Barriers to Directly Acting Antiviral Agent Use for Chronic Hepatitis C in South and South East Asia

Introduction: Pakistan, with a population of 180 million, has a 5% prevalence of hepatitis C and a 2.5% prevalence of hepatitis B. Although several studies have looked at individual risk factors, in particular, the practice of unsafe injections, there are many unresolved questions regarding the epidemiology of chronic hepatitis B and C infections in Pakistan.

Objective: To assess the potential risk factors for hepatitis B and C infections in Pakistani patients.

Methods: Consecutive patients with chronic hepatitis B or C presenting to a private gastroenterology clinic in Karachi, Pakistan were interviewed regarding potential risk factors for acquiring their infections

Results: 389 patients were interviewed, 239 (61%) with chronic hepatitis C and 150 (39%) with chronic hepatitis B.308 (79%) had more than one potential risk factor for viral infection. 71 (18%) had one risk factor and 12 (3%) had no identifiable risk factors. The following risk factors were identified: blood transfusion (96, 25%), surgery (171, 44%), dental work (202, 52%), injections (310, 80%), body piercings (144, 37%), spousal transmission (15, 4%), IVDU (1, 0.2%), hemodialysis (4, 1%), tattoos (1, 0.2%), sexual (1, 0.2%), and vertical transmission (5, 1%). 74 (11%) patients had a first degree relative with hepatitis B or C. Of the 71 patients with a single risk factor, in 58 (82%) the risk factor was having received an injection.

Conclusion: It is only by understanding the epidemiology of the acquisition of chronic hepatitis B and C infections in Pakistan that effective efforts can be made to control the spread of these infections. Most patients have multiple potential risk factors, highlighting the need for a multipronged approach to the control of these risk factors. Parenteral injections remain the single most common risk factor for infection.

An estimated 50 million dengue infections occur annually across approximately 100 tropical and subtropical countries. There is extensive clinical, biochemical, histological, radiographic, and experimental evidence of liver involvement in dengue virus infections. Transaminase elevations are commonly seen. Most cases of dengueassociated liver disease are mild. Severe acute hepatitis due to the dengue virus is uncommon. Proposed causes of liver dysfunction in dengue virus infections include a direct viral effect on hepatocytes and a dysregulated host immune response against the virus. Several avenues of future research are suggested.

Background: Hepatitis C Virus (HCV) is an endemic disease with chronic sequelae that include cirrhosis and liver cancer. Children acquire the disease mainly via the maternal-infant route. This study investigated its prevalence in pregnant women and the natural history of its vertical transmission.

Methods: This prospective study involved 618 randomly selected pregnant women in Al-Ain City (Abu Dhabi, UAE). Participants were screened in the first trimester by second-generation Enzyme-Linked Immunosorbent Assays (ELISA-2). Positive samples were further tested by third-generation ELISA (ELISA-3), third-generation recombinant immunoblot assay for detection of antibodies (anti-HCV), and Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) to detect HCV-RNA. Infants of mothers with positive anti-HCV antibody or HCV-RNA were followed for several years.

Results: Twenty-five women (4.0%) had positive ELISA-2; of which eleven (1.8%) had positive ELISA-3, nine (1.5%) had positive anti-HCV antibody, and three (0.5%) had positive HCV-RNA. All nine infants of mothers with positive anti-HCV antibody had positive anti-HCV antibody at 1, 6, and 12 months of age. All three infants of mothers with positive HCV-RNA had positive HCV-RNA and elevated Alanine Transaminase (ALT) for several years. All six infants of mothers with negative HCV-RNA had negative HCV-RNA and normal ALT at 1, 6, and 12 months of age.

Conclusion: The prevalence of positive anti-HCV antibody in infants of mothers with positive anti-HCV antibody was 9/9 at 12 months. The prevalence of HCV infection (positive HCV-RNA) among mothers in our region is about 0.5%. The prevalence of positive HCV-RNA in infants of mothers with positive HCV-RNA was 3/3 and of mothers with negative HCV-RNA 0/6 (p=0.012). These results justify long-term monitoring of infants born to mothers with positive anti-HCV or HCV-RNA

Chronic Hepatitis C Virus (HCV) is a worldwide public health problem affecting over 170 million people, or about 3% of the world’s population. In Egypt, the situation is quite worse, with the overall prevalence (percentage of people) positive for antibody to HCV being 14.7% [1].

HCV predominantly affects the liver but it can also produce a number of extra hepatic manifestations. It has been reported that 74% of patients with hepatitis C have at least one extra hepatic manifestation, the most common conditions including essential mixed cryoglobulinemia (40%), arthralgia or joint pain (23%), paresthesia (17%), myalgia (15%), pruritus (15%), and sicca syndrome (11%) [2].

Cryoglobulinemia is a blood disorder caused by abnormal proteins in the blood called cryoglobulins that precipitate or clump together when blood is cooled and then dissolve again when rewarded. These proteins can be deposited in small and medium-sized blood vessels, which can lead to restricted blood flow to joints, muscles, and organs. There are three types of cryoglobulinemia (types I, II and III); types II and III have rheumatoid factor activity whereas type I does not (Table 1). The most common and severe form Is Mixed Cryoglobulinemia (MC), a systemic vacuities involving small and medium-sized arteries and veins. MC is characterized by the deposition of immune complexes containing mainly rheumatoid factor, IgG, HCV RNA, and complement on endothelial surfaces, resulting in vascular inflammation, albeit through poorly understood mechanisms. Moreover, HCV can trigger impairment in lymph proliferation with cryoglobulin production [3].

The syndrome of mixed cryoglobulinemia represents the consequence of an immune complex type vasculitis, characterized by the clinical triad of purpura, arthralgia, and asthenia, and may involve numerous organs, particularly the peripheral nervous system and the kidneys [4].

In a large prospective study of 1614 patients chronically infected with HCV, mixed cryoglobulinemia was the predominant extra-hepatic biologic manifestation, identified in 40% of patients. Using multivariate analysis, four independent factors were found to be significantly associated with the presence of cryoglobulins: female sex, alcohol consumption more than 50 g/d, HCV genotype II or III, and extensive liver fibrosis. Cryoglobulin-positive patients were examined for arthralgias, arterial hypertension, purpura, and systemic vasculitis. Considering the high frequency of positive cryoglobulins in patients with HCV, severely symptomatic mixed cryoglobulinemia with vasculitis was rare, noted in only 2 to 3% of cryoglobulin-positive patients [3,5].

Infection with Hepatitis C Virus (HCV) is the major cause of chronic and persistent hepatitis, liver cirrhosis, and Hepatocellular Carcinoma (HCC) and accordingly main reason for liver transplantation needs. In fact, only a small fraction (20%-30%) of the infected people resolve from the acute phase of HCV infection while majority develop the chronic state which may finally end up with adverse liver diseases (cirrhosis and HCC). Around 170 Million individuals are infected with HCV and at least 350,000 people die each year from this infection while there is no approved vaccine available against this threatening infection to date.

Globally, hepatitis B viral infection is a significant health problem leading to one million deaths annually from liver failure, cirrhosis and hepatocellular carcinoma. It has been estimated that 400 million people worldwide are carries of Hepatitis B Virus (HBV), which is an important cause of morbidity and mortality after kidney transplantation.

Zinc is an essential trace element playing fundamental roles in the cellular metabolism and can be found in all tissues. It acts mostly by binding a wide range of proteins, thus affecting a broad spectrum of biological processes, which include cell division, growth and differentiation.

New conjugated compounds containing the coumarin moiety attached to mono- or bis-heterocyles have been synthesized. In >100 new conjugates of five categories, some of them exhibit significant and appealing activity against Hepatitis C Virus (HCV). The heterocycles therein include adenine, benzimidazole, benzothiazole, benzoxazole, guanine, hypoxanthine, imidazole, imidazopyridine, and purine. Use of the thiomethylene (–SCH2 –) linker to connect a coumarin moiety and a purine or imidazole nucleus leads to the conjugates with greater activity and selectivity than others. Various substituents, including CH3 , F, Cl, Br, OCH3 , OAc, CO2 H, COPh, NO2 , β-D-glucose, and β-D-ribofuranose, are also attached to the core nuclei. Incorporation of a halogen substituent (particularly the Br) onto the coumarin nucleus generally enhances the anti-HCV activity from double-digit to single-digit of µM potency. The structure-activity relationship is established, which is of value to the development of new anti-HCV drugs.

Background and Aim: This study aimed to relate the impact of IL-28B SNP in HCV genotype 2 (GT2) and 3 (GT3) associated with the degree of liver fibrosis, according to Metavir score and sustained virologic response (SVR).

Methods: This cross-sectional study conducted between January 2012 and December 2014, which involved 103 patients treated in the center of application and monitoring of injectable drugs from the city of Rio Grande/ RS-Brazil. The analysis of the region rs12979860 IL-28B, PCR was performed according to the technique of Moreira et al, 2012.

Results: Caucasian patients showed 3.15 times greater chance of having SVR than the non-Caucasian ones (p = 0.046). Patients with higher degrees of fibrosis (F3/F4) obtain lower rates of SVR. Among the GT3, SVR was 84% in patients with lower degrees of fibrosis (F0/F1/F2) and 67.7% in patients with higher degrees of fibrosis. The GT3 showed fibrosis F3/F4 almost twice more than those with GT2 (59.7% versus 33.3%). Patients with a IL-28B CC genotype had about 3.8 times higher chance to present SVR compared to those patients with IL-28B TT genotype. The chance for advanced fibrosis in patients with TT genotype of the IL-28B was 3.6 times higher than in patients with CC genotype.

Conclusions: The results obtained in this study indicate the need of permanent search for predictive response factors to antiviral treatment of genotype 3 patients, especially those with higher degrees of fibrosis, even in the age of direct-acting antivirals.

Background and Objective: Liver transplantation (LT) is an effective treatment method for terminal liver disease but is limited by a lack of donors. Donation after cardiac death (DCD) would effectively alleviate this shortage. Here we summarize our experience with LT using DCD in our hospital.

Methods: We retrospectively analyzed the mortality and adverse reactions of 13 patients who underwent LT for terminal liver disease and their donors in our hospital between November 2011 and August 2013.

Results: The surgeries were successful in all 13 cases. The 1-, 2-, and 3-year survival rates were 92%, 85%, and 72%, respectively.

Conclusions: LT from DCD for patients with terminal liver disease will be an effective treatment method.