Excess mortality rate associated with hepatitis C virus infection: A community-based cohort study in rural Egypt.

BACKGROUND & AIMS: >80% of people chronically infected with hepatitis C virus (HCV) live in resource-limited countries, yet the excess mortality associated with HCV infection in these settings is poorly documented. METHODS: Individuals were recruited from three villages in rural Egypt in 1997-2003 and their vital status was determined in 2008-2009. Mortality rates across the cohorts were compared according to HCV status: chronic HCV infection (anti-HCV antibody positive and HCV RNA positive), cleared HCV infection (anti-HCV antibody positive and HCV RNA negative) and never infected (anti-HCV antibody negative). Data related to cause of death was collected from a death registry in one village. RESULTS: Among 18,111 survey participants enrolled in 1997-2003, 9.1% had chronic HCV infection, 5.5% had cleared HCV infection, and 85.4% had never been infected. After a mean time to follow-up of 8.6years, vital status was obtained for 16,282 (89.9%) participants. When compared to those who had never been infected with HCV in the same age groups, mortality rate ratios (MRR) of males with chronic HCV infection aged <35, 35-44, and 45-54years were 2.35 (95% CI 1.00-5.49), 2.87 (1.46-5.63), and 2.22 (1.29-3.81), respectively. No difference in mortality rate was seen in older males or in females. The all-cause mortality rate attributable to chronic HCV infection was 5.7% (95% CI: 1.0-10.1%), while liver-related mortality was 45.5% (11.3-66.4%). CONCLUSIONS: Use of a highly potent new antiviral agent to treat all villagers with positive HCV RNA may reduce all-cause mortality rate by up to 5% and hepatic mortality by up to 40% in rural Egypt.

Hepatitis C infection and clearance: impact on atherosclerosis and cardiometabolic risk factors.

BACKGROUND: Chronic hepatitis C (HCV) infection is associated with diabetes and favourable lipids. OBJECTIVE: To study the effect of this paradox on atherosclerosis and cardiometabolic response to HCV clearance. DESIGN: Cross-sectional study. SETTING: Egypt. PARTICIPANTS: 329 chronically infected, 173 with cleared infection and 795 never infected participants aged >or=35 attended for baseline investigations. A subsample of 192, 115 and 187, respectively, underwent ultrasound. MAIN OUTCOME MEASURES: Diabetes, fasting glucose, lipids and fat deposition on ultrasound. Carotid intima-media thickness (IMT) measured atherosclerosis. RESULTS: Diabetes prevalence was raised (10.1% (95% CI 6.6 to 13.6), p=0.04) in HCV chronic, and cleared (10.1% (5.6 to 14.8), p=0.08) individuals versus 6.6% (4.9 to 8.3) in those never infected. Mesenteric fat was raised in chronic (36.4 mm (34.5 to 38.2), p=0.004), and cleared infection (37.8 (35.6 to 40.0), p<0.0001) vs never infected (32.7 (31.0 to 34.4)). LDL cholesterol was lower in chronic (2.69 mmol/l (2.53 to 2.86), p<0.001), but similar in cleared (3.56 (3.34 to 3.78), p=0.4) versus never infected (3.45 (3.30 to 3.60)). Carotid IMT did not differ by infection status: 0.73 (0.70 to 0.76, p=0.4), 0.71 (0.66 to 0.75, p=0.9), 0.71 (0.68 to 0.74), respectively. Adjustment for cardiovascular risk factors increased IMT in chronic infection (0.76 (0.72 to 0.79), p=0.02) versus never infected individuals (0.70 (0.67 to 0.73)). CONCLUSIONS: Hepatic function normalisation with HCV clearance may account for reversal of favourable lipids observed with HCV infection. Hyperglycaemia and visceral adiposity appear less amenable to HCV resolution. These different cardiovascular risk patterns may determine equivalent atherosclerosis risk by infection status. However, once these factors were accounted for, those with chronic infection had raised IMT, suggesting a direct effect of infection.

Is the hepatitis C virus epidemic over in Egypt? Incidence and risk factors of new hepatitis C virus infections.

OBJECTIVES: To estimate hepatitis C virus (HCV) incidence rates and identify risk factors for current HCV transmission with emphasis on the role of living with infected household family members in rural Egypt. METHODS: A 4-year population-based, cohort study of seronegative villagers was conducted to identify incident HCV seroconversion cases. A risk factor questionnaire and blood samples for anti-HCV EIA-3 and HCV RNA polymerase chain reaction testing were collected at two rounds of follow-up. Incidence rates, relative risks and 95% confidence interval (CI) were calculated based on a Poisson distribution. A matched case-control analysis to explore specific behavioural predictors of infection was conducted and odds ratios were obtained by conditional logistic regression. RESULTS: Twenty-five participants (11 females) seroconverted in 10,578 person years of follow-up (PY), (incidence rate of 2.4/1000 PY; 95% CI: 1.6-3.5). The median age at seroconversion was 26 years [interquartile range (IQR) 19-35] among males and 20 years (IQR 13-24) among females. The only significant risk factor identified for these cases was receiving injections [adjusted odds ratio (OR(adj))=3.3; 95% CI: 1.1-9.8]. Two of the 17 viraemic seroconvertors were infected with the same strain as at least one of their family members. CONCLUSION: This study identified the important role of injections in spreading HCV infection in this rural community. National healthcare awareness and infection control programmes should be strengthened to prevent further transmission. Screening of families of infected HCV subjects should be an essential part of case management for early detection and management.

Predictors of a sustained virological response in patients with genotype 4 chronic hepatitis C.

OBJECTIVES: To determine the clinical, biological, virological and histological predictive factors associated with a sustained virological response (SVR) to combined interferon therapy among Egyptian patients infected by genotype 4 hepatitis C virus (HCV). PATIENTS AND METHODS: Individual data from 250 patients with genotype 4 chronic hepatitis C, treated with different regimens of combined interferon, were analysed. The primary end point was SVR defined as undetectable HCV RNA by polymerase chain reaction (PCR) 24 weeks after the end of treatment. Multivariate logistic regression analysis was performed to select the independent prognostic parameters associated with SVR. RESULTS: A sustained virological response was achieved among 137/250 (54.8%) patients. Baseline factors independently and negatively associated with SVR were serum alpha-fetoprotein (AFP) level (above 0.3 upper limit of normal) [odds ratio (OR)=0.5, 95% confidence interval (CI): 0.2-0.8], severe fibrosis (Metavir score >F2) (OR=0.4, 95% CI: 0.2-0.8), presence of steatosis (OR=0.5, 95% CI: 0.3-0.97) and standard interferon treatment (OR=0.4, 95% CI: 0.2-0.8). CONCLUSIONS: Among genotype 4 chronic hepatitis C patients, severe fibrosis, severe steatosis, treatment with standard interferon and a high serum AFP level were all negatively associated with SVR. Pretreatment serum AFP level should be considered in the routine assessment of factors predictive of a treatment response.

Serum alpha-foetoprotein level predicts treatment outcome in chronic hepatitis C.

OBJECTIVES: To analyse the association between serum alpha-foetoprotein (AFP) levels and sustained virological response (SVR) in treated patients. METHODS: One-hundred patients with chronic hepatitis C were treated with pegylated interferon alpha-2a plus ribavirin for 48 weeks. The primary endpoint was SVR. Linear regression analysis was performed to identify clinical, biological, and histological factors affecting baseline AFP levels. The association between pretreatment serum AFP and SVR was assessed by multivariate logistic regression analysis. RESULTS: Of 100 patients, 95 were infected with genotype 4, one with genotype 1, and four with undetermined genotype. The median serum AFP level was 4.5 ng/ml and AFP values ranged from 1.2 to 49.8 ng/ml. In multivariate analysis, higher fibrosis stage and higher steatosis score were independently associated with higher serum AFP levels. SVR rate was 61.0% (61/100), and was lower for patients with AFP levels above rather than below the median value (40.8% versus 80.4%, respectively, P < 0.001). In multivariate analysis, including adjustment for age, gender, body mass index, steatosis score, fibrosis stage, ALT level, haemoglobin level, clotting time, HCV RNA viral load, and treatment dose received, a baseline serum AFP level above the median value was associated with a lower SVR rate (OR [95% CI]=0.10 [0.03-0.42], P < 0.001). None of the seven patients with increased (above 15 ng/ml) pretreatment AFP achieved SVR. CONCLUSIONS: In this study, higher baseline serum AFP levels independently predicted a lower SVR rate among patients with chronic hepatitis C. If confirmed with genotypes other than 4, these findings would suggest adding serum AFP to the list of factors predictive of treatment response.

Prevalence of injuries among high school students in Eastern and Western parts of Cairo, Egypt.

BACKGROUND: Injury is the leading cause of death and long term disability and a significant contributor to healthcare costs among children worldwide especially those aged 15-19 years. OBJECTIVES: To determine the prevalence of injuries among secondary school students in Cairo, Egypt and to explore the associated risk factors for sustaining injury. METHODOLOGY: A Cross-sectional study was conducted on secondary school students in eastern and western part of Cairo; self-administered questionnaire was used for assessing injuries sustained in previous 12 months and the associated risk factors for injury. RESULTS: The overall prevalence of injuries was 68.5%. Unintentional injuries were the most common injuries falls (50%) and burns (38.6%). Significant factors associated with sustaining injury were truancy, smoking, alcohol use, quarreling behavior, carrying weapon, threatened by weapon and verbal bullying. CONCLUSION: This study showed a high prevalence of injuries among high school students in Egypt which necessitates raising public awareness about the magnitude and burden of injuries among adolescents.

A novel method to identify routes of hepatitis C virus transmission.

BACKGROUND: We propose a new approach based on genetic distances among viral strains to infer about risk exposures and location of transmission at population level. METHODS: We re-analysed 133 viral sequences obtained during a cross-sectional survey of 4020 subjects living in a hepatitis C virus (HCV) endemic area in 2002. A permutation test was used to analyze the correlation between matrices of genetic distances in the NS5b region of all pairwise combinations of the 133 viral strains and exposure status (jointly exposed or not) to several potential HCV risk factors. RESULTS: Compared to subjects who did not share the same characteristics or iatrogenic exposures, the median Kimura genetic distances of viral strains were significantly smaller between brothers and sisters (0.031 versus 0.102, P<0.001), mother and child (0.044 versus 0.102, P<0.001), father and child (0.045 versus 0.102, P<0.001), or subjects exposed to periodontal treatment (0.084 versus 0.102, P = 0.02). Conversely, viral strains were more divergent between subjects exposed to blood transfusions (0.216 versus 0.102, P = 0.04) or tooth filling or extraction (0.108, versus 0.097, P = 0.05), suggesting acquisition of the virus outside of the village. CONCLUSION: This method provided insights on where infection took place (household, village) for several socio-demographic characteristics or iatrogenic procedures, information of great relevance for targeting prevention interventions. This method may have interesting applications for virologists and epidemiologists studying transmission networks in health-care facilities or among intravenous drug users.

Community transmission of hepatitis B virus in Egypt: results from a case-control study in Greater Cairo.

BACKGROUND: To identify current risk factors for hepatitis B virus (HBV) transmission in Greater Cairo. METHODS: A 1:1 matched case-control study was conducted in two 'fever' hospitals in Cairo. Acute hepatitis B cases were patients with acute hepatitis, positive HBs antigen, and high anti-HBc IgM titres. Control subjects were acute hepatitis A patients (positive anti-HAV IgM) or relatives of patients diagnosed with acute hepatitis C, identified at the same hospitals, with no past HBV infection (negative anti-HBc) and matched to cases on the same age and sex. Conditional logistic regression was used to identify factors associated with acute hepatitis B. RESULTS: Between April 2002 and June 2006, 233 cases and 233 controls were recruited to the study. In multivariate analysis, factors associated with an increased HBV risk in males were illiteracy [odds ratio (OR) = 6.1, 95% confidence interval (CI) = 2.8-13.1], shaving at barbers (OR = 2.1, 95% CI = 1.1-3.9) and injecting drug use (IDU) (OR = 3.4, 95% CI = 1.0-11.4). In females, factors associated with an increased HBV risk were illiteracy (OR = 2.2, 95% CI = 1.0-5.0), recent (<1 year) marriage (OR = 42.0, 95% CI = 3.8-463.9 compared with single women) and giving birth (OR = 3.7, 95% CI = 1.0-13.9). CONCLUSION: In this study, HBV transmission took place primarily in the community, whether as a result of recent marriage (presumably first sexual intercourse), shaving at barbershops or IDU, and was more common among illiterates. Health promotion campaigns should be carried out to increase awareness about community transmission of HBV. In addition to routine immunization for infants and other populations, premarital screening might be useful to identify at-risk spouses in order to propose targeted immunization.

Injection drug use is a risk factor for HCV infection in urban Egypt.

OBJECTIVE: To identify current risk factors for hepatitis C virus (HCV) transmission in Greater Cairo. DESIGN AND SETTING: A 1:1 matched case-control study was conducted comparing incident acute symptomatic hepatitis C patients in two "fever" hospitals of Greater Cairo with two control groups: household members of the cases and acute hepatitis A patients diagnosed at the same hospitals. Controls were matched on the same age and sex to cases and were all anti-HCV antibody negative. Iatrogenic, community and household exposures to HCV in the one to six months before symptoms onset for cases, and date of interview for controls, were exhaustively assessed. RESULTS: From 2002 to 2007, 94 definite acute symptomatic HCV cases and 188 controls were enrolled in the study. In multivariate analysis, intravenous injections (OR = 5.0; 95% CI = 1.2-20.2), medical stitches (OR = 4.2; 95% CI = 1.6-11.3), injection drug use (IDU) (OR = 7.9; 95% CI = 1.4-43.5), recent marriage (OR = 3.3; 95% CI = 1.1-9.9) and illiteracy (OR = 3.9; 95% CI = 1.8-8.5) were independently associated with an increased HCV risk. CONCLUSION: In urban Cairo, invasive health care procedures remain a source of HCV transmission and IDU is an emerging risk factor. Strict application of standard precautions during health care is a priority. Implementation of comprehensive infection prevention programs for IDU should be considered.

HCV-related morbidity in a rural community of Egypt.

The origin of the hepatitis C virus (HCV) epidemic in Egypt has been attributed to intravenous schistosomiasis treatment in rural areas in the 1960s to 70s. The objective of this study was to estimate the HCV-related morbidity in a rural area where mass schistosomiasis treatment campaigns took place 20-40 years before. The study sample included 2,425 village residents aged 18-65 years recruited through home-based visits. Overall, HCV antibody prevalence was 448/2,425 = 18.5% (95% CI = 16.9-20.1%), reaching 45% in males over 40 years, and 30% in females over 50 years. Of those with HCV antibodies, 284/448 (63.4%, 95% CI = 58.7-67.9%) had chronic HCV infection, among which 107/266 (40.2%, 95% CI = 34.3-46.4%) had elevated alanine aminotransferase (ALT). As part of pre-treatment screening, 26 consenting patients had a liver biopsy: 13 (50.0%) had a treatment indication. Thus, of all patients with HCV antibodies, 13 (2.9%) were eligible for treatment and willing to be treated. The relatively low level of morbidity observed in this study is discussed in view of co-factors of HCV infection progression, such as young age at infection, absence of alcohol intake, the prevalence of Schistosoma mansoni infection, and the prevalence of chronic hepatitis B.

Changing pattern of hepatitis C virus spread in rural areas of Egypt.

BACKGROUND/AIMS: To identify patterns of HCV spread in the Nile Delta of Egypt. METHODS: Residents in a Nile Delta village were invited to participate in a cohort study of HCV infection. Risk factors for past or current infection were identified at cohort intake using generalized estimated equations models. Attributable fractions were calculated for all independent risk factors. RESULTS: The prevalence of HCV antibodies increased from 2.7% in those <20 years of age to more than 40% in males aged 40-54 years. The peak in HCV prevalence in the 40-54 year age group corresponds to the aging of the cohort of children infected through schistosomiasis intravenous treatments in the 1960s-70s (accounting for 12.4% of all HCV infections observed today among adults). Following this initial founding event, the HCV epidemic has spread in the community through iatrogenic factors, and particularly injections (37.9% of the overall attributable fraction in adults). In children, however, no iatrogenic factors were associated with increased risk of infection, suggesting a change in the pattern of HCV spread. CONCLUSIONS: While HCV infections in adults could be attributed to iatrogenic factors, and particularly injections, infections in children could not be explained by similar routes of transmission.