Ji-Yao Wang

Prediction of significant fibrosis in HBeAg‐positive patients with chronic hepatitis B by a noninvasive model

A model was constructed consisting of clinical and serum variables to discriminate between hepatitis B e antigen (HBeAg)‐positive chronic hepatitis B (CHB) patients with and without significant fibrosis (stages 2‐4 vs. stages 0‐1). Consecutive treatment‐naive CHB patients who underwent liver biopsy were divided into 2 sequential groups: a training group (n = 200) and a validation group (n = 172). Multivariate analysis identified α2‐macroglobulin, age, gamma glutamyl transpeptidase, and hyaluronic acid as independent predictors of fibrosis. The area under the receiver operating characteristic curve was 0.84 for the training group and 0.77 for the validation group. Using a cutoff score of <3.0, the presence of significant fibrosis (F2 to F4) could be excluded with high accuracy (86.1% negative predictive value [NPV], 70.1% positive predictive value [PPV], and 94.8% sensitivity) in 43 (21.5%) of 200 patients in the training group, and with the same certainty (90.9% NPV, 64.7% PPV, and 98.0% sensitivity) in 22 (12.8%) of 172 patients in the validation group. Similarly, applying a cutoff score of >8.7, the presence of significant fibrosis could be correctly identified with high accuracy (91.1% PPV, 51.6% NPV, and 95.2% specificity) in 41 (20.5%) of 200 patients in the training group, and with the same certainty (84.8% PPV, 52.4% NPV, and 90.4% specificity) in 39 (22.7%) of 172 patients of the validation group. In conclusion, a predictive model with a combination of easily accessible variables identified HBeAg‐positive CHB patients with and without significant fibrosis with a high degree of accuracy. Application of this model may decrease the need for liver biopsy in staging of 35.5% CHB. (HEPATOLOGY 2005;42:1437–1445.)

Submassive hepatic necrosis distinguishes HBV-associated acute on chronic liver failure from cirrhotic patients with acute decompensation.

BACKGROUND & AIMSnDistinguishing between acute on chronic liver failure (ACLF) and decompensated liver cirrhosis is difficult due to a lack of pathological evidence.nnnMETHODSnA prospective single-center study investigated 174 patients undergoing liver transplantation due to acute decompensation of hepatitis B virus (HBV)-associated liver cirrhosis. Two groups were distinguished by the presence or absence of submassive hepatic necrosis (SMHN, defined as necrosis of 15-90% of the entire liver on explant). Core clinical features of ACLF were compared between these groups. Disease severity scoring systems were applied to describe liver function and organ failure. Serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes were used to study systemic and local inflammatory responses.nnnRESULTSnSMHN was identified in 69 of 174 patients proven to have cirrhosis by histological means. Characteristic features of SMHN were extensive necrosis along terminal hepatic veins and spanning multiple adjacent cirrhotic nodules accompanied by various degrees of liver progenitor cell-derived regeneration, cholestasis, and ductular bilirubinostasis. Patients with SMHN presented with more severely impaired hepatic function, a higher prevalence of multiple organ failure (as indicated by higher CLIF-SOFA and SOFA scores) and a shorter interval between acute decompensation and liver transplantation than those without SMHN (p<0.01 for all parameters). Further analyzes based on serum cytokine profile assays, gene expression microarrays and immunohistochemical analyzes revealed higher levels of anti-inflammatory cytokines in patients with SMHN.nnnCONCLUSIONSnSMHN is a critical histological feature of HBV-associated ACLF. Identification of a characteristic pathological feature strongly supports that ACLF is a separate entity in end-stage liver disease.

CSH guidelines for the diagnosis and treatment of drug-induced liver injury

Drug-induced liver injury (DILI) is an important clinical problem, which has received more attention in recent decades. It can be induced by small chemical molecules, biological agents, traditional Chinese medicines (TCM), natural medicines (NM), health products (HP), and dietary supplements (DS). Idiosyncratic DILI is far more common than intrinsic DILI clinically and can be classified into hepatocellular injury, cholestatic injury, hepatocellular-cholestatic mixed injury, and vascular injury based on the types of injured target cells. The CSH guidelines summarized the epidemiology, pathogenesis, pathology, and clinical manifestation and gives 16 evidence-based recommendations on diagnosis, differential diagnosis, treatment, and prevention of DILI.

A multicenter, randomized, double-blind trial comparing the efficacy and safety of TUDCA and UDCA in Chinese patients with primary biliary cholangitis.

Aim:Tauroursodeoxycholic acid (TUDCA) is a taurine conjugated form of ursodeoxycholic acid (UDCA) with higher hydrophility. To further evaluate the efficacy and safety of TUDCA for primary biliary cholangitis (PBC), we performed this study on Chinese patients. Methods:199 PBC patients were randomly assigned to either 250u200amg TUDCA plus UDCA placebo or 250u200amg UDCA plus TUDCA placebo, 3 times per day for 24 weeks. The primary endpoint was defined as percentage of patients achieving serum alkaline phosphatase (ALP) reduction of more than 25% from baseline. Results:At week 24, 75.97% of patients in the TUDCA group and 80.88% of patients in the UDCA group achieved a serum ALP reduction of more than 25% from baseline (Pu200a=u200a0.453). The percentage of patients with serum ALP levels declined more than 40% following 24 weeks of treatment was 55.81% in the TUDCA group and 52.94% in the UDCA group (Pu200a=u200a0.699). Both groups showed similar improvement in serum levels of ALP, aspartate aminotransferase, and total bilirubin (Pu200a>u200a0.05). The proportion of patients with pruritus/scratch increased from 1.43% to 10.00% in UDCA group, while theres no change in TUDCA group (Pu200a=u200a0.023). Both drugs were well tolerated, with comparable adverse event rates between the 2 groups. Conclusions:TUDCA is safe and as efficacious as UDCA for the treatment of PBC, and may be better to relieve symptoms than UDCA.