4Natural history of acute and chronic hepatitis C
Introduction
Hepatitis C virus (HCV) infection is a global health burden affecting approximately 160–170 million people worldwide [1]. It is a major cause of liver cirrhosis and the increasing incidence of hepatocellular carcinoma (HCC) can be explained in part as a late complication of hepatitis C. Since the onset of nonA/nonB-hepatitis and the subsequent identification of HCV, numerous studies aimed to investigate the natural history of acute and chronic HCV infection. However, several limitations in study designs need to be considered and thus only very few unbiased prospective long-term cohort studies are available [2]. A major problem for all studies was that both acute and chronic HCV infection might be entirely asymptomatic. As a result many patients remain clinical unapparent and were not included in observational studies. Due common modes of transmission via blood contact or sexual intercourse, co-infections with the hepatitis B virus (HBV) or the human immune deficiency virus (HIV) are not infrequent in hepatitis C patients and thus it might be difficult to determine the relative role of HCV for the development of clinical endpoints. The same bias has to be considered regarding alcohol consumption which rarely has been defined in most studies. Moreover, it is not possible to determine the mode and exact time of infection in many patients and it was therefore difficult to investigate duration of infection as a variable. Other hurdles in studying the course of HCV infection include weaknesses in early virological diagnostics applied in the 1990s with less sensitive HCV RNA assays or difficulties to determine the HCV genotype and changes in clinical practice with lesser patients undergoing liver biopsy and more patients being treated by specialists in private practice.
Fortunately antiviral therapy for HCV infection has dramatically improved over the last 20 years. Well accepted, international treatment guidelines have been established [3] and the majority of HCV-infected patients in Western countries has access to antiviral treatment which may prevent progression of liver disease and development of clinical complications [2], [4], [5]. However, as a consequence it has been become ethically impossible to study the long-term natural history of the disease in the absence of treatment intervention.
Despite the methodological difficulties to investigate the natural history of acute and chronic HCV infection there have been several well-performed studies unravelling various aspects of HCV-associated liver disease. In this review we summarize the key findings on disease progression and HCV-related morbidity and mortality with a particular focus on factors potentially influencing the outcome of the disease.
Section snippets
Acute hepatitis C
Patients acquire HCV mainly via blood contact. Thus, the main risk groups are intravenous drug users, recipients of blood transfusions before 1992 and health care workers [6]. Sexual transmission accounts only for a minority of cases, however, acute hepatitis C has become a significant problem in HIV-infected MSM in recent years [7]. Within seven and 21 days after viral transmission HCV RNA becomes detectable in serum [8], [9], [10]. However, longer incubation periods can occur, especially in
Chronic hepatitis C
Once chronic HCV infection is established, spontaneous HCV clearance rarely occurs. Chronic hepatitis C can cause continuous liver damage resulting in liver cirrhosis and subsequently hepatocellular carcinoma (HCC). The individual course of liver disease is highly variable. Patients may report symptoms such as right abdominal discomfort, nausea, fatigue, myalgia, arthralgia or loss of weight. However, all of these clinical signs are uncharacteristic and are not associated with severity of liver
Hepatocellular carcinoma
The incidence of HCC has been rising rapidly over the last 30 years in the industrial countries. In the US, HCCs occur currently approximately three times more often than in 1975 [89], [90]. The global HCV epidemic significantly contributes to the emerging incidence of HCC worldwide. Overall, chronic hepatitis C is responsible for approximately 25% of the HCCs worldwide with particular high prevalences of HCCs in East Asia [91]. Since development of HCC in HCV infected patients is a
Mortality and impact of antiviral therapy
HCV infection is associated with an increased risk of both liver-related mortality and overall mortality [103], [104]. In contrast, mortality in patients who cleared HCV infection is similar to the general population [103]. Liver related death is either caused by HCC or hepatic decompensation. The most common clinical sign of a decompensated HCV related liver cirrhosis is ascites, followed by gastrointestinal bleeding and severe infections. In patients with advanced fibrosis a severe clinical
Concluding remarks
HCV infection remains a major global health burden. Hepatitis C causes significant morbidity and mortality which is preventable by successful antiviral therapy in most cases. Still, there is a very large interindividual variability in the natural history of acute and chronic hepatitis C which can be explained in part by a combination of various host, viral and environmental factors. There is an ongoing need to better define the relative contribution of distinct risk factors to personalize
References (111)
Evolving epidemiology of hepatitis C virus
Clin Microbiol Infec
(2011 Feb)- et al.
Impact of peginterferon and ribavirin therapy on hepatocellular carcinoma: Incidence and survival in hepatitis C patients with advanced fibrosis
J Hepatol
(2010 May) - et al.
Hepatitis C virus clearance, reinfection, and persistence, with insights from studies of injecting drug users: towards a vaccine
Lancet Infec Dis
(2012 May) - et al.
Kinetics of the immune response during HBV and HCV infection
Hepatology
(2003 Jul) - et al.
Acute hepatitis C
Hepatology
(2001 Feb) - et al.
Acute hepatitis C: current status and remaining challenges
Journal of Hepatology
(2008) - et al.
Reduced frequencies of NKp30+NKp46+, CD161+, and NKG2D+NK cells in acute HCV infection may predict viral clearance
J Hepatol
(2011 Aug) - et al.
Immediate vs. delayed treatment in patients with acute hepatitis C based on IL28B polymorphism: A model-based analysis
J Hepatol
(2012 Aug) - et al.
Extrahepatic manifestations of Hepatitis C Virus infection: a general overview and guidelines for a clinical approach
Dig Liver Dis
(2007 Jan) - et al.
Natural history and clinical impact of cryoglobulins in chronic hepatitis C: 10-year prospective study of 343 patients
Gastroenterology
(2007 Sep)