Hepatitis: San Francisco

Merriman RB. · Division of Gastroenterology, Department of Medicine, 513 Parnassus Avenue, Room S-357, University of California, San Francisco, CA 94143-0538, USA. · Curr HIV/AIDS Rep. · Pubmed #16970837 No free full text.

Abstract: As persons with HIV live longer, chronic liver disease is increasingly important. Nonalcoholic fatty liver disease (NAFLD) is characterized by excess fat in hepatocytes in patients without significant alcohol use. It can progress from steatosis to nonalcoholic steatohepatitis (NASH) to cirrhosis. Visceral obesity and insulin resistance are integral to the pathogenesis of NAFLD. Patients with HIV are at greater risk of NAFLD due to antiretroviral therapy and viral hepatitis coinfection. Antiretroviral therapy can lead to patterns of injury that include steatosis and NASH. Coinfection with hepatitis C virus increases the risk of insulin resistance and hepatic steatosis, and co-existent features of NASH have also been reported. Histological-based, longitudinal studies are needed that address the interactions of NAFLD and HIV infection, the effects of antiretroviral therapy and hepatotropic virus coinfection, and inform better management strategies.

Diedrich G. · diaDexus Inc., South San Francisco, CA 94080, USA. · FEBS J. · Pubmed #16934030 No free full text.

Abstract: Hepatitis C virus (HCV) exists in different forms in the circulation of infected people: lipoprotein bound and lipoprotein free, enveloped and nonenveloped. Viral particles with the highest infectivity are associated with lipoproteins, whereas lipoprotein-free virions are poorly infectious. The detection of HCV's envelope proteins E1 and E2 in lipoprotein-associated virions has been challenging. Because lipoproteins are readily endocytosed, some forms of HCV might utilize their association with lipoproteins rather than E1 and E2 for cell attachment and internalization. However, vaccination of chimpanzees with recombinant envelope proteins protected the animals from hepatitis C infection, suggesting an important role for E1 and E2 in cell entry. It seems possible that different forms of HCV use different receptors to attach to and enter cells. The putative receptors and the assays used for their validation are discussed in this review.

Terrault NA, Berenguer M. · Department of Medicine/Gastroenterology, University of California San Francisco, San Francisco, CA, USA. · Liver Transpl. · Pubmed #16868944 links to  free full text

Abstract: Chronic infection with hepatitis C virus (HCV) is a growing problem worldwide, with up to 300 million individuals infected, and those with chronic infection are at risk for cirrhosis and hepatocellular carcinoma. HCV infection is the most common indication for liver transplantation in the United States and Europe. Unfortunately, although transplantation is effective for treating decompensated cirrhosis and limited hepatocellular carcinoma associated with hepatitis C, HCV reinfection is virtually the rule among transplant recipients. Reinfection of the graft is associated with more rapidly progressive disease, with a median time to cirrhosis of 8 to 10 yr. Unfortunately, treatment of chronic HCV in liver transplant recipients is suboptimal. Combination therapy with interferon (pegylated and nonpegylated forms) plus ribavirin appears to provide maximum benefits. Drug therapy is usually administered for recurrent disease. No prophylactic therapy is available. Preemptive regimens offer no distinctive advantages over treatments begun for recurrent disease. Overall, treatment is poorly tolerated, with frequent need for dose reductions, especially from cytopenias, and drug discontinuations in up to 50% of patients. Optimizing drug doses is important in maximizing sustained virological response rates. Future therapies may include ribavirin alternatives with lower rates of anemia, alternative interferons with lower rates of cytopenias, and new antiviral drugs that can be used alone or in combination with either interferon or ribavirin to enhance sustained virological response rates and improve tolerability. Liver Transpl 12:1192-1204, 2006. (c) 2006 AASLD.

Feng S, Barr M, Roberts J, Oberbauer R, Kaplan B. · Department of Surgery, Division of Transplantation, University of California, San Francisco, USA. · Am J Transplant. · Pubmed #16771814 No free full text.

Abstract: Although organ transplantation has matured into a proven therapy for end-stage organ failure, the many notable developments of the past 5 years speak to the multitude of remaining challenges. Two new procedures, islet transplantation and adult-to-adult living donor liver transplantation, have emerged to enlarge our therapeutic armamentarium for Type 1 diabetes mellitus and end-stage liver disease, respectively. In cardiac transplantation, the acceptance of ventricular assist devices as destination therapy is a notable event in light of critical shortage of deceased donor organs. Both liver and lung allocation policies have made a dramatic paradigm shift away from waiting time toward the survival benefit of transplantation. Finally, primary threats to post-transplant longevity have gained an increasing share of the spotlight. Recognition of the impact of renal insufficiency for all nonrenal transplant recipients, of recurrent hepatitis C virus for liver recipients, and of accelerated vasculopathy for cardiac have identified novel end points for clinical trials.

Gish RG, Locarnini SA. · Division of Hepatology and Complex GI, Physician Foundation, California Pacific Medical Center, San Francisco, California, USA. · Clin Gastroenterol Hepatol. · Pubmed #16765304 No free full text.

Abstract: The worldwide burden of hepatitis B mandates accurate and timely diagnosis of patients infected with the hepatitis B virus (HBV) and the use of treatment strategies derived from evidence-based guidelines. HBV is a DNA virus that produces a series of viral protein products circulating HBV DNA. Serologic and nucleic acid testing are critical to disease prevention and treatment objectives. Information from such testing helps determine patients' infectivity and immune status, appropriate monitoring strategies, and the efficacy of treatment, as well as providing data that contributes to a better understanding of the natural history and epidemiology of the disease. This article reviews the clinical use of state-of-the-art serologic and nucleic acid tests, including the relevance of hepatitis B e antigen and antibody and HBV DNA measurements as markers of disease activity. Viral load can be used to distinguish between active and inactive disease, define response to therapy, and detect the development of antiviral resistance. Some recent reports have suggested that high viral load is associated with poorer patient outcomes (eg, more rapid progression to cirrhosis and a higher incidence of hepatocellular carcinoma). Durable suppression of HBV DNA is evolving to become the primary goal of therapy, although all currently licensed medications have used histology as the primary end point of therapy. Suggested frequencies for HBV DNA monitoring are presented.

Kohla M, Bonacini M. · Department of Transplantation,California Pacific Medical Center, San Francisco, CA 94115, USA. · Minerva Gastroenterol Dietol. · Pubmed #16557183 No free full text.

Abstract: The hepatitis C virus (HCV) is a single stranded RNA virus. In 60-80% of patients, it is able to escape innate and adaptive immune surveillance. Thus it establishes itself as an agent of chronic hepatitis. Cytotoxic lymphocytes then contribute to liver injury in an attempt to eradicate the virus. On the other hand, strong multispecific T-lymphocyte reaction against HCV proteins is associated with viral clearance. Both CD4+ and CD8+ lymphocyte functions are important to effect this outcome. In chronic infection, genetic and environmental factors determine the progression of inflammation and fibrosis in individual patients. Of these factors, age, gender, race and alcohol use are the most established ones. The development of hepatocellular carcinoma is mainly restricted to patients with cirrhosis.

Gish RG. · Division of Hepatology and Complex GI, Physician's Foundation at California Pacific Medical Center, San Francisco, California 94115, USA. · Clin Gastroenterol Hepatol. · Pubmed #16527686 No free full text.

Abstract: Hepatocellular carcinoma is the third most frequent cause of death from cancer and the eighth most commonly occurring cancer in the world. In the United States, hepatocellular carcinoma appears to be increasing along with evolution of chronic hepatitis infection, especially in the immigrant population, a major risk group. A disease of multifactorial etiology, hepatocellular carcinoma confers many management challenges. Hepatocarcinogenesis is a multistep process involving different genetic alterations that ultimately lead to malignant transformation of the hepatocyte. Early hepatocellular carcinoma is characteristically silent and slow growing with few symptoms until late in disease. Early and accurate diagnosis of hepatic tumors relies on clinical suspicion, screening protocols, serologic testing, radiologic imaging, and tissue confirmation. Lack of clinically validated biomarkers and clinical identification of hepatocellular carcinoma at advanced disease make diagnosis and treatment difficult. Advances in computed tomography and magnetic resonance imaging have markedly increased the sensitivity and specificity of testing, yet they are still flawed with a relatively high false-positive rate. Several surgical and nonsurgical therapies have been developed and used with varying degrees of success. Options include surgical resection, liver transplantation, local ablation therapies, and pharmaceutical interventions. At 5 years after resection, in those patients who are surgical candidates, the recurrence rate ranges between 30% and 60%. In patients with nonresectable disease, the prognosis is dismal, with a median survival of less than 12 months even with chemotherapy. The medical community faces numerous challenges in hepatocellular carcinoma and must work toward better management and multidisciplinary care of this complex disease.

Kuo A, Terrault NA. · Division of Gastroenterology, University of California-San Francisco, San Francisco, CA, USA. · Am J Transplant. · Pubmed #16468953 No free full text.

Abstract: Recurrent hepatitis C virus (HCV) disease is the leading cause of graft loss in liver transplant recipients with pre-transplant HCV infection. While natural history is variable, median time to recurrent cirrhosis is less than a decade. Factors contributing to risk of recurrence and rate of fibrosis progression are only partially known. Older donor age, treatment of acute rejection, cytomegalovirus infection and high pre-transplant viral load are most consistently linked with worse outcomes. Whether these factors can be modified to positively impact on HCV disease progression is unknown. The main therapeutic approach for patients with recurrent HCV disease has been the treatment with interferon and ribavirin (RBV) once recurrent disease is documented or progressive. Efficacy is lower than in nontransplant patients and tolerability, especially of RBV, is a major limitation. Stable or improved fibrosis scores are seen in the majority of sustained responders. Optimal dose, duration and timing of treatment have not been determined. Alternative strategies under study include pre-transplant treatment of decompensated cirrhotics, preemptive antiviral therapy started within weeks of transplantation and prophylactic therapy using HCV antibodies. Ongoing studies may establish a future role for alternative treatment approaches. Additionally, limited overall efficacy of interferon-based therapy in the transplant setting highlights the urgent need for new drug therapies.

Wright TL, Avunduk C, Dienstag JL, Freston JW, Jacobson IM, Nord HJ, Sherman M. · University of California-San Francisco, and VA Medical Center 111B, San Francisco, CA 94121, USA. · Am J Gastroenterol. · Pubmed #16448450 No free full text.

Abstract: Physicians involved in the management of patients with chronic hepatitis B infection are frequently faced with complex clinical issues concerning the diagnosis, investigation, and treatment of patients. Guidelines exist within the literature that help with decision making; however, in practice individual nuances are often encountered necessitating decisions that go beyond the current guidelines. Following presentation of the available data, a panel of expert hepatologists and gastroenterologists sought to identify and solve challenges that are faced by clinicians in the daily management of patients with chronic hepatitis B infection. The following summary provides an overview of the outcome of these discussions. Because of the complexities of clinical management, the recommendations reflect the opinion of the majority; however, many recommendations were not unanimous. Furthermore, the recommendations that follow are limited to adult patients; the treatment of children was not discussed. A number of issues were identified, and statements concerning possible management strategies that could be applied were developed.

Wright TL. · University of California-San Francisco, and VA Medical Center 111B, San Francisco, CA 94121, USA. · Am J Gastroenterol. · Pubmed #16448446 No free full text.

Abstract: Chronic hepatitis B virus (HBV) infection affects over 350 million people worldwide and over 1 million die annually of HBV-related chronic liver disease. Although many individuals eventually achieve a state of nonreplicative infection, the prolonged immunologic response to infection leads to the development of cirrhosis, liver failure, or hepatocellular carcinoma (HCC) in up to 40% of patients. In endemic areas, where carrier rates are >5%, most individuals are infected perinatally, by vertical transmission, or in early childhood. In the United States, where prevalence is low except in particular areas and populations (e.g., Alaskan natives, immigrants from highly endemic areas), transmission is generally horizontal, percutaneous, or via sexual contact in adulthood. A variety of host (age at infection, gender, immune status); viral (viral load, genotype, mutation); and external (concurrent viral infections, alcohol consumption, chemotherapy) factors influence disease progression. Several variables (age at infection, gender, ethnicity, immune status) also influence the risk of chronic infection. Perinatal transmission, the most common mode of infection worldwide, can be reduced by appropriate prophylaxis (vaccination of the infant at birth together with hepatitis B immune globulin); anti-viral therapy in late pregnancy may also be beneficial. Five drugs are now FDA-approved for the treatment of HBV (interferon, lamivudine, adefovir, entecavir, and peginterferon alfa-2a), and suppressive anti-viral therapy improves the natural history of HBV. Patients with decompensated cirrhosis or HCC are highly likely to die unless they successfully undergo liver transplantation. While novel anti-viral drugs have improved the management of cirrhosis, strategies to prevent and treat HCC remain inadequate.

Sylvestre D. · Department of Medicine, University of California, San Francisco, CA, USA. · Eur J Gastroenterol Hepatol. · Pubmed #16394792 No free full text.

This publication has no abstract.

Maurer TA. · University of California San Francisco, San Francisco, CA, USA. · Top HIV Med. · Pubmed #16377853 links to  free full text

Abstract: Although some dermatologic diseases have decreased markedly in frequency in the potent antiretroviral therapy era, other conditions remain common. Among patients with low CD4(+) cell counts who are not on or not adherent to antiretroviral therapy, notable conditions include psoriasis, photodermatitis, prurigo nodularis, molluscum, and adverse drug reactions. Conditions that remain relatively common despite adequate antiretroviral therapy include eczema, xerosis, warts, and Kaposi's sarcoma. Disorders that are associated with immune reconstitution under potent antiretroviral therapy include acne, staphylococcal infections, and erythema nodosum. In addition, HIV and hepatitis C virus (HCV) coinfection is associated with a number of skin disorders.

Gish RG. · California Pacific Medical Center, Liver Transplant Program, Division of Hepatology and Complex GI, 2340 Clay Street, #223, San Francisco, CA 94612, USA. · J Antimicrob Chemother. · Pubmed #16293677 links to  free full text

Abstract: Nucleos(t)ide analogues have proven useful in the treatment of viral infections. Ribavirin is a nucleoside, guanosine analogue, whose mechanisms of action include inhibition of inosine monophosphate dehydrogenase (IMPDH), which is the key step in de novo guanine synthesis, a requirement for viral replication. In combination with pegylated interferon alfa, ribavirin is the standard of care for the treatment of chronic hepatitis C today. However, the medication is associated with significant haemolytic anaemia, which may require dose reduction, discontinuation or treatment with recombinant human erythropoietin. Dose reduction also appears to decrease sustained viral clearance rates. Newer IMPDH inhibitors are in various stages of development. Viramidine, a liver-targeting prodrug of ribavirin, has demonstrated significant antiviral activity and erythrocyte-sparing properties. It is currently in Phase 3 trials. Clinical trials of merimepodib, another investigational IMPDH inhibitor, have completed enrolment for a Phase 2b study as a third medication for administration with pegylated interferon plus ribavirin. Although other IMDPH inhibitors also have antiviral activity, these medications appear best suited as immunosuppressive medications at this time.

Terrault NA. · Division of Gastroenterology, University of California at San Francisco, San Francisco, CA 94143-0538, USA. · Clin Gastroenterol Hepatol. · Pubmed #16234060 No free full text.

Abstract: The course of hepatitis C is accelerated after transplantation, with an average of 25% of patients developing cirrhosis within 5 years of transplantation. Consequently, the 5- and 10-year graft survival rates in hepatitis C virus (HCV)-infected patients are significantly lower than in HCV-uninfected patients. Therapeutic interventions to prevent HCV recurrence and/or alter the rate of disease progression after transplantation are desirable. Prophylactic therapy in the form of polyclonal HCV antibodies has not been effective at prevention of HCV re-infection, but one study suggests that higher-dose therapy may modify the severity of early disease recurrence. Pre-emptive antiviral therapy has modest efficacy and generally is poorly tolerated. Live donor liver transplant recipients and recipients with low model of end-stage liver disease scores pretransplantation may tolerate pre-emptive therapy best. The treatment of recurrent established disease with a combination of interferon and ribavirin has been the mainstay of management. Similar to pre-emptive therapy, tolerance is reduced and dose reductions are frequent. The sustained virologic response rates are less than 45% in studies to date. Histologic and biochemical improvements generally are more frequent than virologic responses. Overall, the treatment of HCV disease in transplant recipients leaves much to be desired and there is an urgent need of new HCV therapies in this patient population.

Gish RG. · Department of Medicine, Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, 2340 Clay Street, Room 232, San Francisco, CA 94115, USA. · Clin Liver Dis. · Pubmed #16207563 No free full text.

Abstract: The World Health Organization places hepatitis B virus (HBV) in the top 10 causes of death worldwide. It is estimated that there are over 400 million carriers of HBV as well. At least 20% to 30% of hepatitis B surface antigen (HBsAg) carriers will die of complications of chronic liver disease, including cirrhosis and liver cancer. The serious consequences of end-stage liver disease and liver cancer occur in 30% of chronic carriers and confront patients and physicians throughout the world. Vaccination is the major form of treatment (prevention) that may eventually eliminate HBV worldwide. This article discusses the currently available treatments as well as evolving treatments for chronic HBV infection.

Gish RG. · Department of Medicine, Division of Hepatology and Complex GI, Physicians Foundation, California Pacific Medical Center, San Francisco, California 94115, USA. · Semin Liver Dis. · Pubmed #16103979 No free full text.

Abstract: Currently approved treatments for chronic infection with hepatitis B virus (HBV) are limited by low rates of sustained response, side effects, and in some cases, the emergence of drug resistance. Thus, new treatments, characterized by more potent antiviral effects less toxicity, and minimal or no risk of resistance, are needed. During the last few years, several agents have been developed that have increased potency and reduced potential for resistance--among them, entecavir and pegylated interferons. In addition, several novel anti-HBV agents recently evaluated in phase II clinical trials, such as tenofovir, clevudine, telbivudine, pradefovir, and valtorcitabine, appear to be promising agents for the treatment of chronic hepatitis B. This article describes the clinical experience with new antiviral agents and the implications of the trial results for practice guidelines.

Peters MG. · Division of Gastroenterology, Box 0538, University of California, 513 Parnassus Ave, Room S-357, San Francisco, CA 94143-0538, USA. · Curr HIV/AIDS Rep. · Pubmed #16091258 No free full text.

Abstract: Since viral hepatitis is one of the most common causes of morbidity and mortality in HIV, it is critical to recognize and treat these patients appropriately. Hepatitis B infection is particularly difficult to manage as it changes with shifts in immune status. Inactive infection may flare up with restoration of CD4 cell count. In addition, many drugs used to treat HIV are also active against hepatitis B. Thus, patients may require therapy for both diseases or only for hepatitis B. The practicing physician must be aware of which drug to use with antiretrovirals and which can be used for hepatitis B alone. Current therapies for HIV that have hepatitis B activity include lamivudine, emtricitabine, and tenofovir. Therapies for hepatitis B without HIV activity are adefovir and entecavir. The major advances in the past year include emerging data on epidemiology, occult infection, genotypes, and newer therapies. Long-term management of hepatitis B includes monitoring for hepatocellular carcinoma. Two recent consensus conferences have provided excellent reviews of management of coinfection .

Hurst EA, Mauro T. · Department of Dermatology, University of California, San Francisco, CA 94143, USA. · Arch Dermatol. · Pubmed #16027302 links to  free full text

Abstract: BACKGROUND: At least 2.7 million Americans are infected with chronic hepatitis C. An increasing number are treated with interferon alfa plus ribavirin regimens. Not surprisingly, this immune stimulation is associated with the development of autoimmune and cutaneous diseases. Several cases of sarcoidosis have been reported with hepatitis C treatment, most recently in association with pegylated interferon alfa plus ribavirin. Systemic manifestations of sarcoidosis are usually treated with oral steroids, which unfortunately often increase the hepatitis C viral load. Thus, it is important to ascertain whether systemic corticosteroids are required to treat interferon alfa-associated sarcoidosis. OBSERVATIONS: We report the third case of cutaneous sarcoidosis in association with pegylated interferon alfa plus ribavirin treatment. Our patient had both cutaneous and pulmonary involvement, which has been spontaneously resolving since his treatment regimen was completed. In addition, we review the 12 previously reported cases of cutaneous sarcoidosis that occurred in patients undergoing hepatitis C treatment with interferon alfa. CONCLUSIONS: As the number of patients being treated with interferon alfa and ribavirin for hepatitis C increases, it is essential that dermatologists recognize the association of this treatment with sarcoidosis, because skin lesions may provide the first clue to diagnosis. Development of sarcoidosis may relate to hepatitis C as a possible antigenic trigger in the presence of an enhanced helper T cells type 1 response from treatment. Sarcoidosis with skin lesions in patients undergoing hepatitis C treatment often follows a benign course, and interferon alfa therapy may sometimes be continued with resolution of sarcoidosis occurring spontaneously or within a few months of completing treatment. Cautious use of systemic corticosteroids is warranted given their adverse effects on hepatitis C viral loads.

Biggins SW, Terrault NA. · Division of Gastroenterology, Department of Medicine, University of California, San Francisco, 513 Parnassus Ave, S357, Box 0538 San Francisco, CA 94143, USA. · Clin Liver Dis. · Pubmed #16023980 No free full text.

Abstract: Chronic hepatitis C virus (HCV) infection is the most common indication for liver transplantation in the United States and Europe, and more than 20,000 patients worldwide have undergone transplantation for complications of chronic hepatitis C. In North America, HCV accounts for 15% to 50% of the liver transplants performed in United States transplant programs. To maximize the long-term survival of liver transplant recipients who have HCV infection, eradication of infection is the ultimate goal. Pretransplant antiviral therapy with the goal of achieving viral eradication before transplantation is a consideration in some patients, especially those who have mildly decompensated liver disease. This article focuses on the management of liver transplant recipients who have HCV infection at the time of transplantation. Prophylactic and preemptive therapies, as well as treatment of established recurrent disease, are the strategies reviewed.

Kerbleski M. · Department of Veterans Affairs, San Francisco Veterans Affairs Medical Center California 94121, USA. · Gastroenterol Nurs. · Pubmed #15976556 No free full text.

Abstract: More than 4 million Americans are infected with the hepatitis C virus. Although overshadowed by acquired immune deficiency syndrome, the hepatitis C epidemic is now recognized as a major health problem. Prevalence is estimated to be anywhere from 1.2% to 10% in specific populations. Nurses continue to express confusion in understanding the disease process; therefore, many opportunities are missed to counsel patients and families who may be at risk or who have hepatitis C. Many patient questions go unanswered because nurses mistakenly assume the medical provider will educate these patients and families. However, nurses have more contact with patients, and one of the nurse's roles is to provide health education. The Society of Gastroenterology Nurses and Associates and the Joint Commission on Accreditation of Healthcare Organizations agree it is the nurse's role to educate patients. Accurate hepatitis C virus information helps nurses guide patients and families in understanding this disease process.

Terrault N, Roche B, Samuel D. · University of California at San Francisco, San Francisco, CA, USA. · Liver Transpl. · Pubmed #15973718 links to  free full text

This publication has no abstract.

Daugherty T, Bonacini M. · California Pacific Medical Center, 2340 Clay Street, 2nd Floor, San Francisco, CA 94115, USA. · Expert Rev Anti Infect Ther. · Pubmed #15954854 No free full text.

Abstract: Hepatitis C is found in approximately a third of patients infected with HIV. Therapy of hepatitis C in HIV patients is very important from several view points. First, hepatitis C in the setting of immunosuppression may progress faster, although recent data show that mortality from liver disease was decreased in highly active antiretroviral therapy. HIV/hepatitis C coinfection is associated with more frequent elevation in liver tests (drug-induced liver injury) during highly active antiretroviral therapy, and in some studies, hepatitis C has been associated with lower CD4+ recoveries. The therapeutic standard of care is a combination of peginterferon and ribavirin at a fixed dose, 800 mg/day, although higher ribavirin doses may further improve virologic outcomes. In patients that do not respond virologically, maintenance therapy with peginterferon monotherapy is a potential avenue to stem the advance of liver fibrosis, although controlled data in coinfected patients are needed to issue formal recommendations.

Gish RG, Afdhal NH, Dieterich DT, Reddy KR. · Liver Transplant Program and Division of Hepatology and Complex GI, California Pacific Medical Center, 2340 Clay Street #232, San Francisco, CA 94115, USA. · Clin Gastroenterol Hepatol. · Pubmed #15822034 No free full text.

Abstract: The most common chronic blood-borne infection in the United States is caused by hepatitis C virus. An estimated 3.9 million people (1.8%) in the United States have been infected with the hepatitis C virus, excluding certain subpopulations who are at high risk for hepatitis C virus infection. Among these subpopulations are an estimated 255,000 (15%) of prison inmates and 175,000 (22%) of homeless people. Prevalence of hepatitis C virus infection is also high among veterans (6.6% overall and even higher among homeless veterans). The single most important risk factor for hepatitis C virus infection is injection drug use; up to 90% of illicit injection drug users are infected with hepatitis C virus. This review describes the prevalence of hepatitis C virus in special populations and discusses the treatment options for patients with severe disease, transplant recipients, and patients at high risk for infection. Close monitoring and management of therapeutic side effects are required to assist these patients in adhering to therapy.

Quan DJ, Peters MG. · Department of Clinical Pharmacy, University of California, San Francisco, 521 Parnassus Avenue, Room C-152, Box 0622, San Francisco, CA 94143-0622, USA. · Clin Liver Dis. · Pubmed #15481345 No free full text.

Abstract: For the management of HBV infection, an increasing number of nucleotide and nucleoside analogs are active against wild-type HBV and some against HBV with YMDD and other compensatory mutations. Table 2 depicts the IC50 and susceptibilities of HBV to various antiviral agents. The dichotomy between in vitro and in vivo susceptibilities to YMDD mutants is due to a change in IC50 between wild-type and mutant virus. Thus a drug may have less activity in vitro but at doses used in vivo show activity against YMDD and other compensatory mutations. Some HBV drugs share activity against HIV, which may be useful in the co-infected patient. Other nucleoside analogs are in various stages of development, including MCC-478 and DAPD. In the future, clinicians will have a plethora of reagents to chose from, and combination therapies may be invoked.

Lai CJ, Terrault NA. · Division of General Internal Medicine, University of California San Francisco, S357, 513 Parnassus Avenue, San Francisco, CA 94143-0538, USA. · Gastroenterol Clin North Am. · Pubmed #15324948 No free full text.

Abstract: Chronic hepatitis B virus infection (HBV) may result in significant morbidity, including cirrhosis, end-stage liver disease, and hepatocellular carcinoma. The management of chronic HBV cirrhosis is advancing rapidly. Current treatment options for patients with HBV-related cirrhosis include interferon-alpha (IFN-alpha), lamivudine and adefovir dipivoxil. IFN-a is used less commonly today because of its toxicity, difficulty with administration, and the availability of safer drugs. Lamivudine, an oral nucleoside analog, has proven to be at least as effective, and is safer, than IFN-a in the treatment of HBV-related cirrhosis. It is plagued by the development of resistant viral mutants, however. The newest oral nucleotide analog, adefovir dipivoxil, has shown excellent efficacy in treatment-naïve and lamivudine-resistant HBV patients and has lower rates of resistance in the short-term.