SciCombinator

Discover the most talked about and latest scientific content & concepts.

Concept: Cirrhosis

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In clinical practice, establishing a subsequent optimum treatment for chronic hepatitis B patients with a history of multiple NAs treatment failures, including a suboptimal response to a final therapy with combined ETV and ADV, is a complicated but crucial challenge. This study investigated the efficacy and safety of a tenofovir rescue regimen in these patients. A total of six eligible patients were enrolled and were switched to a tenofovir rescue regimen. At baseline, the genotypes and genotypic mutations of the reverse transcriptase and surface gene were determined by ultra-deep pyrosequencing, and further clonal analyses of the reverse transcriptase domain were performed to identify multidrug-resistant HBV strains. In addition, HBV DNA levels, serology, and biochemistry parameters were monitored at baseline and every 3 months, and abdominal ultrasonography was performed at baseline and every 6 months. All patients were confirmed to harbor LAM-related resistant HBV strains. After switching to the tenofovir rescue treatment, all patients had an undetectable level of HBV DNA within 6 months and achieved normalization of the ALT level within 9 months. These virological and biochemical responses persisted until the end of the observation period. None of the patients developed clinical deterioration or any adverse events related to the tenofovir therapy during the median 16.5-month follow-up. In conclusion, the tenofovir rescue regimen can be employed confidently as a highly effective and safe treatment choice following a suboptimal response to ETV plus ADV therapy for a subset of chronic hepatitis B patients with a history of multiple unsuccessful antiviral treatments. J. Med. Virol. 00: 1-9, 2015. © 2015 Wiley Periodicals, Inc.

Concepts: Antiretroviral drug, DNA, Genetics, Cirrhosis, Hepatitis, Hepatitis C, Hepatitis B, Hepatitis A

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The objectives of this study were to establish a simple model based on quantitative serum markers of hepatitis B virus (HBV) infection to understand the complex immune response to HBV. Patients samples were obtained from individuals with active HBV infection (alanine transaminase [ALT]-positive, aspartate aminotransferase [AST]-positive and HBsAg-positive), or patients who had recovered from infection (ALT-negative, AST-negative, anti-HBs-positive and either HBsAg, HBeAg, anti-HBe or anti-HBc positive). HBV quantitative markers, including HBsAg, anti-HBs, HBeAg, anti-HBe, and anti-HBc, were measured using a chemiluminescent microparticle immunoassay. Based on cut-off values, anti-HBs levels were converted to a ratio (sample value/cut-off value, RV). Anti-HBe and anti-HBc levels were determined using a competition method, resulting in the use of a ratio (cut-off value/sample value, RV) for determination of anti-HBe and anti-HBc values. The greater RV value in a patient was considered as a trait marker for HBV infection (TMHB) of this patient. Patients with TMHB including HBsAg or HBeAg were defined as TMHB-Ag; and patients with TMHB including anti-HBs, anti-HBe, or anti-HBc TMHB were defined as TMHB-Ab. The percentage of patients determined to be TMHB-Ag was 96.3% in the HBV group. The percentage of patients determined to be TMHB-Ab was 94.7% in recovery group. TMHBs could be used to analyze different status of HBV infection. J. Med. Virol. © 2015 Wiley Periodicals, Inc.

Concepts: Cirrhosis, Hepatitis, Sociology, Aspartate transaminase, Alanine transaminase, Hepatitis B, Hepatitis B virus, Hepadnaviridae

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The TGF-β1/IL-31 pathway plays an important role in the process of cell injury and inflammation. The purpose of this work was to explore the role of the TGF-β1/IL-31 pathway in cytopathic process of hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF). The quantitative serum levels of TGF-β1, IL-9, IL-10, IL-17, IL-22, IL-23, IL-31, IL-33 and IL-35 were analyzed among chronic hepatitis B (CHB, n=17), ACLF (n=18) and normal control subjects (NC, n=18). Disease severity in patients with ACLF was assessed using the MELD and Child-Pugh scores. Serum TGF-β1 levels were strongly positively correlated with IL-31 in all subjects, and both of them were positively correlated with IL-17, IL-22 and IL-33. In CHB and ACLF patients, serum levels of TGF-β1 and IL-31 were both increased significantly compared with NC and positively correlated with Total bilirubin (TBil) and Alfa-fetoprotein (AFP) levels. ACLF patients showed the highest levels of TGF-β1 and IL-31 which were positively correlated with Child-Pugh scores. Furthermore, the recovery from the liver injury in CHB was accompanied by decreased TGF-β1 and IL-31 levels. More importantly, serum levels of TGF-β1 and IL-31 were markedly up-regulated in ACLF non-survivors, and IL-31 displayed the highest sensitivity and specificity (85.7% and 100.0%; respectively) in predicting non-survival of ACLF patients. Increasing activity of TGF-β1/IL-31 pathway is well correlated with the extent of liver injury, disease severity and non-survival of ACLF patients while reducing activity is detected along the recovery of liver injury in CHB, suggesting its potential role in the pathogenesis of liver injury during chronic HBV infection.

Concepts: Sensitivity and specificity, Cirrhosis, Hepatitis, Liver, Bilirubin, Hepatitis B, Hepatitis A, Jaundice

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Nonalcoholic fatty liver disease is a common cause of chronic liver disease and has been an increasingly studied topic of research as the obesity epidemic has been growing. There is a significant morbidity and mortality with uncontrolled steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. The prevalence of this disease has been estimated to be roughly one-third of the western population, thought to be largely due to diet and sedentary lifestyle. Several treatments have been studied including vitamin E, insulin-sensitizing agents and ursodeoxycholic acid; however, the only treatment shown to improve the histologic changes of nonalcoholic fatty liver disease is weight loss. Given the proven benefit of weight loss, there may be reason to screen at-risk populations; however, limited availability of other disease-modifying treatments may limit the cost-benefit ratios. A better understanding of the diagnosis and management of this condition is required to alter the course of this modifiable disease.

Concepts: Cancer, Nutrition, Medical terms, Obesity, Cirrhosis, Non-alcoholic fatty liver disease, Fatty liver, Steatohepatitis

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Objective: To estimate the level of access to diagnosis, management and treatment for people living with chronic hepatitis B (CHB) in Australia, and to identify the gaps in clinical care for people living with CHB. Methods: Analysis of publicly available population level data including infectious disease notifications, Medicare and Pharmaceutical Benefits Scheme utilisation data, census-based estimates of CHB prevalence and burden, and mathematical modelling. Results: In 2012, of the estimated 218,567 Australians living with CHB, 57% had been diagnosed, 17,367 people (8%) received recommended HBV DNA viral load testing (without treatment) and 10,987 (5%) received antiviral therapy. Conclusions: This analysis reveals substantial gaps in the cascade of care for CHB in Australia, most notably in diagnosis (with 43% undiagnosed) and in recommended yearly monitoring (87% not in care). The number receiving therapy represents only one-third of those estimated to require treatment to prevent progressive liver disease and liver cancer. Implications: These findings demonstrate that the majority of those affected are not receiving guideline-based care; highlight the need for improvements in opportunistic screening, engagement in care, and access to therapy; and provide a method to assess the impact of public health and clinical interventions in response to CHB over time.

Concepts: Medicine, Cancer, Cirrhosis, Hepatitis, Hepatocellular carcinoma, Hepatitis C, Hepatitis B, Hepatitis A

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Occult hepatitis B infection (OBI) is characterized by negative hepatitis B surface antigen (HBsAg) and detectable hepatitis B virus (HBV)-DNA in the liver and/or serum, with or without hepatitis B core antibody (anti-HBc). Anti-HBc is the most sensitive marker of previous HBV. HBV reactivation in patients under immunosuppressive treatment is life-threatening, occurring in both overt and occult HBV especially in hematological malignancies.

Concepts: Immune system, Protein, Cirrhosis, Types of cancer, Lymphoma, Hepatitis B, Hepatitis B virus, Hematological malignancy

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The sustained viral response (SVR) is the optimal outcome of hepatitis C therapy, yet more detailed data is required to confirm its clinical value. Individuals receiving treatment in 1996-2011 were identified using the Scottish HCV clinical database. We sourced data on ten clinical events: liver, non-liver and all-cause mortality; and first hospitalisation for severe liver morbidity (SLM), cardiovascular disease, respiratory disorders, neoplasms, alcohol-intoxication, drug-intoxication and violence-related injury (N.B. the latter three events were selected a priori to gauge on-going chaotic lifestyle behaviours).We determined the association between SVR attainment and each outcome event, in terms of the relative hazard reduction and absolute risk reduction (ARR), We tested for an interaction between SVR and liver disease severity (mild vs. non-mild), defining mild disease as an aspartate aminotransferase-to-platelet ratio index (APRI) <0.7. Our cohort comprised 3385 patients (mean age: 41.6 years), followed-up for a median 5.3 years (IQR 3.3-8.2). SVR was associated with a reduced risk of liver mortality (adjusted hazard ratio [AHR]:0.24, P<0.001), non-liver mortality (AHR:0.68,P=0.026); all-cause mortality (AHR:0.49, P<0.001), SLM (AHR:0.21,P<0.001), cardiovascular disease (AHR:0.70,P=0.001); alcohol intoxication (AHR: 0.52,P=0.003) and violence-related injury (AHR:0.51,P=0.002) After 7.5 years, SVR was associated with significant ARRs for liver mortality, all-cause mortality. SLM and cardiovascular disease; each 3.0%-4.7%.However, we detected a strong interaction; in that ARRs were considerably higher for individuals with non-mild disease, than for individuals with mild disease.

Concepts: Epidemiology, Medical statistics, Actuarial science, Relative risk, Cirrhosis, Hepatitis C, Hepatitis A, Liver disease

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Alcohol abuse is a leading cause of liver disease characterized by liver inflammation, fatty liver, alcoholic hepatitis, or liver cirrhosis. Immunomodulatory effects of alcohol on monocytes and macrophages contribute to alcoholic liver disease. Alcohol use, an independent risk factor for progression of hepatitis C virus (HCV) infection-mediated liver disease, impairs host defense and alters cytokine production and monocyte/macrophage activation. We hypothesized that alcohol and HCV have synergistic effects on the phenotype and function of monocytes. Our data show that acute alcohol binge drinking in healthy volunteers results in increased frequency of CD16(+) and CD68(+) and M2-type (CD206(+), dendritic cell [DC]-SIGN(+)-expressing and IL-10-secreting) circulating CD14(+) monocytes. Expression of HCV-induced CD68 and M2 markers (CD206 and DC-SIGN) in normal monocytes was further enhanced in the presence of alcohol. The levels of microRNA (miR)-27a was significantly upregulated in monocytes cultured in the presence of alcohol or alcohol and HCV as compared with HCV alone. The functional role of miR-27a in macrophage polarization was demonstrated by transfecting monocytes with an miR-27a inhibitor that resulted in reduced alcohol- and HCV- mediated monocyte activation (CD14 and CD68 expression), polarization (CD206 and DC-SIGN expression), and IL-10 secretion. Overexpression of miR-27a in monocytes enhanced IL-10 secretion via activation of the ERK signaling pathway. We found that miR-27a promoted ERK phosphorylation by downregulating the expression of ERK inhibitor sprouty2 in monocytes. Thus, we identified that sprouty2 is a target of miR-27a in human monocytes. In summary, our study demonstrates the regulatory role of miR-27a in alcohol-induced monocyte activation and polarization.

Concepts: Immune system, Monocyte, Cirrhosis, Hepatitis, Alcoholism, Hepatitis C, Alcohol abuse, Binge drinking

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Quantification of hepatitis B surface antigen (HBsAg) is an emerging serologic test and may be useful for identifying treatment strategies for chronic hepatitis B (CHB). This study aimed to evaluate HBsAg titers during the natural course of CHB and identify correlations between HBsAg titers and hepatitis B virus (HBV) DNA concentrations across different CHB phases measured using an immunoradiometric assay (IRMA).

Concepts: Cirrhosis, Hepatitis, Hepatitis C, Hepatitis B, Hepatitis A, Hepatitis B virus

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