inPractice Hepatology

  • Editor in Chief: Stefan Zeuzem, MD

    1. 1-1

      Virology and Immunology of Hepatitis Viruses

      • Authors: Esperance Anne Kreek Schaefer, MD, MPH; Raymond T. Chung, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: The 5 major hepatitis viruses are designated as A, B, C, D, and E. Despite a sha... (more)

        Abstract: The 5 major hepatitis viruses are designated as A, B, C, D, and E. Despite a shared host environment in the liver and, specifically, in the hepatocyte, the viral hepatitides represent a widely disparate and heterogeneous group of viruses. They belong to different families and have different replication cycles: One, hepatitis D, even more closely represents a plant viroid than human virus. They can be broadly categorized into enteric pathogens (hepatitis A and E) and parenteral pathogens (hepatitis B, C, and D). The enteric viruses cause self-limited acute infections, whereas the hepatitis resulting from the parenteral pathogens may either be self-limited or progress to chronic liver disease. Treatment advances have stemmed from a vigorous inquiry into the molecular mechanisms of viral propagation and host response. ( less )

    2. 1-2

      Hepatitis A Virus and Hepatitis E Virus: Different Viruses With Similar Stories

      • Authors: Kenneth E. Sherman, MD, PhD;

      • Last Reviewed: 4/1/2016

      • Abstract: Hepatitis A and hepatitis E are highly prevalent viruses that cause acute hepati... (more)

        Abstract: Hepatitis A and hepatitis E are highly prevalent viruses that cause acute hepatic injury. Both hepatitis A and hepatitis E are found worldwide and share many characteristics in terms of transmission, epidemiology, and clinical presentation. Both diseases are generally self-limiting with a low mortality, but hepatitis E can be fatal for pregnant women. In Western countries, hepatitis E is underrecognized and underappreciated as a pathogen, and infection is widely (and mistakenly) believed to represent an adventitious event associated with foreign travel, rather than a result of an infectious endogenous agent with local sources of spread, often from swine. Prevention modalities exist for both viral infections but are more available and are much more commonly applied for hepatitis A than for hepatitis E. ( less )

    1. 2-1

      Hepatitis B Epidemiology, Pathogenesis, Diagnosis, and Natural History

      • Authors: Marc G. Ghany, MD;

      • Last Reviewed: 4/1/2016

      • Abstract: Despite the availability of an effective vaccine, hepatitis B virus (HBV) remain... (more)

        Abstract: Despite the availability of an effective vaccine, hepatitis B virus (HBV) remains a significant global health problem, with more than 240 million persons chronically infected worldwide. Chronic HBV infection is associated with a risk of significant clinical sequelae, including cirrhosis, hepatic decompensation, and hepatocellular carcinoma. In geographic regions of high HBV prevalence, HBV is generally acquired early in life through vertical transmission; conversely, in regions of low HBV prevalence, the infection is usually acquired later in life through injection drug use or unprotected sexual intercourse. HBV genotypes also vary based on geography; studies have reported differences in natural history, clinical outcomes, and responses to therapy based on genotype. HBV diagnosis is based on molecular tests, including serologic and molecular markers associated with HBV infection, in addition to HBV quantification. Results of these serologic tests, along with other assessments, can be used to estimate a patient’s disease state and provide guidance on the best course of action for managing the disease and preventing adverse clinical outcomes. ( less )

    2. 2-2

      Management of Hepatitis B Infection

      • Authors: Harry L. A. Janssen, MD, PhD; Milan J. Sonneveld, MSc;

      • Last Reviewed: 5/25/2018

      • Abstract: Chronic hepatitis B virus (HBV) infection affects an estimated 257 million perso... (more)

        Abstract: Chronic hepatitis B virus (HBV) infection affects an estimated 257 million persons worldwide, with the majority of patients residing in Southeast Asia and sub-Saharan Africa. If left untreated, HBV-infected persons are at risk for developing cirrhosis, hepatic decompensation, and hepatocellular carcinoma. Numerous agents are available for the treatment of hepatitis B, and each comes with its own advantages and drawbacks. In addition, there are several nuances in treating HBV-infected patients who have developed resistance to their first course of HBV therapy. In this module, Harry L. A. Janssen, MD, PhD, and Milan J. Sonneveld, MD, PhD, provide an in-depth discussion of current treatments for hepatitis B and strategies for the optimal use of these agents. ( less )

    3. 2-3

      Hepatitis B Management in Special Populations

      • Authors: Tram T. Tran, MD;

      • Last Reviewed: 6/4/2018

      • Abstract: Various guidelines have provided treatment algorithms for the management of pati... (more)

        Abstract: Various guidelines have provided treatment algorithms for the management of patients with chronic hepatitis B virus (HBV) infection, but often patients present with characteristics that do not fit neatly into these treatment algorithms. Therefore, there is a need to review the data on treating these special populations of HBV-infected patients and provide guidance on how to effectively manage these patients. In this module, Alessandra Mangia, MD, discusses strategies for the management of HBV in special patient populations, including coinfected populations (HIV/HBV, hepatitis C virus/HBV, hepatitis D virus/HBV), women of childbearing age and/or those who are pregnant, populations at risk for disease reactivation, those receiving liver transplantations, and patients presenting with cultural barriers to HBV treatment. ( less )

    4. 2-4

      Hepatitis Delta Virus

      • Authors: Mario Rizzetto, MD;

      • Last Reviewed: 6/1/2018

      • Abstract: Hepatitis D is caused by the hepatitis D virus (HDV), a unique human pathogen de... (more)

        Abstract: Hepatitis D is caused by the hepatitis D virus (HDV), a unique human pathogen dependent for infection on the hepatitis B virus (HBV). Serologic assays for antibodies to the hepatitis D antigen and sensitive polymerase chain reaction tests for HDV RNA in serum are available for screening and diagnosis. Infection is acquired by simultaneous coinfection with HBV or by superinfection following a prior HBV infection. Superinfection often evolves to chronicity and leads to severe and progressive chronic hepatitis D. HDV is endemic in many areas of the developing world where HBV is also endemic. In comparison, prevalence of HDV has declined in industrialized countries in the last 20 years with improved control of HBV infection. However, HDV has not been eradicated in Europe, and immigration from endemic areas is replenishing the reservoir of infection in Western Europe. Treatment of patients with HDV remains a challenge, with limited  options and low efficacy. Indeed, only one quarter of patients with chronic hepatitis D respond to standard treatment with peginterferon alfa. In this module, Mario Rizzetto, MD, reviews the biology, epidemiology, pathogenesis, natural history, clinical presentation, and current treatment recommendations for HDV. ( less )

    1. 3-1

      Hepatitis C Virus Epidemiology, Pathogenesis, Diagnosis, and Natural History

      • Authors: Francesco Negro, MD;

      • Last Reviewed: 5/23/2018

      • Abstract: The current global burden of hepatitis C virus (HCV) infection is high, with an ... (more)

        Abstract: The current global burden of hepatitis C virus (HCV) infection is high, with an estimated 71 million individuals with chronic infection.[ref: WHO 2017] Within the United States, it is estimated that approximately 3.5 million people are infected with HCV and the estimated number of new cases in 2015 was approximately 33,900, a number that has increased since 2010, especially among young white individuals residing in nonurban regions.[ref: CDC 2015] The number of deaths from HCV increased to 19,629 in 2015[ref: CDC 2015] and by 2007 had overtaken HIV/AIDS as a cause of death in the United States.[ref: Ly 2012] This mortality is expected to increase, as those infected by transfusion before HCV testing become apparent.[ref: Blatt 2004] Although improved screening of the blood supply has substantially reduced the incidence of HCV infection in the United States during the last 2 decades, the burden of infection continues to increase as a result of slowly progressing HCV-mediated liver disease, including advanced fibrosis, cirrhosis, and hepatocellular carcinoma, among patients initially infected several decades ago. Continued assessment of the evolving epidemiology of HCV infection and careful monitoring of changes in transmission trends are critical to continue to reduce the incidence of new infections. In addition, a clear understanding of the pathogenesis and natural history of the disease, including the effects of host, viral, and environmental factors on the risk of liver disease progression, is essential for optimizing management strategies for infected patients. In this module, Francesco Negro, MD, provides an in-depth review of past and current HCV transmission trends, the latest understanding of HCV pathogenesis, key assays and recommendations for the diagnosis of HCV, and the natural history of both acute and chronic HCV infection. ( less )

    2. 3-2

      Management of Hepatitis C Infection

      • Authors: Jordan J. Feld, MD, MPH; Hemant Shah, MD, MScCH HPTE;

      • Last Reviewed: 5/9/2018

      • Abstract: In patients with chronic hepatitis C virus (HCV) infection, the goal of therapy ... (more)

        Abstract: In patients with chronic hepatitis C virus (HCV) infection, the goal of therapy is virologic cure. Eradication of HCV RNA, which remains undetectable long term off therapy, is referred to as a sustained virologic response. In general, all patients with chronic HCV infection should be considered as treatment candidates. There are 4 main classes of direct-acting antiviral agents: protease inhibitors, nucleotide polymerase inhibitors, nonnucleotide polymerase inhibitors, and non–structural protein 5a (NS5A) inhibitors, which can be used in various combinations for differing durations depending on the viral genotype/subtype and the severity of liver disease. Peginterferon can be avoided in all clinical scenarios whereas ribavirin is used to enhance treatment efficacy in more challenging patient populations. The choice of regimen, the duration of therapy, and response rates are influenced by a range of host and viral factors, including baseline comorbidities, HCV genotype, HCV RNA, baseline resistance associated variants (RAVs), cirrhosis status, and treatment history. Antiviral treatment of patients with acute HCV infection significantly reduces the risk of developing chronic infection. In this module, Jordan J. Feld, MD, MPH, and Hemant Shah, MD, MScCH HPTE, describe recommendations on the management of patients with HCV infection. ( less )

    3. 3-3

      Hepatitis C Management in Special Populations

      • Authors: Mark S. Sulkowski, MD;

      • Last Reviewed: 12/11/2017

      • Abstract: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carci... (more)

        Abstract: Hepatitis C virus (HCV) is a leading cause of cirrhosis and hepatocellular carcinoma across the globe. With more than 130-170 million people estimated to be chronically infected worldwide and 350,000 HCV-related deaths each year, HCV is a substantial public health concern. In the United States, HCV is the leading cause of death from liver disease and is the most common indication for a liver transplantation. Although HCV is a widespread health problem, disease management is particularly challenging in several key subpopulations, including patients with renal disease or HIV coinfection, children and adolescents, and liver transplantation recipients. This continuing medical education–certified module reviews the transmission, prevalence, and natural history of HCV infection in these populations and provides an in-depth analysis of how HCV treatment must be tailored for these patients. ( less )

    1. 4-1

      Other Viruses That Affect the Liver

      • Authors: Joshua Levitsky, MD, MS; Lisa B. VanWagner, MD, MS;

      • Last Reviewed: 4/1/2016

      • Abstract: Human viral hepatitis results from a wide range of pathogens beyond the classic ... (more)

        Abstract: Human viral hepatitis results from a wide range of pathogens beyond the classic hepatotropic viruses, hepatitis A through E. Secondary and exotic hepatotropic viruses may cause hepatic injury ranging from mild and transient elevation of aminotransferases to acute hepatitis and, occasionally, to fulminant hepatitis. In this comprehensive chapter, Joshua Levitsky, MD, MS, and Lisa VanWagner, MD, MSCI, review the range of viruses that can cause hepatic disease, focusing on the manifestations in patients with solid organ transplantations. ( less )