Hepatitis: Los Angeles area

Macnaughton TB, Lai MM. · Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles 90033, USA. · Curr Top Microbiol Immunol. · Pubmed #16903219 No free full text.

Abstract: HDV replicates its circular RNA genome using a double rolling-circle mechanism and transcribes a hepatitis delta antigen-encodeing mRNA from the same RNA template during its life cycle. Both processes are carried out by RNA-dependent RNA synthesis despite the fact that HDV does not encode an RNA-dependent RNA polymerase (RdRP). Cellular RNA polymerase II has long been implicated in these processes. Recent findings, however, have shown that the syntheses of genomic and antigenomic RNA strands have different metabolic requirements, including sensitives to alpha-amanitin and the site of synthesis. Evidence is summarized here for the involvement of other cellular polymerases, probably pol I, in the synthesis of antigenomic RNA strand. The ability of mammalian cells to replicate HDV RNA implies that RNA-dependent RNA synthesis was preserved throughout evolution.

Liu ZX, Kaplowitz N. · Research Center for Liver Diseases, Keck School of Medicine, University of Southern California, Los Angeles, 90033, USA. · Expert Opin Drug Metab Toxicol. · Pubmed #16859400 No free full text.

Abstract: Acetaminophen (APAP) hepatotoxicity is currently the single most important cause of acute liver failure in the US, and is associated with a significant number of deaths. The toxic response to APAP is triggered by a highly reactive metabolite N-acetyl-p-benzoquinone-imine. Following the hepatocellular initiation events, such as glutathione depletion and covalent binding, intracellular stress simultaneously activates signal transduction and transcription factor pathways that are protective or toxic (directly or through sensitisation). Subsequently, pro- and anti-inflammatory cascades of the innate immune system are simultaneously activated, the balance of which plays a major role in determining the progression and severity of APAP-induced hepatotoxicity. The threshold and susceptibility to APAP hepatotoxicity is determined by the interplay of injury promoting and inhibiting events downstream of the initial production of toxic metabolite. The environmental and genetic control of these intracellular and intercellular responses to toxic metabolites may be of critical importance in determining susceptibility to APAP hepatotoxicity and presumably idiosyncratic drug hepatotoxicity.

Lane TE, Hardison JL, Walsh KB. · Department of Molecular Biology and Biochemistry, University of California, 3205 McGaugh Hall, Irvine, CA 92697-3900, USA. · Curr Top Microbiol Immunol. · Pubmed #16570854 No free full text.

Abstract: Encounters with neurotropic viruses result in varied outcomes ranging from encephalitis, paralytic poliomyelitis or other serious consequences to relatively benign infection. One of the principal factors that control the outcome of infection is the localized tissue response and subsequent immune response directed against the invading toxic agent. It is the role of the immune system to contain and control the spread of virus infection in the central nervous system (CNS), and paradoxically, this response may also be pathologic. Chemokines are potent proinflammatory molecules whose expression within virally infected tissues is often associated with protection and/or pathology which correlates with migration and accumulation of immune cells. Indeed, studies with a neurotropic murine coronavirus, mouse hepatitis virus (MHV), have provided important insight into the functional roles of chemokines and chemokine receptors in participating in various aspects of host defense as well as disease development within the CNS. This chapter will highlight recent discoveries that have provided insight into the diverse biologic roles of chemokines and their receptors in coordinating immune responses following viral infection of the CNS.

Jamal MM, Saadi Z, Morgan TR. · Long Beach VA Medical Center and University of California, Irvine, Long Beach, CA 90822, USA. · Dig Dis. · Pubmed #16508293 No free full text.

Abstract: BACKGROUND/AIMS: Alcohol use and hepatitis C are prominent risk factors for liver injury and this review offers the current understanding of each factor's effects on liver disease. METHODS: A Medline database search was preformed for English articles with a focus on alcohol, hepatitis C and liver disease. Article citations were also considered for further applicable articles, and the strongest studies were included in our review. RESULTS: Up to 60% of patients with hepatitis C have a past history of alcohol use. In patients with hepatitis C, chronic alcohol consumption of more than 5 drinks/day increases the rate of liver fibrosis, risk for cirrhosis, hepatocellular carcinoma, and, possibly, death from liver disease. Numerous studies have further found that even moderate amounts of alcohol can be detrimental to hepatitis C patients. The prevalence of hepatitis C is higher in alcoholics with advanced liver disease than in alcoholics without liver disease. Also, recent alcohol use decreases the response rate to interferon treatment. CONCLUSIONS: Hepatitis C and alcohol use are often co-occurring risk factors for liver disease, and though their interaction is not clear, it is known that heavy drinking significantly promotes liver disease progression.

Kim JW, Park SH, Louie SG. · School of Pharmacy, University of Southern California (USC), Los Angeles, 90089, USA. · Ann Pharmacother. · Pubmed #16507625 No free full text.

Abstract: OBJECTIVE: To review available literature on the pharmacology, pharmacokinetics, dosing and administration, efficacy, and safety of the antiviral nucleoside analog telbivudine. DATA SOURCES: Information was obtained from searching MEDLINE (1966-December 2005), International Pharmaceutical Abstracts (1970-December 2005), and the Cochrane Database of Systematic Reviews (4th quarter 2005) using the search words telbivudine, L-dT, L-deoxythymidine, L-nucleosides, and nucleosides. Abstracts from the Annual Meeting of the American Association for the Study of Liver Diseases and European Association for the Study of the Liver were also searched, including bibliographies from the identified articles. STUDY SELECTION AND DATA EXTRACTION: Data from double-blind, placebo-controlled clinical trials and unpublished information were extracted. DATA SYNTHESIS: Telbivudine is a novel, orally administered nucleoside analog under development for use in the treatment of chronic hepatitis B. In contrast to other nucleoside analogs, telbivudine has not been associated with inhibition of mammalian DNA polymerase with mitochondrial toxicity. Telbivudine demonstrated potent activity against hepatitis B with significantly higher rate of response and superior viral suppression compared with lamivudine, the standard treatment. Telbivudine has been generally well tolerated, with low adverse effect profile, and at its effective dose, no dose-limiting toxicity has been observed. CONCLUSIONS: Telbivudine is a novel oral nucleoside analog effective in the treatment of chronic hepatitis B infection.

Shaye OS, Levine AM. · Division of Hematology, Department of Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · J Natl Compr Canc Netw. · Pubmed #16507274 No free full text.

Abstract: Marginal zone lymphomas (MZLs) comprise 3 distinct entities: extranodal MZL of mucosa-associated lymphoid tissue (MALT), splenic MZL, and nodal MZL. Gastric MALT lymphoma is the most common extranodal MZL and often develops as a result of chronic Helicobacter pylori gastritis. Such cases frequently respond to antibiotics directed against H. pylori. Antigen-driven lymphomatous disease can also be seen in the association of Borrelia burgdorferi with MALT lymphoma of the skin, Chlamydia psittaci with MALT lymphoma of the ocular adnexa, Campylobacter jejuni with immunoproliferative disease of the small intestine, and hepatitis C with splenic MZL. This article discusses the pathogenesis and clinical features of MZL and the treatment options available to patients.

Khalsa AM. · University of Southern California, Keck School of Medicine, Los Angeles, USA. · Am Fam Physician. · Pubmed #16445273 links to  free full text

Abstract: The epidemic of human immunodeficiency virus (HIV) continues, and the infection is converting into a treatable chronic disease; therefore, it is increasingly important for family physicians to be current with and comfortable in providing basic care to patients infected with HIV. Important aspects of counseling and patient education include stabilization of psychosocial issues and prevention of HIV transmission through behavior change counseling. Reporting HIV and acquired immunodeficiency syndrome (AIDS) is mandatory in most states, whereas partner notification laws vary from state to state. Baseline evaluation includes screening for comorbid conditions such as viral hepatitis, syphilis, and tuberculosis, as well as common HIV-related manifestations such as recurrent candidal infections and thrombocytopenia. Baseline testing includes CD4+ T-lymphocyte cell counts and HIV viral RNA levels to assess HIV disease stage, and numerous studies to screen for opportunistic infections. Initial preventive interventions include patient education to reduce exposure to infections, treatment of comorbid conditions such as human papillomavirus-related dysplasia, and vaccinations such as for pneumococcus and hepatitis B. Prophylaxis against opportunistic pathogens is recommended when CD4+ cell counts fall below 200 cells per mm3. Lastly, the indications for antiretroviral therapy include symptomatic patients or those with AIDS, and pre-AIDS patients with CD4+ cell counts of 200 to 350 cells per mm3 or HIV RNA above 55,000 to 100,000 copies per mL.

Nyamathi AM, Christiani A, Windokun F, Jones T, Strehlow A, Shoptaw S. · UCLA School of Nursing, UCLA, Los Angeles, CA 90095-1702, USA. · AIDS. · Pubmed #16251826 No free full text.

Abstract: OBJECTIVES: Homeless youth are at a high risk of substance abuse, mental illness and blood-borne infections, such as hepatitis C. In this paper, we review the implications of these conditions, discuss the unique challenges faced by homeless youth, and explore potential strategies for harm reduction and intervention in this vulnerable population. RESULTS: Interventions that combine youth-centered, service-based care, street outreach, case management, and motivational interviewing with integrated health services such as hepatitis A/B vaccination, and mental health and substance abuse programmes, are presented as innovative approaches to address the healthcare needs of homeless youth. CONCLUSION: Recommendations for age-appropriate interventions and further research are made.

Wagner GJ, Ryan GW. · RAND Corporation, Santa Monica, CA 90407, USA. · AIDS. · Pubmed #16251817 No free full text.

Abstract: Hepatitis C virus (HCV)-related liver disease is among the leading causes of mortality among HIV patients, yet very few co-infected patients receive pegylated-interferon and ribavirin combination therapy, the standard of care for chronic HCV. Whereas factors related to the provider, patient and clinic setting all contribute to HCV treatment decision-making, the decision of the provider to recommend or defer treatment is perhaps the most critical determinant of whether a patient receives treatment. This paper reviews the literature related to the medical, behavioral and mental health variables that contribute to providers' assessment of treatment readiness, and associations with treatment response, adherence and retention. A greater understanding of the multilevel factors contributing to HCV treatment decision-making, as well as patient characteristics that predict treatment outcome and adherence, can inform the development of interventions aimed at improving HCV care for HIV patients.

Tangkijvanich P, Yee HF. · Department of Medicine (Digestive Diseases), UCLA School of Medicine, Los Angeles, California 90095, USA. · Eur J Surg Suppl. · Pubmed #16144208 No free full text.

Abstract: Cirrhosis, a pathological condition defined by deranged hepatic architecture resulting from progressive fibrosis, is the final common pathway through which nearly all chronic diseases of the liver produce morbidity and mortality. Historically, treatments for hepatic fibrosis have been directed against specific causes of chronic liver injury, and include corticosteroids for autoimmune hepatitis, interferon for hepatitis B and C, and iron depletion for haemochromatosis. However, there is no effective treatment for most causes of chronic liver disease. Fortunately, the past decade has witnessed great advances in our understanding of the fundamental pathophysiological mechanisms underlying fibrosis of the liver. It is now recognised that hepatic stellate cells (myofibroblast-like cells that encircle the sinusoids) are primarily responsible for hepatic fibrosis and subsequent progression to cirrhosis. In response to liver injury stellate cells undergo a phenotypic transformation that is termed activation, and characterised by chemotaxis, proliferation, contraction, fibrogenesis, and extracellular matrix degradation. Under conditions of persistent injury the behavioural responses of these stellate cells act in concert to bring about fibrosis of the liver. Recent investigations elucidating the signal transduction pathways that link hepatic injury to stellate cell function suggest novel targets at which treatment for fibrosis may be directed. For example, antagonism of TGF-beta receptor signaling has been shown to modulate fibrosis in animal models. This work, as well as other studies in both humans and animals, indicates that hepatic fibrosis may be slowed or reversed. These results suggest that a rational approach to treatment can be developed based on our detailed understanding of the molecular and cellular mechanisms underlying cirrhosis, which will have a major impact on the clinical management of patients with chronic liver disease.

Kim AI, Saab S. · Department of Medicine, West Los Angeles VA Medical Center, Los Angeles, California, USA. · Am J Med. · Pubmed #16084169 No free full text.

Abstract: Hepatitis C virus is a leading cause of chronic liver disease, with over 170 million people infected worldwide. It is also the leading indication for liver transplantation. Complications from chronic hepatitis C infection include cirrhosis, hepatic decompensation, and hepatocellular carcinoma. As a result, treatment strategies to prevent such complications have been widely researched, although many questions remain unanswered. To date, the standard therapy for chronic hepatitis C infection is the combination of peginterferon and ribavirin. Treatment strategies differ based on factors such as genotype and liver biopsy results. Other strategies must be considered for special groups, such as patients with acute hepatitis C infection, hepatitis C/human immunodeficiency virus (HIV) coinfection, and prior nonresponse to interferon or relapse after its use. The goal of therapy is to achieve a sustained virologic response (ie, no detectable hepatitis C ribonucleic acid 6 months after completion of therapy). The substantial adverse effects associated with both interferon alfa and ribavirin often make it difficult for patients to continue with their therapies.

Lai MM. · Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, 2011 Zonal Ave., HMR503C, Los Angeles, California 90033, USA. · J Virol. · Pubmed #15956541 links to  free full text

This publication has no abstract.

Yeh SH. · UCLA Center for Vaccine Research, Los Angeles Biomedical Research Institute at Harbor-UCLA, 1124 W. Carson St, Liu Research Building, Torrance, CA 90502, USA. · Expert Rev Vaccines. · Pubmed #15889985 No free full text.

Abstract: PEDIARIX is the first pentavalent combination vaccine licensed for use in infants in the USA. This vaccine is indicated for the prevention of diphtheria, tetanus, pertussis, hepatitis B and poliovirus. This article reviews the available data regarding the vaccine's immunogenicity and safety.

Han SH. · Pfleger Liver Institute, David Geffen School of Medicine at UCLA, 200 UCLA Medical Plaza, Suite 214, Los Angeles, CA 90095, USA. · Expert Opin Investig Drugs. · Pubmed #15882124 No free full text.

Abstract: Telbivudine, beta-L-2'-deoxythymidine (LdT), is a new beta-L-nucleoside analogue with potent inhibitory activity against the hepatitis B virus. In in vitro studies and animal models, telbivudine has demonstrated potent and specific antiviral activity against hepatitis B. Additionally, in preclinical animal toxicology studies, telbivudine showed no adverse side effects or adverse effects on mitochondrial function. The promising results of the early in vitro and animal telbivudine studies prompted the development and initiation of Phase I and II human clinical trials. The Phase I clinical study demonstrated that end-of-treatment virological response rates were better for telbivudine recipients at multiple dosing levels as compared with placebo patients. The subsequent Phase IIb human clinical study demonstrated superior antiviral efficacy of telbivudine, significantly better ALT normalisation and better hepatitis B e-antigen loss as compared with lamivudine. Telbivudine was well tolerated with no identified safety issues. Virological breakthrough with telbivudine was significantly lower than with lamivudine.

Giboney PT. · Keck School of Medicine, University of Southern California, Los Angeles, California, USA. · Am Fam Physician. · Pubmed #15791889 links to  free full text

Abstract: Mild elevations in liver chemistry tests such as alanine transaminase and aspartate transaminase can reveal serious underlying conditions or have transient and benign etiologies. Potential causes of liver transaminase elevations include viral hepatitis, alcohol use, medication use, steatosis or steatohepatitis, and cirrhosis. The history should be thorough, with special attention given to the use of medications, vitamins, herbs, drugs, and alcohol; family history; and any history of blood-product transfusions. Other common health conditions, such as diabetes, heart disease, and thyroid disease, can cause or augment liver transaminase elevations. The recent American Gastroenterological Association guideline regarding the evaluation and management of abnormal liver chemistry tests proposes a practical, algorithmic approach when the history and physical examination do not reveal the cause. In addition to liver chemistries, an initial serologic evaluation includes a prothrombin time; albumin; complete blood count with platelets; hepatitis A, B, and C serologies; and iron studies. Depending on the etiology, management strategies may include cessation of alcohol use, attention to medications, control of diabetes, and modification of lifestyle factors such as obesity. If elevations persist after an appropriate period of observation, further testing may include ultrasonography and other serum studies. In some cases, biopsy may be indicated.

Spiegel BM, Younossi ZM, Hays RD, Revicki D, Robbins S, Kanwal F. · Division of Gastroenterology, VA Greater Los Angeles Healthcare System, USA. · Hepatology. · Pubmed #15791608 No free full text.

Abstract: Hepatitis C virus (HCV) diminishes health related quality of life (HRQOL), and it is now common to measure HRQOL in clinical trials. We sought to summarize the HRQOL data in HCV, and to establish the minimally clinically important difference (MCID) in HRQOL scores in HCV. We performed a systematic review to identify relevant studies, and converted HRQOL data from each study into clinically interpretable statistics. An expert panel used a modified Delphi technique to estimate the MCID in HCV. We found that patients with HCV scored lower than controls across all scales of the SF-36. Patients achieving sustained virological response (SVR) scored higher across all scales versus patients without SVR, especially in the physical health domains. HRQOL differences did not correspond with differences in liver histology or ALT levels. Based upon the published data, the expert panel concluded that the SF-36 vitality scale was most relevant in patients with HCV, and generated a mean MCID of 4.2 points on this scale. In conclusion, patients with HCV have a clinically significant decrement in HRQOL versus controls, and physical HRQOL improves in patients achieving SVR but not in those without SVR. The data further suggest that traditional outcomes fail to capture the full spectrum of illness related to chronic HCV. A difference of 4.2 points on the SF-36 vitality scale can be used as an estimate of the MCID in HCV, and this value may be used as the basis for power calculations in clinical trials evaluating HRQOL. Supplementary material for this article can be found on the HEPATOLOGY website (http://www.interscience.wiley.com/jpages/0270-9139/suppmat/index.html).

Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. · Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center, Los Angeles, CA, USA. · Aliment Pharmacol Ther. · Pubmed #15606388 links to  free full text

Abstract: BACKGROUND: The natural history of hepatitis C virus infection among patients on long-term dialysis treatment remains incompletely understood. Efforts to elucidate the natural history of hepatitis C virus in this population are difficult because of the slowly progressive nature of hepatitis C virus with often an unrecognized onset in patients whose life-expectancy is substantially diminished by end-stage renal disease. AIM: To conduct a systematic review of the published medical literature concerning the impact of hepatitis C virus infection on the survival of patients receiving chronic dialysis. The relative risk of mortality was regarded as the most reliable outcome end-point. METHODS: We used the random effects model of DerSimonian and Laird to generate a summary estimate of the relative risk for mortality with hepatitis C virus across the published studies. RESULTS: We identified four clinical trials (2341 unique patients); three (75%) of them were prospective, cohort studies; the fourth was a case-control study. Pooling of study results demonstrated that presence of antihepatitis C virus antibody was an independent and significant risk factor for death in patients on maintenance dialysis. The summary estimate for relative risk was 1.57 with a 95% confidence interval (CI) of 1.33-1.86. A test for homogeneity of the relative risks across the four studies gave a P-value of 0.77. As a cause of death, hepatocellular carcinoma and liver cirrhosis were significantly more frequent among antihepatitis C virus-positive than -negative dialysis patients. CONCLUSIONS: This meta-analysis demonstrates that antihepatitis C virus-positive patients on dialysis have an increased risk of mortality compared with hepatitis C virus-negative patients. The excess risk of death in hepatitis C virus-positive patients may be at least partially attributed to chronic liver disease with its attendant complications. Clinical trials with extended follow-up are currently under way to assess the effect of hepatitis C virus treatment on the excess risk of mortality in this population.

Poordad FF. · Cedars-Sinai Medical Center, Liver Transplant Dept, 8635 W Third Street, Suite 590W, Los Angeles, CA 90048, USA. · Curr Opin Investig Drugs. · Pubmed #15573871 No free full text.

Abstract: IDN-6556 is a lead compound from a class of small-molecule caspase protease inhibitors, and is currently under development by Idun as a potential treatment for acute alcoholic and infectious hepatitis. In October 2003, a phase II trial of IDN-6556 began in 100 patients undergoing liver transplantation.

Morgan TR, Mandayam S, Jamal MM. · Gastroenterology Section, VA Medical Center, Long Beach, California, USA. · Gastroenterology. · Pubmed #15508108 No free full text.

Abstract: More than 18 million adults in the United States abuse alcohol, a prevalence 5 times higher than that of hepatitis C. Chronic alcohol use of greater than 80 g/day for more than 10 years increases the risk for hepatocellular carcinoma (HCC) approximately 5-fold; alcohol use of less than 80 g/day is associated with a nonsignificant increased risk for HCC. The risk for HCC in decompensated alcohol induced cirrhosis approaches 1% per year. The risk does not decrease with abstinence, and HCC can occur in a noncirrhotic liver. Alcohol use in chronic hepatitis C doubles the risk for HCC as compared with the risk in hepatitis C alone. Furthermore, there may be synergism between alcohol and hepatitis C in the development of HCC, and in these patients HCC may occur at an earlier age and the HCC may be histologically more advanced. Studies in the United States and Italy suggest that alcohol is the most common cause of HCC (accounting for 32%-45% of HCC). The mechanisms by which alcohol causes HCC are incompletely understood, but may include chromosomal loss, oxidative stress, a decreased retinoic acid level in the liver, altered DNA methylation, and genetic susceptibility. Alcohol use is increasing in many countries, suggesting that alcohol will continue to be a common cause of HCC throughout the world.

Yu MC, Yuan JM. · Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA. · Gastroenterology. · Pubmed #15508106 No free full text.

Abstract: Chronic infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are the most important risk factors for the development of hepatocellular carcinoma (HCC) in humans. HBV is the primary cause of HCC in high-risk areas including China and Africa, whereas in developed countries such as the United States, HCV plays a more prominent role and is at least partially responsible for the increase in HCC incidence in this country. Humans are exposed to hepatocarcinogenic aflatoxins through ingestion of moldy foods, a consequence of poor storage of susceptible grains. Highly exposed populations are primarily in sub-Sahara Africa and Asia, where dietary aflatoxins significantly enhance the carcinogenic effects of viral hepatitis. Heavy, long-term alcohol use is a risk factor for HCC, whereas moderate use (1-3 drinks/day) is not. Constituents of cigarette smoke are hepatic carcinogens in animals, and there is mounting evidence that the liver is an organ susceptible to tobacco carcinogenicity. Diabetic patients are at risk for HCC probably as a result of the hepatic injury, fibrosis, and eventual cirrhosis resulting from fatty liver disease. Given the current epidemic of obesity and diabetes in the United States, this risk factor will be increasingly important. Increased risk for HCC is evident in young noncirrhotic users of oral contraceptives in the United States and Europe. In summary, risk factors for HCC are identifiable in most patients and primarily are associated with chronic hepatic injury.

Vaziri ND. · Division of Nephrology and Hypertension, Department of Medicine, Physiology, and Hypertension, University of California Irvine, Irvine, CA, USA. · Semin Nephrol. · Pubmed #15490413 No free full text.

Abstract: Oxidative stress has emerged as a constant feature of chronic renal failure (CRF). The presence of oxidative stress in CRF is evidenced by an overabundance of lipid, carbohydrate, and protein oxidation products in the plasma and tissues of uremic patients and animals. We recently have shown that oxidative stress in CRF animals is associated with and, in part, owing to up-regulation of superoxide-producing enzyme, nicotinamide-adenine dinucleotide phosphate (NAD(P)H) oxidase, and down-regulation of superoxide dismutase (SOD). The functional significance of these findings was confirmed by favorable response to administration of the cell-permeable SOD-mimetic agent, tempol, in CRF rats. Oxidative stress in CRF plays an important role in the pathogenesis of the associated hypertension (oxidation of NO and arachidonic acid and vascular remodeling), cardiovascular disease (oxidation of lipoproteins, atherogenesis), neurologic disorders (nitration of brain proteins, oxidation of myelin), anemia (reduction of erythrocyte lifespan), inflammation (nuclear factor kappa B activation), fibrosis, apoptosis, and accelerated aging. The CRF-induced oxidative stress is aggravated by diabetes, uncontrolled hypertension, and autoimmune diseases, which independently increase production of reactive oxygen intermediates, and frequently are associated with CRF. In addition, dialysis treatment (blood interaction with dialyzer membrane and dialysate impurities), acute and chronic infections (blood access infection, hepatitis, and so forth), and excessive parenteral iron administration intensify CRF-associated oxidative stress and its adverse consequences in patients with end-stage renal disease. The problem is compounded by limited intake of fresh fruits and vegetables (K(+) restriction), which contain numerous natural phytochemicals and antioxidant vitamins.

Poordad FF. · Hepatology & Liver Transplant Center, University of California, Los Angeles, Cedars-Sinai Medical Center 8635 W. 3rd Street, Suite 590W, Los Angeles, CA 90048, USA. · Clin Liver Dis. · Pubmed #15481350 No free full text.

Abstract: Current prophylactic measures have greatly reduced recurrence rates of hepatitis B after liver transplantation. HBIG remains a critically important compound and although there is variability in dosing regimens and target anti-HBs levels, it is the backbone of recurrence prevention. Adjuvant therapies with nucleoside/nucleotide analogs alone have been limited by drug-resistant strains of HBV, but the armamentarium of these molecules continues to grow and hence the management of the post-LT HBV patient will evolve further. Currently lamivudine with HBIG remains an excellent option provided the patient has not developed resistance, especially in the pre-LT period. Adefovir is the drug of choice in that setting and perhaps the preferred drug in the pre-LT setting to allow the use of lamivudine post-LT. Further testing with tenofovir and newer compounds in development will expand these options. The use of multiple nucleoside analogs is an intriguing option, based on the HIV experience of reducing drug resistance and optimizing viral suppression, and will likely be further studied.

Han SH. · Division of Digestive Diseases, Pfleger Liver Institute, David Geffen School of Medicine at UCLA, 200 Medical Plaza, Suite 214, Los Angeles, CA 90095-7302, USA. · Clin Liver Dis. · Pubmed #15481347 No free full text.

Abstract: Several extrahepatic manifestations are associated with chronic HBV infection, many with significant morbidity and mortality. The cause of these extrahepatic manifestations is generally believed to be immune mediated. PAN is a rare, but serious, systemic complication of chronic HBV affecting the small- and medium-sized vessels. PAN is seen more frequently in North American and European patients and rarely in Asian patients. PAN ultimately involves multiple organ systems, some with devastating consequences, though the hepatic manifestations are often more mild. The optimal treatment of HBV-associated PAN is thought to include a combination of antiviral and immunosuppressive therapies. HBV-associated GN occurs mainly in children, predominantly males, in HBV endemic areas of the world, but is only occasionally reported in the United States. In children, GN is usually self-limited with only rare progression to renal failure. In adults, the natural disease course of GN may be more relentless, slowly progressing to renal failure. Immunosuppressive therapy in HBV-related GN is not recommended, but antiviral therapy with alpha-interferon has shown promise. The serum-sickness like "arthritis-dermatitis" prodrome is seen in approximately one third of patients acquiring HBV. The joint and skin manifestations are varied, but the syndrome spontaneously resolves at the onset of clinical hepatitis with few significant sequelae. Occasionally, arthritis following the acute prodromal infection may persist; however, joint destruction is rare. The association between HBV and mixed essential cryoglobulinemia remains controversial; but a triad of purpura, arthralgias, and weakness, which can progress to nephritis, pulmonary disease, and generalized vasculitis, has characterized the syndrome. Finally, skin manifestations of HBV infection typically present as palpable purpura. Though papular acrodermatitis of childhood has been reported to be caused by chronic HBV, this association remains controversial.

Tran TT, Martin P. · Cedars Sinai Medical Center, Geffen School of Medicine, UCLA, 8635 W. 3rd Street, Suite 590W, Los Angeles, CA 90049, USA. · Clin Liver Dis. · Pubmed #15481339 No free full text.

Abstract: Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despite recommendations and implementation of vaccination programs, the health and economic burdens are still significant. People in endemic areas and immigrants from these areas need to be adequately screened and treated. HBeAg-negative chronic hepatitis is increasingly recognized with additional challenges in management. Programs implementing primary prophylaxis strategies such as vaccination of high-risk adult and adolescent groups should continue.

Fabrizi F, Bunnapradist S, Lunghi G, Aucella F, Martin P. · The Center for Liver and Kidney Diseases and Transplantation, Cedars-Sinai Medical Center and UCLA School of Medicine, University of California at Los Angeles, Los Angeles, CA, USA. · Minerva Urol Nefrol. · Pubmed #15467503 links to  free full text

Abstract: Hepatitis C virus (HCV) infection is frequent among patients receiving long-term dialysis in developed and developing countries. It is difficult to assess the natural history of HCV in the dialysis population; however, recent studies have demonstrated that positive anti-HCV status is a significant and independent risk factor for mortality among dialysis patients. Recent meta-analyses have shown that interferon (IFN) initial monotherapy is effective in the treatment of chronic hepatitis C among dialysis patients, but tolerance to IFN mono-therapy was rather poor. Large, multicenter and prospective trials based on pegylated IFN for the treatment of chronic hepatitis C are planned. The frequency of HBV infection in patients undergoing maintenance dialysis in the industrialized world is low but not negligible; persistent HBsAg seropositivity is much higher in less-developed countries. Recent surveys have shown that detectable HBsAg/ HBV DNA status in serum is an independent and significant predictive factor for hepatocellular dysfunction in dialysis patients. No significant difference in morbidity and mortality between dialysis patients according to hepatitis B surface antigen status has been consistently shown. Preliminary reports suggest that lamivudine appears to be safe and effective in patients receiving long-term dialysis.