An-Luo-Hua-Xian Pill Can Improve the Regression of Liver Fibrosis in Chronic Hepatitis B Patients Treated With Entecavir

Background & Aims: Chronic hepatitis B (CHB) can cause liver fibrosis and lead to cirrhosis even cancer, antiviral therapy can reverse liver fibrosis with limited effect, thus we aimed to evaluate the effect of An-Luo-Hua-Xian pill (ALHX) on fibrosis regression in CHB patients treated with ETV.Methods: Treatment naïve patients with CHB from Oct 1st, 2013 to Dec 31st, 2020 were randomly treated with ETV alone or combined with ALHX (ETV+ALHX). Patients’ demographic, laboratory and liver histology data before and after 78 weeks of treatment were collected. Ishak fibrosis score (F) was used and fibrosis regression means F decreased ≥1 after treatment.Results: In total, 394 patients with a second liver biopsy after treatment were included in per-protocol population: 132 patients in ETV group and 262 patients in ETV+ALHX group. After 78 weeks of treatment, the fibrosis regression rate in the ETV+ALHX group were significantly higher than ETV group in baseline F≥3 patients: 124/211 (58.8%) verse 45/98 (45.9%), p=0.035. The degradation rate of liver stiffness measurement (LSM) is also consistent with it: 154/262 (73.0%) in ETV+ALHX group and 60/132 (61.2%) in ETV group, p=0.037. Logistic regression analysis showed that combined with ALHX was related to fibrosis regression (OR=1.94, p=0.018), and family history of hepatocellular carcinoma was on the contrary (OR=0.41, p=0.031).Conclusions: ETV combined with ALHX can significantly increase liver fibrosis regression in CHB patients.

Impact of metformin use on the recurrence of hepatocellular carcinoma after initial liver resection in diabetic patients

Background Metformin is proposed to have chemopreventive effect of various cancer currently. However, the anti-cancer effect of metformin for diabetic patients with hepatocellular carcinoma (HCC) undergoing liver resection remains unclear. The aim of our cohort study was to assess whether metformin influence the recurrence of HCC. Methods We retrospectively enrolled 857 HCC patients who received primary resection from April 2001 to June 2016. 222 patients were diagnosed with diabetes mellitus (DM) from medical record. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by multivariate analysis. Results During the follow-up period (mean, 75 months), 471 (54.9%) patients experienced recurrence, and 158 (18.4%) patients died. Multivariate analysis revealed that DM (p = 0.015), elevated AST (p = 0.006), hypoalbuminemia (p = 0.003), tumor number (p = 0.001), tumor size (p < 0.001), vascular invasion (p <0.001), high Ishak fibrosis score (p <0.001), hepatitis B (p = 0.014), hepatitis C (p = 0.001) were independent predictors for RFS. In diabetic patients, only HbA1c>9% (p = 0.033), hypoalbuminemia (p = 0.030) and vascular invasion (p = 0.001) were independent risk factors for HCC recurrence; but the metformin use revealed no significance on recurrence. DM is a risk factor of HCC recurrence after resection. Adequate DM control can reduce the recurrence of HCC. However, the use of metformin does not reduce the risk of HCC recurrence in diabetic patient after initial resection. Hence, metformin may not have protective influences on HCC recurrence in diabetic patients who undergo initial liver resection.

An Easy-to-use Clinical Nomogram for Predicting the Prognosis of Patients with Hepatocellular Carcinoma Concomitantly Suffer from Severe Fibrosis or Cirrhosis: A Population-based Analysis.

Background Patients with hepatocellular carcinoma (HCC) concomitantly suffer from liver cirrhosis may have worse prognosis. Based on Surveillance, Epidemiology, and End Results (SEER) database, we evaluated the overall survival (OS) and cancer-specific survival (CSS) of these patients. Methods A total of 2,369 patients were selected from the SEER database. They were classified into F0 (n=691) and F1 (n=1,678) groups by different Ishak fibrosis score. Propensity score matching (PSM) and Kaplan-Meier method were performed to evaluate the OS and CSS. The F1 group were randomized into training sub-set (n = 1,176, 70%) and validation sub-set (n = 502, 30%) for further construction and validation of nomogram . Results After matched, there were statistically significant worse outcome for F1 group patients compared with F0 group (n=587, OS: P<0.001, CSS: P<0.001). Six independent predictors for both OS and CSS were identified to construct the nomograms by COX regression analyses. The nomogram performed well concerning its ability of discrimination and calibration and its net benefits compared with the conventional staging system. Conclusions Patients with HCC concomitantly suffer from severe fibrosis or cirrhosis has a significant worse survival compared with none or moderate fibrosis patients. The validated nomograms provided useful prediction of survival.

Comparative effectiveness of nonsurgical therapies for localized hepatocellular carcinoma: Analysis of the National Cancer Database.

425 Background: Data guiding selection of optimal nonsurgical therapies for management of localized hepatocellular carcinoma (HCC) are lacking. Because there are limited prospective comparative data for these treatment modalities, we aimed to compare the effectiveness of chemotherapy (systemic or arterial directed) versus radiofrequency ablation (RFA) versus radioembolization (RE) in nonsurgically managed patients with stage I and II HCC using the National Cancer Database. Methods: We identified patients who received chemotherapy, RFA or RE for nonsurgically managed Stage I (T1N0M0) and II (T2N0M0) HCC between 2008 and 2013. Patients excluded included those who received upfront lobectomy or resection or extended lobectomy or hepatectomy or transplant, and if they had Ishak fibrosis score of 5-6 or total bilirubin > 3 mg/dl or international normalized ratio (INR) of > 3. Overall survival (OS) was compared between treatment groups using propensity score matched (1:1:1) and weighted analyses. We also verified balance of all available confounders, and assessed sensitivity to unobserved confounding. Results: Overall 2622 (73.2%), 837 (23.3%) and 125 (3.5%) patients with nonsurgically managed stage I and II HCC received chemotherapy, RFA and RE, respectively. RE treated patients tend to be older, live in the areas with a higher median income and higher percentage of high school- educated residents, and have stage II disease. The propensity matched cohort included 303 patients with baseline characteristics well balance between all arms. After propensity matching, 5-year OS was 17.4% (95% CI, 6.6% to 32.3%) in the chemotherapy group, 27.2% (95% CI, 14.2% to 42%) in the RFA group and 36.6% (95% CI, 23.1% to 50.1%) in RE group (p = 0.48). Conclusions: To our knowledge, this is the first study comparing various different nonsurgical therapies for localized HCC. All chemotherapy, RFA and RE are effective treatment options for nonsurgically managed patients with stage I and II HCC. Although these data are retrospective, RE appears to be a reasonable first-line treatment of nonsurgically managed stage I and II HCC in carefully selected patients.

Factors Associated with the Progression of Fibrosis on Liver Biopsy in Alaska Native and American Indian Persons with Chronic Hepatitis C

BACKGROUND: Various factors influence the development and rate of fibrosis progression in chronic hepatitis C virus (HCV) infection.OBJECTIVES: To examine factors associated with fibrosis in a long-term outcomes study of Alaska Native/American Indian persons who underwent liver biopsy, and to examine the rate of fibrosis progression in persons with subsequent biopsies.METHODS: A cross-sectional analysis of the demographic, inflammatory and viral characteristics of persons undergoing liver biopsy compared individuals with early (Ishak fibrosis score of lower than 3) with those with advanced (Ishak score of 3 or greater) fibrosis. Persons who underwent two or more biopsies were analyzed for factors associated with fibrosis progression.RESULTS: Of 253 HCV RNA-positive persons who underwent at least one liver biopsy, 76 (30%) had advanced fibrosis. On multivariate analysis, a Knodell histological activity index score of 10 to 14 and an alpha-fetoprotein level of 8 ng/mL or higher were found to be independent predictors of advanced liver fibrosis (P<0.0001 for each). When surrogate markers of liver inflammation (alanine aminotransferase, aspartate aminotransferase/alanine aminotransferase ratio and alpha-fetoprotein) were removed from the model, type 2 diabetes mellitus (P=0.001), steatosis (P=0.03) and duration of HCV infection by 10-year intervals (P=0.02) were associated with advanced fibrosis. Among 52 persons who underwent two or more biopsies a mean of 6.2 years apart, the mean Ishak fibrosis score increased between biopsies (P=0.002), with progression associated with older age at initial biopsy and HCV risk factors.CONCLUSIONS: The presence of type 2 diabetes mellitus, steatosis and duration of HCV infection were independent predictors of advanced fibrosis in the present cohort, with significant fibrosis progression demonstrated in persons who underwent serial biopsies.