Differences in efficacy of radiofrequency ablation (RFA) and surgical resection (SR) are not clear for patients with hepatocellular carcinoma (HCC).
From 2002 to 2007, 419 patients with HCCs ≤5 cm ...were enrolled consecutively in the study. Among these patients, 190 and 229 patients received RFA and SR, respectively, as their first treatment. Factors were analyzed in terms of overall survival and recurrence by multivariate analysis and propensity score matching analysis.
The SR group had younger age, a higher male-to-female ratio, higher prevalence of hepatitis B virus, lower prevalence of hepatitis C virus, better liver function reserve, and larger tumor size than the RFA group. The cumulative 5-year overall survival rates were 79.3% in the SR group and 67.4% in the RFA group. During the follow-up period, tumors recurred in 244 patients in a median time of 14.5 ± 15.7 months. Before propensity-score matching, the RFA group had shorter overall survival time (P = .009) and higher tumor recurrence rate (P < .001) than the SR group. After matching, RFA was comparable to SR in overall survival time (P = .519), but the RFA group still had a greater incidence of tumor recurrence (P < .001). In patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 HCC, RFA was as effective as SR for overall survival time and recurrence.
Patients with small HCCs have a higher rate of tumor recurrence following RFA than surgery, but overall survival rates are comparable between therapies. RFA is as effective as surgery in patients with BCLC stage 0 HCC.
Background
Honokiol, a small active molecular compound extracted from magnolia, has recently been shown to inhibit hepatitis C virus (HCV) infection in vitro.
Aims
This study further characterized ...aspects of the HCV lifecycle affected by the antiviral functions of honokiol.
Methods
The influence of honokiol on HCV infection, entry, translation and replication was assessed in Huh‐7.5.1 cells using cell culture‐derived HCV (HCVcc), HCV pseudo‐type (HCVpp) and sub‐genomic replicons.
Results
Honokiol had strong antiviral effect against HCVcc infection at non‐toxic concentrations. Combined with interferon‐α, its inhibitory effect on HCVcc was more profound than that of ribavirin. Honokiol inhibited the cell entry of lentiviral particles pseudo‐typed with glycoproteins from HCV genotypes 1a, 1b, and 2a, but not of the vesicular stomatitis virus. It had inefficient activity on HCV internal ribosome entry site (IRES)‐translation at concentrations with significant anti‐HCVcc effects. The expression levels of components of replication complex, NS3, NS5A and NS5B, were down‐regulated by honokiol in a dose‐dependent manner. It also inhibited HCV replication dose dependently in both genotypes 1b and 2a sub‐genomic replicons.
Conclusions
Honokiol inhibits HCV infection by targeting cell entry and replication and, only at a concentration >30 μM, IRES‐mediated translation of HCV life cycle. Based on its high therapeutic index (LD50/EC90 = 5.4), honokiol may be a promising drug for the treatment of HCV infection.
The age and risk level that warrants hepatocellular carcinoma (HCC) screening remains to be defined. To develop risk scores for stratifying average‐risk population for mass HCC screening, we ...conducted a pooled analysis using data from three cohorts involving 12,377 Taiwanese adults 20‐80 years of age. During 191,240.3 person‐years of follow‐up, 387 HCCs occurred. We derived risk scores from Cox's model in two thirds of participants and used another one third for model validation. Besides assessing discrimination and calibration, we performed decision curve analysis to translate findings into public health policy. A risk score according to age, sex, alanine aminotransferase, previous chronic liver disease, family history of HCC, and cumulative smoking had good discriminatory accuracy in both model derivation and validation sets (c‐statistics for 3‐, 5‐, and 10‐year risk prediction: 0.76‐0.83). It also performed well across cohorts and diverse subgroups. Decision curve analyses revealed that use of the score in selecting persons for screening improved benefit at threshold probabilities of >2% 10‐year risk, compared with current guidelines and a strategy of screening all hepatitis B carriers. Using 10‐year risk 2% as a threshold for initiating screening, the screening age ranged from 20 to ≥60 years, depending on the tertile of risk scores and status of hepatitis B/C virus infection. Combining risk‐score tertile levels and hepatitis virus status to stratify participants was more sensitive than current guidelines for HCC detection within 10 years (89.4% vs. 76.8%), especially for young‐onset HCCs <50 years (79.4% vs. 40.6%), under slightly lower specificity (67.8% vs. 71.8%). Conclusion: A simple HCC prediction algorithm was developed using accessible variables combined with hepatitis virus status, which allows selection of asymptomatic persons for priority of HCC screening. (Hepatology 2015;61:1934‐1944)
Background & Aims The chronic, persistent pain associated with chronic pancreatitis (CP) has many characteristics of neuropathic pain, initiated and maintained by the activation of spinal microglia. ...We investigated whether activated microglia in the thoracic spinal cord contribute to chronic pain in a rat model of CP. Methods CP was induced in Sprague–Dawley rats by an intraductal injection of 2% trinitrobenzene sulfonic acid. Hyperalgesia was assessed by the measurement of mechanical sensitivity of the abdomen and nocifensive behavior to electrical stimulation of the pancreas. Three weeks after induction of CP, spinal samples were analyzed by immunostaining and immunoblot analyses for levels of CD11 (a marker of microglia, determined with the antibody OX42) and phosphorylated p38 (P-p38, a marker of activation of p38 mitogen-activated protein kinase signaling). We examined the effects of minocycline (inhibitor of microglia) and fractalkine (microglia-activating factor) on visceral hyperalgesia in rats with CP. Results Rats with CP had increased sensitivity and nociceptive behaviors to mechanical probing of the abdomen and electrical stimulation of the pancreas. The dorsal horn of the thoracic spinal cords of rats with CP contained activated microglia (based on increased staining with OX42), with an ameboid appearance. Levels of P-p38 increased in rats with CP and colocalized with OX42-positive cells. Intrathecal injection of minocycline reversed and prevented the increase of nocifensive behaviors and levels of P-p38 in rats with CP. Fractalkine induced hyperalgesia in rats without CP, which was blocked by minocycline. Conclusions Activated spinal microglia have important roles in maintaining and initiating chronic pain in a rat model of CP. Microglia might be a target for treatment of hyperalgesia caused by pancreatic inflammation.
Progression of gastric variceal hemorrhage (GVH) is poorer than esophageal variceal bleeding. However, data on its optimal treatment are limited. We designed a prospective study to compare the ...efficacy of endoscopic band ligation (GVL) and endoscopic N-butyl-2-cyanoacrylate injection (GVO). Liver patients with cirrhosis with or without concomitant hepatocellular carcinoma (HCC) and patients presenting with acute GVH were randomized into two treatment groups. Forty-eight patients received GVL, and another 49 patients received GVO. Both treatments were equally successful in controlling active bleeding (14/15 vs. 14/15, P = 1.000). More of the patients who underwent GVL had GV rebleeding (GVL vs. GVO, 21/48 vs. 11/49; P = .044). The 2-year and 3-year cumulative rate of GV rebleeding were 63.1% and 72.3% for GVL, and 26.8% for both periods with GVO; P = .0143, log-rank test. The rebleeding risk of GVL was sustained throughout the entire follow-up period. Multivariate Cox regression indicated that concomitance with HCC (relative hazard: 2.453, 95% CI: 1.036-5.806, P = .041) and the treatment method (GVL vs. GVO, relative hazard: 2.660, 95% CI: 1.167-6.061, P = .020) were independent factors predictive of GV rebleeding. There was no difference in survival between the two groups. Severe complications attributable to these two treatments were rare. In conclusion, the efficacy of GVL to control active GVH appears not different to GVO, but GVO is associated with a lower GV rebleeding rate.
In obesity, there are no effective therapies for parallel immune and metabolic abnormalities, including systemic/tissue insulin-resistance/inflammation, adiposity and hepatic steatosis. Caffeine has ...anti-inflammation, antihepatic steatosis, and anti-insulin resistance effects. In this study, we evaluated the effects and molecular mechanisms of 6 wk of caffeine treatment (HFD-caf) on immunological and metabolic abnormalities of high-fat diet (HFD)-induced obese rats. Compared with HFD vehicle (HFD-V) rats, in HFD-caf rats the suppressed circulating immune cell inflammatory TNFα, MCP-1, IL-6, intercellular adhesion molecule 1 (ICAM-1), and nitrite profiles were accompanied by decreased liver, white adipose tissue (WAT), and muscle macrophages and their intracellular cytokine levels. Metabolically, the increase in metabolic rates reduced lipid accumulation in various tissues, resulting in reduced adiposity, lower fat mass, decreased body weight, amelioration of hepatic steatosis, and improved systemic/muscle insulin resistance. Further mechanistic approaches revealed an upregulation of tissue lipogenic (SREBP1c, fatty acid synthase, acetyl-CoA carboxylase)/insulin-sensitizing (GLUT4 and p-IRS1) markers in HFD-caf rats. Significantly, ex vivo experiments revealed that the cytokine release by the cocultured peripheral blood mononuclear cell (monocyte) and WAT (adipocyte), which are known to stimulate macrophage migration and hepatocyte lipogenesis, were lower in HFD-V groups than HFD-caf groups. Caffeine treatment simultaneously ameliorates immune and metabolic pathogenic signals present in tissue to normalize immunolgical and metabolic abnormalities found in HFD-induced obese rats.
Portal hypertension is characterized by exaggerated activation of the renin-angiotensin-aldosterone axis. Natriuretic peptide system plays a counter-regulatory role, which is modulated by neprilysin. ...LCZ696 (sacubitril/valsartan) is a dual angiotensin receptor and neprilysin inhibitor. This study evaluated the effect of LCZ696 on portal hypertensive rats.
Portal hypertension was induced by partial portal vein ligation (PVL) in rats. LCZ696, valsartan (angiotensin receptor blocker), or normal saline (control) was administered in PVL rats for 10 days. Then, hemodynamic and biochemistry data were obtained. The hepatic histology and protein expressions were surveyed. On the parallel groups, the portal-systemic shunting degrees were determined.
LCZ696 and valsartan reduced mean arterial pressure and systemic vascular resistance. LCZ696, but not valsartan, reduced portal pressure in portal hypertensive rats (control vs. valsartan vs. LCZ696: 15.4 ± 1.6 vs. 14.0 ± 2.3 vs. 12.0 ± 2.0 mmHg, control vs. LCZ696:
< 0.05). LCZ696 and valsartan improved liver biochemistry data and reduced intrahepatic Cluster of Differentiation 68 (CD68)-stained macrophages infiltration. Hepatic endothelin-1 (ET-1) protein expression was downregulated by LCZ696. The portal-systemic shunting was not affected by LCZ696 and valsartan.
LCZ696 and valsartan reduced mean arterial pressure through peripheral vasodilation. Furthermore, LCZ696 significantly reduced portal pressure in PVL rats via hepatic ET-1 downregulation.
The mechanisms by which bariatric surgeries, including gastric bypass (GB) and sleeve gastrectomy (SG), achieve remission of type 2 diabetes mellitus (T2DM) and sustained weight reduction are ...unknown. We hypothesized that the novel anorexic hormone nesfatin-1 and another new hormone obestatin might contribute to the marked improvement in glycemic homeostasis and weight loss in diabetics after GB and SG.
A hospital-based, prospective study was conducted. Overnight fasting plasma concentrations of nesfatin-1 and obestatin were analyzed in T2DM patients before surgery, and at 3 and 12 months after laparoscopic GB (n =12) and SG (n = 6).
At 12 months, reductions of body mass index (BMI), fasting blood glucose, and glycated hemoglobin were similar between GB and SG groups (P all > 0.05). Plasma nesfatin-1 levels in patients undergoing GB or SG significantly decreased after surgeries (P both < 0.05). In contrast, plasma obestatin concentrations significantly increased in patients after SG (P < 0.05) but without any alteration after GB. The alterations of plasma nesfatin-1 were significantly and negatively associated with the reduction of fasting blood glucose (P <0.05) at 12 months after GB and SG. In the SG group, the reduction of nesfatin-1 significantly and positively correlated with the decrease of BMI (P < 0.05).
GB and SG produce differential influences with regards to circulating nesfatin-1 and obestatin levels in non-morbidly obese, T2DM patients. Circulating nesfatin-1 may modulate glucose homeostasis in two surgical procedures, and participate in regulating body weight in SG.
Rheumatoid arthritis (RA) is a chronic inflammatory disease that damages the synovial joints, and patients with it are often anorexic and cachectic with high morbidity and mortality. Biological ...therapy with anti-tumor necrosis factor (TNF)-α has been proven effective as a treatment for RA. However, the long-term effects of anti-TNF-α therapy on body weight, appetite, plasma gut hormones and leptin have not been investigated.
Twenty RA patients received subcutaneous injections of etanercept, a chimeric protein of human IgG1 Fc and TNF receptor p75, twice weekly for 12 consecutive months. Sequential changes in body weight, body fat, appetite rating, lipid profiles, gut hormones and leptin were measured at baseline and at 3 and 12 months after treatment. Ten RA patients who received non-biological disease modifying anti-rheumatic drugs were enrolled as the controls and were appraised at baseline and at 12 months after treatment (a nonrandomized study).
Significant weight gain, hyperuricemia, decreased fasting plasma glucose-dependent insulinotropic polypeptide (GIP) levels, and loss of post-oral glucose suppression of plasma leptin concentration were found in the patients after the 12-month course of etanercept therapy, but not in the controls. A transient decrease in fasting plasma acyl ghrelin occurred at 3 months during etanercept treatment. Appetite score and serum lipid profiles did not change in either group.
Long-term therapy with anti-TNF-α is promising in ameliorating body mass decrease in patients with active RA. Plasma levels of ghrelin, GIP and leptin may play significant roles in maintaining energy homeostasis in the anti-inflammatory responses during RA remission.
PDF
