Immunity to hepatitis A virus in liver transplant recipients: A population-based study in Iran.

BACKGROUND: Acute hepatitis A is usually a self-limited viral disease but can be severe and even fatal in special groups of patients including those with chronic liver disease and recipients of liver transplantation. To take appropriate preventive measures, it is important to determine the immune status against the hepatitis A virus in patients at risk of grave clinical outcomes following infection. To assess the need for immunization against hepatitis A, we aimed to determine the immune status against hepatitis A in a population of liver transplant recipients. We also investigated the association between hepatitis A immune status and demographic factors such as age and sex, underlying liver disease, source of drinking water, geographical area of residence and socioeconomic status. METHODS: This cross-sectional study was performed on 242 recipients of allogenic liver transplants at Abu Ali Sina Organ Transplant Hospital in Shiraz, Iran, between January 2017 and April 2017. The level of immunity was assessed using hepatitis A antibody detection kits. RESULTS: The rate of immunity against hepatitis A was detected as 88.8% in our study population. In the multivariable logistic regression model, younger age (OR=1.175, P<0.001) and higher education level (OR=2.142, P=0.040) were the main determinants of non-immune status. However, hepatitis A immunity was independent of gender, monthly family income, water supply source, residential area and underlying liver disorder. CONCLUSION: Although a significant proportion of liver transplant recipients in this study showed evidence of natural immunity to hepatitis A, a considerable proportion of younger patients and those with a higher level of education were non-immune. The results of this study signify the importance of screening for hepatitis A immunity in this at-risk population of patients and the need for vaccinating non-immune patients.

The combination of sofosbuvir and daclatasvir is effective and safe in treating patients with hepatitis C and severe renal impairment.

BACKGROUND AND AIM: Many of the treatment regimens available for hepatitis C include sofosbuvir. Unfortunately, sofosbuvir has not been recommended for use in patients with severe renal impairment leaving these group of patients with very few options. Nevertheless, there are many reports in which these patients have been treated with sofosbuvir-containing regiments without important adverse events. This study aims at determining the safety and effectiveness of a sofosbuvir-based treatment in patients with severe renal impairment, including those on hemodialysis. METHOD: We enrolled subjects with hepatitis C and estimated glomerular filtration rate under ml/min/1.73m2 from 13 centers in Iran. Patients were treated for 12 weeks with a single daily pill containing 400-mg sofosbuvir and 60-mg daclatasvir. Patients with cirrhosis were treated for 24 weeks. Response to treatment was evaluated 12 weeks after end of treatment (sustained viral response [SVR]). ClinicalTrials.gov identifier: NCT03063879. RESULTS: A total of 103 patients were enrolled from 13 centers. Seventy-five patients were on hemodialysis. Thirty-nine had cirrhosis and eight were decompensated. Fifty-three were Genotype 1, and 27 Genotype 3. Twenty-seven patients had history of previous failed interferon-based treatment. Three patients died in which cause of death was not related to treatment. Six patients were lost to follow-up. The remaining 94 patients all achieved SVR. No adverse events leading to discontinuation of medicine was observed. CONCLUSIONS: The combination of sofosbuvir and daclatasvir is an effective and safe treatment for patients infected with all genotypes of hepatitis C who have severe renal impairment, including patients on hemodialysis.

The Impact of IFN-γ Gene Polymorphisms on Spontaneous Clearance of HCV Infection in Fars Province, Southern of Iran.

BACKGROUND: Certain polymorphisms in cytokine genes such as IFN-γ may influence the outcome of hepatitis C virus (HCV) infection. Here the frequency of the genotype, allele, and haplotype of IFN-γ gene at some loci is investigated in HCV-infected patients. METHODS: Totally 255 patients with chronic HCV infection and 44 spontaneously cleared individuals were included. The chronic or clearance states were confirmed using enzyme-linked immunosorbent assay (ELISA) and two different qualitative reverse transcriptase polymerase chain reaction (RT-PCR) techniques. IFN-γ gene polymorphisms were performed by PCR using sequence-specific primers and PCR-RLFP on extracted genomic DNA. RESULTS: The frequency of GG genotype (P = 0.0001, OR: 5.69 and CI: 2.21-14.62) and allele (P = 0.0003, OR: 2.73 and CI: 1.54-4.83) of IFN-γ gene at +2109 locus was significantly higher in cases that spontaneously cleared the infection. Haplotype analysis showed the association of AG haplotype (P = 0.0046, OR = 6.14 and CI = 1.56-25) with spontaneous clearance of the infection. CONCLUSION: Our finding indicated that individuals with GG genotype at +2109 loci of IFN-γ gene and also AG haplotype (A allele at +874 loci and G allele at +2109 loci) may clear HCV infection more frequently than those with AA and AG genotype at +2109 loci and AA, TA, and TG haplotype.

Prevalence of glucose-6-phosphate dehydrogenase (G6PD) deficiency among the fulminant hepatitis A virus infection patients.

Background: Hepatitis A is a widespread viral infection with significant public health implications. Assessing glucose 6-phosphate dehydrogenase (G6PD) deficiency in hepatitis A patients is essential for various reasons, including prognosis, disease severity evaluation, encephalopathy risk identification, tailored management, and advancing scientific understanding. This study aimed to investigate the prevalence and clinical implications of G6PD impairment in individuals with fulminant hepatitis A. Methods: A cross-sectional descriptive analysis was conducted, involving hospitalized patients with fulminant hepatitis A. Demographic data, prevalence rates, and clinical findings were recorded in a database. The diagnosis of hepatitis A infection was confirmed using an anti-HAV IgM antibody test, and G6PD enzyme activity was measured with a fluorescent spot assay. Results: Out of 81 patients with hepatitis A, 57 (70.4%) were males, and 24 (29.5%) were females, with an average age of 24.6 years. Dark yellow urine and anorexia were the most common clinical symptoms. Notably, 30 (37%) patients lacked G6PD. The group with G6PD deficiency showed significantly higher rates of encephalopathy and mortality (P<0.01), along with elevated bilirubin (P=0.00), abnormal coagulation parameters, and low hemoglobin levels (P=0.00). Conclusion: In light of these findings, the present study proposes the implementation of routine G6PD level assessments and the evaluation of other relevant markers in regions where hepatitis A is endemic. Furthermore, the study underscores the need for vigilant monitoring of hemolysis and encephalopathy in affected patients to optimize clinical management and reduce morbidity and mortality associated with this condition.

Prevalence of Colonic Polyps Detected by Colonoscopy in Symptomatic Patients and Comparison Between Different Age Groups. What Age Should be Considered for Investigation?

<b>Introduction:</b> The Burden of Colorectal cancer (CRC) as one of the most common malignancies is considerable worldwide, with 1.8 million diagnoses each year. Although it is well established that most CRCs arise from colonic polyps, guidelines and recommendations indicate different ages as starting points for endoscopic examination of the colon, either as cancer screening programs or in symptomatic patients. Most standard guidelines adapt the cut-off age of 50. However, this has been challenged by the results of recent studies. This multicentric prospective study aimed to investigate the frequency, distribution, and histopathological findings of colonic polyps in patients who underwent colonoscopy with special attention to the age group of 40-49-year-olds compared with 50-59 in the population.</br></br> <b>Material and methods:</b> This multicentric, prospective study was designed to enroll adult patients referred to three universityaffiliated endoscopy units. As many as 723 patients met all the inclusion criteria. Data analysis was performed on endoscopic and histopathological characteristics of all detected lesions, including colonic polyps and neoplastic lesions.</br></br> <b>Results:</b> A total of 723 patients with a mean age of 46.03 (16.8) years were included in this study. Rectal bleeding was the most frequent symptom (40.9%). One hundred and thirteen patients (15.6%) were found to have colonic polyps, and 11 cases (1.52%) of CRC were detected. Most polyps were located in the left colon (67.5%). There was no statistical difference in the prevalence of adenomatous polyps between the age group of 40-49 years and 50-59 years (P = 0.77). Detailed examination of data using receiver operating characteristic (ROC) curve analysis not only showed age is a risk factor for the presence of colonic polyps but also revealed the cut-off age of 42.5 for the presence of all types of colonic polyps (44.5 years for adenomatous polyps).</br></br> <b>Conclusion:</b> This study has showed a similar polyp prevalence in the age group of 40-49 years as compared to 50-59. Our study suggests that appropriate colon examination should be performed at a younger age to achieve early detection of colonic polyps, specifically in patients with red flag symptoms.

The frequency and distribution of thiopurine S-methyltransferase alleles in south Iranian population.

Thiopurine methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs such as 6-mercaptopurine, 6-thioguanine, and azathiopurine. Variability in TPMT activity is mainly due to genetic polymorphism. The frequency of the four allelic variants of the TPMT gene, TPMT*2 (G238C), TPMT*3A (G460A and A719G), TPMT*3B (G460A) and TPMT*3C (A719G) were determined in an Iranian population from south of Iran (n = 500), using polymerase chain reaction (PCR)-RFLP and allele-specific PCR-based assays. Four hundred seventy four persons (94.8%) were homozygous for the wild type allele (TPMT*1/*1) and twenty five people were TPMT*1/*3C (5%). One patient was found to be heterozygous in terms TPMT*1 and *2 alleles with genotype of TPMT*1/*2 (0.2%). None of the participants had both defective alleles. The TPMT*3C and *2 were the only variant alleles observed in this population. The total frequency of variant alleles was 2.6% and the wild type allele frequency was 97.4%. The TPMT*3B and *3A alleles were not detected. Distributions of TPMT genotype and allele frequency in Iranian populations are different from the genetic profile found among Caucasian or Asian populations. Our findings also revealed inter-ethnic differences in TPMT frequencies between different parts of Iran. This view may help clinicians to choose an appropriate strategy for thiopurine drugs and reduce adverse drug reactions such as bone marrow suppression.

HBsAg Loss as a Treatment Endpoint for Chronic HBV Infection: HBV Cure.

Despite the availability of effective vaccines and antiviral therapy over the past two to three decades, chronic hepatitis B virus (HBV) infection remains a major global health threat as a leading cause of cirrhosis and liver cancer. Functional HBV cure defined as hepatitis B surface antigen (HBsAg) loss and undetectable serum HBV DNA is associated with improved clinical outcomes in patients with chronic HBV infection. However, spontaneous loss of HBsAg is rare and occurs in only 1% of all HBsAg-positive individuals annually. Furthermore, the rate of functional cure with currently available antiviral therapy is even lower, <1% patients on treatment per year. Nonetheless, HBsAg loss has become the new target or therapeutic endpoint for antiviral treatment. Recently, there has been much excitement surrounding the development of novel antiviral agents such as small interfering RNA (siRNA), core assembly modulators (CAMs), nucleic acid polymers (NAPs) among others, which may be used in combination with nucleos(t)ide analogs and possibly immunomodulatory therapies to achieve functional cure in a significant proportion of patients with chronic hepatitis B. Novel assays with improved sensitivity for detection of very low levels of HBsAg and to determine the source of HBsAg production will also be required to measure efficacy of newer antiviral treatments for HBV cure. In this narrative review, we will define HBV cure, discuss various sources of HBsAg production, evaluate rates of HBsAg loss with current and future antiviral agents, review clinical factors associated with spontaneous HBsAg loss, and explore clinical implications of functional cure.

Precore/core mutations of hepatitis B virus genotype D arising in different states of infection.

Aim of the study: Precore/core variations and liver disease progression have been suggested. In this study, we aimed to determine the frequency of precore/core mutations in hepatitis B virus (HBV)-infected patients at various clinical stages. Material and methods: In total, 73 HBV-infected patients including 26 inactive carriers (IC), 20 chronic active (CA), and 27 patients with liver cirrhosis/hepatocellular carcinoma (C/HCC) were randomly selected. The HBV DNA was extracted from the sera and subjected to nested PCR for amplification of precore/core region. The PCR product was then sequenced by the Sanger method. Results: The stop codon of W28*(G1896A) was determined as the most prevalent mutation (55%) of the precore region. The comparison of groups also demonstrated that core substitutions at residues of S21, E40 and I105 (< 0.05) correlated with the development of the inactive carrier state. Furthermore, the total substitutions in Th epitopes (117-131) were significantly higher in the C/HCC group than the IC and CA groups (p = 0.001). Conclusions: Our results indicated a high frequency of W28* mutation in HBV studied patients. Moreover, variations including S21, E40 and I105 and R151 that were mapped onto cellular epitopes might be related to inactive state development.

Hyponatremia a valuable predictor of early mortality in patients with cirrhosis listed for liver transplantation.

The current policy for organ allocation in liver transplantation is to give priority to the sickest patients mostly using model for end-stage liver disease (MELD) score in ranking. However, other factors as serum sodium may be of value in predicting early mortality. In this single-center study, patients with cirrhosis over age 14 on the liver transplant wait-list from September 1998 to June 2007 were followed for six months from the time of listing to evaluate the value of hyponatremia on mortality. Of 612 listed patients, 51 were transplanted who were excluded from survival analysis and 55 died without transplantation within the first three months. The numbers of transplanted and dead patients during months 3-6 were 29 and 24, respectively. Both MELD score and serum sodium at the time of listing were independent predictors of early mortality. On bivariate analysis, serum sodium of <130 mEq/L beside MELD was a significant predictor of mortality within 90 and 180 d. Serum sodium level <135 mEq/L masked the difference in mortality between patients with refractory and non-refractory ascites. Serum sodium level of <130 mEq/L and an increased MELD score are significant predictors of early mortality in patients listed for liver transplantation.

Recent advances in Wilson disease.

Wilson disease (WD) is rare genetic disorder that presents with varied phenotype that can at times make the diagnosis challenging. Medical treatments are available, but there are still unmet needs for patients. Since life-long therapy is necessary, adherence to medical therapy and best practices for monitoring and individualizing therapy continue to evolve. Studies are ongoing that address some of these issues. In the current review we focused our attention to recent advances in the diagnosis of WD, current medical treatments, future potential therapies and treatment monitoring. We include discussion of new methodology for detection and quantitation of ophthalmologic signs of WD, new brain imaging modalities for early detection of neurologic involvement in patients and potential new diagnostic methodology using blood samples that may be applicable to newborn screening and adult disease diagnosis. In addition, there are new strategies aimed at improving adherence and outcomes with currently available therapies, including once daily chelation dosing and discussion of the efficacy of different zinc salt compounds. With respect to new therapies with different mechanisms of action, we discuss studies on Bis-choline tetrathiomolybdate (TTM) in patients, pre-clinical studies of a novel chelator methanobactin and other animal studies exploring cures for WD with gene therapy using adeno-associated vectors (AAVs) that introduce ATP7B into liver cells. There are also promising advances in the more accurate measurement of non-ceruloplasmin bound copper and exchangeable copper in the circulation which would potentially help with monitoring and individualization of treatment and possibly play a role in future disease diagnosis.

Combination of FIB-4 with ultrasound surface nodularity or elastography as predictors of histologic advanced liver fibrosis in chronic liver disease.

Reliable and available non-invasive methods for hepatic fibrosis assessment are important in chronic liver disease (CLD). Our aim was to compare stepwise algorithms combining standard ultrasound with serum markers and transient elastography (TE) for detecting advanced fibrosis (F3-4) and cirrhosis. Retrospective single center study between 2012 and 2018 of CLD patients with biopsy, TE, blood tests, and liver ultrasound parameters of surface nodularity (SN), lobar redistribution, and hepatic vein nodularity. Our cohort included 157 patients (51.6% males), mean age 47.6 years, predominantly non-alcoholic fatty liver disease and viral hepatitis (61%), with F3-4 prevalence of 60.5%. Area under the curve for F3-4 was 0.89 for TE ≥ 9.6 kPa and 0.80 for FIB-4 > 3.25. In multivariate modeling, TE ≥ 9.6 kPa (OR 21.78) and SN (OR 3.81) had independent association with F3-4; SN (OR 5.89) and TE ≥ 10.2 kPa (OR 15.73) were independently associated with cirrhosis. Two stepwise approaches included FIB-4 followed by SN or TE; sensitivity and specificity of stepwise SN were 0.65 and 1.00, and 0.89 and 0.33 for TE ≥ 9.6 kPa, respectively. Ultrasound SN and TE were independently predictive of F3-4 and cirrhosis in our cohort. FIB-4 followed by SN had high specificity for F3-4.

Hepatitis E Virus Seroprevalence Among Liver Transplant Recipients with Persistent Elevation of Liver Enzymes: A Single Center Report.

BACKGROUND: Chronic hepatitis E infection has been reported in solid organ transplant recipients following acute hepatitis due to the compromised immune status. Almost all reports are from areas where hepatitis E virus (HEV) genotypes 3 and 4 are the dominant genotypes. This study was conducted to investigate the role of hepatitis E infection as an etiology for liver enzymes elevation in liver transplant recipients from the largest liver transplant program in Iran. METHODS: In a prospective study from June to December 2015, in a single liver transplantation center in Iran, all adult liver recipients who were investigated for the etiology of persistent elevation of liver enzymes were tested for HEV serology status. RESULTS: Of 122 patients included in the study, 19 (15.6%) were positive for HEV serology. Seropositive patients were significantly older than seronegative ones (mean age 43.79 vs. 31.58, P < 0.001); however, they were not different in other characteristics including sex distribution and mean of liver enzymes in each occasion. Liver biopsies were done in 16 HEV seropositive patients and none of the biopsies showed evidence for acute or chronic viral hepatitis. CONCLUSION: In this study, with 15.6% rate of HEV seropositivity in liver recipients with persistent elevation of liver enzymes, we were not able to confirm any clinical evidence for active acute or chronic hepatitis E infection. This could theoretically be attributed to the fact that the dominant prevalent HEV genotype in our endemic area is not associated with a chronic form of infection.

Correction: Effectiveness of Polypill for Prevention of Cardiovascular Disease (PolyPars): Protocol of a Randomized Controlled Trial.

This corrects the article "Effectiveness of polypill for prevention of cardiovascular disease (PolyPars): protocol of a randomized controlled trial" published on 2020: Volume 23, Issue 08, Pages 548-556. Correction to: Arch Iran Med. 2020;23(8):548-556. doi: 10.34172/aim.2020.58. In the original version of this article, the recruitment period was wrongly reported to last from December 2014 to December 2015 in abstract and methods sections of the article. This is corrected into "from December 2015 to December 2016" in the PDF and HTML versions of the article. Also the "PolyIran" is changed to "PolyPars" in the last paragraph of the discussion section in the PDF and HTML versions of the article.

Captopril and combination therapy of captopril and pentoxifylline in reducing proteinuria in diabetic nephropathy.

Chronic kidney disease is a worldwide health problem. Type II diabetes mellitus is now a major cause of end stage renal disease. The effect of diabetes mellitus through the dysregulation of the innate immunity results in increased tumor necrosis factor-alpha. This can lead to an increasing protein trafficking through the glomerular capillary, which can have an intrinsic renal toxicity. Seventy-four patients with type II diabetes mellitus with overt proteinuria were included in the study. They were randomly assigned to two groups of 37 patients (group 1: captopril 25 mg three times a day, group 2: captopril 25 mg and pentoxifylline 400 mg each three times per day). In the course of the study, two patients were excluded from each group. Daily urinary protein excretion was assessed at baseline and at two and six months. The reduction of urinary protein to creatinine clearance ratio in group 2 was 15.16 points more than in group 1 from baseline to the end of the study (p = 0.001). The difference in reduction only started after two months of pentoxifylline use. The differences in HbA1c and duration of diabetes mellitus at baseline in the two groups had not adversely affected the outcome of the study. There was a modest decrease in systolic blood pressure in group 2 as well (p = 0.041). Combining an angiotensin-converting enzyme inhibitor and pentoxifylline can lead to a greater reduction in proteinuria.

Liver transplantation for inherited metabolic disorders of the liver.

PURPOSE OF REVIEW: Liver transplantation is curative, life saving or both for a range of inherited diseases affecting the liver. Indications, timing and outcome of transplantation for these diseases are the focus of this review. RECENT FINDINGS: Liver transplant represents a mode of gene replacement therapy for several disorders, including Wilson disease, hemochromatosis, tyrosinemia, urea cycle defects and hypercholesterolemia in which the primary defect residing in the liver results in hepatic complications or severe extrahepatic disease. Liver transplant is also an important therapeutic modality in multisystemic genetic disorders with major hepatic disease such as glycogen storage disease types I, III and IV and porphyria. For familial amyloidosis and primary hyperoxaluria, liver replacement eliminates the source of the injurious products that results in extrahepatic disease. Innovations in medical and surgical management of these patients have led to improved outcomes providing an important benchmark for future gene therapy of these disorders. SUMMARY: Recent developments have refined the indications for liver transplant in the treatment of inherited metabolic diseases. The full potential of liver transplant in these disorders can be harnessed by careful patient selection, optimizing timing and perioperative metabolic management of these patients.

Endoscopic findings in hemodialysis patients upon workup for kidney transplantation.

Upper gastrointestinal (GI) abnormality is believed to be higher in patients with end-stage renal disease (ESRD) which can make a big trouble for whom undergo kidney transplant. We conducted this study to assess upper GI findings of patients with ESRD. In the present retrospective study we recorded upper GI endoscopy results in hemodialysis patients who were candidate for renal transplantation during a 10-year period. We reviewed files of 1256 patients with a mean age of 37.6 ± 13.4 years. Half of patients (50.6%) had an abnormal endoscopy. Two most common abnormalities were mild gastritis (35.6%) and gastro-esophageal reflux disease (16.7%). GI ulcers were observed in 11% of patients. Duodenal ulcer was the most common ulcer which was seen in 6.8% of patients. Helicobacter pylori was positive in 32.9% of patients and correlated with GI lesions (P = 0.000, r = 0.371). Longer dialysis duration and older patients revealed more upper GI abnormality (P = 0 .032, <0.001). As long as more than half of our patients have at least one upper GI involvement, we recommended that endoscopy must be done as a pretransplantation evaluation for patients without symptoms who have risk factors for ulcers.

A preliminary report on the use of Midodrine in treating refractory gastroesophageal disease: Randomized Double-Blind Controlled Trial.

BACKGROUND: Gastroesophageal reflux disease (GERD) is a common disease with various clinical presentations. Acid suppression with proton pump inhibitors and lifestyle modification may not lead to satisfactory response in a substantial portion of patients. We investigated the possible effect of midodrine in patients with refractory GERD. METHODS: Patients suffering from GERD and were refractory to one-month course of pantoprazole 40mg twice daily entered the study. This was a pilot, randomized, double-blind, and placebo-controlled study. After randomization, one group received Midodrine 5mg before meals for one month, and the other group received placebo for the same period. Meanwhile, pantoprazole was continued 40mg twice daily in both arms. The severity of symptoms was evaluated by the visual scoring system. Quality of life (QoL) in both groups was measured using a standardized version of Quality of Life in Reflux and Dyspepsia questionnaire (QOLRAD). RESULTS: A total of twenty patients were enrolled in this study. There was a significant interaction between the groups and time on all measured scores based on QOLRAD questionnaire. All the markers in the Midodrine group had significant improvement over time, but the placebo group did not show any significant improvement. Both visual severity score and total QoL score in Midodrine arm showed a U shape change during  6 weeks. CONCLUSIONS: Midodrine before a meal could be useful in alleviating symptoms and improving QoL in the patients with refractory gastroesophageal disease.

Effectiveness of Polypill for Prevention of Cardiovascular Disease (PolyPars): Protocol of a Randomized Controlled Trial.

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in Iran. A fixed-dose combination therapy (polypill) was proposed as a cost-effective strategy for CVD prevention, especially in lower-resource settings. We conducted the PolyPars trial to assess the effectiveness and safety of polypill for prevention of CVD. METHODS: The PolyPars trial is a pragmatic cluster randomized controlled trial nested within the Pars Cohort Study. Participants were randomized to an intervention arm and a control arm. Participants in the control arm received minimal non-pharmacological care, while those in the intervention arm received polypill in addition to minimal care. The polypill comprises hydrochlorothiazide 12.5 mg, aspirin 81 mg, atorvastatin 20 mg, and either enalapril 5 mg or valsartan 40 mg. The primary outcome of the study is defined as the first occurrence of acute coronary syndrome (non-fatal myocardial infarction and unstable angina), fatal myocardial infarction, sudden cardiac death, new-onset heart failure, coronary artery revascularization procedures, transient ischemic attack, cerebrovascular accidents (fatal or non-fatal), and hospitalization due to any of the mentioned conditions. The secondary outcomes of the study include adverse events, compliance, non-cardiovascular mortality, changes in blood pressure, fasting blood sugar, and lipids after five years of follow-up. RESULTS: From December 2014 to December 2015, 4415 participants (91 clusters) were recruited. Of those, 2200 were in the polypill arm and 2215 in the minimal care arm. The study is ongoing. This trial was registered with ClinicalTrials.gov number NCT03459560. CONCLUSION: Polypill may be effective for primary prevention of CVDs in developing countries.