The Global Threat Posed By Hepatitis C Biology Essay

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Following the identification of a Non-A, non-B viral hepatitis (NANBH) in 1975 that had been found to be associated with blood transfusion in majority, efforts were concentrated to identify the distinct virus. Finally, in 1989 Choo and coworkers of Chiron Co-operation group were able to discover a single-stranded RNA virus of 9.5kb and 40-50 nm diameter that belongs to Flaviviridae and recognized as Hepatitis C virus (HCV) (1-4). Even though humans are the only known host for HCV, experimental transmission of HCV has been established in to the chimpanzees (5).

Scope of hepatitis C

Hepatitis C could manifests as acute or chronic infection. In general acute hepatitis C presents as milder disease and only up to 20-30% individuals develop symptoms (5). However, up to 80% cases are predisposed to develop chronic infection and subsequently up to 20% individuals develop cirrhosis within 20-30 years in up to 20% cases. Following the development of cirrhosis there is a significant risk to develop hepatocellular carcinoma (HCC) (5-7). Globally up to 27% cases of cirrhosis and 25% HCC have been estimated to due to HCV (12).Nonetheless, 7,96000 and 6,16000 deaths were attributed to cirrhosis and primary hepatocellular carcinoma in 2002(8) and perhaps up to 20% of these deaths were attributable to HCV infection(9). 20%, 70%, 40%, 60% and 30% cases of acute hepatitis, chronic hepatitis, cirrhosis, HCC and liver transplants respectively is of alarming for industrialized countries where the access to health care facilities are relatively easy(10). On the other hand inadequate detection, non-availability of treatment due to high cost in developing countries are the main factors leading to increase number of untreated patients as well as increase mortality due to HCV related liver (8). Hence, the chronicity of HCV infection leading to major complications has made HCV a major health care burden globally.

Economic burden of hepatitis C

The tendency to develop chronic disease and subsequent complications of cirrhosis including HCC justifies early detection and treatment of HCV infection. The improvement in sustained viral response with currently available pegylated interferon and ribavirin therapy favors treatment of eligible patients. Similarly, liver transplantation improves the survival for patients with decompensated cirrhosis and HCC. However, the cost of antiviral therapy and liver transplantation is very high and is huge socioeconomic and health burden especially for developing countries(11). Moreover, unavailability of liver transplantation and referrals to centers other than native country adds further cost. In 1995, 27,000 hospitalizations were due to HCV related liver disease. Moreover,

Global burden of hepatitis C

HCV is the most common cause of transfusion related hepatitis that affects in general 3% or 170 million individuals throughout the world. However, the prevalence of hepatitis C varies widely with the geographical locations as well as within the populations(12). The prevalence of chronic hepatitis C ranges from 0.1 to 5% in different countries (3, 10)

The WHO prevalence was higher in some countries in Africa (5.3% or 31.9 million), the eastern Mediterranean (4.6% or 21.3 million), South-East Asia (2.15% or 32.3 million) and the Western Pacific (3.9% or 62.2 million), as compared with some countries in the Americas (1.7% or 13.1 million) and Europe (1.03% or 8.9 million)(9).

In 2004, the Global Burden of Hepatitis C Working Group, serving as a consultant to the WHO, estimated the global prevalence to be slightly lower at 2.2% or 130 million individuals. The lowest HCV prevalence of 0.01% to 0.1% is from countries in the United Kingdom and Scandinavia, while the highest prevalence of 15% to 20% is from Egypt (3). North America 2%(13)

The incidence of new symptomatic infection has been estimated to be 1-3 cases/ 1 000 000 persons annually. The actual incidence of new infections is obviously much higher (the majority of cases being asymptomatic). The incidence is declining for two reasons: (a) transmission by blood products has been reduced to near zero and (b) universal precautions have markedly reduced transmission in medical settings. Intravenous drug use remains the main mode of transmission, but, even here, the rate of transmission is diminishing due to a heightened awareness of the risk of needle sharing and, in some countries, the availability of needle-exchange programmes(10).

In France, the prevalence of anti-HCV-positive adults is estimated to be between 1.1 and 1.2%, out of whom 80% are viraemic. Therefore, it is estimated that 400 000-500 000 subjects have chronic HCV infection. The prevalence varies widely in different populations: 60% in intravenous drug users, 25% in incarcerated subjects and 25% among HIV-positive patients (25 000-30 000 subjects have HCV/HIV co-infection)( Consensus Conference. Treatment of hepatitis C. Guidelines.Gastroent´erol Clin Biol 2002; 26: B312-20).

Americas:

In United States of America (USA)CHC is the leading cause of liver transplantation (14) and between 1990-2000 five-fold increase in annual number of liver transplantations for patients with HCV has been reported (15). Centers for Disease Control (CDC) conduct National Health and Nutrition Examination Survey (NHANES) periodically in USA. According to a recent NHANES (1999-2002) 1.6% 4.1 million people found seropositive for HCV(16). However, further evaluation by testing HCV RNA reveled 1.3% or 3.2 million individuals affected by chronic hepatitis C infection(17). Furthermore, the HCV prevalence was higher among men (2.1% vs. 1.1%), non-Hispanic blacks than whites (91.5% vs. 3%) and Mexican Americans (1.3%). Although the overall HCV prevalence was nearer to 1.8% (18) that was found in NHANES III (1988-1994) an upward shift of peak age group infected was reported from 45 to 49 years (NHANES IV) to 35 to 39 years (NHANES III). This was probably due to involvement of most individuals belonging to birth cohort between 1945- 1964(16). Earlier than the implementation of universal screening of blood donors in 1992, transfusion of contaminated blood and blood products was the principal mode of responsible for HCV transmission. Whereas currently IVDU and percutaneous exposure due to high-risk sexual behaviors are the major factors responsible for HCV spread(3). However, one should keep this in mind that underrepresentation of incarcerated and homeless individuals in NHANES data might have lead to underestimation of overall HCV prevalence (22).

In a study conducted in 2002 all new entrants into the Maryland Division of Correction and the Baltimore City Detention Center were evaluated between 28 January and 28 March 2002. 29.7% Out of 3914 inmates and detainee, 29.7% were found to be affected by HCV(19). Moreover, 44% of 418 homeless veterans were found affected by HCV in another study that was significantly associated with history of substance abuse (odds ratio 6.86, P < 0.001] and service during the Vietnam era (OR 4.66, P 0.01)(20).

Although the overall estimated numbers of incident HCV cases have been declined to 30,000/year (21, 22), HCV-associated morbidity and mortality have been predicted to increase significantly in next 20-30 years due to the chronicity related to HCV (3, 15, 22-24). Currently the estimated HCC development rate among patients with cirrhosis in USA is 3%-4% /year (25) that has been equivalent to three folds increase than 1993(26). Moreover, HCV is estimated to cause 8000 to 10,000 deaths per year related to liver complications and HCC(3).

In Canada, the estimated prevalence of HCV infection is 0.8% and majority of the cases lies between 15 to 39 years of age. According to the national "Enhanced Hepatitis Strain Surveillance System", the incidence of HCV per 100,000 individuals has been declined from 3.3 to 2.1 cases from 1998 to 2004. (Public Health Agency of Canada. Evaluation of the hepatitis C prevention, support and research program 1999/2000-2005/2006. Available at: http://www.phac-aspc.gc.ca/publicat/2008/er-re-hepc/er-re-hepc1-eng.php#ref. Accessed March 9, 2009). This decline is attributed to the safe blood transfusion practices. Currently IDU is the major factor associated with HCV spread, however the sexual transmission found uncommon(27).

In Latin America, in general HCV seroprevalence is 1.23% with some variability from region to region that ranged 0.2-3.4%. Blood transfusion and high risk sexual behaviors were found to be the main risk factors associated with HCV (28, 29).

England

In England 0.6% of adult population aged 15-59 have been found to be affected by HCV. However, this proportion represents a decline from 1.07% HCV prevalence that has been documented in 1986. According to the estimations of UK Health Protection Agency, among people affected by HCV approximately 6000 and 1500 individuals will develop cirrhosis and end-stage liver disease or HCC respectively by 2010 and further increase in these rates are expected in next decades (30-32). Furthermore, in a cross sectional study by Balogun and colleague(33) changes in HCV sero-prevalence was studied in general population of England. Sera of adult patients submitted to 19 laboratories of England were tested to determine average HCV prevalence between 1986 and 2000. The results showed HCV seroprevalence 1.07(39/3647), 0.55(31/5634), 0.73(43/5924) and 1.20(61/5068) for the year 1986, 1991, 1996 and 2000 respectively. Higher HCV prevalence was found among males and birth cohort of 1950-1970. Moreover, higher HCV prevalence was found in London (1.27), Eastern (1.41) and South West (1.25) regions of UK.

IDUs have been found to be at the highest risk to acquire HCV in UK (34). IDUS usually begins in late adolescence and early adulthood. Considering lower HCV prevalence in general population and greater HCV acquisition risk with IDU focused and targeted strategies are required to identify high risk populations and to implement preventive strategies to avoid HCV transmission via IDU in (33, 35, 36).

Africa

According to the WHO estimates 5.3% or 31.9 million individuals are affected by hepatitis C in Africa(6). However, variability in different regions of Africa have been found like 6%, 2.4% and 1.6% HCV prevalence have been found in Central Africa, west Africa and east Africa respectively. Furthermore, clusters of higher prevalent areas have been notified like Burundi with 11.3% and Cameroon with 13.8% HCV prevalence(37). The individuals > 40 years of age are affected mostly. Like other developing countries unsafe therapeutic injections and blood transfusions are the most common attributable factor responsible for HCV spread. Whereas, beside the cases with HCV and HIV co-infection vertical transmission is uncommon and so is correct for IDU (38-41).

Eastern Mediterranean

Eastern Mediterranean region includes Egypt……… According to the WHO estimates the over al HCV prevalence in this region is 4.6% (6) with the highest prevalence of 11-14% in Egypt(42, 43). The prevalence across the Egypt is variable i.e. 8% in Cairo & Alexandria at 8%, 8-16% in middle and upper Egypt and 15% in lower Egypt or rural areas of Nile Delta(43). Use of intravenous therapy for schistosomiasis which is quite common here is the major attributable factor for spread of (44). The infection is more common in males, older patients and genotype 4 is the most prevalent genotype (90%). Up to 60-78.5% HCC are attributed to HCV in Egypt (45, 46).

Another country with high endemicity for HCV is Pakistan. The Pakistan Medical Research Council estimate the prevalence of HCV at 4.9% or 8.8 million people.49

The prevalence of the disease has increased since 2005, when the Prime Minister Program for Prevention and Control of Hepatitis started to provide free treatment to poor patients on a limited scale, and more people underwent testing and sought treatment. The pattern of transmission in Pakistan is not well documented, but parenteral exposure to infected needles and blood are believed to be important risk factors. Inaddition, community barber shops where infected razors can transmit the infection are another route. IVDU and sexual transmission are minor contributors in HCV transmission in this country(47).

South-East Asia

The available data from this region lacks large population based studies. However according to WHO estimates 2.1% individuals are affected by HCV in this region (9). Based upon reports available from the member countries WHO reported HCV prevalence in 1999 was 2.9%, 2.4%, 1.3%, 1.2%, 2.5%, 1.8%, 1.1%, 1.6% and 1.4% has been found in Thailand, Bangladesh, Bhutan, India, Indonesia, Maldives, Nepal, Korea and Sri Lanka respectively(reference).

Population based data is scanty from India. However, among voluntary blood donors HCV prevalence was found 1.5-4.3%(48) but it was much higher(55.3% to 87.3%) in commercial blood donors at (49). In few studies conducted in selected group of population HCV prevalence was…… (48). In a study of 10,737 inhabitants of west Bengal individuals older tha 60 years had the highest prevalence with equivalent involvements of both gender (50). Hepatitis C is incriminated as the cause of liver cirrhosis in 3.3% to 31.5% of cases and of HCC in 15.1% to 42% of cases(17). Transfusion of contaminated blood and blood products is the most common factors associated with HCV(Hazra SC, Chatterjee S, Das Gupta S, et al. Changing scenario of transfusionrelated viral infections. J Assoc Physicians India 2002;50:879-81).However, there is growing evidence about HCV spread via IVDU and 92% of 77 IDUs from Manipur Saha were found affected by HCV(48).

In Thailand, the evidence is based upon data from voluntary blood donors that showed HCV seroprevalence of 1.37%-2.9% in different studies (51, 52). On the other hand much higher HCV prevalence ranged 86-92.5% (53, 54), and 9.5% 9.5%(55) was found in IDUs and commercial sex workers respectively representing these factors next to unsafe injection practices and blood transfusion (53).

Up to 2.1% HCV seroprevalence among blood donors have been reported from Indonesia and prior blood transfusion, IVDU, surgery, and acupuncture were found to be associated factors(56). Similarly 2.5% HCv seroprevalence have been reported from Myanmar (Kyi KP, Aye M, Oo KM, et al. Population and patients with liver ailments in Myanmar. Reg Health Forum 2002;6(1):1-6. Available at: http://www.searo.who.int/EN/Section1243/Section1310/Section1343/Section1344/Section1355_5302.htm. Accessed March 11, 2009)

Western Pacific

According to WHO estimates HCV prevalence is 3.9% in this region(9). In 1992-1995's national survey 3.2% of China's population was found HCV seropositive and IDU was the most important risk factor (57); hence 61.4% of IDUs were affected by HCV throughout the country (58). In Japan, 2% population i.e. 2 million people individuals are affected by HCV (59) which is the major cause of HCC here (60).Blood transfusions, IVDU, and unsafe needle use in medical practice before 1980. Are common risk factors and individuals > 70 years of age are affected most (61).

In Australia according to the estimates of 2001, 210,000 individuals are affected by HCV and incidence of new HCV cases were estimated to be 16,000 annually (62). About 80% to 90% of HCV infections are attributed to IVDU due to continued increasing practices of IDU despite introduction of needle and syringe programs in the late 1980s(63). While in, Samoa and American Samoa lower HCV prevalence of 0.2% to 0.6% have been reported that is probably due to the low rate of IVDU as well as unsafe medical practices in these countries(64).

Over the period 1990-2000 approximately 160 000 notifications of HCV infection were received by State and Territory health jurisdictions making it the most commonly notified communicable disease in Australia. HCV transmission are particularly high in both younger and incarcerated IDUs.

Europe

5 million HCV carriers in western Europe(10)

France 1.1-1.2%, 400 000-500 000 subjects have chronic HCV infection (Consensus Conference. Treatment of hepatitis C. Guidelines. Gastroent´erol Clin Biol 2002; 26: B312-20)

scarcity of HCV incidence data that are comparable across countries of the WHO European region. Pan-European HCV incidence data available from the WHO Health for All Database

[World Health Organization: WHO Health for all database. 2006 [http://data.euro.who.int/hfadb], which presents annual case numbers of acute hepatitis C (ICD-10 Code B17.1) submitted by countries of the WHO European region, proved to be the most comparable due to the use of a standardised case-definition. Data were available for the period 1997 to 2004. All countries except Monaco and Turkey provided at least one estimate, and only a few countries reported data on an annual basis.

To cope with temporal variation, we averaged annual incidence figures reported during the observed time period.

Averaged annual incidence rates for acute hepatitis C vary across countries from 0.00 to 39.21 cases per 100000 residents. However, the geographic distribution of incidence rates in the WHO European region shows no clear pattern. Applying a population size weight yielded an average annual incidence rate of 6.19 per 100000 (95% CI 4.90-7.48) for the

WHO European region (excluding Monaco and Turkey)(65).

According to the WHO prevalence estimates for 32 countries of the European region HCv prevalence rage 0.003% to 4.5% with the higher rates of >1.25 in Southern and Eastern European countries and lower i.e ≤ 0.1% rates in Northern Europe.

According to WHO prevalence data, approximately 7.3 million (1.1%) people in our 22 focus countries are estimated to be infected with HCV. Based on the higher national estimates, 8.8 million (1.3%) people are estimated to be infected. HCV caused more than 86000 deaths in the WHO European region in 2002, accounting for 35% of cirrhosis and 32% of liver cancer deaths in that year. Country-specific HCV-related mortality ranges from 0.1 to 31.5 deaths(65)

per 100000 residents. High death rates (> 12 deaths per 100000) are predominantly found in the centre of the region. HCV-related liver cancer mortality (Figure 4) displays a notable East-West

gradient, with high death rates (> 3 per 100000) in Western Europe and low death rates (<= 1 per 100000) in Eastern Europe. The death rates for HCV-related cirrhosis (Figure 5) provide a complementary picture(65).

Asia

Mediterranean and some Asians countries 3-4%(13)

Central Africa and Egypt 10%(13)

Genotypes

Based upon the heterogenecity of HCV genome 11 HCV genotypes (genotypes 1 to 11) and many subtypes (a, b, c, and so forth) have been reported. Up to 60% HCv cases worldwide are due to genotypes 1a and 1b. However, genotype 1a is predominantly located in Northern Europe and North America, while genotype 1b is predominantly found in Southern and Eastern Europe and Japan. Genotype 2 is predominant genotype in Europe, genotype 3 is endemic in South-East Asia, and genotype 4 is characteristic for the Middle East, Egypt, and central Africa. Genotype 5 is almost exclusively found in South Africa, and genotypes 6 to 11 are mostly distributed in Asia.

The identification of genotype is important with respect to the response to the treatment as genotype 2 & 3 are known to have best response with anti-viral therapy while genotype 1 has poorer response. While, intermediate response was found in case of genotype 4 (16, 66, 67).

Risk factors/ epidemiology of HCV transmission:

The Primary mode of transmission for HCV is via transfusion of contaminated blood or blood products (68). Iatrogenic transmission via contaminated equipments, needles and procedures like hemodialysis are also common especially in developing countries (3, 68, 69). Like in Egypt where the highest HCv prevalence have been reported reuse of needles for schistosomiasis vaccination program was a major attributable source of transmission (44).

However, in developed countries like United States >50% of the cases are attributed by illegal drug use mainly IDUs followed by intranasal cocaine(68).

Although HCV is most efficiently transmitted by large or repeated percutaneous exposures to blood, other routes, such as sexual transmission, perinatal transmission, and acquisition from mucous membrane exposure, have been described(7).

Transmission has also been linked to folk remedies and other community-based

needle practices, including acupuncture.13

Hepatitis C virus is most efficiently transmitted by direct percutaneous exposure to infectious blood, such as through blood transfusion from infectious donors and sharing of contaminated equipment among injecting drug users (70). Haemodialysis patients and healthcare workers who are exposed to needlestick injuries in an occupational setting are also at risk from exposure to infectious blood, as are infants born to infected women. In addition, HCV can be transmitted by sexual or household exposure to an infected contact; however, the efficiency of transmission in these settings appears to be low. Although an average prevalence of HCV infection of 4-5% has been found among household and sex contacts of infected persons in a number of studies, most of these studies were conducted in countries where transmission of HCV infection may be associated with common exposures to contaminated equipment used in traditional and non- traditional medical procedures in the past(70, 71).

Hepatitis C is an RNA virus known to infect humans and chimpanzees, causing a similar disease in these 2 species. HCV is the most common cause of transfusionrelated hepatitis, and is one of the leading causes of end-stage-liver disease requiring liver transplantation in the United States. HCV is transmitted most efficiently by parenteral

means, particularly with large or repeated exposure to infected blood products or transplantation of infected tissue or organ grafts, and IVDU. Less frequently, it can be transmitted by mucosal exposures to blood or serum-derived fluids through perinatal or sexual means(17)

Parenteral routes, mainly transfusion of contaminated blood or blood products, use of contaminated syringes, needles, IDUs, transplantation of infected tissue or organ grafts have been considered as the most efficient ways to transmit HCV infection. Though it's less frequent but, HCV can be transmitted by mucosal exposures to blood or serum-derived fluids through perinatal or sexual means (8, 17). Moreover, another major risk factor for acquisition of HCV is intravenous drug abuse(3).

While on one hand regular practice of screening of blood and blood products started in 1991 had lead to a significant decrease in the incidence of transfusion associated HCV in developed countries, due to lack of regular screening in developing countries transfusion related transmission of HCV is still one of the manor cause (reference). Moreover, there is growing evidence about per mucosal spread of HCV among HIV-infected men, who have sex with men (MSM), especially in USA and Europe. The HCV transmission in such cases correlates with the numbers of sexual partners, the sharing of drugs through the nasal or anal route and high-risk sexual practices (70). The risk of HCV transmission from infected mother to infant is estimated < 5%. However, this risk increases more than two folds if the mother is co-infected with HCV and HIV as compared to those infected with HCV alone(12).

USA

The prevalence of HCV infection was higher among non-Hispanic blacks than among non-Hispanic whites and Mexican Americans and higher among men than among women(16, 18). The peak age group of HCV infection, which was 35-39 years in 1988-1994, has increased over time to 45-49 years in 1999-2002. The prevalence of infection was higher in individuals who had ever used injection drugs than in those who had used noninjection drugs or who had never used these drugs. Prevalence also increased with increasing numbers of lifetime sexual partners and was higher among those with a history of blood transfusion before 1992. Taken together,

these findings indicate that most individuals with HCV were born between 1945 and 1964 and can be identified with current screening criteria(16). Associated risk factors included a

history of injection drug use, receipt of blood transfusion prior to 1992, history of tattooing, combat job as a medical worker, history of incarceration over 48 h, more than 15 lifetime sexual partners, and sexual relations with a prostitute(22).

Strategies to prevent and control hepatitis C

The HCV genome includes approximately 10,000 nucleotides, which are translated into a large polyprotein and processed into at least 10 proteins. The genome has been sequenced, and the functions for most of the proteins have been identified.

HCV is a genetically heterogeneous virus because of its ability to mutate rapidly. This may allow it to escape detection by the immune system and may account for the variable clinical course of HCV infection. The heterogeneity of the virus and the absence of a protective antibody response no doubt contribute to the difficulty in developing effective vaccines and other therapeutics(68).

The high mutability of the HCV genome and limited knowledge in the protective immune response following infection has hindered progress in vaccine development. For this reason, no vaccine is available against HCV(6).

Measures to prevent and control hepatitis C are limited. The high mutability of the HCV genome and limited knowledge in the protective immune response following infection has hindered progress in vaccine development. For this reason, no vaccine is available against HCV(9).

The development of a vaccine is not likely in the foreseeable future, and immune globulin is not effective for post-exposure prophylaxis. Currently available prevention measures include primary prevention activities that reduce the risk of becoming infected with HCV and secondary prevention activities that reduce the risk for chronic disease in HCV-infected persons(70).

Primary prevention

From a global perspective, the greatest impact on the disease burden associated with HCV infection will likely be achieved by focusing efforts on primary prevention. Primary prevention strategies can reduce or eliminate the risk of transmission from (1) nosocomial exposures, including transfusion of blood and blood products, and other percutaneous exposures to blood such as through use of unsterile medical and dental equipment and unintensional needlesticks and (2) high risk practices (e.g. injecting drug use, unprotected sex with multiple partners).

Measures to prevent HCV transmission from percutaneous exposures to blood in health care and other settings are similar to those for HBV (see above).

The primary methods to prevent HCV transmission from blood and blood products are exclusion of donors who are judged to be at increased risk of infection by history or who have serologic markers of HCV infection. In addition, plasma derivatives (e.g. clotting factor concentrates, immune globulin) should either undergo viral inactivation or be HCV RNA negative by poly-

merase chain reaction. Transmission of HCV associated with high-risk practices (e.g. injecting drug use, unprotected sex with multiple partners) can be prevented by identifying and counseling persons with a history these practices and by educational efforts to prevent initiation of these practices. Primary prevention of drug injection will eliminate the greatest risk factor for HCV infection in many countries. Educational efforts to prevent initiation of drug injection are especially important for children and adolescents because HCV infection is rapidly acquired after initiation of injecting drug use. Although consistent data are lacking about the extent to which sexual activity contributes to HCV transmission, persons having unprotected sex with multiple partners are at risk for sexually-transmitted diseases (e.g. acquired immunodeficiency syndrome, hepatitis B, syphilis, gonorrhea and chlamydia). Community-based services such as drug- and STD-treatment services can also be used to facilitate prevention or reduction of high-risk behaviors. In addition, programs to increase access to sterile syringes (e.g. syringe exchange programs) can be used to promote safer injection practices among injecting drug users(70).

Secondary prevention

Secondary prevention activities reduce the risk for chronic disease by identifying HCV-infected persons through diagnostic testing and by providing appropriate medical management and antiviral therapy. In particular, counseling of HCV-infected persons to reduce or abstain from alcohol intake may prevent disease progression. Antiviral treatment is also available, and treatment guidelines have been developed. However, treatment is costly and beyond the resources available in many countries. Moreover, the benefits of early detection and treatment of persons with asymptomatic infection have not been clearly established, a high proportion of persons do not respond to currently available treatment, and the long-term benefit of treatment has not been determined(70).

Challenges

Systematic screening of blood donors is, however, not universal, and new cases of post-transfusion HCV continue to occur in resource poor settings(12). The unintended transmission of HCV during national campaigns, such as that for the parenteral treatment of schistosomiasis in Egypt, has also contributed to a

national prevalence of up to 15% in some countries(44).

Identification of host and viral epidemiologic characteristics associated with disease progression may provide important information on the mechanisms through which HCV infection causes hepatic fibrosis/cirrhosis.

SUMMARY

The global epidemiology of hepatitis B and C continues to evolve, mostly toward

a decline in the prevalence of the disease. Improvement in the control of hepatitis B

has been largely achieved with implementation of a more global HBV vaccine

program. The most recent available data from 2001 indicate that 126 (66%) of 191

WHO member states had universal infant or childhood HBV vaccination programs.

In the 6 WHO regions, the proportion of children younger than 1 year who were vaccinated

fully was 65% in the Western Pacific region, 58% in the Americas region, 45% in

the European region, 41% in the Eastern Mediterranean region, 9% in the South-East

Asian region, and 6% in the African region. Overall, an estimated 32% of children

younger than 1 year were vaccinated fully with the 3-dose hepatitis B vaccination

series worldwide. Although significant progress has been made, there still is a large

void to be filled in the global prevention of HBV transmission.130

The transmission of HCV has been greatly impacted by mandatory screening of

blood donors in most countries in the world. However, IVDU continues to be a major

source of infection, and the practice may be on the rise in several areas. Continuing

public education regarding the risks of exposure to infected paraphernalia as well

as household items such as razors is necessary. To date, there is no effective vaccine

available for HCV, which greatly limits the ability to prevent the disease from the grass

roots. The efficacy of antiviral therapy for HCV, although steadily escalating, still has

a large room for improvement. Treatment of HCV is also costly and access to the

medications is limited, particularly in underdeveloped countries. Efforts need to be

continued to address these public health issues that afflict many parts of the world.

In last few years, the natural history of chronic HCV infection has been better understood. In last few years considerable progress has been made in the knowledge of epidemiology, natural history, factors influencing the course of liver diases and mainly the efficacy of therapy. Still important efforts are needed for screening campaigns for the early diagnosis in order to improve the management of these patients.

The principal challenges to reducing this burden lie in the identification and delivery of care to the major infected populations, and the provision of more effective therapies for the eradication of HCV.

Future projections predict a four-fold increase in USA between 1990 and 2015 in persons at risk of chronic liver disease, suggesting a continued increase in the burden of HCV in the US in the foreseeable future(10).

The HCV epidemic is still growing in importance. Although the incidence of HCV is falling in some countries, the burden of disease arising from the pool of chronic infection continues to rise. It has been

estimated that, by 2030, HCV will cause substantially higher morbidity and mortality in industrialized countries than HIV. Urgent intervention is required to prevent this outcome. Major barriers, however, remain to the delivery of effective care for HCV, particularly to populations of IDUs where the prevalence and incidence of HCV is highest. Investment in more effective treatments for HCV has so far met with limited success. There are, however, grounds for optimism. National strategies are beginning to take account to the need to access and treat HCV in IDUs and new models for the more effective delivery of care are currently being validated. Further, novel model systems for the development and screening of HCV drugs will lead to the provision of new tools with which to reduce the burden of this important disease.

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