Hepatitis: Los Angeles area

Finn RS, Zhu AX. · Department of Medicine, Division of Hematology/Oncology, Geffen School of Medicine at UCLA, 10833 Le Conte Avenue, 11-934 Factor building, Los Angeles, CA 90095, USA. · Expert Rev Anticancer Ther. · Pubmed #19374603 No free full text.

Abstract: Hepatocellular carcinoma (HCC) is one of the most common malignancies worldwide and one of the few malignancies with an increasing incidence in the USA. While the relationship between HCC and its inciting risk factors (e.g., hepatitis B, hepatitis C and alcohol liver disease) is well defined, driving genetic alterations are still yet to be identified. Clinically, HCC tends to be hypervascular and, for that reason, transarterial chemoembolization has proven to be effective in managing many patients with localized disease. More recently, angiogenesis has been targeted effectively with pharmacologic strategies, including monoclonal antibodies against VEGF and the VEGF receptor, as well as small-molecule kinase inhibitors of the VEGF receptor. Targeting angiogenesis with these approaches has been validated in several different solid tumors since the initial approval of bevacizumab for advanced colon cancer in 2004. In HCC, only sorafenib has been shown to extend survival in patients with advanced HCC and has opened the door for other anti-angiogenic strategies. Here, we will review the data supporting the targeting of the VEGF axis in HCC and the preclinical and early clinical development of bevacizumab.

Yamamoto M, Little G, Imagawa DK. · Department of Surgery, University of California, Irvine Medical Center, Orange, CA 92868-3298, USA. · Expert Rev Anti Infect Ther. · Pubmed #19344245 No free full text.

Abstract: Before the availability of hepatitis B immunoglobulin (HBIG) in hepatitis B-positive transplant recipients, the acute mortality was very high, in many centers up to 50% within 60 days post-transplant. The overall reinfection rate was approximately 60% within the initial 6 months, increasing to 80-90% within the initial 12 months and, in many cases, leading to allograft loss and death or retransplantation. These recurrent infections were often more severe and more rapidly progressing than the initial infection, probably due to high-dose immunosuppressive regimens. The poor prognosis before introduction of HBIG made hepatitis B liver disease an absolute contraindication for liver transplantation, leaving these patients with very limited treatment options. This changed in the late 1980s with the introduction of HBIG, which reduced the incidence of hepatitis B in the transplanted liver to approximately 15-50%, with concomitant improvement in graft and overall survival. The prognosis was further improved by a combination of long-term HBIG and antiviral therapy, in particular lamivudine, which reduced the reinfection rate, in most cases to between 0 and 5%. Owing to the cost and relative inconvenience of HBIG, some transplant centers have experimented with early discontinuation of HBIG and replacement with antiviral monotherapy. A number of studies, however, have found significantly higher recurrence rates associated with lamivudine monotherapy (40-50%) compared with combination therapy and, hence, lamivudine monotherapy is not recommended.

Hunt DR, Saab S. · Department of Medicine, Harbor-UCLA Medical Center, Torrance, California, USA. · Am J Gastroenterol. · Pubmed #19240708 No free full text.

Abstract: Viral hepatitis is a common problem in the incarcerated population. It causes significant morbidity and mortality, and incarcerated inmates receive their health care almost exclusively from corrections-based health systems. The seroprevalence of hepatitis B and C infections is increased in this population, and a number of risk factors for viral hepatitis are particularly common and infer higher risk among inmates, including injection drug use (IDU), high-risk sexual activity, and tattoos. IDU, in particular, has been identified as an important and common risk factor for viral hepatitis in inmates, and variable rates of IDU among inmates have been found to be the most important cause of the marked variability of seroprevalence rates for exposure to hepatitis C virus. A number of risk reduction and management strategies have been identified that can decrease transmission to other inmates. Prison-based hepatitis A and hepatitis B vaccination programs, needle exchange programs, methadone maintenance programs, risk education programs, and hepatitis C virus antiviral programs, for example, have been shown to be safe and effective risk reduction and management strategies. Preliminary studies have shown that these strategies are underutilized in the United States. Reasons for this phenomenon are multifactorial, involving financial as well as ethical and political considerations. Additional funding, research, and formal consideration / discussion of the complex issues involving viral hepatitis in the US incarcerated population are clearly important for the sake of inmates and the community at large. In this article, the published medical literature regarding this important topic is reviewed.

Ledezma B. · Angeles Clinic and Research Institute, Santa Monica, CA, USA. · Oncol Nurs Forum. · Pubmed #19136343 No free full text.

Abstract: PURPOSE/OBJECTIVES: To discuss the response patterns and side effects related to ipilimumab, a new immunotherapeutic agent under investigation in the treatment of advanced melanoma and other malignancies. DATA SOURCES: Published articles, abstracts, research data, and clinical experience. DATA SYNTHESIS: Ipilimumab is a fully human monoclonal antibody that inhibits the activity of cytotoxic T-lymphocyte antigen-4 (CTLA-4), a naturally immunosuppressive molecule. The most common side effects are immune mediated (e.g., inflammatory diarrhea, pruritus) and appear to occur as a direct result of CTLA-4 inhibition and enhanced immune system activation. Side effects generally are grade I or II and resolve with standard treatments. Most grade III or IV events are managed successfully after swift diagnosis and treatment with corticosteroids; steroid-refractory events resolve after treatment with infliximab or mycophenolate. CONCLUSIONS: The response patterns and side effects associated with ipilimumab therapy greatly differ from those common to other advanced melanoma therapies (e.g., chemotherapy, cytokines, vaccines). IMPLICATIONS FOR NURSING: Nurses have an important role in educating patients about the differences between anti-CTLA-4 therapy and chemotherapy. In addition, teaching patients to recognize ipilimumab's side effects and report them early can result in fast treatment to prevent symptom progression from grade I or II to III or IV. Communication between nurses and patients throughout the treatment process will help patients benefit maximally from the new therapeutic strategy.

Tan JA, Joseph TA, Saab S. · Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. · Hepatology. · Pubmed #18924228 No free full text.

Abstract: The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1. CONCLUSION: Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy.

Mason HM, Arndt PA. · Department of Transfusion Medicine and Serology, Harbor UCLA Medical Center, Torrance, CA 90509-2910, USA. · J Pediatr Hematol Oncol. · Pubmed #18797203 No free full text.

Abstract: SUMMARY: A 13-year-old girl with cold agglutinin syndrome caused by anti-i was serologically positive for Epstein-Barr virus. The anti-i had a high titer at 4 degrees C and high thermal amplitude (reacting up to 37 degrees C with both cord i RBCs and the patient's autologous RBCs). The patient's hemoglobin dropped to 48 g/L. The age of the patient, the severity of the hemolysis, and the antibody specificity were unusual features of cold agglutinin syndrome. Transfusions with adult (I) red blood cells were effective.

Smith JP. · Department of Gastroenterology and Hepatology, Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, California 90073, USA. · Pharmacotherapy. · Pubmed #18752386 No free full text.

Abstract: Chronic hepatitis C is associated with substantial morbidity and mortality and poses a considerable socioeconomic burden. Improved treatment regimens, including the standard of care pegylated interferon alfa and ribavirin, have increased sustained virologic response rates; however, treatment has a long duration and is often associated with adverse events that may affect adherence. The goal of therapy is viral eradication and reduced disease-related complications such as fibrosis, cirrhosis, and hepatocellular carcinoma. The clinical outcome of hepatitis C virus infection is altered with antiviral treatment, which can be influenced by host (e.g., weight, ethnicity, health) and viral (e.g., genotype, baseline viremia) factors. Overall, sustained virologic response was attained by 54-63% of patients in clinical trials treated with pegylated interferon alfa-2a or -2b and ribavirin. However, this benefit is not without risk. Interferon-induced adverse events include flu-like symptoms, bone marrow suppression, and emotional or cognitive effects, whereas hemolytic anemia accounts for most ribavirin dosage reductions. These adverse events may be ameliorated with dosage adjustments, symptom therapy, and judicious use of preventive strategies (e.g., antidepressants, hematopoietic growth factors). Appropriate management of adverse events can increase treatment adherence, thereby enhancing outcomes and improving quality of life. Pharmacists are in an ideal position to improve the treatment of patients with chronic hepatitis C by providing education about the disease and its treatments and associated adverse events and by emphasizing the importance of treatment adherence for successful outcomes.

Tan J, Surti B, Saab S. · Department of Medicine, David Geffen School of Medicine, University of California-Los Angeles, Los Angeles, CA 90095, USA. · Liver Transpl. · Pubmed #18668664 links to  free full text

Abstract: As the treatment of cirrhosis improves, pregnancy in patients with cirrhosis is likely to become more common. Although maternal and fetal mortality is expected to similarly improve, pregnant patients with cirrhosis face unique risks. These include higher rates of spontaneous abortion and prematurity and a potential for life-threatening variceal hemorrhage, hepatic decompensation, splenic artery aneurysm rupture, and postpartum hemorrhage. Pregnancy outcome may be influenced by the underlying etiology of liver disease, as in viral and autoimmune hepatitis. Medications also impact the course of pregnancy, and must be tailored appropriately during this time.

Hu KQ. · Division of Gastroenterology and Hepatology, University of California, Irvine School of Medicine, Irvine, California, USA. · Am J Gastroenterol. · Pubmed #18479498 No free full text.

Abstract: Hepatitis B virus(HBV) infection is one of the major global public health problems. Based on the second National Health and Nutrition Examination Survey (NHANES II), it is estimated that 1.25 million people are HBV infected in the United States. However, Asian and Pacific Islander Americans (APIAs) were underrepresented in this survey, and studies on the community HBV screening reported 6-15% of HBV infection in this special population. This article systematically reviews recent research advances in the possible barriers of hepatitis B care in APIAs that can be classified into three major categories, i.e., provider-, patient-, and resource-related barriers. The article also provides an overview of multiple approaches to effectively reduce these barriers so that we can evolve better strategy and deliver appropriate care to this special population and eventually reduce health disparity of CHB in APIAs.

Ji C. · USC-UCLA Research Center for Alcoholic Liver and Pancreatic Diseases, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · J Gastroenterol Hepatol. · Pubmed #18336657 links to  free full text

Abstract: Accumulation of unfolded or malfolded proteins induces endoplasmic reticulum (ER) stress which elicits a complex network of interacting and parallel responses that dampen the stress. The ER stress response in the liver is controlled by intrinsic feedback effectors and is initially protective. However, delayed or insufficient responses or interplay with mitochondrial dysfunction may turn physiological mechanisms into pathological consequences including apoptosis, fat accumulation and inflammation all of which have an important role in the pathogenesis of liver disorders such as genetic mutations, viral hepatitis, insulin resistance, ischemia/reperfusion injury, and alcoholic and non-alcoholic steatosis. In both alcohol and non-alcohol-induced ER stress, a common candidate is hyperhomocysteinemia. Betaine supplementation and/or expression of betaine-homocysteine methyltransferase (BHMT) promote removal of homocysteine and alleviate ER stress, fatty accumulation and apoptosis in cultured hepatocytes and mouse models. The rapidity and magnitude of homocysteine-induced activation of each of the main ER resident transmembrane sensors including inositol requiring enzyme 1 (IRE-l alpha), activating transcription factor 6 (ATF-6) and RNA-activated protein kinase (PKR)-like ER kinase (PERK) appear different in different experimental models. Dissection and differentiation of ER stress signaling may reveal clues on the specific importance of the ER stress response in contributing to liver injury and thus provide better strategies on prevention and treatment of liver disease.

Tsukamoto H, She H, Hazra S, Cheng J, Wang J. · USC-UCLA Research Center of ALPD and Cirrhosis, Department of Pathology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA. · J Gastroenterol Hepatol. · Pubmed #18336651 No free full text.

Abstract: Alcoholic and non-alcoholic steatohepatitis (ASH and NASH) constitute two major types of chronic liver disease with worldwide prevalence and are histologically indistinguishable with shared pathogenetic mechanisms. More importantly, they have synergistic interactions for liver pathology. Comparative studies on ASH and NASH have been hampered by the use of different animal models with confounding variables, particularly those with extreme genetic, toxic, and malnutrition etiologies. The mouse intragastric model circumvents these problems and reproduces the natural course and etiological background of ASH and NASH. Further, our recent work reproduces a profound synergism between the two in the model. Intracellular accumulation of neural lipids is a hallmark biochemical feature of ASH and NASH. Although impaired lipid oxidation and export may contribute to this pathological change, enhanced lipogenic regulation is frequently encountered, as characterized by induction of lipogenic or adipogenic transcription factors (peroxisome proliferator-activated receptor [PPAR gamma], liver X receptor alpha[LXR alpha], sterol-regulatory element-binding protein-1c [SREBP-1c]). In contrast, we have recently defined transdifferentiation of hepatic stellate cells (HSC), a pivotal event in liver fibrogenesis, as an 'antilipogenic' or 'anti-adipogenic' phenomenon. Thus, there is an apparent paradox between hepatocytes and HSC in steatohepatitis in terms of the outcome of lipogenic regulation. Our recent work suggests that defective insulin signaling in activated HSC may be responsible for this paradox. Further, activated Wnt signaling is implicated in 'anti-adipogenic' stellate cell transdifferentiation in liver fibrogenesis.

Poordad F, Reddy KR, Martin P. · Hepatology and Liver Transplantation, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. · Clin Infect Dis. · Pubmed #18171217 No free full text.

Abstract: BACKGROUND: Rapid virologic response (RVR), defined as an undetectable serum hepatitis C virus (HCV) RNA level at week 4 of treatment, is emerging as an important milestone in the treatment of patients who have chronic hepatitis C by use of pegylated interferon-alfa and ribavirin--the current standard of care. This assessment is being used to individualize treatment duration, which is currently recommended as 48 weeks in patients infected with HCV genotype 1 (G1) and 24 weeks in those infected with HCV G2 or G3. METHODS: We collated information from studies including assessment of HCV RNA level at week 4, specifically highlighting the relationship between RVR and other predictors of treatment outcome and the manner in which RVR can be used to optimize treatment outcomes for specific patient groups. RESULTS: The role of RVR in the treatment of patients with chronic hepatitis C varies according to viral genotype. Among patients with HCV G2/G3 infection, several studies have shown that shortening the treatment duration to 12-16 weeks is effective among those who attain RVR. In contrast, RVR may be used as an indicator for both shortened and extended treatment durations among patients with HCV G1 infection. HCV G1-infected patients with low baseline viral load who attain RVR may be effectively treated for 24 weeks, whereas patients who do not attain RVR may be candidates for an extended 72-week regimen. CONCLUSIONS: RVR is rapidly becoming a new tool for predicting treatment outcomes in patients with chronic hepatitis C and represents a key opportunity to individualize therapy according to treatment-related viral kinetics.

Liebman H. · Hematology Section, Department of Medicine, University of Southern California-Keck School of Medicine, Division of Cancer Medicine and Blood Diseases, Los Angeles, CA. · Semin Hematol. · Pubmed #18096469 No free full text.

Abstract: Immune thrombocytopenic purpura (ITP) can be classified as primary (known also as idiopathic thrombocytopenic purpura) or as secondary to an underlying condition such as a malignant or nonmalignant disorder. Commonly occurring conditions associated with secondary ITP include lymphoproliferative disorders (chronic lymphocytic leukemia [CLL], Hodgkin's disease and non-Hodgkin's lymphomas), autoimmune collagen vascular diseases (systemic lupus erythematosus [SLE], thyroid disease, antiphospholipid syndrome [APS]), and chronic infections (human immunodeficiency virus [HIV], Helicobacter pylori, hepatitis C virus [HCV]). The mechanism of platelet destruction in thrombocytopenias associated with lymphoproliferative disorders and collagen vascular diseases is identical to the autoimmune mechanism seen in primary ITP. Drug-induced thrombocytopenias are uncommon and generally resolve quickly upon drug discontinuation, but are often attributed to other causes. Platelet destruction in infection-associated ITP occurs via various mechanisms including accelerated platelet clearance due to immune complex disease as seen in HIV infection or cross-reactivity of anti-platelet glycoprotein antibodies and viral antigens in HIV, HCV, and H pylori infections (antigenic mimicry). In patients with HCV-related cirrhotic liver disease, splenic sequestration secondary to portal hypertension and decreased production of thrombopoietin may further contribute to development of thrombocytopenia. The current treatment paradigm for secondary ITP varies according to the underlying condition. Standard treatments for primary ITP (corticosteroids, IVIG, anti-D, splenectomy) are often successful in secondary ITP. In cases of ITP with H pylori and HCV infection, treatment should focus on the underlying disorder.

Pham PT, Pham PC, Lipshutz GS, Wilkinson AH. · Kidney and Pancreas Transplantation, Department of Medicine, University of California, Los Angeles, CA 90095-1693, USA. · Endocrinol Metab Clin North Am. · Pubmed #17983926 No free full text.

Abstract: This article presents an overview of the literature on the current diagnostic criteria for new onset diabetes mellitus after transplantation (NODAT) and discusses suggested risk factors for the development of NODAT, its potential pathogenic mechanisms, and its impact on post-transplant outcomes after solid organ transplantation. Suggested guidelines for early identification and management of NODAT are also discussed.

Kaplowitz N, Than TA, Shinohara M, Ji C. · Department of Medicine, USC-UCLA Research Center for Alcoholic and Pancreatic Diseases and USC Research Center for Liver Diseases, Keck School of Medicine University of Southern California, Los Angeles, California CA 90033, USA. · Semin Liver Dis. · Pubmed #17979073 No free full text.

Abstract: Endoplasmic reticulum stress, initiated by protein overload or malfolding, activates a complex network of interacting and parallel responses that dampen the stress. However, when the protective response is insufficient, a set of responses leads to apoptosis. Coupled with the latter are promotion of lipid synthesis and proinflammatory responses. Evidence has been mounting for an important role of the endoplasmic reticulum (ER) stress response in the pathogenesis of chronic viral hepatitis, insulin resistance and nonalcoholic fatty liver disease, ischemia-reperfusion injury, genetic disorders of protein malfolding, and alcoholic liver disease. In the latter, a key candidate for inducing ER stress is hyperhomocysteinemia. Betaine treatment promotes removal of homocysteine and prevents ER stress, fatty liver, and apoptosis in a mouse model of alcohol-induced liver disease. With increasing interest in the potential role of ER stress in liver disease, greater understanding of pathophysiology, prevention, and treatment of liver disease is anticipated.

Martyak LA, Taqavi E, Saab S. · Department of Medicine, University of California at Los Angeles, Los Angeles, CA 90095, USA. · Liver Int. · Pubmed #17976155 No free full text.

Abstract: BACKGROUND: Hepatitis B viral (HBV) reactivation in patients undergoing chemotherapy is associated with significant morbidity and mortality. Lamivudine has been suggested to be useful as a prophylaxis for HBV reactivation; however, its impact on overall survival and HBV reactivation-related liver disease survival is unclear. OBJECTIVE: To determine the effect of lamivudine prophylaxis on the rate of HBV reactivation, overall survival and HBV reactivation-related survival in patients with HBV undergoing chemotherapy. METHODS: A comprehensive search of MEDLINE, Cochrane Collaboration Database, reference lists and abstracts from national meetings. Statistical analysis was performed using revman. RESULTS: Eleven studies met the defined inclusion criteria and were included in the analysis. Two-hundred and twenty patients received lamivudine prophylaxis and 400 did not receive prophylaxis. Patients given lamivudine prophylaxis had an 87% decrease in HBV reactivation [risk ratio (RR) 0.13, 95% confidence interval (CI), 0.07-0.24] than patients not given prophylaxis [absolute risk reduction (ARR) -0.46, 95% CI, -0.61 to -0.31]. The number needed to treat to prevent one reactivation was 3. The Lamivudine prophylaxis group was also associated with a 70% reduction in reactivation-related mortality (RR 0.30, 95% CI, 0.1-0.94) compared with controls (ARR -0.03, 95% CI, 0.07-0.00). There was a reduction in treatment delays and premature termination of chemotherapy in the lamivudine prophylaxis arm (RR 0.41, 95% CI, 0.27-0.63; ARR -0.33, 95% CI, -0.33 to -0.15). There was no significant heterogeneity in the comparisons. CONCLUSION: Lamivudine prophylaxis during chemotherapy is effective in reducing the rate of HBV reactivation, and reactivation-related liver mortality. Patients with lamivudine prophylaxis had less chemotherapy treatment delays and premature termination of their chemotherapy. Few patients need to be treated to prevent reactivation. Patients with HBV undergoing chemotherapy should be started on lamivudine prophylaxis.

Liebman HA, Stasi R. · University of Southern California-Keck School of Medicine, Los Angeles, California, USA. · Curr Opin Hematol. · Pubmed #17934365 No free full text.

Abstract: PURPOSE OF REVIEW: The American Society of Hematology and British Committee for Standards in Haematology guidelines for the diagnosis and management of immune thrombocytopenic purpura focused entirely on primary disease, and secondary forms were not addressed. The guidelines did not address thrombocytopenia resulting from autoimmune disorders or chronic infections such as Helicobacter pylori, hepatitis C virus or HIV. RECENT FINDINGS: Antiphospholipid antibodies can be detected in roughly 50% of patients diagnosed with primary immune thrombocytopenic purpura, and are not associated with distinctive clinical features. The incidence of thrombotic events is controversial. The prevalence of H. pylori infection in adult patients may not be different from that of the general healthy population matched for age and geographical area. Eradication of the infection can produce platelet responses in a variable number of individuals and is less costly and toxic when compared with standard therapy. Finally, patients with risk factors (multiple sex partners, intravenous drug abuse, blood transfusion recipients) and chronic thrombocytopenia should be screened for hepatitis C virus or HIV infection and should be treated for these infections, not immune thrombocytopenic purpura. SUMMARY: In secondary forms of immune thrombocytopenic purpura, when the hematologist plays a consultative role, priority should be treatment of the underlying disorder.

Tsukamoto H. · Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis, Department of Pathology, Keck School of Medicine of the University of Southern California, 1333 San Pablo Street, MMR-402, Los Angeles, CA 90033-9141, USA. · J Gastroenterol. · Pubmed #17701122 No free full text.

Abstract: The concept that alcoholic liver disease (ALD) is as a toxic disease does not mirror the exact nature of the disease. ALD should be defined as an alcohol-associated lifestyle disease, the predisposition to which is largely governed by gene-environment interactions, much like other chronic diseases such as diabetes, atherosclerosis, and neurodegenerative diseases. The epidemiology and pathogenesis of ALD need to be re-addressed from this viewpoint. Specifically, the interactions between alcohol and secondary risk factors (high-fat diet, iron, tobacco, medications, female gender) and comorbidities (viral hepatitis, diabetes) are of urgent epidemiological importance. Molecular characterization of the interfaces of these interactions is essential for revelation or acquisition of new pathogenetic, preventive, and therapeutic insights.

Finch CE, Morgan TE. · Davis School of Gerontology and USC College, Dept. Biological Sciences, University of Southern California, Los Angeles, CA 90089-0191, USA. · Curr Alzheimer Res. · Pubmed #17430245 No free full text.

Abstract: Alzheimer disease (AD) includes inflammatory processes in the senile plaques and surrounding glia, with increased expression of acute phase proteins such as C-reactive protein (CRP) and IL-6. Increased IL-6 expression during normal brain aging suggests a link of age-related inflammation to the onset of AD during aging. Blood levels of CRP and IL-6 are also associated with higher risk of Alzheimer disease and cognitive decline during aging. Some infections are known to induce inflammation and amyloid deposits. For example, HIV induces the deposition of the same beta-amyloid as in Alzheimer disease. The ApoE4 allele may increase HIV-associated dementia, in addition to its well-known effect on accelerating the onset age of AD. Many other adverse effects of apoE4 are recognized, which suggested the hypothesis that apoE4 persists in human populations because of balancing selection (Charlesworth-Martin hypothesis). The apoE4 allele was acquired during human evolution and may have conferred initial advantages in pathogen resistance. As evidence for this hypothesis, apoE4 carriers have less severe liver damage during hepatitis C infections. As human lifespan lengthened and cognitive and cardiovascular health became more important, the apoE3 allele spread, while the E4 allele was maintained in all populations by balancing selection.

Dennert G, Aswad F. · Department of Molecular Microbiology and Immunology, University of Southern California, Keck School of Medicine, Los Angeles, CA 90033-0800, USA. · Crit Rev Immunol. · Pubmed #17341188 No free full text.

Abstract: NKT cells expressing invariant T-cell receptors are an abundant cell population in the mouse liver, and much evidence has been accumulating which shows that they play an important role in immune responses in this organ. In this review, the putative function of NKT cells in autoimmune hepatitis is discussed based on results from various mouse models. Features and functions of invariant NKT cells are summarized to set the stage to explain how these cells induce liver injury following the injection of mitogen concanavalin A or NKT-cell receptor ligand alpha-GalCer. Results are discussed which show that alcohol consumption can aggravate liver injury by NKT cells, whereas expression of a hepatitis C virus protein in hepatocytes can protect against injury. Hepatocytes, therefore, can modulate sensitivity to NKT-cell-mediated attack. Moreover, experiments that elucidate how NKT cells induce liver injury and how they are regulated to perform this function are discussed. Specific attention is given to the recently discovered role of purinergic receptor P2X7 in regulating NKT cells. The conclusion is drawn that the P2X7 receptor constitutes a sensor that senses purine-based danger signals, which trigger mechanisms that cause inhibition or stimulation of NKT-cell functions.

Rongey C, Kaplowitz N. · Robert Wood Johnson Clinical Scholars Program, University of California at Los Angeles, 911 Broxton Avenue, Los Angeles, CA 90024, USA. · World J Gastroenterol. · Pubmed #17109510 links to  free full text

Abstract: The treatment of alcoholic hepatitis remains one of the most debated topics in medicine and a field of continued research. In this review, we discuss the evolution of scoring systems, including the recent development of the Glasgow alcoholic hepatitis score, role of liver biopsy and current treatment interventions. Studies of treatment interventions with glucocorticoids, pentoxifylline, infliximab, s-adenosyl-methionine, and colchicine are reviewed with discussion on quality. Glucocorticoids currently remain the mainstay of treatment for severe alcoholic hepatitis.

Han SH. · David Geffen School of Medicine at UCLA, Los Angeles, California 90095-7302, USA. · Drugs. · Pubmed #17040114 No free full text.

Abstract: Chronic hepatitis B virus infection afflicts 400 million people worldwide and untreated will progress to cirrhosis in 15-40% of individuals, with an associated increased risk for the development of hepatocellular carcinoma. The 'inactive carrier state' carries a benign prognosis with a very low risk of cirrhosis or hepatocellular carcinoma. However, the hepatitis B e antigen (HBeAg)-positive chronic hepatitis state is an active disease state with increased risk for progressing to cirrhosis and hepatocellular carcinoma. The HBeAg-negative mutant variety of chronic hepatitis B has been associated with a higher incidence of cirrhosis at initial presentation and more frequent progression to hepatocellular carcinoma compared with the wild-type hepatitis B.Five medications are currently approved by the US FDA for the treatment of chronic hepatitis B: interferon-alpha, lamivudine, adefovir dipivoxil, entecavir and peginterferon-alpha-2a. Interferon-alpha therapy has been shown to increase the rate of HBeAg and hepatitis B DNA loss with a small chance of hepatitis B surface antigen loss, but has significant adverse effects and is ineffective against the HBeAg-negative mutant. Lamivudine is a safely used, orally administered drug with good efficacy, but is associated with the development of a lamivudine-resistant (Lam-R) mutant in a large proportion of patients after long-term therapy. High relapse rates after lamivudine therapy make this medication less effective in the HBeAg-negative mutant also. Adefovir dipivoxil is a safely used, orally administered drug, which is effective against the Lam-R mutant. Adefovir dipivoxil is effective against the wild-type and HBeAg-negative hepatitis B and has a very low incidence of resistance development. Entecavir is a highly potent and selective new oral drug against hepatitis B. It has demonstrated no resistance development in treatment-naive patients, but a low incidence of resistance in patients infected with prior Lam-R mutants. Peginterferon-alpha-2a is administered once weekly and has improved efficacy compared with standard interferon-alpha and lamivudine. However, it has a similar adverse-effect profile to standard interferon-alpha. Pharmacoeconomic studies have demonstrated a cost benefit in treating chronic hepatitis B patients compared with no therapy. However, results have been conflicting, with earlier studies showing a cost advantage of lamivudine over interferon-alpha and a more recent, comprehensive study favouring interferon-alpha monotherapy in HBeAg-negative patients and adefovir dipivoxil 'salvage' after lamivudine resistance development in HBeAg-positive patients.

Kalantar-Zadeh K, Daar ES, Eysselein VE, Miller LG. · Division of Nephrology and Hypertension, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, 1124 West Carson Street, C1-Annex, Torrance, CA 90509-2910, USA. · Int Urol Nephrol. · Pubmed #17009087 No free full text.

Abstract: Among the 350,000 maintenance dialysis patients in the USA, the mortality rate is high (20-23% per year) as is the prevalence of hepatitis C virus (HCV) infection (5-15%). An additional same number of dialysis patients in the USA may be infected with HCV but have undetectable HCV antibodies. Almost half of all deaths in dialysis patients, including HCV-infected patients, are due to cardiovascular disease. Since over two-thirds of dialysis patients die within 5 years of initiating dialysis and because markers of malnutrition-inflammation complex syndrome (MICS), rather than traditional cardiovascular risk factors, are among the strongest predictors of early death in these patients, the impact of HCV infection on nutritional status and inflammation may be a main cause of poor survival in this population. Based on data from our cross-sectional and limited longitudinal studies, we hypothesize that HCV infection confounds the association between MICS and clinical outcomes in dialysis patients and, by doing so, leads to higher short-term cardiovascular events and death. Understanding the natural history of HCV and its association with inflammation, nutrition and outcomes in dialysis patients may lead to testing more effective anti-HCV management strategies in this and other similar patient populations, providing benefits not only for HCV infection but the detrimental consequences associated with this infection. In this article, we review the link between the HCV infection and mortality in dialysis patients and compare HCV antibody to molecular methods to detect HCV infection in these individuals.

Cameron AM, Busuttil RW. · Dumont-UCLA Liver Transplant Center, David Geffen School of Medicine at UCLA, Department of Surgery, 10833 LeConte Ave, 77-132 CHS, Los Angeles, CA 90095, USA. · Expert Opin Biol Ther. · Pubmed #16989581 No free full text.

Abstract: The hepatitis C virus (HCV) infects 3% of the world's population, or approximately 170 million people. Most of those acutely infected progress to chronic infection and are unresponsive to existing antiviral treatment. Over a 20-year period, chronic HCV infection leads to cirrhosis and the sequelae of end-stage liver disease, including hepatic encephalopathy, ascites, variceal haemorrhage and hepatocellular carcinoma. Orthotopic liver transplantation (OLT) is the optimal treatment for decompensated HCV cirrhosis, but is limited by organ availability and universal graft reinfection. This review discusses the results with OLT for HCV from the Dumont-UCLA Liver Transplant Center and discusses future directions in the management of HCV.

Desai SB, Furst DE. · Department of Rheumatology, University of California, Los Angeles, CA 90095-1670, USA. · Best Pract Res Clin Rheumatol. · Pubmed #16979537 No free full text.

Abstract: Worldwide, over 400,000 patients have been treated with tumour necrosis factor (TNF)-alpha antagonists for indications that include rheumatoid arthritis, juvenile rheumatoid arthritis, inflammatory bowel disease, psoriatic arthritis and ankylosing spondylitis. Since their approval, concerns regarding safety have been raised. There is a risk of re-activation of granulomatous diseases, especially tuberculosis, and measures should be taken for detection and treatment of latent tuberculosis infections. Preliminary data suggest that anti-TNF therapy may be safe in chronic hepatitis C. However, TNF-alpha antagonists have resulted in re-activation of chronic hepatitis B if not given concurrently with antiviral therapy. Solid tumours do not appear to be increased with anti-TNF therapy. Variable rates of increased lymphoma risk have been described with anti-TNF therapy compared with the general population, although no increased risk was found compared with a rheumatoid arthritis population. Large phase II and III trials with TNF-alpha antagonists in advanced heart failure have shown trends towards a worse prognosis, and should therefore be avoided in this population. Both etanercept and infliximab are associated with the formation of autoantibodies, and these autoantibodies are rarely associated with any specific clinical syndrome. Rare cases of aplastic anaemia, pancytopenia, vasculitis and demyelination have been described with anti-TNF therapy. This chapter will discuss the safety profile and adverse events of the three commercially available TNF-alpha antagonists: etanercept, infliximab and adalimumab. The data presented in this review have been collected from published data, individual case reports or series, package inserts, the Food and Drug Administration postmarketing adverse events surveillance system, and abstracts from the American College of Rheumatology and European Congress of Rheumatology meetings for 2005.