Hepatitis C Among People Who Inject Drugs (PWID) in Latin America and the Caribbean: A Meta-Analysis of Prevalence Over Three Decades.

OBJECTIVE: People who inject drugs (PWID) are known to be more susceptible to infections such as hepatitis C virus (HCV). This systematic review and meta-analysis aimed to estimate the prevalence of hepatitis C among PWID in Latin America and the Caribbean (LAC). METHOD: The MEDLINE, Embase, and LILACS databases were searched without language restriction from inception to 2021. Articles were screened based on titles and abstracts. After reading the full texts, the articles were selected based on eligibility criteria. RESULTS: Of the 486 identified publications, 123 full texts were assessed, and 23 studies with a mean quality score of 7.2 were included. A total of 11,419 PWID were included in the meta-analysis, and the estimated overall prevalence of hepatitis C among PWID in LAC was 57.0%, which was higher than the United Nations Office on Drugs and Crime global prevalence of 50.2%. In meta-analyses of subgroups divided according to the risk of exposure to HCV infection (in addition to the imminent risk of injected drugs), the estimated prevalence of hepatitis C in PWID in the lowerrisk population (general) was 57.0%. The prevalence of hepatitis C in PWID who were infected with HIV was 61.0%. The estimated hepatitis C prevalence was also assessed for three periods: in 1991-2000, it was 59.0%; in 2001-2010, it was 63.0%; and in 2011-2020, it was 48.0%. CONCLUSIONS: The high estimated prevalence of hepatitis C in LAC reinforces the need for increased diagnostic efforts, strategies for treating drug addiction and hepatitis C, and harm reduction policies that target PWID.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis.

BACKGROUND: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. OBJECTIVE: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. METHODS: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. RESULTS: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. CONCLUSION: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Effect of MTTP -493G/T, I128T, Q95H and Q244E polymorphisms on hepatic steatosis in patients with chronic hepatitis

Abstract Background: Chronic hepatitis C is characterized by a progressive deterioration of liver function and is involved in metabolic complications, such as hepatic steatosis. Objective: The aim of this study was to investigate the role of host and viral characteristics associated with -493G/T (rs1800591), I128T (rs3816873), Q95H (rs61733139), and Q244E (rs17599091) Single Nucleotide Polymorphisms (SNPs) in the Microsomal Triglyceride Transfer Protein (MTTP) gene on hepatic steatosis in chronic hepatitis C. Methods: SNPs were genotyped by PCR-RFLP and analyzed in combination with host and viral characteristics by multiple logistic regression in different genetic models of inheritance. Results: The authors analyzed 236 patients with chronic hepatitis C, and 53% had hepatic steatosis. The mutated allele frequencies were > 5%, and the genotypes were in Hardy-Weinberg equilibrium (p ≥ 0.05). It was observed that patients with HCV genotype 3 infection (OR = 2.74, 95% CI 1.24‒6.06, p = 0.013), female sex (OR = 2.28, 95% CI 1.21‒4.28, p = 0.011) and moderate- and high-intensity liver inflammatory activity (A2-A3) (OR = 3.61, 95% CI 1.86‒7.01, p < 0.001) alone exhibited a higher risk of steatosis. The results of multiple logistic regression analysis for interaction showed that for the -493G/T SNP, when the GT/TT genotype (dominant model) and the GT genotype (codominant model) were each combined with HCV genotype 3 infection, an 11.51-fold (95% CI 2.08‒63.59, p = 0.005) and a 15.69-fold (95% CI 2.46‒99.85, p = 0.004) increased risk of steatosis, respectively, was observed. For the I128T SNP, when both the IT/TT genotype (dominant model) and the IT genotype (codominant model) were combined with HCV genotype 3 infection, an 8.51-fold (95% CI 1.59‒45.54, p = 0.012) and an 8.40 fold (95% CI 1.51‒46.91, p = 0.015) increased risk of steatosis, respectively, was observed. Conclusion: The present study showed that the viral genotype combined with the -493G/T and I128T SNPs in the MTTP gene influences hepatic steatosis.

Study of CXCL9-11 gene polymorphisms in liver fibrosis among patients with chronic hepatitis C.

Several factors are associated with the progression of chronic hepatitis C: comorbidities, lifestyle, and pathogenic factors, including immune response, apoptosis and heredity. Single nucleotide polymorphisms (SNPs) in the PNPLA3 and TM6SF2 genes are more widely studied genetic risk factors, while CXCL9-11 chemokines produced by hepatocytes in the process of infection are less well studied. Our aim was to evaluate the influence of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 in liver fibrosis when analysed together with PNPLA3 rs738409 and TM6SF2 rs58542926. The study included 219 patients with chronic hepatitis C. SNP genotyping was performed by real-time PCR. Univariate and multivariate analyses were used to detect the association between SNPs and advanced fibrosis in a recessive genetic model. All SNPs had a minimum allele frequency >5%, and CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 were in high linkage disequilibrium (D' ≥ 0.84). In the multivariate analysis, we observed that male gender (P = 0.000), older age (P = 0.025), moderate to intense inflammatory activity (P = 0.002), moderate to accentuated hepatic steatosis (P = 0.026) and the CT genotype of the TM6SF2 rs58542926 SNP (P = 0.014) presented significant associations with advanced fibrosis. Overall, the CXCL9 rs10336, CXCL10 rs3921, CXCL11 rs4619915 and PNPLA3 rs738409 SNPs did not influence liver fibrosis among patients with chronic hepatitis C.

The influence of gene-chronic hepatitis C virus infection on hepatic fibrosis and steatosis.

Host single nucleotide polymorphisms (SNPs) in different genes can play a role in chronic hepatitis C virus (HCV) infection and influence the presence of hepatic fibrosis and comorbidities such as hepatic steatosis. We assessed the combined effect of SNPs in the PNPLA3, MTTP, TM6SF2, and IFNL3/IFNL4 genes in 288 Brazilian patients who were chronically infected with HCV. Hepatic fibrosis was observed in 246 (85.4%) patients and hepatic steatosis in 141 (49.0%) patients. PNPLA3 rs738409 (CG/GG) (P = 0.044) and TM6SF2 rs58542926 (CT) (P = 0.004) were alone associated with fibrosis, and PNPLA3 rs738409 (P < 0.05, in distinct genetic models) was associated with steatosis. Multiple logistic regression of each SNP combined with HCV genotype 3 infection showed that MTTP rs1800591 (GT/TT) combined with HCV genotype 3 was associated with a 6.72-fold increased chance of hepatic steatosis (P = 0.013). In the analysis of SNPs combined 2 by 2, no influence on hepatic fibrosis or steatosis was observed.

Meta-Analysis of the Prevalence of HBV Infection Among Alcohol Users Worldwide.

AIMS: To investigate the prevalence of hepatitis B virus (HBV) infection among alcohol users. METHODS: A systematic search of articles in the PubMed, Web of Science and EMBASE databases was conducted. The methodological quality of each study was scored, and a meta-analysis was performed taking into account the heterogeneity expected among the studies. Publication bias was assessed using Begg's and Egger's tests. RESULTS: The search identified 998 reports that yielded 18 eligible studies. The studies comprised 12,204 alcohol users, who were mostly men. The mean score on the quality evaluation was 6.9, and 11 studies were classified as having a low risk of bias. The estimated worldwide prevalence of HBV was 20.0% (95%CI: 19.0-20.0). The heterogeneity among the studies was substantial (I2 = 96.7%). In subgroup analyses, it was observed that among alcohol user dependents with no description of liver damage, alcohol users with different stages of chronic liver disease and alcohol users who all had cirrhosis, the estimated prevalence was 10.0% (95%CI: 8.0-14.0), 14.0% (95%CI: 13.0-15.0) and 32.0% (95%CI: 29.0-35.0), respectively. The meta-regression analysis showed that the study quality score had an influence on the investigated prevalence (P = 0.005). Nevertheless, the funnel plot showed asymmetry, and there was evidence of publication bias according to Egger's test (P = 0.003) but not Begg's test (P = 0.869). CONCLUSIONS: The prevalence of HBV among alcohol users was high. HBV infection and alcohol consumption are factors affecting the development and worsening of liver disease; therefore, we suggest that adult alcohol users should be carefully monitored.

MTTP polymorphisms and hepatic steatosis in individuals chronically infected with hepatitis C virus.

Polymorphisms in the microsomal triglyceride transfer protein (MTTP) gene were genotyped in individuals who were chronically infected with hepatitis C virus (HCV). In the 236 patients, the frequencies of risk alleles of the -164T/C (rs1800804), -400A/T (rs1800803) and H297Q (rs2306985) polymorphisms were 0.30, 0.41 and 0.50, respectively. A significant association between the risk alleles of the -164T/C and -400A/T polymorphisms combined with HCV genotype 3 infection and the occurrence of steatosis was detected (p = 0.004 and p = 0.032), suggesting that a combination of host and viral factors can potentially be used to predict hepatic steatosis.

The rs738409 polymorphism of the PNPLA3 gene is associated with hepatic steatosis and fibrosis in Brazilian patients with chronic hepatitis C.

BACKGROUND: Prospective studies have shown that 80% of acute hepatitis C virus (HCV) cases progress to chronic infection; approximately 10-20% of patients with these conditions will develop liver cirrhosis within 2 to 3 decades, and 1-5% will develop liver cancer. Some studies have indicated that the rs738409 polymorphism of the PNPLA3 gene is associated with steatosis and the progression of advanced fibrosis. This study assessed the contribution of the PNPLA3 rs738409 polymorphism with regard to the steatosis and degree of liver fibrosis in Brazilian patients diagnosed with chronic hepatitis C. METHODS: A total of 290 patients were evaluated at the Clinics Hospital of the School of Medicine, University of São Paulo, between 2010 and 2015. The inclusion criteria were age ≥ 18 years and positive anti-HCV antibody and HCV RNA tests. The participants were evaluated based on medical consultation, blood tests, and liver biopsies conducted before specific antiviral therapies were applied. The associations between the rs738409 PNPLA3 gene polymorphism and steatosis and advanced fibrosis were tested under a recessive inheritance model using logistic regression analysis, including age, gender, BMI, ethnicity/color, HOMA-IR, alcohol intake, HCV genotype 3, and the rs58542926 TM6SF2 gene polymorphism as covariates. RESULTS: The mean age of the patients was 54.9 years old (range, 28 to 82 years), and 124 (42.8%) patients were male; 226 (77.9%) were white, 43 (14.8%) were pardo, and 21 (7.2%) were black Brazilians. Of the patients included in this study, 133 (45.9%) presented with the CC genotype, 63 (21.7%) with the CG genotype, and 94 (32.4%) with the GG genotype of the PNPLA3 gene I148M variant. We observed that the associations between PNPLA3 rs738409 GG genotype and steatosis was significant (OR: 2.16; 95% CI 1.26-3.72). The same genotype was associated to advanced fibrosis too (OR:2.64; 95% CI 1.26-5.53). CONCLUSIONS: Associations between the rs738409 polymorphism of the PNPLA3 gene genotype GG and hepatic steatosis and advanced fibrosis were observed. Studies are still needed to clarify the influence of these polymorphisms on hepatic steatosis and degree of fibrosis among individuals diagnosed with chronic hepatitis C.

Genetic variation in the microsomal triglyceride transfer protein (-493G/T) is associated with hepatic steatosis in patients infected with hepatitis C virus.

BACKGROUND: In chronic hepatitis C, the fibrosis progression rates are extremely variable and can be influenced by factors associated with the host, virus and environment. Among the associated metabolic factors, hepatic steatosis is characterized by an accumulation of triglycerides in hepatocytes. In the host, genetic determinants of hepatic steatosis are observed, such as single-nucleotide polymorphisms (SNPs) in the microsomal triglyceride transfer protein (MTTP) gene. The MTTP -493G/T SNP appears to play an important role in the regulation of gene expression and influences the plasma concentration of circulating low-density lipoprotein (LDL). The present study investigated the influence of this SNP in the development of hepatic steatosis in patients with chronic hepatitis C and evaluated the association of hepatic steatosis with certain characteristics of these patients and the hepatitis C virus (HCV). METHODS: Two hundred thirty-nine patients with chronic hepatitis C were genotyped for the MTTP -493G/T SNP by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The association between hepatic steatosis and selected characteristics of the patient and virus was evaluated using bivariate and multivariate analyses. RESULTS: The most prevalent MTTP -493G/T genotype was GG (46%) followed by GT (43.5%) and TT (10.5%). Multivariate analysis of the total cohort revealed associations between the presence of hepatic steatosis and inflammatory activity of moderate to high intensity (P < 0.001), advanced age (P = 0.010), elevated gamma glutamyl transpeptidase (GGT) levels (P = 0.010) and low LDL levels (P = 0.022). Hepatic steatosis was also associated with the TT/GT genotype of the MTTP -493G/T SNP in patients infected with HCV genotype 3 (P < 0.001). CONCLUSIONS: In chronic hepatitis C patients infected with HCV genotype 3 and with the TT/GT genotype of the MTTP -493G/T SNP, a significant increase in hepatic steatosis was observed, which may indicate that this SNP has a significant influence on the accumulation of triglycerides in hepatocytes. Furthermore, associations were observed between hepatic steatosis and inflammatory activity of moderate to high intensity, advanced age, elevated GGT and low LDL levels.

Seroprevalence of hepatitis C virus among people living with HIV/AIDS in Latin America and the Caribbean: a systematic review.

BACKGROUND: Studies have shown that the immunosuppression induced by the human immunodeficiency virus (HIV) accelerates the natural history of liver disease associated with hepatitis C virus (HCV), with 3- to 5-fold higher odds of coinfected individuals developing cirrhosis. However, estimates of the seroprevalence of hepatitis C among people living with HIV/acquired immune deficiency syndrome (AIDS) (PLHA) in Latin America and the Caribbean (LAC) are widely variable. METHODS: We performed a systematic review to estimate the seroprevalence of HCV among PLHA. We searched studies on HIV and HCV infections in LAC included in the PubMed, LILACS and Embase databases in December of 2014 with no time or language restrictions. The following combinations of search terms were used in the PubMed and Embase databases: (HIV OR Acquired Immunodeficiency Syndrome Virus OR AIDS OR HTLV OR Human Immunodeficiency Virus OR Human T Cell) AND (HCV OR HEPATITIS C OR HEPATITIS C VIRUS OR HEPACIVIRUS) AND (name of an individual country or territory in LAC). The following search terms were used in the LILACS database: (HIV OR AIDS OR Virus da Imunodeficiencia Humana) AND (HCV OR Hepatite C OR Hepacivirus). An additional 11 studies were identified through manual searches. A total of 2,380 publications were located, including 617 duplicates; the remaining articles were reviewed to select studies for inclusion in this study. RESULTS: A total of 37 studies were selected for systematic review, including 23 from Brazil, 5 from Argentina, 3 from Cuba, 1 from Puerto Rico, 1 from Chile, 1 from Colombia, 1 from Mexico, 1 from Peru and 1 from Venezuela. The estimated seroprevalence of HCV infection varied from 0.8 to 58.5 % (mean 17.37; median 10.91), with the highest in Argentina and Brazil and the lowest in Venezuela and Colombia. CONCLUSIONS: Investigation of HCV infection among PLHA and of HIV infection among people living with HCV is highly recommended because it allows for better follow up, counseling and treatment of HIV/HCV-coinfected patients. Future studies with larger sample sizes are needed in both South and Central America to understand and address the risk factors associated with the acquisition of infection.