Hepatic Fibrosis Scores Research Articles

Magnetic Resonance Elastography: A Novel Technique for the Detection of Hepatic Fibrosis and Hepatocellular Carcinoma After the Fontan Operation

ObjectiveTo evaluate the utility of magnetic resonance elastography (MRE) in screening patients for hepatic fibrosis, cirrhosis, and hepatocellular carcinoma after the Fontan operation. Patients and MethodsHepatic MRE was performed in conjunction with cardiac magnetic resonance imaging in patients who had undergone a Fontan operation between 2010 and 2014. Liver stiffness was calculated using previously reported techniques. Comparisons to available clinical, laboratory, imaging, and histopathologic data were made. ResultsOverall, 50 patients at a median age of 25 years (range, 21-33 years) who had undergone a Fontan operation were evaluated. The median interval between Fontan operation and MRE was 22 years (range, 16-26 years). The mean liver stiffness values were increased: 5.5±1.4 kPa relative to normal participants. Liver stiffness directly correlated with liver biopsy-derived total fibrosis score, time since operation, mean Fontan pressure, γ-glutamyltransferase level, Model for End-Stage Liver Disease score, creatinine level, and pulmonary vascular resistance index. Liver stiffness was inversely correlated with cardiac index. All 3 participants with hepatic nodules exhibiting decreased contrast uptake on delayed postcontrast imaging and increased nodule stiffness had biopsy-proven hepatocellular carcinoma. ConclusionThe association between hepatic stiffness and fibrosis scores, Model for End-Stage Liver Disease scores, and γ-glutamyltransferase level suggests that MRE may be useful in detecting (and possibly quantifying) hepatic cirrhosis in patients after the Fontan operation. The correlation between stiffness and post-Fontan time interval, mean Fontan pressure, pulmonary vascular resistance index, and reduced cardiac index suggests a role for long-term hepatic congestion in creating these hepatic abnormalities. Magnetic resonance elastography was useful in detecting abnormal nodules ultimately diagnosed as hepatocellular carcinoma. The relationship between stiffness with advanced fibrosis and hepatocellular carcinoma provides a strong argument for additional study and broader application of MRE in these patients.

Association of Myxovirus Resistance Gene Promoter Polymorphism with Response to Combined Interferon Treatment and Progression of Liver Disease in Chronic HCV Egyptian Patients.

To evaluate the frequency of single-nucleotide polymorphism at the -88 myxovirus resistance (MxA) gene promoter region in relation to the status of hepatitis C virus (HCV) progression and response to combined interferon (IFN) in chronic HCV Egyptian patients. One hundred ten subjects were enrolled in the study; 60 HCV genotype 4-infected patients who underwent combined IFN therapy and 50 healthy individuals. All subjects were genotyped for -88 MxA polymorphism by the restriction fragment length polymorphism technique. There was an increasing trend of response to combined IFN treatment as 34.9% of GG, 64.3% of GT, and 66.7% of TT genotypes were sustained responders (P=0.05). The T allele was significantly affecting the response rate more than G allele (P=0.032). Moreover, the hepatic fibrosis score and hepatitis activity were higher in GG genotypes compared with the GT and TT genotypes. The multivariate analysis showed that the MxA GG genotype was an independent factor increasing the no response to IFN therapy (P=0.04, odds ratio [OR] 3.822, 95% confidence interval [CI] 1.056-11.092), also MxA G allele (P=0.0372, OR 2.905, 95% CI 1.066-7.919). MxA -88 polymorphism might be a potential biomarker to predict response to IFN and disease progression in chronic HCV-infected patients.

Serum Soluble CD14 in Egyptian Patients with Chronic Hepatitis C: Its Relationship to Disease Progression and Response to Treatment.

Hepatitis C virus (HCV) is a major public health problem. Soluble CD14 (sCD14) level was shown to be associated with HCV infection. In this study, we aimed to investigate the relationship between sCD14 concentration and disease progression, as well as the response to pegylated interferon/ribavirin (peg-IFN/RBV) therapy in Egyptian patients with chronic hepatitis C (CHC). The ELISA technique was used to test 80 patients with CHC and 20 healthy control persons for serum levels of sCD14 (pretreatment and after 12 weeks of treatment). CHC patients were 65 males and 15 females. Normal healthy controls included 20 age- and sex-matched volunteers. The mean age of the CHC patients was 39.94 years, while that of the controls was 39.2 years The serum sCD14 level was significantly higher in chronic HCV-infected patients (3.6±0.18 μg/mL) compared to healthy control subjects (3.1±0.18 μg/mL). The serum sCD14 level was significantly directly correlated with the hepatic fibrosis score (r=0.24, P=0.03), histological activity index (r=0.26, P=0.02), and serum aminotransferases [r=0.28, P=0.005 for alanine aminotransferase (ALT) and r=0.30, P=0.003 for aspartate aminotransferase (AST)]. The pretreatment sCD14 level was not significantly correlated to the treatment response, but it increased after 12 weeks of peg-IFN/RBV therapy and values were significantly higher in nonresponders (P=0.02). The pretreatment sCD14 level cannot predict the treatment response in chronic HCV patients receiving peg-IFN/RBV therapy. However, the serum sCD14 level after 12 weeks of treatment can serve as a negative predictor of treatment response.

Vitamin D Status and Bone Mineral Density in Obese Children with Nonalcoholic Fatty Liver Disease

Whether nonalcoholic fatty liver disease (NAFLD) is related to vitamin D and bone health in obese children is unknown. The aim of this study was to evaluate vitamin D status and bone mineral density (BMD) in obese children according to their condition within the NAFLD spectrum. Anthropometric data, laboratory tests, and abdominal ultrasonography were obtained from 94 obese children. The subjects were divided into three groups according to NAFLD spectrum: normal liver, simple steatosis, and nonalcoholic steatohepatitis (NASH). Although there were no differences in vitamin D levels between the three groups, these groups showed significant differences in highly sensitive C-reactive protein (P=0.044), homeostasis model assessment of insulin resistance (HOMA-IR) (P=0.02), hepatic fibrosis scores (P<0.05), and trunk fat percentage (P=0.025). Although there were significant differences in BMDs, the age-matched BMD z-scores were not significantly different between the three groups. Serum vitamin D levels were negatively correlated with age (r=-0.368, P=0.023), serum uric acid levels (r=-0.371, P=0.022), fibrosis 4 (FIB4) (r=-0.406, P=0.011), and HOMA-IR (r=-0.530, P=0.001) in obese children with NASH. Multiple regression analysis for vitamin D in the NASH group revealed age and HOMA-IR as significant factors. In conclusion, inflammatory markers, hepatic fibrosis scores, trunk fat, and insulin resistance may reflect the spectrum of NAFLD in obese children, whereas vitamin D levels and BMD may not. In patients with NASH, however, low serum vitamin D is associated with hepatic fibrosis and insulin resistance, but not with bone health status.

Protective effect of thymoquinone on cholestatic rats with liver injury.

The aim of this study was to investigate the protective effects of thymoquinone treatment on cholestatic rats with liver injury. Thirty-two Sprague-Dawley rats were divided randomly into four groups: normal control, bile duct ligation model control, low-dose thymoquinone (25 mg/kg), and high-dose thymoquinone (50 mg/kg). Thymoquinone gavage was administered continuously 3 days before bile duct ligation, and saline, at the same volume, was administered to the control group. The rats were sacrificed after 2 weeks of treatment, and the liver tissues were obtained and frozen. The contents of hydroxyproline (HP), malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the homogenate of the liver tissues were determined to evaluate the changes in hepatic tissue pathology by fibrosis scoring. The HP and MDA levels were significantly lower and the SOD and GPx levels were significantly higher in the thymoquinone-treatment group than the corresponding levels in the model control group, and the differences were statistically significant (P < 0.05) and dose-dependent. The hepatic necrosis areas and hepatic fibrosis scores of the thymoquinone-treatment groups were significantly lower than those of the model group (P < 0.05). Thymoquinone increased the antioxidative capacity of liver and reduced the oxidative stress damage to the liver. Thymoquinone can be used as a liver protectant in patients with cholestasis.

Congestive hepatic fibrosis score: a novel histologic assessment of clinical severity

Chronic right heart failure predisposes to hepatic passive congestion and centrizonal necrosis that may lead to hepatic fibrosis (cardiac sclerosis). Although there have been several studies on the histologic features of congestive hepatopathy, there is no available grading system. In this study we developed a novel grading system for congestive hepatic fibrosis. Liver biopsies were examined in patients with chronic heart failure of various etiologies including congenital heart disease, idiopathic cardiomyopathy, ischemic heart disease, and valvular heart disease. The cases with available echocardiography and/or right heart catheterization were included. Cases with other types of underlying chronic liver diseases, alcoholic liver disease, significant steatosis (>20%), malignant neoplasm, and acute heart failure or shock were excluded. After exclusion, 42 cases were included in the study. We herein proposed a novel congestive hepatic fibrosis score and correlated it with the right heart structure and function obtained by echocardiography and/or right heart catheterization. Our results showed that congestive hepatic fibrosis score is well correlated with the right atrial pressure (P for trend <0.001). The presence of portal fibrosis (congestive hepatic fibrosis scores 2 and 3) is associated with significantly higher right atrial pressure than those with no fibrosis (P<0.001) or with centrizonal fibrosis only (P=0.02). Congestive hepatic fibrosis score is also significantly associated with increasing severity of right atrial dilatation (P=0.03) and right ventricular dilatation (P=0.02), indicators for chronic volume and/or pressure overload. Other histopathologic features include sinusoidal dilatation and centrizonal hepatocyte atrophy. In summary, although sinusoidal dilatation and centrizonal fibrosis are the hallmarks of hepatic passive congestion, the presence of portal fibrosis is suggestive of more advanced disease, as it correlates with more severe impairment of right heart function, regardless of the etiologies of right heart failure. Congestive hepatic fibrosis score is a useful indicator of clinical severity.

Fontan hepatic fibrosis and pulmonary vascular development.

Fontan patients are at risk for hepatic fibrosis; however, risk factors are unclear. We performed a multivariate analysis in a small cohort of 14 patients (7-24years old, mean 15) with Fontan circulation,undergoing cardiac catheterization and transvenous liver biopsies, all demonstrating fibrosis. Wefound by stepwise regression analysis that the history of pulmonary atresia was a predictor of higher total hepatic fibrosis scores than a history of unobstructed pulmonary blood flow (p=0.002). Other variables including age, time from Fontan, hemodynamic measurements, and laboratory values were not predictiveoftotal fibrosis scores at p values <0.05. Hepatic fibrosis scores between those born with pulmonary atresia versus unrestricted pulmonary blood flow may reflect differences in pulmonary circulatory physiology, resulting from differences in pulmonary vascular development.

The development of the pediatric NAFLD fibrosis score (PNFS) to predict the presence of advanced fibrosis in children with nonalcoholic fatty liver disease.

BackgroundNoninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis.MethodsConsecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0–4). Advanced fibrosis was defined as fibrosis stage ≥3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis.ResultsOur cohort consisted of 242 children with a mean age of 12.4±3.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0–2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z = 1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) – (1.1*log(platelets) – (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p = 100×exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index.ConclusionNoninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.

A switch to Raltegravir improves antiretroviral associated hepatotoxicity in individuals co-infected with HIV and hepatitis C

Raltegravir is a switch option for HIV/HCV co-infected individuals due to its hepatic neutral profile. We evaluated the effect of a switch to Raltegravir from other antiretroviral agents in HIV and HCV-co-infected individuals naïve to HCV therapy. Observational, single-centre study. Data on alanine aminotransferase levels, HCV-VL, CD4 cell count, HIV viral load levels and hepatic fibrosis score were collated six months pre-switch, at the time of switch and six months post switch to Raltegravir therapy. Results were compared utilizing the Kruskal-Wallis test. Twenty-seven individuals were identified. Median age was 43 years, median duration of HIV infection was 7 years and median documented period of HCV infection at the time of switch was 26 months. A sustained improvement in ALT levels was observed. Median ALT levels were 254 IU/L at the time of switch, decreasing significantly to 176 IU/L, (p = 0.0226) and 90 IU/L (p = 0.0138) 1 month post switch and 6 months post switch respectively. The median Hepatitis C viral load level at the time of the switch was 341,783 copies/mL, which decreased to 224,066 copies/mL 6 months after switch (p = 0.04). A switch to Raltegravir in individuals with HIV/HCV co-infection was effective in maintaining HIV virological suppression with improvement in drug-associated hepatotoxicity as measured by ALT.

40 The Development of the Pediatric NAFLD Fibrosis Score (PNFS) to Predict the Presence of Advanced Fibrosis in Children With Nonalcoholic Fatty Liver Disease

Background: Noninvasive hepatic fibrosis scores that predict the presence of advanced fibrosis have been developed and validated in adult patients with NAFLD. The aims of our study were to assess the utility of commonly used adult fibrosis scores in pediatric NAFLD and to develop a pediatric specific fibrosis score that can predict advanced fibrosis. Methods: Consecutive children with biopsy-proven NAFLD were included. Fibrosis was determined by an experienced pathologist (F0–4). Advanced fibrosis was defined as fibrosis stage $3. The following adult fibrosis scores were calculated for each child: AST/ALT ratio, AST/platelet ratio index (APRI), NAFLD fibrosis score (NFS), and FIB-4 Index. Multivariable logistic regression analysis was performed to build a new pediatric model for predicting advanced fibrosis. Results: Our cohort consisted of 242 children with a mean age of 12.463.1 years and 63% were female. 36 (15%) subjects had advanced fibrosis. APRI and FIB-4 were higher in patients with advanced fibrosis compared to those with fibrosis stage 0–2; however, AST/ALT ratio and NFS were not different between the two groups. We used our data to develop a new model to predict advanced fibrosis which included: ALT, alkaline phosphatase, platelet counts and GGT. The multivariable logistic regression model (z) was defined as follows: z=1.1+(0.34*sqrt(ALT))+(0.002*alkaline phosphatase) – (1.1*log(platelets) – (0.02*GGT). This value was then converted into a probability distribution (p) with a value between 0 to 100 by the following formula: p=1006exp(z)/[1+exp(z)]. The AUCROC for this model was 0.74 (95% CI: 0.66, 0.82). This was found to be significantly better than APRI, NAFLD Fibrosis Score and FIB-4 Index. Conclusion: Noninvasive hepatic fibrosis scores developed in adults had poor performance in diagnosing advanced fibrosis in children with NAFLD. We developed a new pediatric NAFLD fibrosis score with improved performance characteristics.

Tryptase inhibitor APC 366 prevents hepatic fibrosis by inhibiting collagen synthesis induced by tryptase/protease-activated receptor 2 interactions in hepatic stellate cells.

Protease-activated receptor (PAR) 2 is a G-protein-coupled receptor that is activated by mast cell tryptase. PAR-2 activation augments profibrotic pathways through the induction of extracellular matrix proteins. PAR-2 is widely expressed in hepatic stellate cells (HSCs), but the role of tryptase/PAR-2 interaction in liver fibrosis is unclear. We studied the development of bile duct ligation (BDL)-induced hepatic fibrosis in rats treated with mast cell tryptase inhibitor APC 366, and showed that APC 366 reduced hepatic fibrosis scores, collagen content and serum biochemical parameters. Reduced fibrosis was associated with decreased expression of PAR-2 and α-smooth muscle actin (α-SMA). Our findings demonstrate that mast cell tryptase induces PAR-2 activation to augment HSC proliferation and promote hepatic fibrosis in rats. Treatment with tryptase antagonists may be a novel therapeutic approach to prevent fibrosis in patients with chronic liver disease.

The Evaluation of Hepatic Fibrosis Scores in Children with Nonalcoholic Fatty Liver Disease

The Evaluation of Hepatic Fibrosis Scores in Children with Nonalcoholic Fatty Liver Disease

Liver function test abnormalities in Nigerian patients with human immunodeficiency virus and hepatitis B virus co-infection

Data on baseline hepatic function of HIV and hepatitis B virus (HBV) co-infected patients are limited in sub-Saharan Africa. We assessed liver function test (LFT) abnormalities in Nigerian patients with HIV/HBV co-infection to highlight the impact of HIV on HBV-related liver disease in sub-Saharan Africa. A cross-sectional study involving 100 HIV/HBV co-infected patients and 100 age- and sex-matched HBV mono-infected controls. Blood testing for HIV antibodies, CD4+ cell count, hepatitis B surface antigen (HBsAg), hepatitis B e antigen (HBeAg), LFTs, platelet count, fasting blood glucose and lipid profile were carried out. Non-invasive hepatic fibrosis scores (aspartate aminotransferase-platelet ratio index [APRI] and FIB-4) were also calculated. Co-infected patients had deranged liver enzymes more than the controls (77% versus 64%, P = 0.04). The predominant patterns of enzyme derangement in co-infected patients were either predominantly ↑ALP (30% versus 4%, P < 0.0001) or mixed (30% versus 15%, P = 0.01) but predominantly ↑AST/ALT in the controls (25% versus 9%, P = 0.003). Co-infected patients had higher fibrosis scores for both APRI (P = 0.002) and FIB-4 (P = 0.0001). On further analysis, LFT abnormalities and fibrosis scores were only significantly higher in co-infected patients in the immune clearance and HBeAg-negative chronic hepatitis phases. LFT abnormalities are common in Nigerians with HBV infection and co-infection with HIV negatively impacts on hepatic function.

Sa1025 Hepcidin and Chronic Hepatitis C Virus: Exploring the Controversy

Background and aim of the work: There are currently about 170 million hepatitis C virus (HCV) infected persons worldwide .Hepcidin has a central role in iron homoeostasis, as it decreases iron release from macrophages and iron absorption from intestinal enterocytes, its correlation to chronic hepatitis C (CHC), hepatic iron load, and fibrosis is controversial between different studies. Thus, we aim to asses plasma hepcidin levels in CHC patients and to investigate the association of this molecule with iron parameters, hepatic inflammatory and fibrotic scores. Patients and methods: 38 CHC patients mean age 42.0 ±7.4 years 34 males and 4 females (group1) and 38 age and sex matched healthy controls (group 2) were included in the study. Both groups were subjected to blood tests for serum ferritin, serum iron, serum hepcidin, complete blood picture (CBC). Group 1 patients were subjected to ultrasound guided liver biopsy for assessment of hepatic activity and fibrosis scores according to METAVIR as well as hepatic iron stores. Results: Mean serum hepcidin and ferritin levels were significantly higher among cases with HCV compared to controls (77.4±48.5ng/ml vs43.9±22.9 ng/ml p=0.000 and 165.9±120.9ng/ml vs and 98.5±77.6 ng/ml p=0.005, respectively).There is a significant positive correlation between serum hepcidin level and serum ferritin level(r=0.563), Metavir fibrosis score (r=0.666) Metavir activity scores(r= 0.36,) and hepatic iron stores(r=0.378). Serum Hepcidin was significantly higher among CHC patients with fibrosis stage (F3-F4) than those with fibrosis stage (F0-F2) (117.4±51.4 ng/ml vs 51.3 ± 21.9ng/ml respectively p=0.000 ), also it was significantly higher among CHC patients with activity scores(A2-A3) than among those with activity score(A0-A1) (200.6±117.2 vs 153.6± 121.9 respectivelyp=0.03).Serum Hepcidin could predict stage 3 fibrosis at a cut off level of 73.8 with a sensitivity of 80% and specificity of 83%. Conclusion: Serum Hepcidin is significantly higher among CHC patients than normal controls and is positively correlated to stage of hepatic fibrosis , grade of hepatic inflammation and serum ferritin

Noninvasive diagnosis of pediatric nonalcoholic fatty liver disease

Because nonalcoholic steatohepatitis can progress towards cirrhosis even in children, early detection of hepatic fibrosis and accurate diagnosis of nonalcoholic fatty liver disease (NAFLD) are important. Although liver biopsy is regarded as the gold standard of diagnosis, its clinical application is somewhat limited in children due to its invasiveness. Noninvasive diagnostic methods, including imaging studies, biomarkers of inflammation, oxidative stress, hepatic apoptosis, hepatic fibrosis, and noninvasive hepatic fibrosis scores have recently been developed for diagnosing the spectrum of NAFLD, particularly the severity of hepatic fibrosis. Although data and validation are still lacking for these noninvasive modalities in the pediatric population, these methods may be applicable for pediatric NAFLD. Therefore, noninvasive imaging studies, biomarkers, and hepatic fibrosis scoring systems may be useful in the detection of hepatic steatosis and the prediction of hepatic fibrosis, even in children with NAFLD.

A Prospective Evaluation of Transient Elastography in Non-Alcoholic Fatty Liver Disease - BMI and Subcutaneous Fat Thickness Do Not Affect Accuracy

Purpose: Transient elastography (TE) has emerged as an important non-invasive technique of evaluating hepatic fibrosis. However, recent data suggest that greater hepatic steatosis may downgrade TE values relative to the degree of hepatic fibrosis on biopsy in nonalcoholic fatty liver disease (NAFLD) patients. This prospective study evaluates the relationship between TE values and hepatic steatosis as measured on magnetic resonance imaging (MRI) of the liver. Other variables which may affect TE accuracy in NAFLD were also investigated, including higher patient body mass index (BMI) and greater subcutaneous fat overlying the liver. Methods: All adult patients at a tertiary care centre in London, Canada, who met diagnostic criteria for NAFLD were invited to participate in this study. All patients underwent liver biopsy, TE and had anthropomorphic measurements, liver transaminases and measures of metabolic dysfunction measured. Liver biopsies were read by a single, blinded pathologist and scored according to the validated nonalcoholic steatohepatitis activity score (NAS). The FibroScan 502 system (Echosens) was used to conduct TE measurements for all study patients. Subcutaneous fat and hepatic steatosis measured as hepatic fat fraction was measured using Magnetic Resonance Imaging with Iterative Decomposition of water and fat with Echo Asymmetry and Least-squares estimation (IDEAL-MRI), a computer-based quantification method separating fat and water signals in MRI images allowing accurate, validated and reproducible measurement of subcutaneous fat thickness. Linear regression analysis was used to evaluate the correlation between BMI and TE values; subcutaneous fat thickness and TE values; and degree of fibrosis on liver biopsy and TE values. Results: Linear regression demonstrated a positive correlation between TE values and the degree of fibrosis on liver biopsy (P<0.001). There was no correlation between subcutaneous fat thickness and TE values (P=0.699), between BMI and TE values (P=0.883), between subcutaneous fat thickness and liver fibrosis score (p=0.183), nor between BMI and liver fibrosis score (p=0.057). There was no correlation between hepatic fat fraction and TE values (p=0.152), nor hepatic fat fraction and liver fibrosis score (p=0.0118). Conclusion: This study demonstrates that TE correlates well with the degree of hepatic fibrosis on liver biopsy in NAFLD patients, and suggests that common anthropomorphic features of such patients such as increased hepatic steatosis, increased BMI, and peri-hepatic subcutaneous fat does not adversely affect the reliability of TE. This finding supports the continued use of this important diagnostic modality in a population that is becoming increasingly prevalent.

Clinical and pathological features in 138 cases of drug-induced liver injury

To explore the categories of drugs causing hepatotoxicity and analyze the clinical and histological features of the corresponding drug-induced liver injury (DILI), in order to gain insights into potential diagnostic factors for DILI. A total of 138 DILI patients treated at our hospital from April 2008 to April 2010 were retrospectively analyzed. The responsible drug for each DILI case was recorded. The Roussel Uclaf Causality Assessment Method (RUCAM) had been used to diagnose DILI. Only cases that had scored as highly probable or probable (more than or equal to 6 points by RUCAM) were included in this study. The patients' general condition, clinical manifestations, and serum biochemical and immunological parameters were assessed. Sixty-six of the patients underwent liver biopsy, and were assessed for liver pathological changes. Clinical and laboratory test data were collected and used to classify the total 138 cases as hepatocellular injury, cholestatic, or mixed hepatocellular-cholestatic types. Within our patient population, the leading cause of DILI was Chinese herb medicine, accounting for 53.62% of cases. Antibiotics were implicated in 7.97% of cases, and dietary supplement in 6.52% of cases. Correlation between the clinical features and histological injury pattern was stronger at the time of biopsy (more than or equal to 3 days after laboratory results) (kappa = 0.63, P less than 0.05) than at the onset of DILI (kappa = 0.25, P less than 0.05). All modified hepatic activity index (HAI) necroinflammatory scores and fibrosis scores were more severe in the cholestatic and mixed injury types than in the hepatocellular injury type (P less than 0.01 and P less than 0.05, respectively). Chinese herbal medicine, dietary supplements and antibiotics were the main causes of DILI in our patient population. The clinical and histological features correlated well, especially at later stages of DILI. The degree of inflammation and fibrosis was significantly higher in cholestatic and mixed hepatocellular-cholestatic injury types than in the hepatocellular injury type. Assessment of both clinical and pathological features may represent a more accurate diagnostic method for DILI.

Noninvasive Parameters and hepatic fibrosis scores in children with nonalcoholic fatty liver disease

To evaluate the noninvasive parameters and hepatic fibrosis scores in obese children with nonalcoholic fatty liver disease (NAFLD). A total of 77 children diagnosed with NAFLD via liver biopsy were included and divided into 2 subgroups according to the histopathologic staging of hepatic fibrosis: mild (stage 0-1) vs significant fibrosis (stage 2-4). Clinical and laboratory parameters were evaluated in each patient. The aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio, AST/platelet ratio index (APRI), PGA index, Forns index, FIB-4, NAFLD fibrosis score, and pediatric NAFLD fibrosis index (PNFI) were calculated. No clinical or biochemical parameter exhibited a significant difference between patients with mild and significant fibrosis. Among noninvasive hepatic fibrosis scores, only APRI and FIB4 revealed a significant difference between patients with mild and significant fibrosis (APRI: 0.67 ± 0.54 vs 0.78 ± 0.38, P = 0.032 and FIB4: 0.24 ± 0.12 vs 0.31 ± 0.21, P = 0.010). The area under the receiving operating characteristic curve of FIB4 was 0.81, followed by Forns index (0.73), APRI (0.70), NAFLD fibrosis score (0.58), AST/ALT ratio (0.53), PGA score (0.45), and PNFI (0.41). APRI and FIB4 might be useful noninvasive hepatic fibrosis scores for predicting hepatic fibrosis in children with NAFLD.

Rate of Progression of Hepatic Fibrosis in Patients With Chronic Hepatitis C: Results From the HALT-C Trial

The gradual accumulation of hepatic fibrosis in chronic liver disease results in clinical complications. The rate of hepatic fibrosis score progression (RFSP) in predicting clinical outcomes was assessed by extending the 4-year Hepatitis C Antiviral Long-term Treatment Against Cirrhosis (HALT-C) Trial to include preenrollment liver biopsies. The RFSP was calculated from the linear regression slope of Ishak fibrosis score vs time in 457 patients with liver biopsies (≥10-mm length) prior to the HALT-C Trial (575 biopsies) plus 1101 on-study biopsies (total 1676 biopsies). Individual slopes were calculated if duration from first to last biopsy was > 4 years. The RFSP as average fibrosis score vs average time in intervals (0-3 and >3 years prestudy, screening, month 24 and 48 on-study) in 455 patients in cohorts of baseline Ishak score ranged from 0.005 with Ishak score 2 to 0.124 with Ishak 6. The RFSP in individual patients (-0.35 to +0.97 Ishak units/year) had a mean of 0.12 ± 0.23 in 344 patients with prestudy and on-study biopsies (group A) and only 0.17 ± 0.22 in 169 with prestudy and screening biopsies (group B). Group A patients with RFSP slope ≥ 0.2 (95 patients, 27.6%) had higher 7-year cumulative rates of non-hepatocellular carcinoma outcomes (46% vs 8%, respectively) and with a hepatocellular carcinoma (10% vs 3%, respectively) than RFSP slope < 02 (249 patients, 72.4%) (P < .0001). RFSP and screening Ishak score correlated independently (P <.0001) with clinical outcomes in multivariate analysis. Rapid RFSP (>0.2), which occurred in 26.7% of HALT-C Trial patients, correlated strongly with clinical outcomes.

Antifibrotic Effects of Triptolide on Hepatic Stellate Cells and Dimethylnitrosamine‐intoxicated Rats

Triptolide (C₃₈H₄₂O₆N₂, TP, a diterpene triepoxide derived from Tripterygium wilfordii Hook F.), is a potent immunosuppresive and antiinflammatory agent. The present study investigated whether TP exerted antihepatofibrotic effects in vitro and in vivo. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) or transforming growth factor (TGF)-β1. The inhibitory effects of TP on the nuclear factor-κB (NFκB) signaling cascade and fibrosis markers, including α-smooth muscle actin (α-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats. The rats were randomly assigned to one of three groups: control rats, DMN rats receiving vehicle only and DMN rats receiving TP (20 μg/kg). Treatment was given by gavage twice daily for 3 weeks starting 1 week after the start of DMN administration. TP (5-100 nM) concentration-dependently inhibited the NFκB transcriptional activity induced by TNF-α, lipopolysaccharide and phorbol 12-myristate 13-acetate in HSC-T6 cells. In addition, TP also suppressed TNF-α and TGF-β1-induced collagen deposition and α-SMA secretion in HSC-T6 cells. In vivo, TP treatment significantly reduced hepatic fibrosis scores, collagen contents, IL-6 and TNF-α levels, and the number of α-SMA and NFκB-positive cells in DMN rats. The results showed that TP exerted antifibrotic effects in both HSC-T6 cells and DMN rats.