Journal of Clinical and Translational Hepatology最新文献

Background and aims: Direct evidence on the outcomes of hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB) patients with normal alanine transaminase after long-term antiviral treatment is lacking.

Methods: HBeAg-negative patients with normal ALT and positive HBV DNA (≥20 IU/mL) were retrospectively enrolled. The endpoints included virological response (HBV DNA<100 IU/mL), changes in aspartate aminotransferase to platelet ratio index (APRI) and fibrosis-4 index (FIB-4), and the incidence of liver nodules, cirrhosis, and hepatocellular carcinoma (HCC).

Results: This cohort (n=194) was divided into three subgroups, untreated (n=67), treatment-continued (n=87), and treatment-discontinued patients (n=40), with a median follow-up of 54 months. The treatment-continued group achieved 100% (95% CI: 94.7-100) virological response, and significantly reduced APRI and FIB-4 scores (both p<0.001). The risk of liver nodules and cirrhosis in that group was reduced by 76% (HR: 0.24, 95% CI: 0.11-0.54, p<0.001) and 89% (HR: 0.11, 95% CI: 0.14-0.91, p=0.041) vs. the untreated group and by 77% (HR: 0.23, 95% CI: 0.10-0.49, p<0.001) and 95% (HR: 0.05, 95% CI: 0.01-0.44, p=0.006) vs. the treatment-discontinued group. For patients with HBV DNA≥2,000 IU/mL, adherence to treatment lowered the risks of liver cirrhosis by 92% (95% CI: 0.01-0.67) and 93% (95% CI: 0.01-0.53) vs. the untreated and treatment-discontinued patients, respectively. No patient adhering to treatment developed HCC, but one in each of the remaining groups did.

Conclusions: Continuous nucleos(t)ide analog (NA) treatment has a satisfactory effectiveness and helps to lower the risk of liver cirrhosis in HBeAg-negative CHB patients with normal alanine transaminase, especially in those with HBV DNA≥2,000 IU/mL.

Intrahepatic cholangiocarcinoma (iCCA) can originate from the large bile duct group (segment bile ducts and area bile ducts), small bile duct group (septal bile ducts and interlobular bile ducts), and terminal bile duct group (bile ductules and canals of Hering) of the intrahepatic biliary tree, which can be histopathological corresponding to large duct type iCCA, small duct type iCCA and iCCA with ductal plate malformation pattern, and cholangiolocarcinoma, respectively. The challenge in pathological diagnosis of above subtypes of iCCA falls in the distinction of cellular morphologies, tissue structures, growth patterns, invasive behaviors, immunophenotypes, molecular mutations, and surgical prognoses. For these reasons, this expert consensus provides nine recommendations as a reference for standardizing and refining the diagnosis of pathological subtypes of iCCA, mainly based on the 5^th edition of the World Health Organization Classification of Tumours of the Digestive System.

Background and aims: Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity but can develop in normal-weight people (lean NAFLD). We compared outcomes in lean, overweight, and obese NAFLD.

Methods: This retrospective chart review included patients at Stanford University Medical Center with NAFLD confirmed by imaging between March 1995 and December 2021. Lean, overweight, and obese patients had body mass index of <25.0, >25.0 and <29.9, and ≥30.0 kg/m² for non-Asian and >23.0 and ≥27.5 for overweight and obese Asian patients.

Results: A total of 9061 lean (10.2%), overweight (31.7%), and obese (58.1%) patients were included. Lean patients were 5 years older than obese patients (53±17.4 vs. 48.7±15.1 years), more were female (59.6% vs. 55.2%), white (49.1% vs. 46.5%), had NASH (29.2% vs. 22.5%), cirrhosis (25.3% vs.19.2%), or nonliver cancer (25.3% vs. 18.3%). Fewer had diabetes (21.7% vs. 35.8%) or metabolic comorbidities (all p<0.0001). Lean NAFLD patients had liver-related mortality similar to other groups but higher overall (p=0.01) and nonliver-related (p=0.02) mortality. After multivariable model adjustment for covariates, differences between lean and obese NAFLD in liver-related, nonliver-related, and overall mortality (adjusted hazard ratios of 1.34, 1.00, and 1.32; p=0.66, 0.99, and 0.20, respectively) were not significant.

Conclusions: Lean NAFLD had fewer metabolic comorbidities but similar adverse or worse outcomes, suggesting that it is not benign. Healthcare providers should provide the same level of care and intervention as for overweight and obese NAFLD.

Background and aims: Intrahepatic cholangiocarcinoma (ICC) is a subtype of primary liver cancer for which effective therapeutic agents are lacking. Fibroblast growth factor receptor 2 (FGFR2) has become a promising therapeutic target in ICC; however, its incidence and optimum testing method have not been fully assessed. This study investigated the rearrangement of FGFR2 in intrahepatic cholangiocarcinoma using multiple molecular detection methods.

Methods: The samples and clinical data of 167 patients who underwent surgical resection of intrahepatic cholangiocarcinoma in Zhongshan hospital, Fudan university were collected. The presence of FGFR2 gene rearrangement was confirmed using fluorescence in situ hybridization (FISH) and targeted next-generation sequencing (NGS). FGFR2 protein expression was determined using immunohistochemistry (IHC). The concordance between the methods was statistically compared. PD-L1 expression was also assessed in this cohort. The clinicopathological characteristics and genomic profile related to FGFR2 rearrangements were also analyzed to assist candidate-screening for targeted therapies.

Results: FGFR2 rearrangement was detected in 21 of the 167 ICC cases (12.5%) using FISH. NGS analysis revealed that FGFR2 rearrangement was present in 16 of the 20 FISH-positive cases, which was consistent with the FISH results (kappa value=0.696, p<0.01). IHC showed that 80 of the 167 cases (48%) were positive for FGFR2 expression, which was discordant with both FISH and NGS results. By comparison, FGFR2-positivity tended to correlate with unique clinicopathological subgroups, featuring early clinical stage, histologically small duct subtype, and reduced mucus production (P<0.05), with improved overall survival (p<0.05). FGFR2-positivity was not associated with PD-L1 expression in ICCs. In genome research, we identified eight partner genes fused with FGFR2, among which FGFR2-BICC1 was the most common fusion type. BAP1, CDKN2A, and CDKN2B were the most common concomitant genetic alterations of FGFR2, whereas KRAS and IDH1 mutations were mutually exclusive to FGFR2 rearrangements.

Conclusions: FISH achieved satisfactory concordance with NGS, has potential value for FGFR2 screening for targeted therapies. FGFR2 detection should be prioritized for unique clinical subgroups in ICC, which features a histological small duct subtype, early clinical stage, and reduced mucus production.