Concomitant gallstone disease was not associated with long-term outcomes in ursodeoxycholic acid-treated patients with primary biliary cholangitis.

OBJECTIVES: Primary biliary cholangitis (PBC) is a rare disease characterized by intrahepatic cholestasis, whereas gallstone disease (GD) is common. In this study, we aimed to investigate the prevalence and impact of GD on the prognosis of PBC in China. METHODS: Medical records of the PBC patients were retrospectively reviewed and their follow-up data were obtained via regular structured, standardized telephone interviews. GD was defined as gallstones on ultrasonography or a history of cholecystectomy for gallstones. Propensity score matching (PSM) and Cox regression analysis were performed. The primary end-point was liver-related death and/or liver transplantation. RESULTS: A total of 985 ursodeoxycholic acid (UDCA)-treated PBC patients were enrolled with a median follow-up duration of 5.3 years (range 1.0-20.9 years). Among them, 258 (26.2%) had GD, including 157 (22.9%) of non-cirrhotic and 101 (33.8%) of cirrhotic patients. Compared with PBC without GD, those with GD were older, more often had type 2 diabetes mellitus, and had a more severe liver disease at baseline. After PSM (1:2), 229 PBC patients with GD were matched with 458 PBC patients without GD based on age, sex, cirrhosis, and total bilirubin level. The transplant-free survival and incidence of hepatic events were similar between the two groups. Furthermore, multivariate Cox regression analysis showed that concomitant GD was not independently associated with a worse prognosis for PBC patients. CONCLUSION: Concomitant GD was common but was not associated with long-term outcomes in patients with UDCA-treated PBC.

Azonal steatosis correlates with disease severity and poor outcome of nonalcoholic fatty liver disease.

OBJECTIVES: In this study we aimed to assess the clinicopathological characteristics and long-term prognosis of patients with nonalcoholic fatty liver disease (NAFLD) having distinct steatosis distribution patterns. METHODS: Clinicopathological data of 238 individuals with biopsy-confirmed NAFLD were collected. Nonalcoholic steatohepatitis-clinical research network (NASH-CRN) and steatosis, activity and fibrosis (SAF)/fatty liver inhibition of progression (FLIP) algorithm were used. Cumulative incidence of liver-related events (LREs) was compared by Kaplan-Meier analysis. Univariate and multivariate logistic regression analyses were used to identify independent predictors for steatosis distribution. RESULTS: Eligible patients were categorized into three groups based on their steatosis distribution, including azonal steatosis (AS) (62 [26.1%]), perivenular steatosis (PVS) (147 [61.8%]), and the pan-acinar steatosis (PAS) groups (29 [12.1%]). There were significantly higher ballooning grade and disease activity (P < 0.05), more severe fibrosis (P < 0.001), and a higher cumulative incidence of LREs (hazard ratio [HR] 8.0, 95% confidence interval [CI] 2.34-27.35, P < 0.0001) in the AS group than in the PVS and PAS groups after a median of 3.6-year follow-up. Multivariate logistic regression analysis revealed age (odds ratio [OR] 1.11, 95% CI 1.06-1.16, P < 0.001) might be independently associated with AS distribution, and PNPLA3 rs738409 CG/GG genotype (OR 3.36, 95% CI 0.98-11.47, P = 0.053) might also play a role. CONCLUSIONS: AS is associated with more severe disease activity and fibrosis stage in NAFLD, and predisposes toward poor prognosis. Age might be an independent predictor for AS in NAFLD, while PNPLA3 rs738409 CG/GG genotype might also play a role.

Histological assessment based on liver biopsy: the value and challenges in NASH drug development.

Nonalcoholic steatohepatitis (NASH) is increasingly recognized as a serious disease that can lead to cirrhosis, hepatocellular carcinoma (HCC), and death. However, there is no effective drug to thwart the progression of the disease. Development of new drugs for NASH is an urgent clinical need. Liver biopsy plays a key role in the development of new NASH drugs. Histological findings based on liver biopsy are currently used as the main inclusion criteria and the primary therapeutic endpoint in NASH clinical trials. However, there are inherent challenges in the use of liver biopsy in clinical trials, such as evaluation reliability, sampling error, and invasive nature of the procedure. In this article, we review the advantages and value of liver histopathology based on liver biopsy in clinical trials of new NASH drugs. We also discuss the challenges and limitations of liver biopsy and identify future drug development directions.

Multicenter prospective study to validate a new transient elastography device for staging liver fibrosis in patients with chronic hepatitis B.

OBJECTIVES: To validate the operational and diagnostic performances of a new device for transient elastography (TE), FibroTouch, for liver fibrosis in patients with chronic hepatitis B (CHB). METHODS: In this prospective multicenter study, adult patients with CHB and valid liver pathological results were recruited to validate the operational and diagnostic performance of a TE device by FibroTouch for staging liver fibrosis. RESULTS: In total, 517 patients with histologically proven CHB were enrolled. All had achieved at least 10 successful liver stiffness measurements (LSM), resulting in a success rate of 99.1% and reliable evaluations of 95.2%. Altogether 412 patients were included to analyze the diagnostic performance of FibroTouch. The area under the receiver operating characteristic curve for the LSM was 0.846 (95% confidence interval [CI] 0.808-0.880) for fibrosis stage ≥ F1, 0.850 (95% CI 0.811-0.883) for ≥ F2, 0.908 (95% CI 0.876-0.934) for ≥ F3 and 0.874 (95% CI 0.836-0.903) for F4. The diagnostic accuracy of LSM was superior to that of gamma-glutamyl transpeptidase-to-platelet ratio (GPR), aminotransferase-to-platelet ratio index (APRI), or fibrosis index based on 4 factors (FIB-4) index in staging fibrosis F2-F4 (P = 0.007 to < 0.0001). Optimal LSM cut-off values for diagnosing fibrosis stage ≥ F1, ≥ F2, ≥ F3, and F4 were 5.5 kPa, 7.85 kPa, 10.0 kPa, and 12.7 kPa, respectively. CONCLUSION: FibroTouch has a high success rate and good reliability in staging liver fibrosis in patients with CHB.

Non-obese patients with nonalcoholic fatty liver disease may use a lower liver stiffness cut-off to assess fibrosis stages.

OBJECTIVE: We aimed to estimate the optimal cut-off values of liver stiffness measurement (LSM) for diagnosing and staging fibrosis in non-obese and obese patients with nonalcoholic fatty liver disease (NAFLD). METHODS: NAFLD patients diagnosed by liver biopsy according to the Nonalcoholic Steatohepatitis Clinical Research Network scoring system were enrolled in this study. Non-obesity was defined as a body mass index (BMI) less than 25 kg/m2 . LSM was performed by experienced physicians within 2 weeks before or after liver biopsy. RESULTS: A total of 158 patients were included. Average BMI of the non-obese (n = 68) and obese (n = 90) groups was 23.2 ± 1.6 and 27.9 ± 2.5 kg/m2 , respectively. After adjusted for age, fibrosis stage, steatosis grade and type 2 diabetes mellitus, the obese group had a LSM of 3.522 kPa higher than the non-obese patients (P = 0.003). LSM values of the non-obese patients had a lower trend when stratified by fibrosis stage, especially in cirrhosis (F4; P = 0.021). Applying separate cut-off values for patients with NAFLD in individual fibrosis stage, 5.8 vs 7.5 kPa (≥ F1), 7.6 vs 8.5 kPa (≥ F2), 9.1 vs 11.2 kPa (≥ F3), and 12.5 vs 14.3 kPa (F4), improved their diagnostic odds ratios compared with overall cut-off values. In the non-obese NAFLD group, using a separate cut-off avoided underestimating 9.1% of patients with cirrhosis. CONCLUSIONS: Non-obese NAFLD group had lower LSM than the obese group. Different cut-off values should be used to measure liver fibrosis stage in non-obese and obese NAFLD patients.

Histologic pattern is better correlated with clinical outcomes than biochemical classification in patients with drug-induced liver injury.

Histologically, drug-induced liver injury could be classified into acute hepatitis, chronic hepatitis, acute cholestasis, chronic cholestasis, and cholestatic hepatitis. The correlation between these histologic patterns and long-term clinical outcomes has not been well established. Therefore, we conducted a retrospective cohort study to investigate the association of histologic patterns and long-term clinical outcomes defined as biochemical normalization, persistent abnormal liver biochemistry or death at designated time points. In this study, biochemical classification was determined by R-values; histologic injury pattern was determined by morphological features. Predictive ability of clinical outcomes by these two classifications was assessed using Receiver Operating Characteristic Curves. Logistic regression was performed to identify histologic factors associated with outcomes. Totally, 88 patients with drug-induced liver injury were included for final analysis. Biochemical and histologic classification were consistent in 50 (57%) cases. 53 (60%) cases showed biochemical normalization within 6 months, and a further 11 (13%), 16 (18%), and 6 (7%) cases within 1, 2, and 3 years, respectively. Compared with biochemical classification, histologic injury pattern had better predictive ability for abnormal biochemistry at 6 months (Areas under Receiver Operating Characteristic Curves 0.92 versus 0.60, P < 0.001) and 1 year (Areas under Receiver Operating Characteristic Curves 0.94 versus 0.69, P < 0.001). Interlobular bile duct loss in >25% portal areas was independently associated with abnormal biochemistry at 6 months, 1 year, and 2 years. In conclusion, histologic injury pattern is better correlated with clinical outcome at 6 months and 1 year than biochemical classification. Moderate bile duct loss is an important histologic feature associated with persistent biochemical abnormality at 6 months, 1 year, and 2 years.

Impact of reimbursement program on liver-related mortality in patients with chronic hepatitis B in Beijing, China.

OBJECTIVE: Since July 1, 2011 antiviral therapy for hepatitis B virus infection has been listed as a reimbursable expense for medical insurance in Beijing. This study aimed to assess the impact of this program on liver-related death for patients with chronic hepatitis B (CHB). METHODS: Profiles of patients with CHB discharged between January 2008 and December 2015 were retrieved from the Beijing hospital discharge database. Liver-related deaths in these patients occurring between January 2008 and December 2017 were retrieved by linking them to the death certification database. Liver-related mortality (number of deaths divided by the observed person-years) before and after this program was launched was calculated and compared. A Poisson regression was performed to assess the strength of association (risk ratio [RR]) between the reimbursement program and liver-related mortality. RESULTS: Information on 35 943 discharged patients (17 114 patients with non-cirrhotic and 18 829 with compensated cirrhotic CHB) was retrieved. Altogether 3 832 liver-related deaths during the 190 695 person-years were observed. After the reimbursement program was launched, liver-related mortality per 100 person-years dropped from 0.38% to 0.16% for patients with non-cirrhotic CHB, and from 4.03% to 3.39% for those with compensated cirrhosis. The program was associated with a lower risk of developing liver-related death for patients with non-cirrhotic CHB (RR 0.40, 95% confidence interval [CI] 0.30-0.52) and those with compensated cirrhosis (RR 0.84, 95% CI 0.78-0.89). CONCLUSION: Coverage of antiviral therapy by basic medical insurance reduced the risk of developing liver-related death for patients with non-cirrhotic and with compensated cirrhotic CHB.

[Clinical analysis of intrahepatic cholestasis of pregnancy].

OBJECTIVE: To generate a comprehensive clinical profile of intrahepatic cholestasis of pregnancy (ICP) by systematically reviewing ICP cases managed in our hospital. METHODS: The recorded clinical data, including diagnosis, complications, management, and maternal and infant outcomes, of nine ICP cases were collected retrospectively and reviewed systematically. RESULTS: Seven of the nine total ICP patients presented with pruritus. All nine of the ICP patients showed bile acid level beyond the normal range. ICP complications included gestational hypertension (n = 3), diabetes mellitus (DM, n = 1) and impaired glucose tolerance (IGT, n = 1), and pre-eclampsia (n = 1). The infant of one patient with severe ICP showed meconium-stained liquor. All nine of the ICP patients underwent surgical delivery, of which three were delivered preterm (between the 35th and 36th week of gestation). All mothers' total bile acids declined to normal levels after delivery, and all infants survived without complication. CONCLUSION: ICP does not increase the puerpera mortality rate and does not represent a poor prognosis for infants. Bile acid levels in the ICP patients, however, may be related to the extent of premature delivery time. While the standard drug treatment of ursodeoxycholic acid is suitable for most ICP cases, those with insufficient gestational age may benefit from adjuvant corticosteroid therapy to promote fetal lung maturation prior to preterm delivery. Severe ICP cases should be managed by inducing artificial labor or performing Caesarean section.

[A noninvasive diagnostic model of liver fibrosis using serum markers in primary biliary cirrhosis].

OBJECTIVE: To verify and assess diagnostic value of noninvasive diagnostic model of liver fibrosis in primary biliary cirrhosis (PBC) based on conventional laboratory markers. METHODS: Seventy-three patients with PBC diagnosed by liver biopsy between January 2003 and June 2011 in Beijing Friendship Hospital, Capital Medical University were recruited in this study. Correlation analysis and logistic regression analysis between the conventional laboratory markers and histology stages were assessed. A liver fibrosis diagnostic model was established based upon aforementioned biomarkers and verified by its sensitivity and specificity for predicting the liver fibrosis. RESULTS: The predictive model (H index) consisting of five conventional laboratory markers, i.e., platelet count, serum cholinesterase, albumin, HDL-C and prothrombin time activity, could predict advanced fibrosis (stages III-IV) with an AUC(ROC) of 0.861. The sensitivity of predicting the absence of advanced fibrosis using H index < -2.20 was 96.6% and the specificity of predicting the presence of advanced fibrosis using H index > 0.41 was 93.2%. CONCLUSION: The established noninvasive diagnostic model consisting of five laboratory markers could accurately distinguish pathological changes of early stage PBC (stages I-II) from advanced stage PBC (stages III-IV).

[The clinical profiles of primary biliary cirrhosis with a suboptimal biochemical response to ursodeoxycholic acid].

To observe the characteristics of primary biliary cirrhosis (PBC) with a suboptimal biochemical response to ursodeoxycholic acid. A total of 38 Chinse PBC patients (5 male patients, 33 female patients, average age 55 years old) with treatment of ursodeoxycholic acid in our hospital from January 1999 to January 2009 were erolled and studied retrospectively. 17 suboptimal biochemical responders mainly presented with liver diseases related symptoms including jaundice (41.1%), fatigue, anorexia (23.5%), edema and abdominal distension (11.7%). 21 good biochemical responders mainly presented with abnormal liver function tests without symptoms. The suboptimal biochemical responders had significantly higher baseline levels of total serum bilirubin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, immunoglobulin G and globulin as compared to the good biochemical responsers. There were no differences in gender, age and the dose of UDCA. PBC patients with liver diseases related symptoms, marked abnormal liver tests and characteristics of autoimmune hepatitis may have a suboptimal biochemical response to ursodeoxycholic acid treatment.

[The clinicopathological analysis of 88 patients with abnormal liver function test of unknown etiology].

OBJECTIVE: To evaluate the clinical and histological features of patients with abnormal liver tests of unknown etiology, and then to investigate the diagnosis and differential diagnosis. METHODS: Patients with abnormal liver function test hospitalized and had liver biopsies during 2008 - 2009 constituted this retrospective study cohort. After excluding those patients diagnosed with hepatotropic viral hepatitis, space occupying lesions of the liver, alcoholic liver disease and obstruction of bile duct caused by stone or malignancy and AMA/AMA-M(2) positive of primary biliary cirrhosis (PBC), the clinical and histological characteristics were evaluated. RESULTS: Out of the 180 patients who underwent liver biopsy, 88 patients were included in the present analysis. The final diagnosis involved 15 categories of diseases, with drug-induced liver injury (DILI) [34.09% (30/88)], autoimmune liver diseases [22.73% (20/88)], and nonalcoholic fatty liver disease (NAFLD) [12.50% (11/88)] being the most common causes, following by genetic and other rare diseases. CONCLUSION: DILI, autoimmune liver disease and NAFLD were the most common causes of abnormal liver tests in these non-viral liver diseases. Some rare diseases such as hereditary metabolic liver disease also represent a considerable proportion in patients with abnormal liver function test.

[Clinical and pathological features of 27 cases of primary sclerosing cholangitis].

OBJECTIVE: To elucidate clinical and pathological features of primary sclerosing cholangitis (PSC) in order to improve clinician's awareness of this rare disease. METHODS: We retrospectively analyzed clinical data and follow-up information of 27 PSC patients who were admitted to Beijing Friendship Hospital from January 1990 to November 2009. The patients were classified into classic PSC and small-duct PSC according to biochemistry and imaging results. After 3 to 6 months of therapy, those patients with serum ALT < or = 1.5, TBil < or = 2 and ALP < or = 2.5 ULN were determined as good responders. The treatment results between the two groups were compared. RESULTS: 9 out of 27 cases of PSC were small duct PSC and 18 cases were large bile duct or classic PSC. Male patients (7) were less than females (20) and the average age was 47.6 years. Main clinical symptoms included jaundice (85.2%), pruritis (48.1%),fatigue (68.4 %), abdominal pain (40.7%) and fever (14.8%), main physical sign included hepatomegaly (44.4%), splenomegaly (48.1 %) and ascites (14.8%). Laboratory features included elevated IgG (81.8%), positive ANA (69.6%) and pANCA (52.9%). 22% of these PSC patients had ulcerative colitis or Sjogren's syndrome. A small percentage of patients were responsive to standard therapy, of which small duct PSC had a better response than classic PSC (66.7 % vs 33.3%, P = 0.041). CONCLUSIONS: Ulcerative colitis (22.2%) is not as common as reported by western countries. Small duct PSC has a better treatment response. Searching of effective treatment regimen for large bile duct PSC is warranted in future studies.

Assessment of hepatic fibrosis by transient elastography in patients with chronic hepatitis B.

Hepatic ultrasonic transient elastography (FibroScan) is a new diagnostic method for the assessment of hepatic fibrosis. There are limited data available on its use as a follow-up tool for patients with chronic hepatitis B. In this study, 134 patients were enrolled. Hepatic fibrosis was evaluated by liver stiffness measurement and biopsy. The biopsy criteria of the Chinese Program of Prevention and Cure for Viral Hepatitis, Metavir classification, and the modified Chevalier's semiquantitative system were used for histological assessment. The liver stiffness value was correlated with fibrosis stage (r = 0.565, P < 0.001) and fibrosis semiquantitative score (r = 0.727, P < 0.001). The liver stiffness value of G2 was significantly higher than that of G1 within the same fibrosis stage for S1, S3, and S4, respectively. Three patients were graded as G1S1, and had moderate steatosis without distinct fibrosis in the portal area and lobule, while their liver stiffness values were higher than 6.2 kPa. Although belonging to the same fibrosis stage, for thinner thicknesses of the fibrous septa, the liver stiffness value and semiquantitative score were correspondingly lower. Liver stiffness values had a good correlation with hepatic collagen content. However, inflammatory activity and steatosis can influence liver stiffness values to some extent. Transient elastography may be useful as an ideal non-invasive post-treatment follow-up tool.

[An analysis of clinical features in HBeAg-negative and HBeAg-positive chronic hepatitis B].

OBJECTIVES: To analyze the frequency and the clinical and virological features of HBeAg-negative and HBeAg-positive chronic hepatitis B. METHODS: Four hundred and seventeen chronic hepatitis B patients, 286 males and 131 females seen in our center were studied. Liver biopsies were taken from 83 patients. RESULTS: The cases with HBeAg-negative chronic hepatitis B were 241 (57.8%), with an average age of 43.7+/-10.8 and a history of 16.8+/-8.5 years. HBeAg-positive chronic hepatitis B cases were 176 (42.2%), with an average age of 36.95+/-11 and a history of 12.3+/-8.0 years. HBeAg-negative patients were significantly older (P < 0.01) in age and had a longer disease history. ALT levels and the percentage of HBV DNA were higher than 10(5) copies/ml in HBeAg-negative patients and were significantly lower than those in the HBeAg-positive patients [(37.66+/-32.93) U/L vs. (82.09+/-107.57) U/L, 38.2% vs. 94.3%, P < 0.01]. Liver biopsies from 47 HBeAg-negative patients showed that the number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 27, 14, 1 and the number of cases with fibrosis scores of S1, S2, S3 and S4 were 10, 12, 5, 20, respectively. In the 36 HBeAg-negative patients the respective number of cases with inflammation scores of G1, G2, G3 and G4 were 5, 14, 15, 2, and with fibrosis scores of S1, S2, S3, S4 were 8, 12, 6, 10. Although histopathological inflammation and fibrosis scores had no statistical difference between HBeAg-negative and positive patients (P > 0.05), 53.2% patients of HBeAg-negative group and 44.5% patients of HBeAg-positive group had a fibrosis score of >or= S3. CONCLUSION: Despite lower serum ALT and HBV DNA, HBeAg-negative chronic hepatitis B still has a significant disease progression. This observation may help to develop better clinical management in HBeAg-negative chronic hepatitis B patients.

[An ultrasonic scoring system for assessing the severity of hepatic fibrosis in patients with chronic hepatitis B].

OBJECTIVE: To discuss the diagnostic value of an ultrasonic assessing system for detecting the severity of hepatic fibrosis in patients with chronic hepatitis B (CHB). METHODS: Ultrasonographic variables were analyzed in 110 CHB patients. An ultrasonic semi-quantitative scoring system using seven ultrasonic morphologic parameters, a Fisher discriminating function and three quantitative ultrasonic parameters was developed. The performance of these methods was also studied and compared. RESULTS: The areas under the curve of the scoring system for different liver fibrosis stages were >or= S2: 0.946, >or= S3: 0.914, and S4: 0.915. The total score was well correlated with the histological stage of fibrosis (r=0.824, P < 0.001). There was a significant difference between the stages of fibrosis. The accuracy of the Fisher discriminating function for identifying three study endpoints was 76.5%, 78.2% and 67.3%. Combining the ultrasonic scoring system and the discriminating function, the specificity was 85%-90% and the accuracy was 77%-84%. CONCLUSION: Our ultrasonic semi-quantitative scoring system is a noninvasive method for quantitating liver fibrosis. If it is used together with a discriminating function, the accuracy of diagnosing liver fibrosis can be significantly increased.

[Malignant tendency of basophilic liver cells in experimental rat hepatocarcinogenesis].

OBJECTIVE: To investigate the malignant tendency of liver basophilic cells in rats by examining the liver dynamic pathological changes during the hepatocarcinogenesis induced by diethylnitrosamine (DEN). METHODS: One hundred forty male Sprague-Dawley rats, about 200 g each, were randomly divided into a normal group and a model group. The model group rats were administered 1% DEN intragastrically once a week for 14 weeks. The normal control group rats were given saline instead of DEN. Seven to ten rats of the model group were sacrificed at 2, 3, 5, 8, 10, 12, 14, 18 weeks. The remaining rats were followed to the end of the experiment at 26 weeks. Histopathological changes of the livers were analyzed, and the localization of GST-P and PCNA in the livers were detected in situ by immunohistochemistry. RESULTS: According to the characteristics of the lesions in the model group, histological liver change patterns were categorized into three phases: (1) liver injury phase (2 to 5 weeks) with centrilobular necrosis, a small amount of collagen deposition in the necrotic regions with fibrous septa development and cell proliferation; (2) the cirrhosis phase (8 to 12 weeks) with significant hepatocellular regeneration and collagen deposition. As the regenerative nodules and fibrous septa formed, cirrhosis with uniform sized nodules developed in all the rats at 12 weeks. In the regenerative nodules, significant hepatocellular metamorphosis was seen; (3) In the carcinomatous transformation and nodular remodeling phase (after 14 weeks), two types of cancer, namely hepatocellular carcinoma and cholangiocarcinoma were found. Incidence of the cancer was 62.5% at 18 weeks. Basophilic cell lesions appeared beginning at 10 weeks. Pale bodies were seen in some basophilic cells. Small cell changes appeared starting at 12 weeks. Some of these cells containing droplets like lipid vacuoles, invaded into the surrounding liver tissues. Both basophilic cell lesions and small cell changes were all positive for proliferating cell nuclear antigen (PCNA). CONCLUSION: Development of foci of basophilic small cells, with cells containing lipid vacuoles and pale bodies, and invading into the surrounding liver tissues are the changes highly suggestive of an early hepatocellular carcinoma transformation.

[Noninvasive assessment of liver fibrosis in chronic hepatitis B using a predictive model].

OBJECTIVE: To develop a diagnostic model comprising clinical and serum markers for assessing HBV-related liver fibrosis. METHODS: 270 chronic hepatitis B patients were randomly allocated to either an estimation group (195 cases) or a validation group (75 cases). Liver biopsies were done and staging of fibrosis was assessed. Twenty-six common clinical and serum markers were analyzed initially in the estimation group to derive a predictive model to discriminate the stages of fibrosis. The model created was then assessed with ROC analysis. It was also applied to the validation group to test its accuracy. RESULTS: Among 13 variables associated with liver fibrosis selected by univariate analysis, age, gamma glutamyltranspeptidase (GGT), hyaluronic acid (HA), and platelet count (PLT) were identified by multivariate logistic regression analysis as independent factors of fibrosis. A fibrosis index constructed from the above four markers was established. In ROC analysis, the AUC was 0.889 for the estimation group and 0.850 for the validation group for discriminating > or =S3 from < or=S2. Using the optimal cutoff score 3.0, the sensitivity of the index was 90.2%, the specificity 76.1%, and the accuracy was 82%. There was a positive linear relationship between the index scores and the fibrosis stages (r = 0.731, P<0.001). The AUC for identifying > or=S2 was 0.873 with sensitivity/specificity of 79%/82%, cutoff score 2.2; The AUC for identifying S4 was 0.872 with sensitivity/specificity of 83%/75%, cutoff score 5.4. There were no significant differences in diagnostic efficacy in the model between the estimation and the validation group (P>0.05). CONCLUSION: A model for assessment of liver fibrosis was established with easily accessible markers. It appears to be sensitive, accurate and reproducible, suggesting it could be used to assist or replace liver biopsy to detect dynamic changes of HBV-related liver fibrosis.