibrosis with an adjusted OR of 1.51 (95% CI: 1.01-2.25; P = 0.04) and 1.49 (95% CI: 1.01-2.20; P = 0.04), respectively. Conclusions: Diabetes is strongly associated with risk of NASH, fibrosis, and advanced fibrosis. Family history of diabetes, especially among nondiabetics, is associated with NASH and fibrosis in NAFLD. (HEPATOLOGY 2012;56:943-951).     

The triglycerides and glucose (TyG) index: A new marker associated with nonalcoholic steatohepatitis (NASH) in obese patients

AimDiagnosis of nonalcoholic steatohepatitis (NASH) relies on liver biopsy. Noninvasive tools would be useful to target patients to refer for a biopsy. We aimed to determine the diagnostic value of the triglycerides and glucose (TyG) index, an insulin-resistance indicator, to predict NASH.MethodsOur study included grade II-III obese patients aged 18-65 years undergoing bariatric surgery and included in the COMET (COllection of MEtabolic Tissues) biobank (NCT02861781). Liver biopsies performed during bariatric surgery were collected from the biobank along with blood derivatives. Biopsies were analysed according to the steatosis, activity and fibrosis (SAF) scoring system to diagnose NASH, nonalcoholic fatty liver disease (NAFLD), and fibrosis. Logistic regression models were performed to identify factors predicting NASH, NAFLD, and fibrosis.ResultsOf 238 analysed subjects (mean age 43±12 years, 33.6% men), 29% had type 2 diabetes. Steatosis was present in 67.2%, while NASH and advanced fibrosis (stage F3) were diagnosed in 18.1% and 2.9% respectively. TyG index was independently associated with NASH (odds ratio (OR): 4.7 [95% confidence interval: 2.3;9.5] P < 0.0001), NAFLD (OR: 2.0 [1.1;3.7] P = 0.03) and stages 2-3 fibrosis (OR: 4.0 [1.5;10.8] P = 0.007). NASH was also predicted by gamma-glutamyl transferase (GGT) with an area under the ROC curve: 0.79 [0.71;0.87 P = 0.04] for GGT and TyG index combined.ConclusionIn our cohort of severely obese patients, TyG index, when associated with GGT level, exhibited high diagnostic performance to predict NASH. Although validation in larger populations is needed, this result may be of considerable clinical value to predict need for liver biopsy.     

The pathologic relevance of metabolic criteria in patients with biopsy-proven nonalcoholic fatty liver disease and metabolic dysfunction associated fatty liver disease: A multicenter cross-sectional study in China

BackgroundThis study aimed to assess the association between metabolic syndrome (MetS) and severity of nonalcoholic fatty liver disease (NAFLD), and to discuss the pathological relevance of the diagnostic criteria in metabolic (dysfunction) associated fatty liver disease (MAFLD).MethodsThis was a multicenter, cross-sectional study. Patients with NAFLD confirmed by liver biopsy were enrolled between July 2016 and December 2018 from 14 centers across the mainland of China. Anthropometric and metabolic parameters were collected to assess the pathological relevance.ResultsOf 246 enrolled patients with NAFLD, 150 (61.0%) had the comorbidity of MetS. With the increase of metabolic components, the proportions of nonalcoholic steatohepatitis (NASH) and significant fibrosis were notably increased. The comorbid three metabolic components significantly increased the proportion of NASH, and further increase of metabolic components did not increase the proportion of NASH. However, the increase of metabolic components was parallel to the increase of the proportion of liver fibrosis. Among the 246 patients, 239 (97.2%) met the diagnostic criteria of MAFLD. Although non-MAFLD patients had less NASH, they present with similar proportion of significant fibrosis and cirrhosis. In the diagnostic criteria of MAFLD, BMI ≥ 23 kg/m² was related to NASH (Mantel-Haenszel Common Estimate OR: 2.975; 95% CI: 1.037–8.538; P = 0.043), and T2DM was related to significant fibrosis (Mantel-Haenszel Common Estimate OR: 2.531; 95% CI: 1.388–4.613; P = 0.002). The homeostasis model assessment of insulin resistance (HOMA-IR) ≥ 2.5 was the most significant factor for NASH (OR: 4.100; 95% CI: 1.772–9.487; P = 0.001) and significant factor for liver fibrosis (OR: 2.947; 95% CI: 1.398–6.210; P = 0.004) after the adjustments of the BMI and diabetes.ConclusionsMetabolic dysregulations are important risk factors in NAFLD progression. The insulin resistance status may play a predominant role in the progression in MAFLD patients.     

Is transient elastography valuable for high‐risk esophageal varices prediction in patients with hepatitis‐B‐related cirrhosis?

Background and Aim: The aim of this study was to evaluate the clinical value of transient elastography (TE) for high‐risk esophageal varices (HREV) prediction in hepatitis‐B‐related cirrhosis patients. Methods: A total of 238 patients with hepatitis B cirrhosis were prospectively enrolled. All patients had undergone TE and upper gastrointestinal endoscopy. Diagnostic value was assessed by the area under ROC curve (AUROC), predictive value and likelihood ratio. Results: The size of esophageal varices correlated with liver stiffness with Kendall's tau_b 0.236 overall and 0.425 in patients with ALT ≥ 5 × upper limit of normal (ULN). The AUROC of TE predicting HREV was 0.73 (95% confidence interval 0.66–0.80) overall and 0.92 (0.82–1.01) for patients with ALT ≥ 5 × ULN. In patients with ALT ≥ 5 × ULN, cut‐off 36.1 kPa predicted HREV with a 100% negative predictive value (NPV), an indefinite negative likelihood ratio (NLR), a 72.7% positive predictive value (PPV) and a positive likelihood ratio (PLR) of 9.3. The AUROC of HREV‐predicting model, constructed by ultrasonography and TE (USLS), was 0.84 (0.77–0.90) in the training set and 0.85 (0.76–0.94) in the validating set. Cut‐off 3.30 excluded HREV with NPV 0.946 and NLR 0.10, and cut‐off 5.98 determined HREV with PPV 0.870 and PLR 10.24. Using USLS, nearly 50% of patients could avoid endoscopic screening. The model's predictive values were maintained at similar accuracy in the validation set. Differences of AUROC in USLS, liver stiffness/spleen diameter to platelet ratio score and ultrasonic score were not significant. Conclusions: TE may predict HREV in patients with ALT ≥ 5 × ULN. Overall, the clinical values of TE and USLS for HREV prediction should be evaluated by further studies.