Book on hepatitis from page 314 to 321

Book on hepatitis from page 314 to 321

314  Hepatology 2012
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Management of HCV/HIV Coinfection  315
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liver transplantation: analysis of United Network for Organ Sharing database.
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didanosine-related mitochondrial toxicity in HIV/HCV-coinfected patients receiving
ribavirin. Antivir Ther. 2004;9:133-8. (Abstract)
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The European AIDS Treatment Network (NEAT) Acute Hepatitis C Infection Consensus Panel.
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safety of peg-interferon-a 2a (40 kd) + ribavirin in patients with HIV-HCV coinfection.
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characteristics of hepatitis C virus infection in HIV-infected individuals with chronic
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coinfection does not influence the CD4 cell recovery in HIV-1-infected patients with
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(Abstract)
Pineda JA, García-García JA, Aguilar-Guisado M, et al. Grupo para el Estudio de las Hepatitis
Víricas de la Sociedad Andaluza de Enfermedades Infecciosas (SAEI).Clinical
progression of hepatitis C virus-related chronic liver disease in human
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Pol S, Thiers V, Nousbaum J, et al. Changing distribution of HCV genotypes in Europe in the
last decades. J Hepatol 1994; 21: S13.
Puoti M, Bonacini M, Spinetti A, Putzolu V, Govindarajan S, Zaltron S, et al. Liver fibrosis
progression is related to CD4 cell depletion in patients coinfected with hepatitis C
virus and human immunodeficiency virus. J Infect Dis. 2001;183:134-7. (Abstract)
316  Hepatology 2012
Qian HZ, Vermund SH, Kaslow RA, et al. Co-infection with HIV and hepatitis C virus in former
plasma/blood donors: challenge for patient care in rural China. AIDS 2006; 20: 1429-1435. (Abstract)
Qurishi N, Kreuzberg C, Lüchters G et al. Effect of antiretroviral therapy on liver-related
mortality in patients with HIV and hepatitis C coinfection. Lancet 2003; 362: 1708-1713. (Abstract)
Rauch A, Kutalik Z, Descombes P, et al. Genetic variation in IL28B is associated with chronic
hepatitis C and treatment failure: a genome-wide association study. Gastroenterology
2010,138:1338-1345. (Abstract)
Rallón NI, Soriano V, Naggie S, et al. IL28B gene polymorphisms and viral kinetics in
HIV/hepatitis C virus-coinfected patients treated with pegylated interferon and
ribavirin. AIDS. 2011;25:1025-33. (Abstract)
Resino S, Asensio C, Bellón JM, et al. Diagnostic accuracy of the APRI, FIB-4, and the Forns
index for predicting liver fibrosis in HIV/HCV-coinfected patients: A validation study. J
Infect. 2011;63:402-5. (Abstract)
Rockstroh JK, Spengler U, Sudhop T, et al: Immunosuppression may lead to progression of
hepatitis C virus associated liver disease in hemophiliacs coinfected with HIV. Am J
Gastroenterol 1996; 91: 2563-2568. (Abstract)
Rockstroh JK, Theisen A, Kaiser R, et al: Antiretroviral triple therapy decreases the HIV viral
load and does not alter hepatitis C virus serum levels in HIV/HCV-coinfected
hemophiliacs. AIDS 1998; 12: 829-830. (Abstract)
Rockstroh JK, Spengler U. HIV and HCV coinfection. Lancet Infect Dis 2004; 4: 437-444.
(Abstract)
Rockstroh JK, Mocroft A, Soriano V, et al: Influence of hepatitis C virus infection on HIV-1
disease progression and response to highly antiretroviral therapy. J Infect Dis 2005;
192: 992-1002. (Abstract)
Rockstroh JK. Hot topics in HIV and hepatitis coinfection: noninvasive diagnosis of liver
disease, liver transplantation, and new drugs for treatment of hepatitis coinfection.
HIV Clin Trials 2009;10:110-5. (Abstract)
Rodríguez-Nóvoa S, Morello J, González M, Vispo E, Barreiro P, González-Pardo G, et al.
Increase in serum bilirubin in HIV/hepatitis-C virus-coinfected patients on atazanavir
therapy following initiation of pegylated-interferon and ribavirin. AIDS. 2008;22:2535-7. (Abstract)
Rodriguez-Torres M, Slim J, Bhatti L, Sterling RK, Sulkowski MS, Hassanein T, et al. Standard
versus high dose ribavirin in combination with peginterferon alfa-2a (40KD) in
genotype 1 (G1) HCV patients coinfected with HIV: Final results of the PARADIGM
study. AASLD 2009, Abstract 1561.
Schmidt AJ, Rockstroh JK, Vogel M, et al. Trouble with bleeding: risk factors for acute hepatitis
C among HIV-positive gay men from Germany--a case-control study. PLoS One
2011;6:e17781. (Abstract)
SeyedAlinaghi S, Jam S, Mehrkhani F, et al. Hepatitis-C and hepatitis-B co-infections in
patients with human immunodeficiency virus in Tehran, Iran. Acta Med Iran 2011;
49:252-7. (Abstract)
Sherman KE, Rockstroh JK, Dieterich DT, et al. Telaprevir in Combination with Peginterferon
Alfa-2a/Ribavirin in HCV/HIV Coinfected Patients: A 24-Week Treatment Interim
Analysis. The 62nd Annual Meeting of the American Association for the Study of
Liver Diseases 2011, San Francisco, USA. Abstract LB-8.
Singal AK, Anand BS. Management of hepatitis C virus infection in HIV/HCV co-infected
patients: clinical review. World J Gastroenterol. 2009;15:3713-24. (Abstract)
Soriano V, Mocroft A, Rockstroh J, et al. Spontaneous viral clearance, viral load, and genotype
distribution of hepatitis C virus (HCV) in HIV-infected patients with anti-HCV
antibodies in Europe. J Infect Dis 2008,198:1337-1344. (Abstract)
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the natural history of chronic parenterally-acquired hepatitis C with an unusually rapid
progression to cirrhosis. J Hepatol 1997; 26: 1-5. (Abstract)
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antiretroviral in adults infected with human immunodeficiency virus and the role of
hepatitis C or B virus infection. JAMA 2000; 283: 74-80. (Abstract)
Sulkowski MS, Moore RD, Mehta SH, et al. Hepatitis C and progression of HIV disease. JAMA
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Management of HCV/HIV Coinfection  317
Sulkowski M, Pol S, Cooper C, et al. Boceprevir Plus Peginterferon/Ribavirin for the Treatment
of HCV/HIV Co.Infected Patients. Infectious Diseases Society of America, 49th
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of hepatitis C virus. Nature 2009,461:798-801. (Abstract)
Thomson EC, Nastouli E, Main J, Karayiannis P, Eliahoo J, Muir D, McClure MO. Delayed anti-HCV antibody response in HIV-positive men acutely infected with HCV. AIDS.
2009;23:89-93. (Abstract)
Thomson E, Fleming VM, Main J, et al. Predicting spontaneous clearance of acute hepatitis C
virus in a large cohort of HIV-1-infected men. Gut. 2011;60:837-45. (Abstract)
Torriani FJ, Rodriguez-Torres M, Rockstroh JK et al: peg-interferon-a 2a + ribavirin for chronic
hepatitis C virus infection in HIV-infected patients. New Engl J Med 2004; 358: 438-450. (Abstract)
Turner J, Bansi L, Gilson R, Gazzard B, Walsh J, Pillay D, et al. The prevalence of hepatitis C
virus (HCV) infection in HIV-positive individuals in the UK - trends in HCV testing and
the impact of HCV on HIV treatment outcomes. J Viral Hepat. 2010; 17:569-77.
(Abstract)
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patients? Clin Infect Dis. 2006;42:262-70. (Abstract)
Vogel M, Voigt E, Michaelis HC, et al. Management of drug-to-drug interactions between
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Vogel M, Rockstroh JK. Liver disease: the effects of HIV and antiretroviral therapy and the
implications for early antiretroviral therapy initiation. Curr Opin HIV AIDS. 2009;4:171-5.
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318  Hepatology 2012
19. HBV/HCV Coinfection
Carolynne Schwarze-Zander and Jürgen Kurt Rockstroh
Epidemiology of HBV/HCV coinfection
Hepatitis B (HBV) and hepatitis C (HCV) viruses are the most common causes of
chronic liver disease worldwide. Due to shared routes of transmission, coinfection
with HBV and HCV is not uncommon among individuals in HBV endemic areas
who also have a high risk of parenteral infections, such as injection drug users
(Pallas 1999), patients on hemodialysis (Reddy 2005), patients undergoing organ
transplantation (Aroldi 2005) and HIV-positive individuals (Zhou 2007). Due to a
lack of large-scale population-based studies the exact number of HBV/HCV
coinfected patients is unknown. Dual infection ranges from 9% to 30%, depending
on the geographic region (Zarski 1998, Liaw 1995). These numbers may
underestimate the true number of people with HBV/HCV coinfection as there is a
well-known entity of occult HBV infection (patients with negative hepatitis B
surface antigen [HBsAg] but detectable serum HBV DNA) in patients with chronic
hepatitis C (Cacciola 1999).
Screening for HBV/HCV coinfection
Persons with a first episode of acute hepatitis should be screened for all viral causes
including HBV and HCV (see Chapter 8 on diagnostic tests in acute and chronic
hepatitis B and Chapter 12 for hepatitis C). Some patients may be inoculated with
both viruses simultaneously and will present with acute hepatitis due to both
viruses. In addition, HBV superinfection in patients with chronic hepatitis C, and
HCV superinfection in patients with chronic hepatitis B have both been reported
(Liaw 2004, Liaw 2000, Liaw 2002). Therefore, episodes of acute hepatitis in
patients with known chronic HBV or HCV infection, especially those with ongoing
risk behaviour for infection with the other virus such as injection drug users, should
prompt screening for superinfection. In addition, in patients with chronic hepatitis
C, ruling out occult HBV infection beyond HBsAg testing, i.e., by polymerase chain
reaction (PCR), should be done when clinically indicated.
HBV/HCV Coinfection  319
Viral interactions between HBV and HCV
Patients with both HBV and HCV infections may show a large spectrum of
virologic profiles. HCV infection can suppress HBV replication and it has been
shown that HBV/HCV-coinfected patients have lower HBV DNA levels, decreased
activity of HBV DNA polymerase, and decreased expression of HBsAg and
hepatitis B core antigen in the liver (Chu 1998). Moreover, patients with chronic
HBV infection who become superinfected with HCV can undergo seroconversion of
HBsAg (Liaw 1994, Liaw 1991). Several authors have reported that HBV can
reciprocally inhibit HCV replication as well (Sato 1994). Specifically, HBV DNA
replication has been shown to correlate  with decreased HCV RNA levels in
coinfected patients (Zarski 1998). Furthermore, coinfected patients have been
shown to have lower levels of both HBV DNA and HCV RNA than corresponding
monoinfected controls, indicating that simultaneous suppression of both viruses by
the other can also occur (Jardi 2001). Thus, HBV or HCV can play the dominant
role, HBV and HCV can inhibit each other simultaneously and they can alternate
their dominance (Liaw 1995). Both viruses have the ability to induce
seroconversion of  the other. The chronology of infection may have a role in
determining the dominant virus. The overall effect appears to be HCV suppression
of HBV (Liaw 2001). Interestingly, recent in vitro studies found no evidence of
direct interference between the two viruses, making also interindividual differences
in innate and/or adaptive host immune responses responsible for viral interference
observed in coinfected patients (Bellecave 2009, Eyre 2009).
Clinical scenarios of HBV and HCV infection
Different scenarios of infection have been described with HBV/HCV coinfection
including acute hepatitis with HBV and HCV (Alberti 1995), occult HBV
coinfection of chronic hepatitis C (Sagnelli 2001), and superinfection by either virus
in patients with preexisting chronic hepatitis due to the other virus (Figure 1).
Frequently the sequence of infection cannot be defined.
Acute hepatitis by simultaneous infection of HBV and HCV
Simultaneous coinfection with HBV and HCV is rarely seen, but the interaction of
HBV and HCV appears to be similar to chronic infection. In acute infection with
HBV and HCV, patients showed delayed HBsAg appearance and a shorter hepatitis
B surface antigenemia compared to those with acute HBV alone (Mimms 1993).
Biphasic alanine aminotransferase (ALT) elevation was found in some patients,
although rates of viral clearance were similar to those in HBV or HCV mono-infected patients (Alberti 1995).
HCV superinfection
HCV superinfection is frequent in endemic areas of HBV infection, such as Asia,
South America and sub-Saharan Africa (Liaw 2002, Liaw 2004), which can result in
the suppression of HBV replication and termination of HBsAg carriage. However,
long-term follow-up analyses have described a higher rate of liver cirrhosis and
hepatocellular carcinoma (Liaw 2004). Fulminant hepatic failure was significantly
higher among patients with underlying HBV infection than those without (23% vs.
3%) (Chu 1999, Wu 1994, Chu 1994).
320  Hepatology 2012
HBV superinfection
HBV superinfection is less common in HCV-infected patients and very limited data
is available. In one report a patient became seronegative for HCV RNA after HBV
superinfection, indicating that superinfection of HBV may lead to suppression of
HCV (Liaw 2000, Wietzke 1999). Other reports have shown that HBV
superinfection may be associated with acute deterioration of liver function among
patients with chronic HCV infection, and the risk of fulminant hepatitis may be
increased (Sagnelli 2002).
Occult HBV infection in patients with HCV infection
Occult HBV infection, defined as detectable HBV DNA in liver or serum and
undetectable HBsAg (Ozaslan 2009, Torbenson 2002), has been identified in up to
50% of patients with chronic HCV. Importantly, a relation to HCV treatment
outcomes has been described (Zignego 1997, Fukuda 2001, Sagnelli 2001). HCV
infection with occult HBV infection has been associated with higher ALT levels,
greater histological activity index and liver disease more often progressing to liver
cirrhosis (Fukuda 1999, Cacciola1999, Sagnelli 2001).
Chronic hepatitis in HBV/HCV coinfection
Patients with detectable serum HBV DNA and HCV RNA are at highest risk of
progression to cirrhosis and liver decompensation and therefore should be
considered for treatment. Active HCV infection (HCV RNA+) in the setting of
inactive HBsAg (HBsAg+/HBV DNA-) behaves similarly to patients with HCV
monoinfection. Another possibility is active HBV infection in patients with inactive
or prior HCV infection (HBV DNA+/HCV RNA-/anti-HCV+). This immune profile
is less common, and may indicate HBV suppression of HCV. A longitudinal study
of virologic monitoring of 103 HBV/HCV coinfected patients revealed fluctuation
of the virological pattern (Raimondo 2006). Thus, close follow-up of levels of
viremia is needed for correct diagnosis and decision on what would be the most
successful treatment.
Table 1 shows the immune profiles found in patients with chronic HBV/HCV
infection.
Table 1. Immune profiles in patients with chronic HBV/HCV hepatitis.
HBV and HCV
active
Occult HBV in
chronic active HCV
HCV active in
HBsAg carrier
HBsAg  +  –  +
HBV DNA  +  +  –
Anti-HCV  +  +  +
HCV RNA  +  +  +
HBV/HCV Coinfection  321
Figure 1. Clinical scenarios of HBV/HCV coinfection (modified after Crockett & Keeffe