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As gut dysbiosis has been implicated in the pathogenesis of nonalcoholic steatohepatitis (NASH), probiotic supplementation might be a potential treatment for this condition. The aim of this study was to evaluate the effects of single- and mixed-strain probiotics on the severity of NASH induced by a high-fat, high-fructose (HFHF) diet and their mechanisms of action. Male Sprague–Dawley rats were divided into four groups (n = 7 per group): control group, NASH group, NASH + single-strain group, and NASH + mixed-strain group. In the single-strain and mixed-strain groups, rats received Lactobacillus plantarum B7 and Lactobacillus rhamnosus L34 + Lactobacillus paracasei B13 by oral gavage once daily, respectively. The duration of the study was 6 weeks. Liver tissue was used for histopathology, hepatic fat content was assessed by Oil Red O staining and hepatic free fatty acid (FFA), and hepatic TLR4 and CD14 expression were assessed by immunohistochemistry. Fresh feces was collected for gut microbiota analysis. Liver histology revealed a higher degree of fat accumulation, hepatocyte ballooning, and lobular inflammation in the NASH group, which improved in probiotics-treated groups. The amounts of hepatic fat droplets and hepatic FFA levels were more pronounced in the NASH group than in the control and treatment groups. Serum TNF- α levels were significantly higher in the NASH group than in control and probiotic groups. The expression of CD14 and TLR4 increased in the NASH group as compared with the control and probiotics-treated groups. Alpha diversity was reduced in the NASH group, but increased in both treatment groups. The relative abundance of Lactobacillus significantly decreased in the NASH group, but increased in both treatment groups. The relative abundance of Akkermansia significantly increased in the NASH group, but decreased in both treatment groups. In conclusion, both single-strain and mixed-strain probiotics could improve NASH histology by suppressing inflammatory responses in the liver, with this improvement potentially being associated with changes in the gut microbiota. [ABSTRACT FROM AUTHOR]

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that is characterized by hepatic inflammation and steatosis. Currently, limited data exist regarding the risk of NASH in transgender women and the treatment options for this particular population. The use of testosterone supplementation is unfavorable for transgender women, and estrogen supplementation is linked to an increased risk of breast cancer; thus, an isoflavone derivative compound known as "genistein" could serve as a viable substitute for a hormone supplement in this context. The purpose of this study was to investigate the treatment effects and mechanisms of actions of genistein and sex hormones in orchidectomized (ORX) rats with nonalcoholic steatohepatitis induced via a high-fat high-fructose diet (HFHF) model. Male Sprague-Dawley rats (n = 42) were randomly assigned into seven groups; control, ORX + standard diet, HFHF, ORX + HFHF, ORX + HFHF diet + testosterone (50 mg/kg body weight (BW) once weekly), ORX + HFHF diet + estradiol (1.6 mg/kg BW daily), and ORX + HFHF diet + genistein (16 mg/kg BW daily). The duration of the study was 6 weeks. Some parts of liver tissue were used for histological examination by H&E staining. The determination of fat accumulation was performed using Oil Red O staining. SREBP1c and FAS gene expression were quantified using real-time PCR technique. The levels of all types of peroxisome proliferator-activated receptors (PPARs; α, δ, γ), proteins, and signal transducer and activator of transcription 1 (STAT1) signaling pathway were determined by both immunoblotting and immunohistochemistry. Rats in the ORX + HFHF group had the highest degree of hepatic steatosis, lobular inflammation, and hepatocyte ballooning, and showed higher levels of genes related to de novo lipogenesis, including SREBP1c and FAS. The expression of PPARγ and STAT1 were upregulated, while the expression of PPARα and PPARδ were downregulated in the ORX + HFHF group. Testosterone, estradiol and genistein treatments improved NASH histopathology together with the reversal of all types of PPAR protein expressions. Interestingly, genistein decreased the levels of STAT1 protein expression more than those of testosterone and estradiol treatment. Genistein and sex hormone treatment could ameliorate NASH through the upregulation of PPARα, and PPARδ, and the suppression of PPARγ and STAT1 expression. [ABSTRACT FROM AUTHOR]

Several risk prediction algorithms have been developed to guide antiviral therapy initiation among patients with chronic hepatitis B (CHB). This study assessed the cost-effectiveness and budget impact of three risk prediction algorithms among patients with CHB in Thailand. A decision tree with a Markov model was constructed. Three risk prediction algorithms were compared with current practices including HePAA, TREAT-B and REACH-B. PubMed was searched from its inception to December 2022 to identify inputs. Tenofovir alafenamide and best supportive care were selected for antiviral-eligible patients, and incremental cost-effectiveness ratios per quality-adjusted life year (QALY) were calculated. Our base case analysis showed that HePAA and REACH-B could provide better QALY (0.098 for HePAA and 0.921 for REACH-B) with decreased total healthcare costs (−10909 THB for HePAA and −8,637 THB for REACH-B). TREAT-B provided worse QALY (−0.144) with increased total healthcare costs (10,435 THB). The budget impacts for HePAA and REACH-B were 387 million THB and 3,653 million THB, respectively. HePAA and REACH-B algorithms are cost-effective in guiding antiviral therapy initiation. REACH-B is the most cost-effective option, but has a high budget impact. Policymakers should consider both cost-effectiveness and budget impact findings when deciding which algorithm should be implemented. [ABSTRACT FROM AUTHOR]

Introduction: Oligonol, an oligomerized-polyphenol from Litchi chinensis extract, has been shown to alleviate metabolic syndrome. The aim of this study was to evaluate the effects of oligonol in patients with nonalcoholic fatty liver disease (NAFLD). Methods: Adult patients with NAFLD defined by magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) ≥11% were enrolled and then randomly assigned to receive either oligonol or placebo capsules. Primary endpoint was ≥30% reduction in MRI-PDFF at 24 weeks. Secondary outcomes were reductions in bodyweight, waist circumference, alanine transaminase, fasting blood sugar, and lipid profiles at week 24. Results: Forty patients were enrolled (n = 20/group). Primary endpoint was achieved in 20% in the oligonol group and 15% in the placebo group (p = 0.50). The authors found a reduction in MRI-PDFF between weeks 0 and 24 in the oligonol group; however, the change was not different from the placebo group. Secondary outcomes were similar between two groups. Discussion: Oligonol has not shown a significant therapeutic effect in NAFLD. Future studies with a longer duration of therapy might be needed to achieve the primary endpoint. Clinical Trial Registration Number: Thai Clinical Trial Registry identification number: TCTR20200814001. [ABSTRACT FROM AUTHOR]

Preclinical data suggest the role of litchi extract in alleviating non-alcoholic fatty liver disease (NAFLD) by modulating gut microbiota. We aimed at investigating whether oligonol, a litchi-derived polyphenol, could improve liver steatosis and gut dysbiosis in patients with NAFLD. Adults with grade ≥2 steatosis, defined by an MRI proton density fat fraction (MRI-PDFF) of ≥11%, were randomly assigned to receive either oligonol or placebo for 24 weeks. The alteration in the MRI-PDFF and gut microbiota composition assessed by 16S ribosomal RNA sequencing were examined. There were 38 patients enrolled (n = 19 in each group). A significant reduction in the MRI-PDFF between week 0 and week 24 was observed in the oligonol group, while there was a non-significant decrease in the placebo group. A significant improvement in alpha-diversity was demonstrated in both of the groups. The oligonol-induced microbiota changes were characterized by reduced abundance of pathogenic bacteria, including Dorea, Romboutsia, Erysipelotrichaceae UCG-003 and Agathobacter, as well as increased abundance of short-chain fatty acids (SCFAs)-producing bacteria, such as Akkermansia, Lachnospira, Dialister and Faecalibacterium. In summary, this study is the first to provide evidence that supports that oligonol improves steatosis through the modulation of gut bacterial composition. Our results also support the beneficial and complementary role of oligonol in treating NAFLD. [ABSTRACT FROM AUTHOR]

Background: Primary extrahepatic malignancy and chronic liver disease co‐exist in a considerable number of patients, creating a dilemma both in the aspects of liver transplant candidacy and cancer therapy. In this review, we will explore several aspects and controversies of liver transplantation in patients with non‐hepatocellular carcinoma malignancy including risks of cancer recurrence after liver transplantation and the ethical dilemma of the selection of liver transplantation candidates with non‐hepatic malignancy. Methods: We performed a search in several online databases and reviewed published articles and ongoing clinical trials in the topics of transplantation and pre‐existing malignancies. Results and Discussion: Liver transplantation can be safely performed in selected patients with pre‐existing extrahepatic malignancies with low recurrence rate if they have an expected 5‐year survival rate of at least 50%. The cancer‐free period before transplantation depends on the type, stage, and location of cancer. A shorter or no wait‐time may be considered in an early stage cancer or carcinoma in situ. The urgency and benefits of liver transplantation should also be taken into consideration when determining a reasonable wait‐time. This is particularly important in patients with decompensated cirrhosis who cannot afford to wait a few years before they can undergo liver transplantation. [ABSTRACT FROM AUTHOR]

Background and Aim: Hepatitis B core‐related antigen (HBcrAg) and hepatitis B virus RNA (HBV RNA) are novel markers that reflect intrahepatic cccDNA and could be useful in the prediction of relapse after nucleos(t)ide analogues (NA) discontinuation. The aim of the study is to perform a systematic review on this issue. Methods: Medline/Pubmed database was searched using text terms related to HBcrAg, RNA, NAs, discontinuation, and relapse. Included studies were those that enrolled adult patients who had been on NAs for more than 6 months with available information on end‐of‐treatment (EOT) HBcrAg and/or HBV RNA and relapse rates. Results: Sixteen studies were included. Virological and clinical relapse rates ranged from 11% to 100% and 11% to 73%, respectively. Low or undetectable EOT HBcrAg levels were associated with low off‐treatment relapse rates in most studies with area under the receiver operating characteristic curve (AUROC) of 0.69–0.70 for predicting virological relapse (VR) and 0.61–0.77 for predicting clinical relapse (CR). Undetectable EOT HBV RNA was associated with a lower risk of off‐treatment relapse with AUROC of 0.65–0.76 for predicting VR and 0.66–0.73 for predicting CR. Combined EOT HBcrAg and HBV RNA performed better in predicting off‐treatment relapse than either test alone with AUROC of 0.816–0.846 for predicting CR. None of the patients with double‐negative HBV RNA and HBcrAg developed CR. Conclusion: Combining HBcrAg with HBV RNA or HBsAg improved the discriminating abilities in the prediction of off‐treatment relapse of each test. Patients with double‐negative HBcrAg and HBV RNA at EOT had low risks of relapse and could be considered for NA discontinuation. [ABSTRACT FROM AUTHOR]

Abstract Background Biliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores. Methods Sixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ≥ 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan). Results BA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 μg/ml, P = 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 μg/ml, P < 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 μg/ml, P < 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (r = 0.58, r = 0.46, and r = 0.60, P < 0.001, respectively). Conclusions Serum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA.

Background and Aim: The prevalence and clinical significance of extrahepatic autoimmune diseases (EHAIDs) have not been evaluated in a large cohort of primary biliary cholangitis (PBC). Methods: The medical records of 1554 patients with PBC from 20 international centers were retrospectively reviewed. Development of decompensated cirrhosis (ascites, variceal bleeding, and/or hepatic encephalopathy) and hepatocellular carcinoma were considered clinical endpoints. Results: A total of 35 different EHAIDs were diagnosed in 440 (28.3%) patients with PBC. Patients with EHAIDs were more often female (92.5% vs 86.1%, P < 0.001) and seropositive for anti‐mitochondrial antibodies (88% vs 84%, P = 0.05) and antinuclear antibodies and/or smooth muscle antibodies (53.8% vs 43.6%, P = 0.005). At presentation, patients with EHAIDs had significantly lower levels of alkaline phosphatase (1.76 vs 1.98 × upper limit of normal [ULN], P = 0.006), aspartate aminotransferase (1.29 vs 1.50 × ULN, P < 0.001), and total bilirubin (0.53 vs 0.58 × ULN, P = 0.002). Patients with EHAIDs and without EHAIDs had similar rates of GLOBE high‐risk status (12.3% vs 16.1%, P = 0.07) and Paris II response (71.4% vs 69.4%, P = 0.59). Overall, event‐free survival was not different in patients with and without EHAIDs (90.8% vs 90.7%, P = 0.53, log rank). Coexistence of each autoimmune thyroid diseases (10.6%), Sjögren disease (8.3%), systemic sclerosis (2.9%), rheumatoid arthritis (2.7%), systemic lupus erythematosus (1.7%), celiac disease (1.7%), psoriasis (1.5%), and inflammatory bowel diseases (1.3%) did not influence the outcome. Conclusions: Our study confirms that EHAIDs are frequently diagnosed in patients with PBC. The presence of EHAIDs may influence the clinical phenotype of PBC at presentation but has no impact on PBC outcome. [ABSTRACT FROM AUTHOR]

Allograft steatosis is an emerging concern after liver transplantation (LT). The use of transient elastography (TE) with controlled attenuation parameter (CAP) may facilitate early detection of and intervention for allograft steatosis. This study aimed to evaluate the prevalence and risk factors of allograft steatosis using TE and CAP. The presence of steatosis and severe steatosis were defined by CAP ≥222 and ≥290 dB/m, respectively. Demographics and clinical characteristics were compared between patients with and without severe steatosis. Regression analyses were performed to determine factors associated with severe steatosis. Of 150 patients, 105 (70%) had steatosis while 40% of these had severe steatosis. Thirty-four (81.0%) patients with severe steatosis had normal alanine transaminase at the time of TE. In multivariable analyses, age at LT (odds ratio [OR] 1.05, 95% confidence interval [CI] 1.01-1.08), post-LT obesity (OR 5.34, 95% CI 1.53-18.65), and alcoholic liver disease (OR 12.86, 95% CI 2.24-73.74) were significant predictors of severe steatosis. Five patients underwent liver biopsies as a result of advance fibrosis seen on TE and were later diagnosed with chronic allograft rejection. Two of these patients had normal liver chemistries, and the remaining 3 had mild elevation of alkaline phosphatase. Steatosis was present in 70% of patients who underwent TE after LT. Advanced age at LT, post-LT obesity, and alcoholic liver disease were significant predictors for severe steatosis. The majority of patients with severe steatosis had normal liver enzymes. TE should be considered as a screening modality for allograft steatosis and fibrosis even when liver chemistries are normal. [ABSTRACT FROM AUTHOR]

Background: There are little data on the pre‐ and post–liver transplantation (LT) outcomes of patients having autoimmune hepatitis‐primary biliary cholangitis (AIH‐PBC), AIH‐primary sclerosing cholangitis (AIH‐PSC), and AIH‐small‐duct PSC (AIH‐SDPSC). The aim of this study was to analyze pre‐ and post‐LT outcomes and survival of patients having different overlap syndromes (OS) undergoing LT. Methods: Patients with compatible clinical and pathologic features of AIH‐PBC (n = 86), AIH‐PSC (n = 22), and AIH‐SDPSC (n = 9) were included in the study. Demographic, laboratory, clinical, and survival data were analyzed. Multivariable analyses were performed to determine factors predicting transplant‐free survival. Results: AIH‐primary sclerosing cholangitis patients were less treatment‐responsive and were more likely to undergo LT than other OS. No survival difference was noted among the 3 groups. Liver decompensation was independently associated with higher mortality (HR 21.78; 95% CI 2.50‐190.01). Thirteen patients with OS underwent LT. One‐year survival post‐LT was 91.7%. Overall recurrence rate for OS post‐LT was 8%. Conclusions: AIH‐primary sclerosing cholangitis patients were more likely to require LT compared with patients having AIH‐PBC. Transplant‐free survival was similar among the three AIH‐overlap syndromes. Allograft recurrence of OS occurred in about 10% of cases. Patients with OS appear to have good short‐ and medium‐term post‐LT outcomes in terms of graft function and overall survival. [ABSTRACT FROM AUTHOR]

Background: Alcohol is a major contributor of chronic liver disease worldwide. Medical treatment for alcoholic liver disease (ALD) is limited. Due to the roles of oxidative stress in the development of ALD, genistein, a natural antioxidant, might be beneficial in alleviating alcohol-induced liver injury. Materials and Methods: Eighteen male Sprague-Dawley® rats were divided into three groups (n = 6 each). Control group received distilled water, while alcohol group received 50% alcohol (8 g/kg body weight [BW] per day), and genistein group received genistein (16 mg/kg BW per day) dissolved in 50% alcohol (8 g/kg BW per day) for 4 weeks. At the end of the study, liver tissue was obtained for histopathology and immunohistochemistry for interleukin-18 (IL-18), hepatic malondialdehyde (MDA), and glutathione (GSH) measurement. Serum samples were analyzed for alanine transaminase (ALT) and tumor necrosis factor-α (TNF-α). Results: Alcohol-fed rats gained significantly less weight than control and genistein ones (48.83 ± 14.59, 142.83 ± 10.06 vs. 69.17 ± 7.33 g, respectively, P < 0.01). Serum ALT levels were also significantly lower in genistein group than in alcohol group (32.43 ± 12.90 vs. 120.30 ± 75.30; P < 0.05). Hepatic MDA levels were higher in alcohol group (0.13 ± 0.02 nmol/mg protein), while the levels were comparable between genistein (0.09 ± 0.02 nmol/mg protein) and control groups (0.1 ± 0.01 nmol/mg protein). There was a trend toward a decrease in GSH levels in alcohol-fed rats as compared to control ones. On the contrary, GSH levels were significantly increased in GSH-treated rats. Markers of inflammatory responses, such as IL-18 and TNF-α, were higher in alcohol group and declined toward the control group with genistein administration. Conclusion: Alcohol-induced hepatic cell damages through oxidative stress and inflammatory responses. Genistein could alleviate alcohol-induced liver injury through its antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

Background & Aims Cirrhosis related to chronic hepatitis B (CHB) is a major risk factor for hepatocellular carcinoma (HCC). The extent to which HCC occurs in U.S. in the absence of cirrhosis in CHB remains unclear. Methods We identified CHB patients who were diagnosed with HCC in the national Veterans Administration (VA) between 2001 and 2013. We defined presence and absence of cirrhosis at the time of HCC diagnosis using explicit histological, radiological, endoscopic, and laboratory criteria. We used multivariable regression analysis to identify demographic and clinical characteristics associated with CHB-related HCC in the absence of cirrhosis. We also examined liver transplant-free survival in CHB-HCC patients with and without cirrhosis. Results Among 8539 CHB patients, 317 developed HCC of whom 30 (9.5%) did not have any evidence of cirrhosis at the time of HCC diagnosis. Compared to HCC patients with cirrhosis, HCC patients without cirrhosis were more likely to be non-white (African American, OR = 6.78; 95% CI 2.05–22.4; Asian, OR 11.6, 95% CI 2.63–50.8), have a family history of HCC (OR 32.9, 95% CI 3.76–288), and hypertension (OR 3.15, 95% CI 1.02–9.75). There was no significant difference in the transplant-free survival between CHB-HCC patients with and without cirrhosis (hazard ratio 0.68, 95% CI 0.43–1.09). Conclusions Fewer than 10% of U.S. based CHB-related HCC patients did not have cirrhosis. Race and family history of HCC were the main risk factors for HCC in the absence of cirrhosis in CHB. These factors may help guide the decision to initiate HCC surveillance in CHB patients without cirrhosis. Lay summary Patients with chronic hepatitis B who are African American, or Asian, older than 40 years of age with family members with liver cancer or high blood pressure are at a higher risk of developing liver cancer in the absence of cirrhosis. These patients should be included in the screening program for liver cancer. [ABSTRACT FROM AUTHOR]

Cirrhotic cardiomyopathy is a cardiac condition observed in patients with cirrhotic regardless of the etiologies. It is characterized by the impaired systolic response to physical stress, diastolic dysfunction, and electrophysiological abnormalities, especially QT interval prolongation. Its pathophysiology and clinical significance has been a focus of various researchers for the past decades. The impairment of β-adrenergic receptor, the increase in endogenous cannabinoids, the presence of cardiosuppressants such as nitric oxide and inflammatory cytokines are the proposed mechanisms of systolic dysfunction. The activation of cardiac renin-angiotensin system and salt retention play the role in the development of cardiac hypertrophy and impaired diastolic function. QT interval prolongation, which is observed in 40-50 % of cirrhotic patients, occurs as a result of the derangement in membrane fluidity and ion channel defect. The increased recognition of this disease will prevent the complications of overt heart failure after procedures such as transjugular intrahepatic portosystemic shunt (TIPS) and liver transplantation. Better understandings of the pathogenesis and pathology of cirrhotic cardiomyopathy is crucial in developing more accurate diagnostic tools and specific treatments of this condition. [ABSTRACT FROM AUTHOR]

We reported a rare case of Budd-Chiari syndrome (BCS) associated with tamoxifen use, which was later complicated by heparin-induced thrombocytopenia and thrombosis (HITT). The patient was a 44 year-old woman with a medical history of lobular carcinoma in situ, who had been on tamoxifen for 2 years, presented with abdominal pain and distention. Imaging studies followed by a liver biopsy confirmed the diagnosis of BCS. On extensive work-up, the patient was found to have an unclassified myeloproliferative disorder with positive JAK-2 V617 mutation. After discontinuing tamoxifen, the patient was started on intravenous heparin. However, later in the course, she developed HITT. Myeloproliferative disorder, in conjunction with tamoxifen, predisposed the patient to be highly thrombophilic resulting in BCS. HITT was found to be relatively common in BCS. Anticoagulation and blood count need to be carefully monitored, and the possibility of HITT emergence in these patients should always be kept in mind. [ABSTRACT FROM AUTHOR]

Background: Biliary atresia (BA) is a progressive inflammatory disorder of the extrahepatic bile ducts leading to the obliteration of bile flow. The purpose of this study was to determine serum adiponectin in BA patients and to investigate the relationship of adiponectin with clinical parameters and liver stiffness scores. Methods: Sixty BA patients post Kasai operation and 20 controls were enrolled. The mean age of BA patients and controls was 9.6 ± 0.7 and 10.1 ± 0.7 years, respectively. BA patients were classified into two groups according to their serum total bilirubin (TB) levels (non-jaundice, TB < 2 mg/dl vs. jaundice, TB ≥ 2 mg/dl) and liver stiffness (insignificant fibrosis, liver stiffness < 7 kPa vs. significant fibrosis, liver stiffness ≥ 7 kPa). Serum adiponectin levels were analyzed by enzyme-linked immunosorbent assay. Liver stiffness scores were examined by transient elastography (FibroScan). Results: BA patients had markedly higher serum adiponectin levels (15.5 ± 1.1 vs. 11.1 ± 1.1 μg/ml, P = 0.03) and liver stiffness than controls (30.1 ± 3.0 vs. 5.1 ± 0.5 kPa, P < 0.001). Serum adiponectin levels were significantly elevated in BA patients with jaundice compared with those without jaundice (24.4 ± 1.4 vs. 11.0 ± 0.7 μg/ml, P < 0.001). In addition, BA patients with significant liver fibrosis had remarkably greater serum adiponectin than insignificant fibrosis counterparts (17.7 ± 1.2 vs. 9.4 ± 1.1 μg/ml, P < 0.001). Subsequent analysis revealed that serum adiponectin was positively correlated with total bilirubin, hyaluronic acid, and liver stiffness (r = 0.58, r = 0.46, and r = 0.60, P < 0.001, respectively). Conclusions: Serum adiponectin and liver stiffness values were higher in BA patients compared with normal participants. The elevated serum adiponectin levels also positively correlated with the degree of hepatic dysfunction and liver fibrosis. Accordingly, serum adiponectin and transient elastography could serve as the useful non-invasive biomarkers for monitoring the severity and progression in postoperative BA. [ABSTRACT FROM AUTHOR]

Background and Aims: Osteoarthritis (OA) is a chronic degenerative joint disorder of the synovial joint characterized by loss of articular cartilage, osteophyte formation, and alterations of subchondral bone. The purposes of this study were to measure adiponectin concentrations in plasma and synovial fluid of patients with knee OA and to analyze the correlation of adiponectin levels with disease severity. Methods: Seventy six OA patients (mean age 69.8 ± 1.1 years) and 24 healthy controls (mean age 71.2 ± 1.5 years) were enrolled in this study. OA grading was performed using the Kellgren-Lawrence (KL) criteria by evaluating x-ray changes observed in anteroposterior knee radiography. Adiponectin levels in plasma and synovial fluid were determined by commercial enzyme-linked immunosorbent assay. Results: Plasma levels of adiponectin were higher in OA patients compared to healthy individuals, but the difference did not reach statistical significance (2428.0 ± 245.1 vs. 2030.3 ± 399.4 ng/mL, p = 0.4). Adiponectin levels in plasma were remarkably higher with regard to paired synovial fluid (2428.0 ± 245.1 vs. 301.3 ± 44.9 ng/mL, p <0.001). Additionally, adiponectin concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity evaluated by KL grading criteria (r = −0.68, p <0.001 and r = −0.47, p <0.001, respectively). Further analysis showed that plasma adiponectin levels positively correlated with synovial fluid adiponectin levels (r = 0.71, p <0.001). Conclusions: Adiponectin levels in both plasma and synovial fluid decreased significantly as the severity of OA increased. These findings suggested that adiponectin may play a protective role in OA. More studies are warranted to gain insight into the potential utility of adiponectin as a biochemical determinant of disease progression and prognosis. [ABSTRACT FROM AUTHOR]

Abstract: Objectives: : The aim of this study was to measure soluble receptor for advanced glycation end products (sRAGE) in plasma and synovial fluid of knee osteoarthritis (OA) patients and to determine the correlation between sRAGE levels and disease severity. Design and methods: : Thirty-six OA patients and 15 healthy controls were enrolled in this study. OA grading was performed using the Kellgren–Lawrence classification. sRAGE levels in plasma and synovial fluid were analyzed by enzyme-linked immunosorbent assay. Results: : Plasma sRAGE levels were significantly lower in OA patients than in healthy controls (P =0.01). sRAGE levels in plasma were remarkably higher with regard to paired synovial fluid (P =0.001). Additionally, sRAGE concentrations in plasma and synovial fluid showed significant inverse correlation with disease severity (r =−0.65, P <0.001 and r =−0.55, P =0.001, respectively). Further analysis showed that there was a strong positive correlation between plasma and synovial sRAGE concentration (r =0.81, P <0.001). Conclusions: : sRAGE levels were significantly lower in OA patients compared with controls, and sRAGE levels in plasma and synovial fluid also decreased significantly as the disease severity increased. Accordingly, sRAGE levels could be used as a biochemical marker for assessing the severity and progression of knee OA. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the protective effects of genistein on lipid accumulation and apoptosis in estrogen deficient rats with NASH. Female Sprague–Dawley rats (n = 48) were divided into ovariectomized (OVX) and non-OVX groups. Each group was then sub-divided into 3 subgroups; control, NASH (rats fed with a high-fat, high-fructose (HFHF) diet), and NASH+Gen (rats fed with HFHF diet plus daily genistein at 16 mg/kg BW). Results showed that HFHF diet induced liver fat accumulation in both non-OVX and OVX rats, which was evidenced by hepatic steatosis on liver pathology and increased hepatic free fatty acid (FFA) and triglyceride levels. Hepatic fat accumulation was significantly more severe in NASH rats with OVX than non-OVX. Hepatocyte apoptosis was more severe in NASH groups compared with that in control groups. Genistein administration significantly improved histopathology of NASH in both non-OVX and OVX rats and attenuated hepatic lipid accumulation, oxidative stress, and hepatocyte apoptosis. Genistein also down-regulated PPARγ and up-regulated adiponectin expression. In summary, NASH could be worsened by estrogen deficiency, indicating the protective action of estrogen on NASH. Genistein administration alleviated hepatic steatosis and apoptosis through the down-regulation of PPARγ and up-regulation of adiponectin expression. [ABSTRACT FROM AUTHOR]

Background and Aims The risk of hepatocellular cancer (HCC) after sustained virological response (SVR) with direct-acting antivirals (DAA) is unclear. Our aim was to examine the risk and determinants of HCC in patients cured with DAA. Methods We conducted a retrospective cohort study of hepatitis C virus patients who were treated with DAA in any of the 129 Veterans Health Administration hospitals between January 1, 2015 and December 31, 2015. We calculated the annual incidence rates of HCC by SVR. We used Cox regression models to compare the risk of HCC in patients with vs those without SVR and to identify factors associated with incident HCC among patients with SVR. We reviewed a sample of HCC patients for tumor size and stage at diagnosis. Results Among 22,500 patients treated with DAA (19,518 with SVR; 2982 without SVR), the mean (standard deviation) age was 61.6 (6.1) years, and 39.0% had cirrhosis. There were 271 new cases of HCC, including 183 in patients with SVR. Compared with patients without SVR, those with SVR had a significantly reduced risk of HCC (0.90 vs 3.45 HCC/100 person-years; adjusted hazard ratio, 0.28, 95% CI=0.22–0.36). Patients with cirrhosis had the highest annual incidence of HCC after SVR (1.82 vs 0.34/100 person-years in patients without cirrhosis; adjusted hazard ratio, 4.73. 95% CI, 3.34-6.68). Most (>44.8%) HCC were classified as stage I. Maximum size of the largest lesion was ≤5 cm in over 75% of cases. Conclusions Among patients treated with DAA, SVR was associated with a considerable reduction in the risk of HCC. We did not find any evidence to suggest that DAAs promote HCC. However, in patients with SVR, the absolute risk of HCC remained high in patients with established cirrhosis. These patients should be considered for ongoing HCC surveillance. [ABSTRACT FROM AUTHOR]

With the wealth of data accumulated from completely sequenced genomes and other high-throughput experiments, global studies of biological systems, by simultaneously investigating multiple biological entities (e.g. genes, transcripts, proteins), has become a routine. Network representation is frequently used to capture the presence of these molecules as well as their relationship. Network biology has been widely used in molecular biology and genetics, where several network properties have been shown to be functionally important. Here, we discuss how such methodology can be useful to translational biomedical research, where scientists traditionally focus on one or a small set of genes, diseases, and drug candidates at any one time. We first give an overview of network representation frequently used in biology: what nodes and edges represent, and review its application in preclinical research to date. Using cancer as an example, we review how network biology can facilitate system-wide approaches to identify targeted small molecule inhibitors. These types of inhibitors have the potential to be more specific, resulting in high efficacy treatments with less side effects, compared to the conventional treatments such as chemotherapy. Global analysis may provide better insight into the overall picture of human diseases, as well as identify previously overlooked problems, leading to rapid advances in medicine. From the clinicians' point of view, it is necessary to bridge the gap between theoretical network biology and practical biomedical research, in order to improve the diagnosis, prevention, and treatment of the world's major diseases. [ABSTRACT FROM AUTHOR]