Hepatitis: Rochester, MN

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Curr Opin Gastroenterol. · Pubmed #17414840 No free full text.

Abstract: PURPOSE OF REVIEW: The aim of this article is to review studies that improve the diagnosis and treatment of autoimmune hepatitis and suggest new drug and molecular interventions. RECENT FINDINGS: Elderly patients have an indolent but aggressive disease that responds well to corticosteroid therapy. Variant syndromes are artificial designations that reflect uncertainties regarding the diagnostic limits of classical disease. Antibodies to cyclic citrullinated proteins and complex assays for antibodies to actin and alpha-actinin may have prognostic value. Defects in the number and function of T regulatory cells may enhance cell-mediated cytotoxicity. HLA DRB113 may be a risk factor in some North American patients, and disease outcome may be influenced by the 'dose' of alleles encoding critical residues. Screening for thiopurine methyltransferase deficiency does not predict azathioprine intolerance. Treatment until normalization of the laboratory and histological features reduces the risk of relapse by 30-50%. Adverse outcomes in pregnancy are associated with antibodies to soluble liver antigen/liver pancreas and Ro/SSA. SUMMARY: Novel serological tests may have prognostic value. Defects in the suppressor activity of regulatory T cells may promote liver injury. Genetic predispositions strongly influence disease occurrence and outcome. Laboratory and histological features should be normal prior to drug withdrawal. Azathioprine toxicities cannot be predicted.

Montano Loza AJ, Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · Nat Clin Pract Gastroenterol Hepatol. · Pubmed #17404588 No free full text.

Abstract: The treatment of autoimmune hepatitis is evolving as the pathogenic pathways that underlie the disease are defined, new immunosuppressive agents are tested, and site-specific molecular interventions become feasible. Prednisone alone or at a reduced dose combined with azathioprine is the conventional treatment. Patients with HLA genotype DRB1*0301 have a poorer treatment response and a more frequent need for liver transplantation than those with HLA genotype DRB1*0401. Therapy to the point when liver test results and histological findings are normal reduces, but does not eliminate, the occurrence of relapse. Treatment failure warrants reassessment with regard to the accuracy of the original diagnosis and the exclusion of variant forms of hepatitis or concomitant alternative diseases. Ciclosporin might be effective as short-term, front-line therapy in infants and adults, and calcineurin inhibitors might salvage patients who are refractory to corticosteroid regimens. Mycophenolate mofetil can induce an improvement in laboratory test results and reduce the requirement for corticosteroids. Sirolimus is effective for treatment of de novo autoimmune hepatitis that develops after liver transplantation. Synthetic peptides that block autoantigen presentation, cytokine manipulations, oral tolerance regimens, T-cell vaccination, and gene therapy are all interventions that will be able to emerge after a reliable animal model of the human disease has been developed.

Rodriguez M. · Department of Neurology and Immunology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Brain Pathol. · Pubmed #17388953 No free full text.

Abstract: Most of the research on multiple sclerosis (MS) has focused on the early events that trigger demyelination and subsequent remyelination. Less attention has been given to the factors that directly mediate the demyelination that is the hallmark of the disease. Effector cells or molecules are those factors directly responsible for mediating the damage in the disease. Similarly, there are effector molecules that are critical for remyelination in the central nervous system (CNS). By understanding those effector molecules in demyelination and remyelination that directly influence the pathologic process, we should be able to generate specific therapies with the greatest potential for benefiting MS patients. This review focuses on effector cells and molecules that are critical for demyelination and remyelination in MS but also in experimental models of the disease including experimental autoimmune encephalomyelitis (EAE), virus-induced models of demyelination (Theiler's virus, murine hepatitis virus), and toxic models of demyelination (lysolecithin, ethidium bromide, and cuprizone). These are models in which the effector molecules for demyelination and remyelination have been most precisely evaluated.

McGovern LM, Boyce TG, Fischer PR. · Department of Pediatric and Adolescent Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · J Travel Med. · Pubmed #17367482 No free full text.

Abstract: With the overall increase in international travel, there is likely to be an increase in travel during pregnancy as well. In developing countries, pregnant women face exposures that can add significant risk for neonatal morbidity and mortality. Infections that can occur in utero or in the early neonatal period include malaria, yellow fever, tuberculosis, hepatitis, human immunodeficiency virus, leishmaniasis, toxoplasmosis, filariasis, Japanese encephalitis, rubella, typhoid fever, leptospirosis, dengue fever, Helicobacter pylori, and trypanosomiasis. When travel and potential exposure cannot be avoided, preventive measures are usually effective. Pretravel consultation should include careful discussion of length of travel, antimalarial prophylaxis, insect avoidance, food and water hygiene, vaccination, and body fluid precautions.

Charlton M. · Transplant Center CH-10, Mayo Clinic and Foundation, 200 First Street SW, Rochester, MN 55905, USA. · Curr Gastroenterol Rep. · Pubmed #17335674 No free full text.

Abstract: Hepatitis C-associated liver failure is the most common indication for liver transplantation. Histologic evidence of recurrence is apparent in approximately 50% of hepatitis C virus (HCV)-infected recipients in the first postoperative year. Approximately 10% of HCV-infected recipients will die or lose their allograft due to hepatitis C-associated allograft failure. HCV-infected recipients who undergo retransplantation have 5-year patient and graft survival rates that are broadly similar to those for transplant recipients who are not HCV infected. Although the choice of calcineurin inhibitor, mycophenolate mofetil, or both has not been clearly shown to affect histologic recurrence of hepatitis C, higher cumulative exposure to corticosteroids is associated with increased mortality and more severe histologic recurrence. In contrast to treatment of non-HCV-infected recipients, treatment of HCV-infected transplant recipients for acute cellular rejection is associated with attenuated patient survival. Steroid-resistant rejection with or without the use of T-cell-depleting therapies is associated with a greater than fivefold increased risk of mortality in HCV-infected liver transplant recipients. Pegylated interferon with or without ribavirin should be considered for treatment of recipients with histologically apparent recurrence of hepatitis C before total bilirubin exceeds 3 mg/dL. The role of hepatitis C immunoglobulin and new immunosuppressive agents in the management of hepatitis C after transplant continues to evolve.

Kamath PS, Kim WR, Anonymous00047. · Advanced Liver Disease Study Group, Miles and Shirley Fiterman Center for Digestive Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Hepatology. · Pubmed #17326206 No free full text.

Abstract: The Model for End-stage Liver Disease (MELD) was initially created to predict survival in patients with complications of portal hypertension undergoing elective placement of transjugular intrahepatic portosystemic shunts. The MELD which uses only objective variables was validated subsequently as an accurate predictor of survival among different populations of patients with advanced liver disease. The major use of the MELD score has been in allocation of organs for liver transplantation. However, the MELD score has also been shown to predict survival in patients with cirrhosis who have infections, variceal bleeding, as well as in patients with fulminant hepatic failure and alcoholic hepatitis. MELD may be used in selection of patients for surgery other than liver transplantation and in determining optimal treatment for patients with hepatocellular carcinoma who are not candidates for liver transplantation. Despite the many advantages of the MELD score, there are approximately 15%-20% of patients whose survival cannot be accurately predicted by the MELD score. It is possible that the addition of variables that are better determinants of liver and renal function may improve the predictive accuracy of the model. Efforts at further refinement and validation of the MELD score will continue.

Juran BD, Lazaridis KN. · Division of Gastroenterology and Hepatology, Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Semin Liver Dis. · Pubmed #17295173 No free full text.

Abstract: The interest in dissecting the genetic and environmental components of complex human disease is growing, fueled by the emerging advances in the field of genomics and related disciplines. Improved understanding of the pathogenesis of complex liver diseases such as gallbladder stones, nonalcoholic fatty liver disease, viral hepatitis, and hepatocellular carcinoma remains a goal of the clinical and experimental hepatologist alike. Despite the scientific progress and technological advancement, elucidating the underlying mechanisms of complex hepatic diseases from the genomic standpoint will be demanding. Complexity of genomic structure and function, disease heterogeneity, influence of the environment on disease development and progression, and epigenetics all contribute to the challenge. To overcome these obstacles, novel conceptual frameworks regarding biological systems and human diseases are necessary in addition to a coordinated endeavor among different scientific disciplines. Deciphering in an integrated fashion the genomic, transcriptional, and translational aspects of the pathogenesis of complex liver diseases will lead to their better prediction, diagnostics, and treatment.

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Curr Opin Rheumatol. · Pubmed #17143100 No free full text.

Abstract: PURPOSE OF REVIEW: To review studies that clarify the rheumatic manifestations of autoimmune hepatitis, elucidate shared pathogenic pathways, and encourage innovative site-specific therapies. RECENT FINDINGS: Autoimmune hepatitis has clinical manifestations, serological markers, pathogenic mechanisms, genetic predispositions, and therapies similar to the rheumatic diseases. The rheumatic manifestations may mask the underlying liver disease and vice versa. Variations in clinical phenotype and outcome for the autoimmune liver diseases may reflect host-specific and region-specific factors, and defects in counter-regulatory suppressor functions by regulatory T cells may facilitate cell-mediated cytotoxicity and autoreactivity. Mixed syndromes with hallmark features of one disease in another probably reflect a genetic predisposition for immune expression that is shared among the diseases. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine are promising treatments, and de-novo autoimmune hepatitis after liver transplantation suggests that the calcineurin inhibitors may have paradoxical effects on self-tolerance. SUMMARY: Clinical phenotypes of autoimmune hepatitis commonly include rheumatic manifestations that can mask the liver disease. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and pharmacological interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are feasible.

Juran BD, Lazaridis KN. · Division of Gastroenterology and Hepatology, Center for Basic Research in Digestive Diseases, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Hepatology. · Pubmed #17133459 No free full text.

Abstract: The concept of genetic susceptibility in the contribution to human disease is not new. What is new is the emerging ability of the field of genomics to detect, assess, and interpret genetic variation in the study of susceptibility to development of disease. Deciphering the human genome sequence and the publication of the human haplotype map are key elements of this effort. However, we are only beginning to understand the contribution of genetic predisposition to complex liver disease through its interaction with environmental risk factors. In the coming decade, we anticipate the development of human studies to better dissect the genotype/phenotype relationship of complex liver diseases. This endeavor will require large, well-phenotyped patient populations of each disease of interest and proper study designs aimed at answering important questions of hepatic disease prognosis, pathogenesis, and treatment. Teamwork between patients, physicians, and genomics scientists can ensure that this opportunity leads to important biological discoveries and improved treatment of complex disease.

Tharayil VS, Roberts LR. · Miles and Shirley Fiterman Center for Digestive Diseases Mayo Clinic College of Medicine Rochester, MN 55902, USA. · Minerva Gastroenterol Dietol. · Pubmed #17108869 links to  free full text

Abstract: Chronic hepatitis B virus (HBV) infection is the most frequent risk factor for development of hepatocellular carcinoma (HCC) worldwide. Studies of the molecular genetics and pathophysiology of HCC suggest that there are significant differences in the allelic imbalance, genome copy number, and gene expression patterns of HBV-induced HCC as compared to HCCs from other causes, which are presumably reflected to differences in the mode of presentation and outcomes of HBV-induced HCCs. Unique features of HBV-induced carcinogenesis include the role of HBV DNA integration in carcinogenesis and the powerful synergism between HBV and dietary aflatoxins in the pathogenesis of HCC. A more complete understanding of the biology of HBV-induced HCCs may reveal well-defined differences in the molecular pathways that regulate growth of these HCCs and allow better-targeted approaches to prevention and therapy of HBV-induced HCCs. This review will attempt to summarize the current knowledge about carcinogenic pathways in HBV-induced HCCs, review the agents currently in development for targeted therapy of HCCs, and propose potentially novel approaches to therapy of HBV-induced HCC.

Vlahakis SR. · Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · J Med Liban. · Pubmed #17087002 No free full text.

Abstract: Hepatitis C virus (HCV) infection is a major cause of liver disease and hepatocellular carcinoma worldwide, as well as the leading cause of liver transplantations in the United States. As a result of similar modes of transmission, approximately 30% of HIV-infected individuals are co-infected with HCV. Among intravenous drug users, almost 90% of people infected with HIV are also infected with HCV. Because of treatment with highly active anti-retroviral therapy, HIV-infected individuals have improved survival and are no longer suffering from opportunistic infections and malignancy as in years past. As a result, co-infection with HCV has now become a frequent cause of morbidity and mortality in HIV-infected individuals. Furthermore, liver disease secondary to HCV infection is now the leading cause of hospital deaths in HIV-infected people in the US. HIV infection accelerates the course of HCV-related liver disease and viremia. It is less clear whether HCV infection affects the clinical course of HIV; however, HCV-related liver disease can limit many individuals from receiving anti-HIV therapy. HIV/ HCV co-infection is common, and serious. Physicians caring for HIV-infected patients worldwide must now address hepatitis C virus co-infection.

Czaja AJ. · Mayo Clinic College of Medicine, Rochester, Minnesota, USA. · MedGenMed. · Pubmed #16926794 links to  free full text

Abstract: CONTEXT: Autoimmune hepatitis has diverse features that can delay its diagnosis and the institution of potentially lifesaving corticosteroid therapy. OBJECTIVE: Review the clinical, laboratory, and histologic features of autoimmune hepatitis and promulgate routine application of its codified diagnostic criteria. DATA SOURCES: Reference lists and MEDLINE. STUDY SELECTION: All clinically pertinent published observations that indicate the diversity of manifestations and pitfalls in diagnosis. DATA EXTRACTION: Findings that had common clinical relevance and the potential to confuse the diagnosis or delay institution of therapy were selected. DATA SYNTHESIS: Autoimmune hepatitis can present acutely and have histologic features of centrilobular zone 3 inflammation. Many patients may be asymptomatic, but they frequently have severe or advanced disease and typically develop symptoms later. Autoantibodies are reflective of immune-mediated mechanisms, but they are not diagnostic, pathogenic, or even required for the diagnosis. Genetic factors affect susceptibility, clinical phenotype, and treatment outcome, and they may be clues to indigenous etiologic agents. Autoimmune hepatitis can recur or develop de novo after liver transplantation, and it should be considered in all transplanted patients with allograft dysfunction. Diagnostic criteria have been codified, and a scoring system quantifies the strength of the diagnosis and accommodates atypical or deficient features. CONCLUSION: Autoimmune hepatitis is an important diagnosis to consider in all patients with chronic hepatitis of undetermined cause.

DiCecco SR, Francisco-Ziller N. · William J. von Liebig Transplant Center, Mayo Clinic Rochester, 201 W. Center Street, Rochester, MN 55902, USA. · Nutr Clin Pract. · Pubmed #16772542 No free full text.

Abstract: Liver disease secondary to alcohol ranges from alcoholic fatty liver disease to acute hepatitis to cirrhotic liver disease. It is imperative that alcohol be discontinued to allow for any potential improvement in liver function, with most benefit being seen in the early stages of the disease. Alcoholic liver disease has a profound effect on nutrient intake, nutrition status, and metabolism, contributing to a high prevalence of malnutrition in this population. Early intervention with nutrition therapy may improve response to treatment, alleviate symptoms, and improve quality and quantity of life. In this review, nutrition assessment parameters and medical nutrition therapy goals for alcoholic liver disease are discussed.

Eid AJ, Brown RA, Patel R, Razonable RR. · Division of Infectious Diseases and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Clin Infect Dis. · Pubmed #16758416 No free full text.

Abstract: BACKGROUND: Infections with parvovirus B19 (PVB19) can cause significant morbidity in transplant recipients. METHODS: To characterize the epidemiology and clinical spectrum of posttransplant PVB19 infection, we reviewed all cases at our institution during a 16-year period, summarized the data from 91 cases published in the medical literature, and performed longitudinal molecular surveillance for PVB19 DNAemia among 47 solid organ and hematopoietic stem cell transplant recipients. RESULTS: The median time to onset of PVB19 disease was 7 weeks after transplantation. Anemia, leukopenia, and thrombocytopenia were present in 98.8%, 37.5%, and 21.0% of patients, respectively. Hepatitis, myocarditis, and pneumonitis were also reported in association with PVB19 disease. Allograft tissue loss or dysfunction was observed at the time of PVB19 disease in 10% of cases. At the onset of disease, PVB19 IgM serological test results were negative in 29% of cases. Almost all patients (96%) with anti-PVB19 IgM had a positive PVB19 polymerase chain reaction assay result. Intravenous immunoglobulin was the most commonly used treatment modality. Three of 98 patients died of myocarditis and cardiogenic shock associated with PVB19 disease. Molecular surveillance throughout the first year after transplantation did not reveal PVB19 DNAemia in 47 anemic solid organ and hematopoietic stem cell transplant patients. CONCLUSIONS: PVB19 is a rare but clinically significant infection that manifests as refractory anemia during the posttransplantation period. The use of polymerase chain reaction for diagnosis is particularly helpful in immunosuppressed transplant patients who may fail to mount antibodies against PVB19 during active infection.

Charlton MR, Pockros PJ, Harrison SA. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Hepatology. · Pubmed #16729327 No free full text.

Abstract: Obesity and the metabolic syndrome have hepatic manifestations, including steatosis and progression of fibrosis. In individuals with chronic hepatitis C, obesity is associated with inflammation, insulin resistance, steatosis, progression of fibrosis, and nonresponse to treatment with interferon or peginterferon alpha and ribavirin. Patients with both hepatitis C and obesity-related nonalcoholic fatty liver disease are at greater risk for more advanced liver disease. We review the mechanisms by which obesity may be associated with decreased efficacy of interferon-based therapies in individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies in obese individuals.

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN 55905, USA. · Curr Opin Gastroenterol. · Pubmed #16550037 No free full text.

Abstract: PURPOSE OF REVIEW: To review studies that improve the diagnosis and treatment of autoimmune hepatitis and presage new drug and molecular site-specific interventions. RECENT FINDINGS: Autoimmune hepatitis can present as acute or chronic hepatitis and as allograft dysfunction after liver transplantation. Elderly patients have an indolent but aggressive disease that responds well to corticosteroid therapy, and human leukocyte antigen DR4 characterizes this population. Geographic and ethnic factors influence clinical phenotype and behavior, and defects in T-regulatory cells may enhance cell-mediated cytotoxicity. Treatment response is the best index of prognosis, and normalization of serum aminotransferase abnormalities prevents disease progression. Mycophenolate mofetil, budesonide, rapamycin, and 6-thioguanine have been effective in small clinical experiences. De-novo autoimmune hepatitis can occur in adults and children after liver transplantation, and rapamycin may be an effective treatment. SUMMARY: Autoimmune hepatitis has a global distribution and diverse clinical manifestations. Phenotypes are affected by regional and ethnic factors which may provide clues to the etiologic agents. Defects in counter-regulatory functions enhance cell-mediated cytotoxicity, and interventions that promise site-specific actions affecting immunocyte differentiation and proliferation are now feasible. Autoimmune hepatitis must be considered in all patients with acute and chronic hepatitis and in all cases of allograft dysfunction after liver transplantation.

Malhi H, Gores GJ, Lemasters JJ. · Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN, USA. · Hepatology. · Pubmed #16447272 No free full text.

Abstract: Death of hepatocytes and other hepatic cell types is a characteristic feature of liver diseases as diverse as cholestasis, viral hepatitis, ischemia/reperfusion, liver preservation for transplantation and drug/toxicant-induced injury. Cell death typically follows one of two patterns: oncotic necrosis and apoptosis. Necrosis is typically the consequence of acute metabolic perturbation with ATP depletion as occurs in ischemia/reperfusion and acute drug-induced hepatotoxicity. Apoptosis, in contrast, represents the execution of an ATP-dependent death program often initiated by death ligand/death receptor interactions, such as Fas ligand with Fas, which leads to a caspase activation cascade. A common event leading to both apoptosis and necrosis is mitochondrial permeabilization and dysfunction, although the mechanistic basis of mitochondrial injury may vary in different settings. Prevention of these modes of cell death is an important target of therapy, but controversies still exist regarding which mode of cell death predominates in various forms of liver disease and injury. Resolution of these controversies may come with the recognition that apoptosis and necrosis frequently represent alternate outcomes of the same cellular pathways to cell death, especially for cell death mediated by mitochondrial permeabilization. An understanding of processes leading to liver cell death will be important for development of effective interventions to prevent hepatocellular death leading to liver failure and to promote cancer and stellate cell death in malignancy and fibrotic disease.

Charlton M. · Department of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN, USA. · J Nutr. · Pubmed #16365102 links to  free full text

Abstract: Altered amino acid metabolism is a hallmark of liver disease, characterized by low levels of circulating BCAAs and elevated levels of circulating aromatic amino acids, and methionine. Although overwhelming evidence indicates that the incidence of complications of liver disease increases with malnutrition, the reported impact of nutritional therapy, specifically BCAA supplementation, on outcomes in patients with liver disease has varied with the indication. Multiple small studies report the beneficial effects of BCAA supplementation, including improved metabolic profiles, as measured by protein sparing and/or normalization of respiratory quotients and clinical improvement of hepatic encephalopathy. Other studies have failed to show a clinical benefit of BCAA supplementation. The data concerning the impact of BCAA supplementation in prophylaxis of long-term morbidity and mortality in patients with cirrhosis is more promising and has been the subject of 2, large randomized controlled trials. In a study of 174 patients with advanced cirrhosis, who were randomized to either BCAA or 1 of 2 control arms, the combined event rates were seen to be significantly reduced in the BCAA supplementation arm, although this was not true for individual complications. In a more recent, larger, randomized controlled trial (n = 646) using a more palatable formulation, investigators demonstrated that long-term BCAA supplementation is associated with decreased frequency of hepatic failure and overall complication frequency. Both studies found improved nutritional status associated with BCAA supplementation. On balance, BCAA supplementation appears to be associated with decreased frequency of complications of cirrhosis and improved nutritional status when prescribed as maintenance therapy. Cost and palatability may limit the potential applicability of this treatment modality.

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · Minerva Gastroenterol Dietol. · Pubmed #16282960 No free full text.

Abstract: Autoimmune hepatitis has a global occurrence and diverse manifestations. Patients are frequently asymptomatic (34%), and an acute, even fulminant, presentation is possible. Concurrent immune disorders may obscure the liver disease, and perivenular (Rappaport zone 3) necrosis is within the histological spectrum. Clinical phenotypes and outcomes vary among different ethnic groups, and genetic factors strongly affect susceptibility. Non-disease specific autoimmune modifiers include female gender and gene polymorphisms that affect immunocyte activation and differentiation. Antibodies to soluble liver antigen/liver pancreas may have prognostic importance and reflect a genetic propensity for severe disease. Subtypes based on serological profiles do not have distinctive outcomes or therapies. Variant forms include patients with bile duct injury or loss, absence of conventional serological markers, abnormal cholangiograms, or coincidental hepatitis C. Treatment is empiric and based on the predominant manifestations (hepatitic, cholestatic, or viral). New treatment strategies must be strengthened by predictive indices that accurately forecast individual differences in disease outcome. Drugs with site-specific actions on immunocyte activation and proliferation (cyclosporine, tacrolimus and myco-phenolate mofetil) must be assessed by clinical trial, and site-specific molecular interventions (blocking peptides, recombinant immune modulators, T cell vaccination, oral tolerance, gene silencing and gene therapy) require confident experimental animal models for evaluation. Better prognostic indices, new immunosuppressive agents, and site-specific molecular interventions promise to improve care.

Poland GA. · Mayo Vaccine Research Group, Program in Translational Immunovirology and Biodefense, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota 55905, USA. · Am J Med. · Pubmed #16271536 No free full text.

Abstract: Hepatitis A and hepatitis B vaccines are now widely available throughout the United States, Europe, and most of the rest of the world. A recombinant hepatitis B vaccine was licensed in the United States in 1986, followed by hepatitis A vaccine in 1995. Official recommendations from the Advisory Committee on Immunization Practices were published for hepatitis B vaccine in 1990, with revisions in 1991, and for hepatitis A vaccine in 1999. Unfortunately, the recommendations are not closely followed, and an insufficient number of persons who are at risk receive these vaccines. In addition, the available recommendations may not cover all who are at risk for infection. This article reviews existing recommendations for the use of hepatitis A and hepatitis B vaccines and offers suggestions for situations in which additional recommendations may be useful. The rationale for revising and expanding the existing recommendations is based on questions raised about the value of risk-based recommendations, data demonstrating increasing rates of hepatitis A and B infections in specific age groups, and the failure to protect 50% of individuals who become infected with vaccine-preventable hepatitis.

Charlton M. · Department of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN 55905, USA. · Liver Transpl. · Pubmed #16237717 links to  free full text

Abstract: 1. Hepatitis C-associated liver failure is the most common indication for liver transplantation, and approximately 10% of HCV-infected recipients will die or lose their allograft secondary to recurrent HCV infection. 2. Risk factors associated with histological recurrence of HCV include donor (age, fat content, ischemic time, and living donor), recipient (age and non-Caucasian race), clinical (rejection and CMV), and viral (viral load and quasispecies). 3. Treatment of recipients with histological recurrence is with pegylated IFN (+/- ribavirin). The role of hepatitis C immunoglobulin in the management of postransplant HCV is still evolving. (

Guicciardi ME, Gores GJ. · Mayo Clinic College of Medicine, 200 First St SW, Rochester, Minnesota 55905, USA. · Gut. · Pubmed #15951554 links to  free full text

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Bonilla Guerrero R, Roberts LR. · Center for Basic Research in Digestive Diseases, Division of Gastroenterology and Hepatology and Mayo Clinic Cancer Center, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN 55905, USA. · J Hepatol. · Pubmed #15826727 No free full text.

This publication has no abstract.

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN 55905, USA. · Curr Opin Gastroenterol. · Pubmed #15818149 No free full text.

Abstract: PURPOSE OF REVIEW: This review aims to demonstrate how recent insights into disease behavior and mechanisms and the availability of new drugs can be assimilated into evolving concepts of diagnosis and treatment. RECENT FINDINGS: Autoimmune hepatitis has a global distribution, and its clinical manifestations are similar in different regions. Concurrent immune diseases are common, and immunoglobulin A nephropathy may explain ascites in some patients. Subclinical celiac disease can cause cryptic liver dysfunction or be associated with autoimmune hepatitis. A fulminant presentation that is associated with de novo rather than exacerbated pre-existent disease is possible, and these patients may have centrilobular zone 3 necrosis. Bile duct injury as a background histologic finding should not change the diagnosis or therapy, and the clinical significance of autoantibodies can be determined only by examination of liver biopsy tissue. Molecular mimicry may be important in breaking self-tolerance, and a murine model based on DNA immunization with self-antigens supports this hypothesis. Corticosteroid therapy reduces or prevents hepatic fibrosis, and noninvasive techniques promise to facilitate the development of treatments that enhance this effect. Mycophenolate mofetil is a possible salvage therapy that requires clinical trial, and liver transplantation has a 5-year patient survival of 78% but is frequently followed by recurrent disease and acute rejection. SUMMARY: Autoimmune hepatitis should be considered in all patients with acute or chronic liver disease. Therapy can reduce or prevent fibrosis. The new immunosuppressive drugs should undergo clinical trial before empiric use. Animal models promise to identify key pathogenic sites that can be targeted by therapies.

Czaja AJ. · Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA. · Ann Hepatol. · Pubmed #15798657 No free full text.

Abstract: Autoimmune hepatitis has a global occurrence, diverse clinical phenotype, and evolving treatment options. The goals of this report are to review the codified diagnostic criteria, spectrum of clinical presentations, proposed pathogenic mechanisms, conventional treatment strategies, and promising interventions. The literature published in English from 1980-2005 was reviewed and an updated current perspective provided. Autoimmune hepatitis affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. Perivenular (zone 3) necrosis is within the histological spectrum. Autoimmune hepatitis can recur or develop de novo after liver transplantation. CD4+ T-helper cells and natural killer T cells have been implicated in the pathogenesis, and molecular mimicry may break self-tolerance. DRB1*0301 and DRB1*0401 are the susceptibility alleles among white North Americans and northern Europeans, whereas diverse alleles of HLA DR4 have been associated with the disease in Japan, mainland China, and Mexico. DRB1*1301 is associated with autoimmune hepatitis in South American children, and it may predispose to an indigenous etiologic agent. Antibodies to soluble liver antigen/liver pancreas may have prognostic importance, and cyclosporine and mycophenolate mofetil must be assessed by clinical trial before incorporation into management algorithms. Site-specific interventions are feasible, and they require a confident experimental animal model for evaluation. Variant syndromes lack diagnostic and therapeutic guidelines. In conclusion, autoimmune hepatitis must be considered in all patients with acute and chronic liver disease and those with allograft dysfunction after transplantation. New immunosuppressive agents and site-specific interventions promise to improve care.