with TB; incarceration is associated with a 23 times higher risk of TB than in the general population.
52,53
Appropriate care for persons being considered for hepatitis C treatment would include screening for active TB, as the co-management of such
persons needs sound clinical judgement and the provision of treatment that takes into consideration the side-effects and interactions of the drugs used to treat HIV,
TB and viral hepatitis.
2.2 Hepatitis C virus
The hepatitis C virus is a small, positive-stranded RNA-enveloped virus that is approximately 9.6 kb in length. The genetic sequence was irst characterized in
1989,
54
placing the virus in the Hepacivirus genus within the Flaviviridae family.
55,56
It has a highly variable genome and multiple genotypes and subgenotypes.
57
The distribution of HCV genotypes and subgenotypes varies substantially in different
parts of the world Figure 2.1. Some genotypes are easier to treat and, thus, the duration of and recommended medicines for therapy vary by genotype. For
this reason, determining a patient’s genotype is important to appropriately tailor therapy. It is possible that this advice may change when antiviral agents that are
active against all genotypes referred to as pangenotypic are licensed.
FIGURE 2.1
Global distribution of genotypes of HCV
Source: Hussain Z. Genomic heterogeneity of hepatitis viruses A–E: role in clinical implications and treatment. In: Serviddeo G, editor. Practical management of chronic viral hepatitis. Rijeka, Croatia: InTech; 2013. www.intechopen.combookspractical-management-of-
chronic-viral-hepatitisgenomic-heterogeneity-of-hepatitis-viruses-a-e-role-in-clinical-implications-and-treatment, accessed 10 February 2014. 1a, 1b, 2b,3a
1, 2, 4 5a
1a, 3a 1b, 3b, 5a, 6a
1a, 1b, 3a, 4 1b, 2a, 6a
3a, 1b 1b
1b 1b
4 1b
1a, 1b, 2a, 3a 1a, 1b, 2a, 2b,3a
1a, 1b, 2a, 2b, 2c, 3a
1a, 1b, 2b,3a
2.3 Natural history of HCV infection
Hepatitis C virus causes both acute and chronic infection. Acute HCV infection is deined as the presence of HCV within six months of exposure to and infection
with HCV. It is usually clinically silent, and is only very rarely associated with life-threatening disease. Spontaneous clearance of acute HCV infection occurs
within six months of infection in 15–45 of infected individuals in the absence of treatment. Almost all the remaining 55–85 of persons will harbour HCV for
the rest of their lives if not treated and are considered to have chronic HCV infection. Anti-HCV antibodies develop as part of acute infection and persist
throughout life. In persons who have anti-HCV antibodies, a nucleic acid test NAT for HCV RNA, which detects the presence of virus, is needed to conirm
the diagnosis of chronic HCV infection.
58,59
Left untreated, chronic HCV infection can cause liver cirrhosis, liver failure and hepatocellular carcinoma HCC; Figure 2.2. Of those with chronic HCV
infection, the risk of cirrhosis of the liver is 15–30 within 20 years.
60,61,62
The risk of HCC in persons with cirrhosis is approximately 2–4 per year.
63
The risk of cirrhosis and HCC varies depending upon certain patient characteristics or behaviours. For example, men, persons who consume excess
alcohol, persons with hepatitis B or HIV coinfection and immunosuppressed individuals are all at higher risk of developing cirrhosis or HCC.
64
Disease associated with HCV is not conined to the liver. Extrahepatic manifestations of HCV include
cryoglobulinaemia, glomerulonephritis, thyroiditis and Sjögren syndrome, insulin resistance, type-2 diabetes mellitus, and skin disorders such as porphyria cutanea
tarda and lichen planus. Persons with chronic HCV infection are more likely to develop cognitive dysfunction, fatigue and depression.
65
These outcomes may
FIGURE 2.2 Natural history of HCV infection
Acute HCV infection
Chronic infection
55-85 Mild
fibrosis
Extrahepatic disease Moderate
to severe fibrosis
Cirrhosis 15-30
Decompensated Cirrhosis Hepatocellular carcinoma
2-4 per year in cirrhosis
be associated with replication of the virus in the brain; however, the causal link between these manifestations and chronic HCV infection is not certain.
66
Natural history of HIVHCV coinfection
Coinfection with HIV adversely affects the course of HCV infection, and coinfected persons have a signiicantly accelerated progression of liver disease to cirrhosis,
decompensated liver cirrhosis and HCC than HCV-monoinfected persons, particularly those with advanced immunodeiciency CD4 count 200 cellsmm
3
.
67-70
In high-income countries, death due to HCV-associated liver disease has become a leading cause of death in people living with HIV in the era of combination ART,
45,71,72
accounting for around 47 of deaths in one series from the United States. It remains unclear whether HCV infection accelerates HIV disease progression, as
determined by AIDS-related events or death.
73
Two large European cohorts have shown that after ART initiation, CD4 recovery was impaired in HIVHCV-coinfected
persons when compared to those infected with HIV alone. HIVHCV-coinfected persons also demonstrated more rapid HIV disease progression compared
to those who were HIV-infected alone, and had an impaired recovery of CD4 cells. However, other studies have shown no such differences in response.
73-77
Assessment of the impact of HCV infection on HIV disease progression may be confounded by the negative health consequences of injecting drug use, which is
strongly linked to HCV infection.
78,79
In persons with HIV infection, HCC tends to occur at a younger age and within a shorter time period.
80
2.4 Prevention of HCV infection
