An expert consensus for the management of chronic hepatitis B in Asian Americans.

BACKGROUND: Hepatitis B virus (HBV) infection is common with major clinical consequences. In Asian Americans, the HBsAg carrier rate ranges from 2% to 16% which approximates the rates from their countries of origin. Similarly, HBV is the most important cause of cirrhosis, hepatocellular carcinoma (HCC) and liver related deaths in HBsAg positive Asians worldwide. AIM: To generate recommendations for the management of Asian Americans infected with HBV. METHODS: These guidelines are based on relevant data derived from medical reports on HBV from Asian countries as well as from studies in the HBsAg positive Asian Americans. The guidelines herein differ from other recommendations in the treatment of both HBeAg positive and negative chronic hepatitis B (CHB), in the approach to HCC surveillance, and in the management of HBV in pregnant women. RESULTS: Asian American patients, HBeAg positive or negative, with HBV DNA levels \u3e2000 IU/mL (\u3e10 CONCLUSIONS: Application of the recommendations made based on a review of the relevant literature and the opinion of a panel of Asian American physicians with expertise in HBV treatment will inform physicians and improve patient outcomes

Expression and function of osteopontin variants in HCV-related liver disease and hepatocellular carcinoma.

Osteopontin (OPN) is a highly secreted multi-functional sialoprotein that is widely expressed in tissues, blood and urine. It is involved in a number of normal physiological functions, but is also significantly elevated in a number of cancers. While OPN is significantly expressed in hepatocellular carcinoma (HCC) little is known as to its role and if it is expressed in the pre-cancerous hepatitis C virus (HCV) infected liver. In this thesis we show that OPN is expressed in the liver and in HCC as three variants, the full-length protein OPN-A and two splice variants OPN-B and OPN-C. Through production of stable Huh-7 cells expressing the OPN variants, we show for the first time that all variants increase proliferation of a range of cultured hepatoma cell lines in a paracrine manner through interactions with the cell surface OPN receptor CD44. Similarly, OPN-A (and to a lesser extent OPN-B and –C) accelerated Huh-7 derived tumor growth in a nude mouse model. We also show for the first time expression of all three OPN variants in the non-diseased liver as it was previously thought that splicing was a feature specific for tumor cells. Clinically, OPN is known to be highly expressed in HCC, however, its expression in chronic hepatitis C is not well documented. In this thesis we show that OPN mRNA expression is elevated in the HCV-infected liver with a trend towards increased expression as liver disease progresses. Consistent with an increase in mRNA, serum OPN levels were also increased in the HCV-infected liver although we could find no correlation with degree of liver disease. However, our sample size was small and this section of the thesis needs repeating with a larger HCV-infected patient cohort. Furthermore, we show that elevated OPN expression is not specific to the HCV-infected liver as OPN is also elevated in the HBV-infected and alcoholic liver suggesting that HCV does not drive OPN expression but is more likely as a result of the inflammatory process in the viral infected liver. Interestingly we also show that there is a shift of OPN expression from bile duct epithelial cells in the non-diseased liver to the hepatocyte in the HCV-infected liver which raises the question as to the role of OPN in hepatocyte transformation to facilitate the development of HCC. Our evaluation of serum OPN expression also suggests that OPN has potential as both a diagnostic and potentially prognostic biomarker for not only HCC (arising from HBV and HCV infections and alcohol abuse) but also the earlier stages of HCV-related liver disease. This work for the first time characterises the expression of all OPN variants in the liver including HCC and may be useful for identifying targeted OPN-based therapeutic approaches for HCC and other cancers. Furthermore it also suggests that monitoring OPN in chronic hepatitis C may be useful in monitoring liver disease progression and early detection of HCC.Thesis (Ph.D.) -- University of Adelaide, School of Molecular and Biomedical Science, 201

Interleukin-22 predicts severity and death in advanced liver cirrhosis: a prospective cohort study

Background: Interleukin-22 (IL-22), recently identified as a crucial parameter of pathology in experimental liver damage, may determine survival in clinical end-stage liver disease. Systematic analysis of serum IL-22 in relation to morbidity and mortality of patients with advanced liver cirrhosis has not been performed so far. Methods: This is a prospective cohort study including 120 liver cirrhosis patients and 40 healthy donors to analyze systemic levels of IL-22 in relation to survival and hepatic complications. Results: A total of 71% of patients displayed liver cirrhosis-related complications at study inclusion. A total of 23% of the patients died during a mean follow-up of 196 +/- 165 days. Systemic IL-22 was detectable in 74% of patients but only in 10% of healthy donors (P 18 pg/ml, n = 57) showed significantly reduced survival compared to patients with regular ([less than or equal to]18 pg/ml) levels of IL-22 (321 days versus 526 days, P = 0.003). Other factors associated with overall survival were high CRP ([greater than or equal to]2.9 mg/dl, P = 0.005, hazard ratio (HR) 0.314, confidence interval (CI) (0.141 to 0.702)), elevated serum creatinine (P = 0.05, HR 0.453, CI (0.203 to 1.012)), presence of liver-related complications (P = 0.028, HR 0.258 CI (0.077 to 0.862)), model of end stage liver disease (MELD) score [greater than or equal to]20 (P = 0.017, HR 0.364, CI (0.159 to 0.835)) and age (P = 0.011, HR 1.047, CI (1.011 to 1.085)). Adjusted multivariate Cox proportional-hazards analysis identified elevated systemic IL-22 levels as independent predictors of reduced survival (P = 0.007, HR 0.218, CI (0.072 to 0.662)). Conclusions: In patients with liver cirrhosis, elevated systemic IL-22 levels are predictive for reduced survival independently from age, liver-related complications, CRP, creatinine and the MELD score. Thus, processes that lead to a rise in systemic interleukin-22 may be relevant for prognosis of advanced liver cirrhosis

EPSTEIN-BARR-VIRUS ASSOCIATED SYNDROMES IN IMMUNOSUPPRESSED LIVER-TRANSPLANT RECIPIENTS - CLINICAL PROFILE AND RECOGNITION ON ROUTINE ALLOGRAFT BIOPSY

The clinical profile and histopathologic changes in needle biopsies of the liver were studied in 10 cases of acute Epstein-Barr virus infection occurring in liver transplant recipients. The systemic viral syndrome in four cases resembled that seen in infectious mononucleosis, whereas in six others it was characterized by atypical signs and symptoms in the form of jaw pain, arthralgias, joint space effusions, diarrhea, encephalitis, pneumonitis, mediastinal lymphodenopathy, and ascites. Laboratory investigation showed marked elevations in hepatocellular enzymes and circulating atypical lymphocytes in the peripheral blood. Pancytopenia was noted in eight cases. A range of histopathologic changes was noted in the allografts ranging from alterations typically observed in infectious mononucleosis to a distinctive constellation characterized by (a) mixed mononuclear portal and sinusoidal infiltrates containing atypical large noncleaved cells and immunoblasts; (b) associated lobular activity indicative of a hepatitic process, and (c) relatively mild duct damage not in proportion to the severity of the inflammatory infiltrates. The patients responded to reduced immunosuppression, but recurrent viral syndromes occurred in four instances and one patient died of systemic lymphoproliferative disease

The new paradigm of hepatitis C therapy: integration of oral therapies into best practices.

Emerging data indicate that all-oral antiviral treatments for chronic hepatitis C virus (HCV) will become a reality in the near future. In replacing interferon-based therapies, all-oral regimens are expected to be more tolerable, more effective, shorter in duration and simpler to administer. Coinciding with new treatment options are novel methodologies for disease screening and staging, which create the possibility of more timely care and treatment. Assessments of histologic damage typically are performed using liver biopsy, yet noninvasive assessments of histologic damage have become the norm in some European countries and are becoming more widespread in the United States. Also in place are new Centers for Disease Control and Prevention (CDC) initiatives to simplify testing, improve provider and patient awareness and expand recommendations for HCV screening beyond risk-based strategies. Issued in 2012, the CDC recommendations aim to increase HCV testing among those with the greatest HCV burden in the United States by recommending one-time testing for all persons born during 1945-1965. In 2013, the United States Preventive Services Task Force adopted similar recommendations for risk-based and birth-cohort-based testing. Taken together, the developments in screening, diagnosis and treatment will likely increase demand for therapy and stimulate a shift in delivery of care related to chronic HCV, with increased involvement of primary care and infectious disease specialists. Yet even in this new era of therapy, barriers to curing patients of HCV will exist. Overcoming such barriers will require novel, integrative strategies and investment of resources at local, regional and national levels

Cancer

BACKGROUNDWorldwide, liver cancer is a leading cause of death for both men and women. The number of Americans who are diagnosed with and die of liver cancer has been rising slowly each year. Using data from the CONCORD-2 study, this study examined population-based survival by state, race, and stage at diagnosis.METHODSData from 37 statewide registries, which covered 81% of the US population, for patients diagnosed during 2001\u20132009 were analyzed. Survival up to 5 years was adjusted for background mortality (net survival) with state- and race-specific life tables, and it was age-standardized with the International Cancer Survival Standard weights.RESULTSLiver cancer was diagnosed overall more often at the localized stage, with blacks being more often diagnosed at distant and regional stages than whites. 5-year net survival was 12.2% in 2001\u20132003 and 14.8% in 2004\u20132009. Whites had higher survival than blacks in both calendar periods (11.7% vs 9.1% and 14.3% vs 11.4%, respectively). During 2004\u20132009, 5-year survival was 25.7% for localized-stage disease, 9.5% for regional-stage disease, and 3.5% for distant-stage disease.CONCLUSIONSSome progress has occurred in survival for patients with liver cancer, but 5-year survival remains low, even for those diagnosed at the localized stage. Efforts directed at controlling well-established risk factors such as hepatitis B may have the greatest impact on reducing the burden of liver cancer in the United States.CC999999/Intramural CDC HHS/United States2018-01-09T00:00:00Z29205306PMC5759038vault:2579