Hepatitis: San Francisco Bay area

Rosenthal P. · University of California, San Francisco, 94143-0136, USA. · J Pediatr Gastroenterol Nutr. · Pubmed #18367947 No free full text.

Abstract: It is becoming increasingly evident that children, like adults, with chronic viral or metabolic liver diseases are at risk for the development of hepatocarcinoma. The aims of this article are to review the risk factors for hepatocarcinoma in chronic viral or metabolic liver disease, outline potential pathogenic mechanisms of hepatocarcinoma, and describe surveillance strategies, clinical evaluation, and management of hepatocarcinoma in children.

Keeffe EB, Dieterich DT, Pawlotsky JM, Benhamou Y. · Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. · Clin Gastroenterol Hepatol. · Pubmed #18328434 No free full text.

Abstract: Licensed oral agents for antiviral therapy in patients with chronic hepatitis B virus (HBV) infection include lamivudine, adefovir, entecavir, and telbivudine. Emtricitabine, tenofovir, and the combination of tenofovir plus emtricitabine in 1 tablet, which are licensed for the treatment of human immunodeficiency virus infection, are additional off-label options for treating HBV infection. Preventing HBV antiviral drug resistance to nucleoside/nucleotide analogues and appropriate management when resistance occurs has become a major focus in the management of chronic hepatitis B. HBV antiviral drug resistance may be best prevented by using an agent or combination of agents with a high genetic barrier to resistance, and 2 potent nucleoside and nucleotide drugs with different resistance profiles may prove to be the optimal first-line treatment for chronic hepatitis B. Frequent assessment of quantitative serum HBV DNA remains the best approach to early detection of resistance, and antiviral therapy should be modified as soon as resistance is detected. Results from several clinical trials have shown that the addition or substitution of newer antiviral agents can restore suppression of viral replication, normalize alanine aminotransferase levels, and reverse histologic progression in patients with resistance to lamivudine, but little information exists regarding the long-term benefits of second-line treatment regimens. Despite the substantial advances in treatment made to date, new agents with novel viral targets will be needed for patients who ultimately may fail second- or third-line therapy.

Gardner MB, Luciw PA. · Center for Comparative Medicine, University of California, Davis, CA 95616, USA. · ILAR J. · Pubmed #18323583 links to  free full text

Abstract: Macaques have served as models for more than 70 human infectious diseases of diverse etiologies, including a multitude of agents-bacteria, viruses, fungi, parasites, prions. The remarkable diversity of human infectious diseases that have been modeled in the macaque includes global, childhood, and tropical diseases as well as newly emergent, sexually transmitted, oncogenic, degenerative neurologic, potential bioterrorism, and miscellaneous other diseases. Historically, macaques played a major role in establishing the etiology of yellow fever, polio, and prion diseases. With rare exceptions (Chagas disease, bartonellosis), all of the infectious diseases in this review are of Old World origin. Perhaps most surprising is the large number of tropical (16), newly emergent (7), and bioterrorism diseases (9) that have been modeled in macaques. Many of these human diseases (e.g., AIDS, hepatitis E, bartonellosis) are a consequence of zoonotic infection. However, infectious agents of certain diseases, including measles and tuberculosis, can sometimes go both ways, and thus several human pathogens are threats to nonhuman primates including macaques. Through experimental studies in macaques, researchers have gained insight into pathogenic mechanisms and novel treatment and vaccine approaches for many human infectious diseases, most notably acquired immunodeficiency syndrome (AIDS), which is caused by infection with human immunodeficiency virus (HIV). Other infectious agents for which macaques have been a uniquely valuable resource for biomedical research, and particularly vaccinology, include influenza virus, paramyxoviruses, flaviviruses, arenaviruses, hepatitis E virus, papillomavirus, smallpox virus, Mycobacteria, Bacillus anthracis, Helicobacter pylori, Yersinia pestis, and Plasmodium species. This review summarizes the extensive past and present research on macaque models of human infectious disease.

Leung JM, O'Brien JG, Wong HK, Winslow DL. · Santa Clara Valley Health and Hospital Systems, 751 South Bascom Ave., San Jose, CA 95128, USA. · Ann Pharmacother. · Pubmed #18252833 No free full text.

Abstract: OBJECTIVE: To report a case of hypersensitivity manifesting in a rash, fever, and life-threatening hepatitis in a patient initiated on efavirenz therapy. CASE SUMMARY: A 30-year-old Latino male newly diagnosed with HIV was started on efavirenz-based highly active antiretroviral therapy (HAART) using tenofovir 300 mg, emtricitabine 200 mg, and efavirenz 600 mg once daily. Eleven days after beginning therapy, he developed a hypersensitivity reaction manifesting in rash and fever preceding severe drug-induced hepatitis. Liver enzyme peak values were aspartate transaminase 3410 U/L and alanine transaminase 2132 U/L. Hepatitis resolved with discontinuation of the HAART. The patient was rechallenged with tenofovir and emtricitabine one year later; no adverse reactions occurred. DISCUSSION: The Naranjo probability scale demonstrated a probable relationship between this adverse reaction and efavirenz. A MEDLINE search (2004 to September 2007) revealed 2 cases of rash preceding hepatitis with the initiation of efavirenz. Both cases were in women; there were no prior reported cases of efavirenz hypersensitivity in men. Although the mechanism of this reaction is unknown, a few factors may have contributed to this reaction. The half-life and the auto-induction of efavirenz may explain the continued rise in liver enzymes and severe hepatitis that continued to occur once the drug was discontinued. Another cause that may have contributed is the metabolism of the medication. CYP2B6 is responsible for almost 90% of the clearance of efavirenz. Data from a recent pharmacokinetic study showed that efavirenz concentrations were higher in both black and Latino patients when compared with those of white patients. In addition, it is highly probable that this patient's liver function was impaired when transaminase levels peaked, resulting in decreased clearance of efavirenz. CONCLUSIONS: Although such a hypersensitivity reaction is rare, efavirenz is the most probable cause of the erythematous maculopapular rash and acute hepatitis in this patient. Monitoring of liver function in patients who present with a rash following initiation of efavirenz-based HAART is recommended. In addition, clinicians should exercise caution in patients presenting with rash, fever, and increased liver enzymes (> 3 times the upper limit of normal or patient baseline). It is strongly recommended that efavirenz therapy be withheld in such cases and reevaluated once liver enzyme levels stabilize.

Gershwin ME, Mackay IR. · Division of Rheumatology, Allergy and Clinical Immunology, University of California at Davis School of Medicine, Davis, CA 95616, USA. · Hepatology. · Pubmed #18098322 No free full text.

Abstract: The most difficult issue in autoimmunity remains etiology. Although data exist on effector mechanisms in many autoimmune diseases, the underlying cause or causes are still generically ascribed to genetics and environmental influences. Primary biliary cirrhosis (PBC) is considered a model autoimmune disease because of its signature antimitochondrial autoantibody (AMA), the homogeneity of clinical characteristics, and the specificity of biliary epithelial cell (BEC) pathology. Twenty years ago, we reported the cloning and identification of the E2 component of pyruvate dehydrogenase (PDC-E2) as the immunodominant autoantigen of PBC, allowing for vigorous dissection of T and B lymphocyte responses against PDC-E2 and development of several valid experimental models. There has also been considerable study of the biology of BECs, which has included the unique properties of apoptosis in which there is exposure of PDC-E2 to the effector processes of the immune system. In this review, we present these data in the context of our proposal that the proximal cause of PBC is autoimmunity directed against well-identified mitochondrially located autoantigens in individuals with inherited deficits of immune tolerance. We present these data under the umbrella of convenient truths that support this thesis as well as some inconvenient truths that are not readily accommodated by current theory. CONCLUSION: We emphasize that the potential initiator of PBC includes inter alia particular environmental xenobiotics; pathogenesis is aided and abetted by genetic weaknesses in mechanisms of immune regulation; and subsequent multilineage immunopathology impacts upon uniquely susceptible BECs to culminate clinically in the chronic autoimmune cholangiolitis of PBC.

Nguyen TT, Taylor V, Chen MS, Bastani R, Maxwell AE, McPhee SJ. · Vietnamese Community Health Promotion Project and UCSF Comprehensive Cancer Center, University of California, San Francisco, CA 94143, USA. · J Cancer Educ. · Pubmed #18067441 No free full text.

Abstract: BACKGROUND: Due to the high prevalence of hepatitis B, Asian Americans have high rates of liver cancer. Screening for hepatitis B leads to monitoring and treatment and prevent further infection through vaccination of contacts. METHODS: We reviewed the published literature up to 2006 on hepatitis B awareness, knowledge, and screening among Asian Americans. RESULTS: Many Asian Americans lack knowledge about hepatitis B and have not been screened. Sociodemographics, knowledge, beliefs, and health care variables are associated with screening. CONCLUSIONS: Further research and health policy changes are needed to address the problem of hepatitis B and liver cancer among Asian Americans.

Monath TP. · Kleiner Perkins Caufield & Byers, Menlo Park, CA, United States. · Antiviral Res. · Pubmed #18061688 No free full text.

Abstract: Yellow fever (YF) is a life-threatening mosquito-borne flaviviral hemorrhagic fever (VHF) characterized by severe hepatitis, renal failure, hemorrhage, and rapid terminal events with shock and multi-organ failure. A live, attenuated vaccine (YF 17D), in wide use for over 60 years, causes a disease identical to wild-type virus at an incidence of 2.5x10(-6). Our current understanding of the pathogenesis and treatment of YF (described in this brief review) is derived from studies of animal models (macaques, hamsters) that reproduce the features of human YF and from descriptive studies of human cases of naturally acquired and vaccine-associated VHF. The least understood, but potentially most important terminal events appear to be due to 'cytokine storm' and represent a potential target for therapeutic interventions. Areas for future study include dissection of cytokine-mediated events in animal models, the pathogenic role of the profound neutrophilia that occurs pre-terminally, the (pathological) role of adaptive immune clearance in pathogenesis, and treatments directed at cytokine storm. Antibody, interferon-alpha, polyICLC and other immune modulators are highly effective when administered before or within a narrow time window after infection, but are ineffective when given after the infection is established. A few antivirals have been evaluated (ribavirin, tiazofurin, carboxamide, pyrazoline compounds). Ribavirin has been used successfully to treat hamsters when the drug is given at high doses up to 2 days after virus infection (shortly before liver infection), but has not shown promise in nonhuman primate models. Future work should focus on evaluating higher doses of ribavirin alone or in combinations with potentially synergistic drugs, including interferons. Also specific inhibitors against other flaviviruses such as dengue virus should be investigated for potential pan-flavivirus activity since recent studies have shown that specific targets such as the flavivirus proteases and helicases are very similar in structure.

Vichinsky E. · Hematology/Oncology Department, Children's Hospital and Research Center at Oakland, Oakland, California 94609, USA. · Am J Hematol. · Pubmed #18058997 No free full text.

Abstract: Deferasirox (Exjade, ICL670) is a once-daily, oral iron chelation agent that is now widely available for the treatment of transfusional hemosiderosis in adult and pediatric patients aged > or =2 years of age. Clinical evaluation has established the efficacy and safety of this novel agent in patients with a variety of chronic anemias. Deferasirox represents a significant advance in the treatment of iron overload, as the availability of an effective oral therapy has the potential to relieve many patients from the burden of frequent parenteral therapy with the previous reference standard iron chelator, deferoxamine. The most common drug-related adverse events seen in the core registration trials were gastrointestinal disturbances, rash, mild and nonprogressive increases in serum creatinine levels, and elevations in liver enzyme levels. Most events were transient, mild-to-moderate in severity, and easily managed without discontinuation of treatment. As with any new agent, it is important that treating physicians are familiar with the adverse event profile of deferasirox and how the associated effects can be readily managed to ensure optimal use of this important treatment.

Keeffe EB. · Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, CA, USA. · Antivir Ther. · Pubmed #18018759 No free full text.

Abstract: The current standard therapy for chronic hepatitis C is peginterferon plus ribavirin and yields a sustained virological response rate of approximately 50% overall. Over the past 2-3 years, many new therapeutic agents directed at a number of different viral targets have entered into development for the treatment of patients with chronic hepatitis C. Many of these agents exhibit high levels of potency against the hepatitis C virus and have a rapid onset of activity. Some agents have been abandoned because of lack of efficacy or toxicity, but many others have shown promise and are undergoing further testing. Although debated, new therapies in the immediate future will most likely be used in combination with peginterferon, either alone or with ribavirin. This concise review is focused on new drugs undergoing development for the treatment of patients with chronic hepatitis C, and on drugs that have shown efficacy in preliminary investigations and progressed to Phase II or III trials. This information should allow physicians involved in the care of patients with chronic hepatitis C to provide realistic expectations of what types of drugs are progressing in clinical development, the likelihood that new treatment will include peginterferon with or without ribavirin, and when these novel therapies might become available.

Keck ZY, Machida K, Lai MM, Ball JK, Patel AH, Foung SK. · Department of Pathology, Stanford Medical School Blood Center, Palo Alto, CA 94304, USA. · Curr Top Microbiol Immunol. · Pubmed #17990788 No free full text.

Abstract: Liver failure associated with hepatitis C virus (HCV) accounts for a substantial portion of liver transplantation. Although current therapy helps some patients with chronic HCV infection, adverse side effects and a high relapse rate are major problems. These problems are compounded in liver transplant recipients as reinfection occurs shortly after transplantation. One approach to control reinfection is the combined use of specific antivirals together with HCV-specific antibodies. Indeed, a number of human and mouse monoclonal antibodies to conformational and linear epitopes on HCV envelope proteins are potential candidates, since they have high virus neutralization potency and are directed to epitopes conserved across diverse HCV genotypes. However, a greater understanding of the factors contributing to virus escape and the role of lipoproteins in masking virion surface domains involved in virus entry will be required to help define those protective determinants most likely to give broad protection. An approach to immune escape is potentially caused by viral infection of immune cells leading to the induction hypermutation of the immunoglobulin gene in B cells. These effects may contribute to HCV persistence and B cell lymphoproliferative diseases.

Kohrt HE, Ouyang DL, Keeffe EB. · Division of Hematology, Department of Medicine, Stanford University Medical Center, 300 Pasteur Drive, S101, Stanford, CA 94305-5109, USA. · Clin Liver Dis. · Pubmed #17981237 No free full text.

Abstract: Chronic hepatitis B virus (HBV) carriers are at considerable risk of reactivation of HBV infection when undergoing chemotherapy or immunosuppressive therapy. Complications of HBV reactivation, including asymptomatic elevation of HBV DNA levels, acute hepatitis, acute liver failure, and delays or dose reductions in chemotherapy, are avoidable with appropriate prophylactic oral antiviral therapy. This article reviews evidence for and presents a grade A recommendation supporting primary prophylaxis among HBV carriers with lamivudine. The dose and duration of prophylaxis, risk of lamivudine resistance, and future directions of prophylactic therapy for HBV reactivation during chemotherapy are discussed. Recommendations are suggested based on expert opinion for prophylaxis with the combination of lamivudine plus adefovir or with entecavir as alternative antiviral strategies that substantially reduce or avoid the risk of HBV antiviral drug resistance.

Gish RG, Locarnini S. · California Pacific Medical Center, 2340 Clay St., Room 223, San Francisco, CA 94115, USA. · Clin Liver Dis. · Pubmed #17981228 No free full text.

Abstract: The global prevalence of chronic hepatitis B and its associated serious sequelae demand technologically advanced techniques of management. Nucleic acid testing (NAT) plays a key role in the diagnosis, surveillance, and treatment of chronic hepatitis B. NAT includes quantitative PCR-based HBV DNA assays, HBV genotyping, tests for mutations associated with resistance to antiviral medications, and assays to detect precore and core promoter mutations. This article reviews the uses of NAT in the diagnosis and management of chronic hepatitis B.

Ku NO, Strnad P, Zhong BH, Tao GZ, Omary MB. · Department of Medicine, Palo Alto VA Medical Center and Stanford University Digestive Disease Center, Palo Alto, CA. · Hepatology. · Pubmed #17969036 No free full text.

Abstract: Keratin polypeptides 8 and 18 (K8/K18) are the cytoskeletal intermediate filament proteins of hepatocytes while K8/K18/K19 are the keratins of hepatobiliary ductal cells. Hepatocyte K8/K18 are highly abundant and behave as stress proteins with injury-inducible expression. Human association studies show that K8/K18 germline heterozygous mutations predispose to end-stage liver disease of multiple etiologies ( approximately 3 fold increased risk), and to liver disease progression in patients with chronic hepatitis C infection. These findings are supported by extensive transgenic mouse and ex vivo primary hepatocyte culture studies showing that K8 or K18 mutations predispose the liver to acute or subacute injury and promote apoptosis and fibrosis. Mutation-associated predisposition to liver injury is likely related to mechanical and nonmechanical keratin functions including maintenance of cell integrity, protection from apoptosis and oxidative injury, serving as a phosphate sponge, regulation of mitochondrial organization/function and protein targeting. These functions are altered by mutation-induced changes in keratin phosphorylation, solubility and filament organization/reorganization. Keratins are also the major constituents of Mallory-Denk bodies (MDBs). A toxin-induced K8>K18 ratio, and keratin crosslinking by transglutaminase-2 play essential roles in MDB formation. Furthermore, intracellular or cell-released K18 fragments, generated by caspase-mediated proteolysis during apoptosis serve as markers of liver injury. Therefore, K8 and K18 are cytoprotective stress proteins that play a central role in guarding hepatocytes from apoptosis. Keratin involvement in liver disease is multi-faceted and includes modulating disease progression upon mutation, formation of MDBs in response to unique forms of injury, and serving as markers of epithelial cell death.

Coffin CS, Terrault NA. · Department of Medicine, University of California at San Francisco, San Francisco, CA 94143, USA. · J Viral Hepat. · Pubmed #17958641 No free full text.

Abstract: Advances in hepatitis B virus (HBV) antiviral prophylaxis have dramatically improved graft and patient survival for patients undergoing liver transplantation for hepatitis B related end-stage liver disease. In particular, the availability of hepatitis B immune globulin (HBIg) in combination with nucleos(t)ide analogues such as lamivudine and adefovir, have transformed outcomes. The availability of newer antivirals such as adefovir, tenofovir and entecavir either as monotherapy or in combination offer an increasing number of antiviral options. Despite these advances, significant challenges remain. Factors that affect the efficacy of anti-viral therapy include detectable HBV viraemia at the time of transplant and emergence of HBV mutants (especially in patients with prior exposure to lamivudine). HBV prophylaxis protocols are expensive especially with use of high-dose HBIg and newer nucleos(t)ide analogues. This review summarizes current HBV prophylaxis protocols and management of recurrent disease post-transplantation. There is an increasing need for individualization of therapy based on prior drug exposures, level of HBV DNA at time of transplantation and type of prophylaxis used.

Bick JA. · California Medical Facility, California Department of Corrections and Rehabilitation, Vacaville, CA 95696, USA. · Clin Infect Dis. · Pubmed #17879924 No free full text.

Abstract: At the end of 2005, approximately 7 million people (or 1 of every 33 American adults) were either in jail, in prison, or on parole. Compared with the general public, newly incarcerated inmates have an increased prevalence of human immunodeficiency virus infection, hepatitis B virus infection, hepatitis C virus infection, syphilis, gonorrhea, chlamydia, and Mycobacterium tuberculosis infection. While incarcerated, inmates are at an increased risk for the acquisition of blood-borne pathogens, sexually transmitted diseases, methicillin-resistant Staphylococcus aureus infection, and infection with airborne organisms, such as M. tuberculosis, influenza virus, and varicella-zoster virus. While incarcerated, inmates interact with hundreds of thousands of correctional employees and millions of annual visitors. Most inmates are eventually released to interact with the general public. Tremendous opportunities exist for infectious diseases specialists and infection-control practitioners to have an impact on the health of correctional employees, the incarcerated, and the communities to which inmates return. This article presents a brief review of some of the most important infection-control challenges and opportunities within the correctional setting.

Bonacini M. · Department of Medicine, University of California at San Francisco, School of Medicine, USA. · J Acquir Immune Defic Syndr. · Pubmed #17704691 No free full text.

Abstract: HIV coinfection is associated with faster progression of liver disease resulting from hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. Thus, liver complications have become a major cause of illness and death in coinfected patients. Controlling HIV through highly active antiretroviral therapy may slow disease progression to nearly the rate of HIV-negative persons. Several antiretroviral regimens have been associated with drug-induced liver injury, however, which is more common in patients coinfected with hepatitis B or C. After development of cirrhosis and decompensation, survival is shorter in coinfected patients. Diagnosis and management of cirrhosis should be the same for coinfected and monoinfected HBV/HCV patients. The main complications of cirrhosis are ascites, spontaneous bacterial peritonitis, bleeding esophageal varices, hepatic encephalopathy, the hepatorenal syndrome, and hepatocellular carcinoma. Liver transplantation is feasible in patients with HIV infection, and early evaluation for this option is crucial because of the accelerated course of complications in HIV coinfection.

Terrault NA, Jacobson IM. · Division of Gastroenterology, University of California-San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143, USA. · Semin Liver Dis. · Pubmed #17701846 No free full text.

Abstract: As our understanding of the natural history of hepatitis B virus (HBV) infection increases, so do the patient circumstances for which anti-HBV therapy is considered. For example, patients with chronic HBV infection that is negative for hepatitis B surface antigen can experience hepatitis flares during or after cytotoxic chemotherapy and thus are potential candidates for anti-HBV therapy. Also, although passive-active immunoprophylaxis is highly effective in preventing the vertical transmission of HBV, high maternal serum HBV DNA concentrations have been associated with the failure of immunoprophylaxis; for this reason, clinicians may consider administering anti-HBV therapy during pregnancy. However, prophylactic anti-HBV therapy can be both complex and controversial. A satellite symposium conducted during the 57th Annual Meeting of the American Association for the Study of Liver Diseases (AASLD) in Boston, Massachusetts, presented approaches to treating HBV infection in patients who are pregnant and in those who are preparing to receive chemotherapy.

Gish RG, Perrillo RP, Jacobson IM. · Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, San Francisco, CA 94115, USA. · Semin Liver Dis. · Pubmed #17701845 No free full text.

Abstract: As of October 2006, 6 medications are approved in the United States for the management of chronic hepatitis B virus (HBV) infection: 2 formulations of interferon and 4 oral nucleos(t)ide analogues. For the treating practitioner, tailoring the pharmaceutical regimen according to patient features and clinical circumstances can be a challenge. First-line therapeutic regimens for the management of HBV infection include monotherapy with a U.S. Food and Drug Administration-approved agent that has potent on-treatment viral response and low rates of resistance; in the future, these regimens may include a combination of more than one nucleos(t)ide analogue or a combination of a nucleos(t)ide analogue and pegylated interferon. The oral nucleos(t)ide analogues are generally better tolerated than interferon; however, they can be expensive when administered for lengthy periods and can also lead to medication resistance. Lamivudine, the first approved nucleoside analogue for the treatment of HBV infection, has a very high resistance profile; in fact, lamivudine exposure increases viral resistance to other commercially available nucleos(t)ide analogues: entecavir, telbivudine, and adefovir. For these reasons, the 2007 American Association for the Study of Liver Diseases (AASLD) guidelines no longer recommend lamivudine as first-line therapy for the management of HBV infection. A satellite symposium conducted during the 57th Annual Meeting of the AASLD in Boston, Massachusetts, presented approaches to customizing the management of chronic HBV infection. The presentation highlighted recent findings suggesting that early, profound, and sustained viral suppression improves the probability of sustained virologic response and reduces the likelihood of nucleos(t)ide resistance.

Terrault NA, Adey DB. · Department of Medicine, Division of Gastroenterology, University of California, San Francisco, San Francisco, California, USA. · Clin J Am Soc Nephrol. · Pubmed #17699464 links to  free full text

Abstract: Liver disease secondary to chronic hepatitis C virus (HCV) infection is an important cause of morbidity and mortality in dialysis patients and kidney transplant recipients. Evaluation of patients with chronic HCV infection is warranted to determine stage of disease and the need for HCV therapy. Although combination therapy with interferon (IFN) plus ribavirin is the standard of care for chronic HCV infection, IFN monotherapy is recommended in dialysis patients because ribavirin is contraindicated in the presence of renal failure. The goals of pretransplantation HCV therapy are to decrease the risk for progression of HCV-associated liver disease, stabilize renal function in patients with HCV-related glomerulopathy, and prevent development of HCV-associated renal disease after transplantation. Posttransplantation HCV therapy is generally not recommended because of concerns regarding risk for precipitating acute rejection; however, antiviral therapy may be indicated to treat HCV-related glomerulopathy or prevent progression of chronic hepatitis C in patients with more advanced stages of fibrosis. When treatment is required, restored renal function allows use of combination therapy with IFN and ribavirin. Limitations of current HCV therapy include lack of tolerability and suboptimal response rates. New antiviral agents that can be used in dialysis patients (e.g., ribavirin alternatives) and in the posttransplantation setting (e.g., IFN alternatives) are needed to improve outcomes in these populations.

Keeffe EB, Zeuzem S, Koff RS, Dieterich DT, Esteban-Mur R, Gane EJ, Jacobson IM, Lim SG, Naoumov N, Marcellin P, Piratvisuth T, Zoulim F. · Stanford University School of Medicine, Stanford, California 94304-1509, USA. · Clin Gastroenterol Hepatol. · Pubmed #17632041 No free full text.

Abstract: An international group of experienced hepatologists and virologists conducted a single-day workshop to review the management of patients with chronic hepatitis B receiving treatment with oral nucleosides or nucleotides. Guidelines regarding on-treatment management and available published data on the importance of serum hepatitis B virus (HBV) DNA as a marker of outcomes were reviewed. On-treatment monitoring strategies to define early virologic responses that might be predictive of better outcomes and a reduced risk of viral resistance were proposed for further study. This treatment plan, labeled the roadmap concept, recommends monitoring of serum HBV DNA levels to identify outcomes of therapy. Primary treatment failure was defined as a reduction of serum HBV DNA levels by less than 1 log10 IU/mL from baseline at week 12. Measurement of the HBV DNA level at week 24 was considered essential to characterize virologic responses as complete, partial, or inadequate. Complete virologic response was defined as negative HBV DNA by a sensitive assay (<60 IU/mL or <300 copies/mL); partial virologic response was defined as HBV DNA levels less than 2000 IU/mL (4 log10 copies/mL), and inadequate virologic response was defined as HBV DNA levels of 2000 IU/mL or greater (4 log10 copies/mL). Strategies are proposed for managing patients in each of these categories, depending in part on the rapidity with which HBV DNA suppression is achieved and the emergence of genotypic mutations that reduce the effectiveness of a specific drug. Future studies of the use of the roadmap concept in improving outcomes of chronic hepatitis B are warranted.

Arora G, Keeffe EB. · Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University School of Medicine, Stanford, California, USA. · Rev Gastroenterol Disord. · Pubmed #17597674 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection is a significant public health problem in the United States, with 1.25 million people infected with the virus. The long-term risks of chronic HBV infection include cirrhosis and hepatocellular carcinoma, which occur in 15% to 30% of those infected at birth or early in life and may lead to liver transplantation or death. During the past few years, the development and increased availability of oral antiviral agents have made treatment simpler, safer, and more tolerable for these patients. This article focuses on 3 of these drugs--lamivudine, adefovir, and entecavir--and their use in patients with chronic HBV infection and advanced hepatic fibrosis or cirrhosis.

Sklan EH, Glenn JS. · Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Palo Alto, California 94305-5187, USA. · Gastroenterology. · Pubmed #17570202 No free full text.

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Kadayifci A, Merriman RB, Bass NM. · Division of Gastroenterology, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143-0538, USA. · Clin Liver Dis. · Pubmed #17544975 No free full text.

Abstract: There is no proven medical treatment of non-alcoholic steatohepatitis (NASH). Most prior therapeutic trials have had methodologic limitations. Insulin sensitizers are the more promising therapeutic candidates among categories that include antioxidants, lipid-lowering agents, and antiobesity drugs. The future will see the evaluation of novel agents and a comprehensive treatment strategy that addresses the risk factors for the metabolic syndrome. This article reviews the current status of medical management options for NASH.

Busch MR. · Blood Systems Research Institute, San Francisco, CA 94118, USA. · Dev Biol (Basel). · Pubmed #17486883 No free full text.

This publication has no abstract.

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.