Predictive Factors for Recovery from Alcoholic Liver Failure.

Alcoholic liver disease is a risk factor for non-virus-related hepatocellular carcinoma (HCC), which is increasing in prevalence. This study aimed to identify the factors for recovery from alcoholic liver failure. Sixty-two consecutive patients hospitalized for alcoholic liver failure at Okayama City Hospital were enrolled. The characteristics of patients who survived to the 1-month follow-up and whose liver function improved to Child-Pugh A at 3 months (CPA3) and 12 months (CPA12) were compared with the rest of the patients. The survivors at 1 month (50 patients) were significantly younger than the deceased patients and had better liver and renal function with higher levels of γ-glutamyl transferase (GGT). The same factors, except renal function, were correlated with achieving CPA3. High AST, ALT, and GGT levels as well as short spleen length, total abstinence, and good Child-Pugh scores at admission were identified as factors for achieving CPA12. The extent of alcohol intake before admission was not identified as a risk factor in any analysis. In conclusion, baseline liver function is crucial for survival and achieving CPA3, whereas high transaminase and γ-GTP levels, the absence of splenomegaly, and total abstinence are significant factors for achieving CPA12.

Abnormal fucosylation of alpha-fetoprotein in patients with nonalcoholic steatohepatitis.

AIM: Nonalcoholic steatohepatitis (NASH) is a risk factor for nonvirus-related hepatocellular carcinoma, which is increasing in prevalence. The aim of this study was to clarify the clinical application of fucosylated alpha-fetoprotein (AFP-L3) in the process of nonalcoholic fatty liver (NAFL) disease development. METHODS: Serum samples from 115 diabetes mellitus (DM), 36 NAFL, and 119 NASH patients were analyzed for AFP-L3 expression using raw data of a micro total analysis system. These data were then compared with the clinical characteristics of the patients. A validation study was also undertaken with 55 samples (17 NAFL and 38 NASH). RESULTS: Trace amounts of AFP-L3 were detected in 3.5%, 16.7%, and 58.0% of patients with DM, NAFL, and NASH, respectively. The odds ratio of AFP-L3 positivity for the diagnosis of NASH in multivariate analysis was 9.81 (95% confidence interval, 3.77-25.5). The rates in patients without fibrosis or with stage 1, stage 2, stage 3, and stage 4 fibrosis were 14.7%, 31.3%, 63.0%, 86.2%, and 100%, respectively. The rates were significantly increased according to the advancement of liver fibrosis (p < 0.001); however, no difference in the positive rate of AFP-L3 was observed between patients with and without fatty livers and between patients with normal and abnormal transaminase. The same relationship was also observed in the validation cohort. CONCLUSION: Abnormal fucosylation of AFP occurred in patients with NASH, so it could be useful for the screening of NASH in patients with DM, as well as for the differential diagnosis of NASH and the evaluation of fibrosis.

Cyclopia Extracts Enhance Th1-, Th2-, and Th17-type T Cell Responses and Induce Foxp3+ Cells in Murine Cell Culture.

Cyclopia genistoides, one of the traditional South African medicinal plants, and other species of the same genus offer noteworthy phenolic profiles, in particular high levels of the anti-allergic xanthone mangiferin. Hot water and 40% ethanol-water (v/v) extracts, prepared from C. genistoides, Cyclopia subternata, and Cyclopia maculata, were tested for immune-regulating activity in vitro using murine splenocytes and mesenteric lymph node cells. The 40% ethanol-water extracts of C. genistoides and C. subternata significantly enhanced production of several types of cytokines, including IL-4, IL-17, and IFN-γ, by antigen-stimulated splenocytes. A concentration-dependent response was observed, noticeably for IFN-γ production. The activity of the extracts did not correlate with the content of any of the major phenolic compounds, indicative that other extract constituents also play a role in immunomodulation. Additionally, the increased ratio of CD4+CD25+Foxp3+ Treg cells to total CD4+ cells indicated induction of Foxp3+ cells when mesenteric lymph node cells were cultured in the presence of these two extracts. This study is the first reporting immunostimulatory activity for Cyclopia, which are widely consumed as the herbal tea known as honeybush, underpinning further investigations into the potential use of its extracts as adjuvants for mucosal immunotherapy.

Establishment and characterization of a novel murine model for pollen allergy.

Although there have been many studies revealing the mechanism and establishing the therapeutical method for allergic rhinitis, no suitable animal models for allergic rhinitis, especially for pollen allergy, are currently available. We therefore aimed in this study to develop a murine model producing IgE in response to an inhaled antigen without using any adjuvants. Ovalbumin (OVA)-specific T cell receptor transgenic mice (DO11.10) inhaled an OVA solution for one h, twice a week, for six weeks. The resulting increase of OVA-specific IgE in the serum was observed depending on the times of inhalation. Spleen cells from mice that had inhaled the antigen produced more IL-4 and less IFN-γ than those from the control mice in vitro. These results indicate that inhaled antigen enhanced the Th2-type responses and induced IgE production in a T cell-mediated manner. Our findings would contribute to studies on prevention and treatment of pollen allergy.

Anti-allergic effect of Cyclopia (honeybush) extracts via anti-degranulation activity in a murine allergy model for inhaled antigen.

The anti-allergic effects of extracts prepared from two species of honeybush, Cyclopia genistoides and Cyclopia subternata, were demonstrated in vivo in a murine allergy model for inhaled antigen induced with ovalbumin (OVA) inhalation to mimic pollen allergy. Intake of the extracts increased the production of OVA-specific immunoglobulin (Ig) E (IgE), IgG1, and IgG2a antibodies in serum and significantly suppressed anaphylactic reaction-induced body temperature decline. Moreover, the extracts significantly inhibited antigen-antibody-induced degranulation in RBL-2H3 cells. They also inhibited body temperature decline when the allergic mice were given them after antigen sensitization, indicating that anti-degranulation activity is the major mechanism underlying the anti-allergic effect of Cyclopia extracts. Despite their qualitative and quantitative differences in phenolic composition, the two extracts exhibited similar effects, suggesting that several active compounds might be involved in the activity. Therefore, oral administration of either Cyclopia extract potentially exerts a systemic anti-allergic effect, supporting the increased consumption of honeybush tea for general wellness and improved quality of life.

A smartphone app-based intervention combined with face-to-face sessions for alcohol dependence at internal medicine clinics: A randomized controlled trial.

BACKGROUND: Addressing the limited access to treatments for alcohol dependence, we developed ALM-002, a therapeutic application to be "prescribed" for non-abstinence-oriented treatment in internal medicine settings. Our objective was to preliminarily assess the efficacy and safety of ALM-002. METHODS: In a multicenter, open-label randomized controlled trial, participants aged ≥20 with alcohol dependence and daily alcohol consumption exceeding 60 g for men and 40 g for women, without severe complications, were randomly assigned to either the intervention group using ALM-002 or the treatment-as-usual control group. Participant in both groups received individual face-to-face sessions by physicians at weeks 0, 4, 8, and 12. The primary endpoint was the change in heavy drinking days (HDDs) from week 0 to week 12. A mixed model for repeated measures was employed. RESULTS: We enrolled 43 participants: 22 in the intervention group and 21 in the control group. A significant reduction in HDDs every 4 weeks from week 0 to week 12 was observed, with a between-group difference of -6.99 days (95% CI: -12.4 to -1.6 days, standardized mean difference: -0.80). CONCLUSIONS: These results indicate the potential of ALM-002 as a viable treatment for alcohol dependence. Further studies are needed to evaluate the clinical potential of ALM-002.

Clinical Outcomes of Next-Generation Microwave Thermosphere Ablation for Hepatocellular Carcinoma with Primarily Hepatitis-Related Etiology.

BACKGROUND AND AIM: We investigated the clinical outcomes of patients with hepatocellular carcinoma (HCC) who underwent next-generation microwave thermosphere ablation (MTA). METHODS: A total of 429 patients with 607 HCCs (maximum tumor diameter ≤40 mm) were included. We defined the following areas of the liver as those where MTA therapy is difficult to perform: caudate lobe and areas near the primary and secondary branches of the intrahepatic portal vein, inferior vena cava, gallbladder, heart, duodenum, abdominal esophagus, collateral veins around the liver, and spleen. Factors which predisposed patients to local tumor recurrence in the context of tumor location and complications were examined. RESULTS: The primary etiologies of HCC were hepatitis-related: 259 (60.4%) cases of HCV, 31 (7.3%) cases of HBV, and two instances of both. Median maximum tumor diameter was 15.0 (interquartile range, 10.0-21.0) mm. There were 86 tumors in areas of the liver where MTA is difficult. The most common area was near the primary and secondary branches of the intrahepatic portal vein (26 nodules). The cumulative local tumor recurrence rates at 1, 2, and 3 years were 4.4%, 8.0%, and 8.5%, respectively. The cumulative local tumor recurrence rate differed significantly by tumor size group: 6.6%, 13.8%, and 29.4% at three years in the ≤20 mm group (n = 483), 20-30 mm group (n = 107), and ≥30 mm group (n = 17), respectively (p < 0.001). The cumulative local tumor recurrence rate was similar despite difficult-to-treat status (p = 0.169). In the multivariable analysis, tumor size (>15 mm) (hazard ratio [HR], 2.15; 95% confidence interval [CI], 1.11-4.16; p = 0.023) and ablative margin (<3 mm) (HR, 2.94; 95% CI, 1.52-5.71; p = 0.001) were significantly associated with local tumor recurrence. Only tumor size (>15 mm) (odds ratio, 3.41 95% CI, 1.53-7.84; p = 0.026) was significantly associated with complications. CONCLUSIONS: MTA is a safe and effective local ablation therapy for HCC, even for tumors located in areas of the liver where local ablation therapy is difficult.

Telmisartan reduced blood pressure and HOMA-IR with increasing plasma leptin level in hypertensive and type 2 diabetic patients.

Telmisartan, a new angiotensin II type 1 receptor blocker (ARB), was recently reported to stimulate PPARgamma, and stronger effects of Telmisartan on insulin sensitivity has been expected than the class effect of ARB. In the present study, we examined the effects of Telmisartan on insulin sensitivity and adipokine levels in hypertensive and type 2 diabetic patients. Outpatients with both hypertension and type 2 diabetes mellitus (n=36; male 23, female 13), received 20-40mg Telmisartan orally once daily for 6 months. Physical examinations and blood or urine tests were performed before and 3 or 6 months after starting Telmisartan treatment. Results were statistically compared using Wilcoxon analysis. Telmisartan treatment for 3 or 6 months reduced systolic and diastolic blood pressure and urinary albumin excretion. Fasting plasma glucose, HbA1c, total and HDL-cholesterol, triglyceride, body weight, BMI and waist length were not changed. Fasting IRI and HOMA-IR were significantly decreased after Telmisartan treatment, suggesting the improved insulin sensitivity. Total and high molecular adiponectin were not changed. Interestingly, serum leptin was significantly increased by 3 months Telmisartan treatment, suggesting a possible involvement of leptin in improved insulin sensitivity. In conclusion, Telmisartan improved insulin resistance with increased serum leptin level in hypertensive and type 2 diabetic patients.