Clinical Liver Disease
© 2014 The American Association for the Study of Liver Diseases
Hepatitis A Viral Infection
Hepatitis A: The Changing Epidemiology of Hepatitis A
HAV infection occurs with clear patterns of geographic distribution and transmission. Socioeconomic conditions, standards of hygiene, sanitation, and access to clean drinking water are all factors strongly associated with the incidence of acute hepatitis A disease and endemicity. Review the factors which can lead to outbreaks, and how vaccination programs have impacted occurence of the disease.
Hepatitis A: Natural History, Immunopathogenesis, and Outcome
Hepatitis A is one of the most common causes of infectious jaundice in the world. Its natural history typically begins with the exposure of a susceptible person to HAV through the fecal-oral route, with the virus arriving at the liver through the GI tract. Learn about the mechanisms of replication, and review the characteristics of each stage in HAV's natural history.
Hepatitis B Viral Infection
Evaluation of the Patient with Chronic Hepatitis B
All newly diagnosed chronic Hepatitis B patients should undergo a complete history, physical assessment, and laboratory assessment in an effort to assess the severity of liver disease and potential need for antiviral therapy. Watch, read, or listen to Dr. Fontana describe recommended testing and markers of HBV replication, as well as other approaches to evaluating the patient.
Predicting Clinical Outcome in a Patient with Chronic Hepatitis B Virus Infection
Hepatitis B can lead to several severe clinical outcomes, including cirrhosis, hepatic decompensation, and hepatocellular carcinoma. While the establishment of a risk prediction tool for various clinical outcomes for patients with HBV is still in a preliminary phase, the use and refinement of these prediction tools may supply HBV patients with a comprehensive individualized management measure based on the risk perspectives. Drs. Yang and Chen explain.
Use of Quantitative Hepatitis B Surface Antigen with Hepatitis B Virus DNA in Clinical Practice
Quantitative Hepatitis B Surface Antigen provides information concerning disease activity over and above an estimation of viral replication. It is an indispensable tool in the clinical assessment and management of chronic hepatitis B viral infection. Drs. Wong and Chan highlight what the clinician needs to know.
Hepatitis B Virus Treatment: Which Patients Require Immediate Treatment
Hepatitis B Virus Treatment: Which Patients Can Have Treatment Deferred?
Treatment can be deferred in chronic HBV patients with inactive or mild liver disease without risk of liver disease progression, while patients with active or advanced liver disease should be treated. Dr. Papatheodoridis reviews approaches to classifying patients and how to determine the most appropriate treatment plans.
Hepatitis B virus Treatment: Which Patients Should Be Treated with Interferon?
Both nucleos(t)ide analogues (NAs) and pegylated interferon (PEG-IFN) have proven to be effective, but current guidelines are lacking clear recommendations as to which treatment strategy should be used as first-line therapy. The authors review the best available evidence regarding which patients should be treated with interferon.
Hepatitis B Virus Treatment: Which Patients Should Be Treated with Nucleos(t)ide Analogue?
Drs. Vigano and Lampertico weigh in on the nucleos(t)ide analogues (NAs)-pegylated interferon (PEG-IFN) debate, addressing first line therapy selection, monitoring of the patient treated with NAs, and when – if ever – it is appropriate to stop treatment. Read, watch, or listen to the discussion.
Hepatitis B Virus Treatment: Management of Antiviral Drug Resistance
Although effective therapies for chronic Hepatitis B are available, antiviral drug resistance represents a serious potential complication. With very few new drugs in the development pipeline, providers must make every effort to prevent resistance by following clear indications for therapy, counseling patients repeatedly on adherence, and monitoring closely for the development of virologic breakthrough. Drs. Tana and Ghany explain.
Hepatitis B Virus in Pregnancy
Watch Tram Tran, MD, an Associate Professor of Medicine from Cedars Sinai Medical Center and a CLD author, discuss HBV treatment in a woman of reproductive age. In the full text of the article, Dr. Tran addresses HBV transmission risk in pregnancy, antiviral therapy in women of childbearing age and treatment in the third trimester, as well as introducing treatment algorithms for the management of HBV in women planning a pregnancy, with an unexpected pregnancy, and during pregnancy.
HBV Treatment in a Patient Who Will Be Receiving Immunosuppressive Therapy
HBV is noncytopathic, with hepatic injury occurring as a result of the host immune response against the virus. As a result, the interaction between HBV and the immune system is critical in determining the outcome of infection. Dr. Feld reviews reverse seroconversion, HBV reactivation, prevention, screening, and management strategies.
Solid Organ Transplantation and Hepatitis B Virus
Read watch or listen to Drs. Villamil and Cairo review the best available evidence on managing the HBV patient who has received a solid organ transplantation. For liver transplant patients, the authors address whether there is a role for hepatitis B immunoglobulin, whether antiviral monotherapy sufficient, and how best to manage liver transplantations from antibody to hepatitis B core antigen (anti-HBc)–positive donors. In the kidney transplant patient, Drs. Villamil and Cairo discuss kidney transplant in HBsAg-positive patients, as well as kidney transplants from anti-HBc–positive donors.
Hepatitis B virus infection in children
Most cases of Hepatitis B that cause long-term morbidity and mortality had their origin during the patient’s childhood, according to Maureen Jonas, MD from Boston Children’s Hospital and Harvard Medical School. Read her article, watch her interview, or listen to the audiocast to better understand the risks of and management strategies for HBV in children, and to review monitoring and treatment algorithms for children with HBV.
Viral Hepatitis B Coinfection with Human Immunodeficiency Virus, Hepatitis D Virus, or Hepatitis C Virus
Patients with chronic Hepatitis B may also have concomitant infection with hepatitis delta virus (HDV), human immuno-deficiency virus (HIV), and/or hepatitis C virus (HCV). Because of the potential for coinfection, patients who are diagnosed with HBV therefore should be tested for their presence. Drs. Nguyen and Sterling review the essentials of diagnosis and management of the coinfected patient.
Hepatopathology of Hepatitis B
This liver biopsy from a patient with markedly active chronic hepatitis B has considerable chronic portal inflammation, predominantly lymphocytes, which migrate out of the portal tract to surround and destroy adjacent hepatocytes. Review this and other histologic features associated with the active immune response to HBV in Dr. Goodman’s review of hepatopathology of HBV.
Hepatitis B Virus: Prevention of Recurrent Infection
Gone are the days when HBV was regarded as a contraindication for liver transplantation. In the last 20 years advances such as HBIG and LAM have made HBV infection one of the best indications for LT, although cost and availability of prophylactic therapies can be challenges. Drs. Villamil and Cairo examine the array of available therapeutic strategies, and provide tips for tailoring treatment according to risk of HBV recurrence.
Hepatitis Delta: Natural History and Outcome
Hepatitis Delta virus is a defective RNA virus that requires the mandatory helper function of hepatitis B virus for its transmission and life cycle. More than 350 million people in the world are considered to have chronic HBV infection, and about 5% of them have serological evidence of exposure to HDV, leading to a burden of at least 15-20 million HDV cases worldwide. While improvement in socioeconomic conditions and vaccination programs have significantly decreased HDV infection over the past two decades, immigration out of regions where the disease is endemic still leads to challenges.
Treatment of Hepatitis Delta
Treatment of HDV infection is challenging, but better outcomes can be achieved by targeting therapy to the individual stages of the disease. Learn about the diagnosis, treatment options, and potential of future therapies for HDV such as prenylation inhibitors.
Hepatitis E: The Endemic Perspective
HEV is endemic in several parts of Africa and Asia, including the Indian subcontinent, where it is often the most common cause of acute hepatitis. Read the review and watch the author interview with Dr. Aggarwal to learn about the key features of this disease from the perspective of a physician-hepatologist working in an area where the disease is endemic.
Hepatitis E: The Nonendemic Perspective
Four major genotypes of HEV have been identified, which may contribute to the observed epidemiological differences between endemic and nonendemic areas of the world. Review the differences between each genotype, and how their epidemiology should inform diagnosis and treatment strategies.
Hepatitis C Viral Infection
The Demographics of Hepatitis C Virus Today
Between 3 and 4 million individuals are chronically infected with hepatitis C virus (HCV) in the US, with up to 170 million worldwide. HCV remains the most common chronic blood borne infection in the US, accounting for up to two-thirds of newly diagnosed cases of chronic liver disease.
A Brief History of Treatment of Viral Hepatitis C
Drs. Strader and Seeff discuss the history of treating HCV and, in the video of their author interview, highlight some of the emerging opportunities for treatment, mapping out a potential future in hepatitis C treatment.
Test your knowledge of hepatitis with CLD's board-style practice questions:
Hepatitis C Viral Infection, continued
The new standard of HCV therapy: Treatment in therapy-naive patients
Patients with HCV infection and their physicians have long been awaiting a more tolerable and effective treatment regimen. New agents - direct acting antivirals or DAAs - are currently in development that directly target the HCV life cycle. Drs. Agrawal and Kwo discuss these new agents and the targets of therapy.
The New Standard of HCV Therapy: Retreatment in Experienced Patients
Until recently, re-treatment options for HCV patients were limited to those who failed a peginterferon interferon and ribavirin regimen. Drs. Gara and Ghany explain this year's two new DAAs, presenting new options for previously untreated and treatment-experienced subjects.
The long-term horizon: Patients who will remain untreated in the era of triple therapy
The DAAs telaprevir and boceprevir have revolutionized HCV therapy by improving therapeutic outcomes for many patients. Although a great leap forward, DAA-based therapy is not a panacea and many patients will not be appropriate candidates for treatment. Drs. Jensen and Aronsohn define who will remain untreated and explore emerging challenges in the era of triple therapy.
The Horizon: New targets and new agents for HCV
Patients with HCV infection and their physicians have long been awaiting a more tolerable and effective treatment regimen. New DAAs directly target the HCV life cycle. Drs. Jazwinski and Muir explain what's next in HCV therapy, explaining the research that contributes to the ultimate goal of using DAAs to target multiple viral and host proteins to increase the anti- viral efficacy, avoid resistance, and improve the side effect profile of HCV treatment.
With the rapid development of DAAs for HCV and the improved SVR rate with the new standard of HCV therapy, healthcare providers are challenged by the need to balance excitement around new therapeutic options with careful selection of patients to optimize benefits and minimize harm. Dr. Lok explains several factors that should inform decision-making around patient selection.
Is There Still a Role for Liver Biopsy in Managing Hepatitis C Virus Infections?
Current guidelines emphasize the importance of liver biopsy in the management of patients with hepatitis C. Recent improvements in antiviral therapy along with the development of alternate modes of evaluating fibrosis have led to a global reassessment of the risks and benefits and the overall wisdom of performing liver biopsy in these patients. Watch, read, or listen to Drs. Jafri and Gordon discuss the potential risks and benefits associated with liver biopsy in managing HCV.
Managing Drug-Drug Interactions With Boceprevir and Telaprevir
Although DAA therapy in combination with PEG-IFN and RIB may result in improved antiviral efficacy and shorter durations of therapy, there are also potentially severe drug-drug interactions involving protease inhibitors and other commonly used agents. Drs. Rangnekar and Fontana provide the information healthcare providers need to familiarize themselves with these interactions before they use these agents.
Importance of Patient Education and Monitoring among HCV-infected Patients Selected for Anti-viral Treatment
Predicting the Response to the Treatment of Hepatitis C Virus Infection
As long as the treatment of HCV is expensive and is associated with adverse events, patients and providers will need to know the likelihood of a response so that they can decide whether the benefits outweigh the risks. Dr. Thomas summarizes approaches that providers can use to provide patients relatively precise estimates of their odds of being cured with today’s standard of care.
Treatment Options for Anti-HCV Treatment-Experienced Patients
The development of new antivirals has allowed significant improvements in the effectiveness of the management of treatment-experienced patients. In order to choose the optimal treatment regiment, though, an assessment of the pattern of previous nonresponsiveness is essential. Dr. Ferenci provides insights into determining this pattern and its impact on designing future treatment plans.
HCV Infection On-Treatment Viral Kinetics: Do They Still Have a Role?
Since the identification of early virological response as a useful stopping rule, the kinetics of viral decline during therapy have been carefully evaluated and have proven useful in a number of different areas of HCV treatment, including predicting favorable responses, developing mathematical models to shed light on the mechanisms of action of antiviral agents, and now, in the era of direct-acting antivirals, for determining the treatment duration. Dr. Feld discusses the role that on-treatment viral kinetics have in the treatment of HCV.
Management of Adverse Events During the Treatment of Chronic Hepatitis C
Adverse events, or side effects, are commonly observed in patients undergoing treatment for chronic hepatitis C. Treatment with telaprevir and boceprevir can worsen side effects frequently associated with PEG-IFN and RBV treatment and can cause different adverse events. Drs. Nguyen and Morgan discuss how to manage various types of adverse events during HCV treatment.
Drug Resistance: Prevalence and Clinical Implications During the Treatment of Chronic Hepatitis C Infection
Read, watch, or listen to Dr. Pawlotsky discuss the principles of HCV resistance to DAAs, the mechanisms of treatment failure during triple- combination therapy, and the consequences and implications of treatment failure on future therapeutic options.
Hepatitis C Viral Infection in Difficult to Treat Populations: An Overview
Major challenges encountered in Hepatitis C treatment include selecting suitable patients for treatment, the optimal approach in the individual patient, and the utilization of an experienced, usually multi-disciplinary team to ensure safe and effective patient outcomes. Dr. Afdhal presents the challenges and potential approaches for managing difficult to treat populations.
Hepatitis C Viral Infection in Patients with Cirrhosis
Cirrhosis develops in up to 25% of patients infected with Hepatitis C over a 30-year period. HCV eradication is associated with improved mortality and reduced cirrhosis-related complications. Although treatment of HCV in patients with cirrhosis poses significant challenges resulting in inferior SVR rates, higher rates of adverse events, and lower tolerance to therapy, aggressive therapy in such patients is strongly supported and leads to improved outcomes. Drs. Bahirwani and Reddy explain.
There are significant challenges to the use of DAAs in patients with HIV/HCV confection, including the potential for interactions between different drugs, addition of drug toxicities, and the ongoing need for therapy with peginterferon. Despite these challenges, preliminary data indicate that the HCV protease inhibitors telaprevir and boceprevir given in combination with peginterferon plus ribavirin increase the cure rate in HIV-infected patients, with manageable toxicity and drug-drug interactions. Dr. Sulkowski explains.
Hepatitis C Viral Infection after Liver Transplantation
Hepatitis C is a leading cause of cirrhosis and hepatocellular carcinoma, and the most common indication for liver transplantation (LT) in the United States and Europe. In contrast to other indications for LT, recurrence of hepatitis C after LT is nearly universal. Drs. Verna and Brown discuss current and potential future approaches to managing HCV in this patient population.
Hepatitis C Viral Infection in Children
Over 130,000 children under the age of 19 are affected by Hepatitis C in the United States. Understanding of the epidemiology, natural history, pathophysiology and treatment options of HCV has greatly advanced in recent years and has led to improved management for children with CHC. Drs. Mogul and Schwarz present a suggested approach for screening and management of children with HCV.
Hepatitis C Viral Infection in Drug Users
Although the majority of new Hepatitis C infections are related to injection drug use, access to care and treatment remains disproportionately limited and treatment efficacy data are still scanty. However, available data suggests that drug users should be offered treatment based on standard natural history considerations and should not be excluded from treatment based on unfounded concerns about reduced adherence and reinfection. Dr. Sylvestre explains.
Hepatitis C Viral Infection in Incarcerated Patients
Within the U.S. corrections system, chronic HCV infection is a major public health concern, affecting 12% to 31% of inmates, compared to approximately 1.6% of the general population. Chronic HCV infection in the prisoner population results in significant morbidity and risk of premature death. However, standard therapy with pegylated interferon and ribavirin is as successful in the prisoner population as in the general population. Dr. Rice and colleagues provide nine concrete recommendations to successfully treat HCV in prisoners.
Access to Care: Management of Hepatitis C Viral Infection in Remote Locations
While new and more effective drug therapies have been developed to help combat Hepatitis C, too few patients have access to treatment. The number of practicing hepatologists continues to grow at a slow rate, and hepatologists primarily practice at academic medical centers, limiting access to care for patients in remote locations. Drs. Arora, Thornton, and Bradford describe a model to train primary care providers to treat liver disease as a solution to the growing need for treatment and the lack of available specialists.
Hepatitis C Viral Infection in Patients with Chronic Kidney Disease
Chronic HCV infection in patients with Chronic Kidney Disease (CKD) undergoing hemodialysis is associated with a 57% higher risk of death compared to HCV-negative hemodialysis controls. Drs. Carrion and Martin review treatment strategies for the CKD patient, both those requiring renal replacement therapy and those who donít, as well as strategies for the renal transplant recipients. The use of Direct-acting antiviral agents for the treatment of hepatitis C in patients with CKD is also discussed.
Hepatitis C Virus: Antiviral Therapy in Wait-Listed Patients
HCV infection universally recurs in patients who are viremic at the time of transplantation, leading to reduced graft survival and increased patient mortality. Review the current interferon-based therapies and learn about emerging drugs and interferon-free treatment from experts Dr. Asmeen Bhatt and Dr. Gregory Everson.
Hepatitis C Virus: Management of Recurrent Disease
Successful treatment of HCV improves survival after liver transplantation, but antiviral therapy for patients awaiting transplantation or on immunosuppression after LT continues to be clinically challenging. In this era of rapidly changing HCV therapy, Dr. Elizabeth Verna explains strategies for eliminating hepatitis C in pre- and post-LT settings.