Cost-effectiveness and economic investment to eliminate chronic hepatitis C in Mexico.

In July 2020, the Mexican Government initiated the National Program for Elimination of Hepatitis C (HCV) under a procurement agreement, securing universal, free access to HCV screening, diagnosis and treatment for 2020-2022. This analysis quantifies the clinical and economic burden of HCV (MXN) under a continuation (or end) to the agreement. A modelling and Delphi approach was used to evaluate the disease burden (2020-2030) and economic impact (2020-2035) of the Historical Base compared to Elimination, assuming the agreement continues (Elimination-Agreement to 2035) or terminates (Elimination-Agreement to 2022). We estimated cumulative costs and the per-patient treatment expenditure needed to achieve net-zero cost (the difference in cumulative costs between the scenario and the base). Elimination is defined as a 90% reduction in new infections, 90% diagnosis coverage, 80% treatment coverage and 65% reduction in mortality by 2030. A viraemic prevalence of 0.55% (0.50-0.60) was estimated on 1st January 2021, corresponding to 745,000 (95% CI 677,000-812,000) viraemic infections in Mexico. The Elimination-Agreement to 2035 would achieve net-zero cost by 2023 and accrue 31.2 billion in cumulative costs. Cumulative costs under the Elimination-Agreement to 2022 are estimated at 74.2 billion. Under Elimination-Agreement to 2022, the per-patient treatment price must decrease to 11,000 to achieve net-zero cost by 2035. The Mexican Government could extend the agreement through 2035 or reduce the cost of HCV treatment to 11,000 to achieve HCV elimination at net-zero cost.

Hepatitis C screening and detection program in a large population: Epidemiological transition and characterization of the disease.

INTRODUCTION: Chronic hepatitis C (CHC) is considered an important public health challenge. Traditionally identified risk factors have undergone an epidemiological transition where other risk factors have become the main cause of new infections. OBJECTIVE: To describe risk factors associated to hepatitis C positivity through the evaluation of the epidemiological profile in hepatitis-C high-risk populations. METHODS: Cross-sectional study was conducted as part of an HCV screening program in Mexican population. All participants answered an HCV risk-factor questionnaire and took a rapid test (RT). All patients reactive to the test were subject to HCV PCR (polymerase chain reaction) confirmation. A logistic regression model was used to examine associations between HCV infection and risk factors. RESULTS: The study included 297 631 participants that completed a risk factor questionnaire and underwent an HCV rapid test (RT). In total, 12 840 (4.5%) were reactive to RT and 9257 (3.2% of participants) were confirmed as positives by PCR test. Of these, 72.9% had at least one risk factor and 10.8% were in prison. Most common risk factors were history of acupuncture/tattooing/piercing (21%), intravenous drug use (15%) and high-risk sexual practices (12%). Logistic regressions found that having at least one risk factor increased the probability of having an HCV-positive result by 20% (OR = 1.20, 95% CI: 1.15-1.26), compared to the population without risk factors. CONCLUSIONS: We identified 3.2% of HCV-viremic subjects, all associated with risk factors and older age. Screening and diagnosis of HCV in high-risk populations (including underserved populations) should be more efficient.

Galectin-3 is overexpressed in advanced cirrhosis and predicts post-liver transplant infectious complications.

BACKGROUND & AIMS: Patients with advanced cirrhosis often have immune dysfunction and are more susceptible to infections. Galectin-3 is a ß-galactoside-binding lectin implicated in inflammation, immune regulation and liver fibrosis. We aim to investigate galectin-3 expression in advanced cirrhosis and its ability to predict post-transplant infectious complications. METHODS: We collected sera and liver samples from 129 cirrhotic patients at the time of liver transplantation and from an external cohort of 37 patients with alcoholic liver disease including alcoholic hepatitis (AH) at the time of diagnosis. Galectin-3 was assessed by ELISA, real-time PCR, immunohistochemistry and RNA-seq. Receiver operating characteristic curves and Cox proportional-hazards regression analysis were performed to assess the predictive power of galectin-3 for disease severity and post-transplant infections. RESULTS: Increased galectin-3 levels were found in advanced cirrhosis. Galectin-3 significantly correlated with disease severity parameters and inflammatory markers. Galectin-3 had significant discriminating power for compensated and advanced cirrhosis (AUC = 0.78/0.84, circulating/liver galectin-3; p < .01), and was even higher to discriminate severe AH (AUC = 0.95, p < .0001). Cox Proportional-hazard model showed that galectin-3, MELD-Na and the presence of SIRS predict the development of post-transplant infectious complications. Patients with circulating galectin-3 (>16.58 ng/ml) were at 2.19-fold 95% CI (1.12-4.29) increased risk, but when combined with MELD-Na > 20.0 and SIRS, the risk to develop post-transplant infectious complications, increased to 4.60, 95% CI (2.38-8.90). CONCLUSION: Galectin-3 is a novel biological marker of active inflammation and disease severity that could be clinically useful alone or in combination with other scores to discriminate advanced cirrhosis and predict post-transplant infectious complications.

Prevalence and predictors of elevated liver enzyme levels in Mexico: The Mexican National Health and Nutrition Survey, 2016.

INTRODUCTION AND OBJECTIVE: To determine the prevalence of elevated liver enzyme levels and the fatty liver index according to specific sociodemographic, clinical, anthropometric, and metabolic risk factors in Mexican adult population. MATERIAL AND METHODS: The present analysis was conducted using data from the Mexican National Health and Nutrition Survey 2016. For the present study, 3,490 adults with complete information on liver enzymes, sociodemographic, lifestyle, and metabolic factors were analyzed. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) levels were determined from blood samples. We computed the fatty liver Index (FLI), as a surrogate marker of non-alcoholic fatty liver disease. The associations are reported as adjusted odds ratios (OR) and 95% confidence intervals (95%CI). RESULTS: At the national level, the prevalence of high serum levels of ALT, AST, and GGT were 7.9%, 13.5, and 12.9 respectively. We observed that men had higher prevalences of altered ALT, GGT and FLI compared to women. Additionally, we observe that individuals with obesity, metabolic syndrome and insulin resistance are significantly more likely to present elevated concentrations of AST, ALT, GGT and FLI. Finally, we found that the subjects of the lowest socioeconomic level and indigenous population were more likely to present elevated levels of AST, ALT, GGT, and FLI. CONCLUSION: In Mexico, non-alcoholic fatty liver disease affect people with obesity, diabetes, and metabolic syndrome as well as men, subjects of low socioeconomic status, subjects who live in rural areas and indigenous population. Interventions to reduce this condition should be a public health priority.

Direct or Collateral Liver Damage in SARS-CoV-2-Infected Patients.

Liver injury can result from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection with more than one-third of COVID-19 patients exhibiting elevated liver enzymes. Microvesicular steatosis, inflammation, vascular congestion, and thrombosis in the liver have been described in autopsy samples from COVID-19 patients. Several factors, including direct cytopathic effect of the virus, immune-mediated collateral damage, or an exacerbation of preexisting liver disease may contribute to liver pathology in COVID-19. Due to its immunological functions, the liver is an organ likely to participate in the viral response against SARS-CoV-2 and this may predispose it to injury. A better understanding of the mechanism contributing to liver injury is needed to develop and implement early measures to prevent serious liver damage in patients suffering from COVID-19. This review summarizes current reports of SARS-CoV-2 with an emphasis on how direct infection and subsequent severe inflammatory response may contribute to liver injury in patients with and without preexisting liver disease.

Differential production of insulin-like growth factor-binding proteins in liver fibrosis progression.

Noninvasive methods for liver disease diagnoses offer great advantages over biopsy, but they cannot be utilized in all cases. Therefore, specific indicators for chronic liver disease management are necessary. The aim was to assess the production of insulin-like growth factor-binding proteins (IGFBPs) 1-7 and their correlation with the different stages of fibrosis in chronic hepatitis C (CHC). A prospective, cross-sectional, multicenter study was conducted. CHC patients were categorized by FibroTest® and/or FibroScan®. Serum concentrations of IGFBPs 1-7 were determined through multiple suspension arrangement array technology. Significant differences were validated by the Kruskal-Wallis and Mann-Whitney U tests. Logistic regression models were performed to assess the association between the IGFBPs and fibrosis stages. The association was determined utilizing odds ratios (ORs), and receiver operating characteristic (ROC) curves were constructed to distinguish the IGFBPs in relation to the diagnosis of fibrosis. IGFBP-1 and IGFBP-7 concentrations were higher in CHC than in the healthy individuals, whereas IGFBP-3, IGFBP-5, and IGFBP-6 were downregulated in the patients. An apparent increase of all the IGFBPs was found at fibrosis stage F4, but with different regulations. IGFBP-2, -4, -6, and -7 had the best OR, showing the relation to fibrosis progression. The ROC curves showed that IGFBP-7 was the only protein that distinguished F1 from F3 and F2 from F3. IGFBPs participate in liver fibrosis progression and could be employed as circulating novel protein panels for diagnosis and as possible therapeutic targets in liver fibrosis progression.

Young adult binge drinkers have immunophenotypic changes in peripheral polymorphonuclear cells and monocytes.

BACKGROUND: High alcohol intake on weekends (binge drinking) is more frequent in young adults, who could undergo early liver damage. Alcohol-induced liver damage is characterized by polymorphonuclear cell (PMN) infiltration, which can be represented in the peripheral blood by altered trafficking and activation profiles. OBJECTIVE: To evaluate the PMN trafficking and activation immunophenotypic profiles in people with a binge drinking pattern. METHODS: People with binge drinking (n = 18, 8 females) or at low risk (n = 16, 13 females) based on their AUDIT and HEPCA scores were studied. Hematic biometry and liver enzyme tests were conducted. Peripheral blood leukocytes were stained for CCR5, CCR4, and CXCR4 (trafficking) and CD69 and CD127 (activation). PMNs and monocytes were analyzed by FACS. The data were analyzed using the T-test and Mann-Whitney's U-test for contrasts and principal component and Fuzzy C means analyses for clustering, with p < 0.05 considered significant. RESULTS: Compared to the low-risk group, the binge group showed higher CCR5 expression on PMNs, decreases in the CD69 percentage and positive PMNs per microliter, and decreased CXCR4 expression on monocytes. Six immunophenotypical clusters were identified, all of which were distributed following the CCR5 and CXCR4 main vectors. CONCLUSION: Young adult binge drinkers have differential PMN trafficking and activation immunophenotypes, which could be related to the initial onset of alcoholic liver disease and a systemic inflammatory state in response to their alcohol consumption pattern. These findings could lead to the future development of an early diagnostic tool.

[A front-of-pack labelling system for food and beverages for Mexico: a strategy of healthy decision-making.] / Sistema de etiquetado frontal de alimentos y bebidas para México: una estrategia para la toma de decisiones saludables.

The Mexican Ministry of Health requested the National Institute of Public Health to constitute a group of independent, free of conflict-of-interest academic experts on front-of-pack labelling (FOP). This group was instructed to created a positioning paper to contribute to the development of a FOP system for industrialized products that offers useful information for purchase decision making. This position paper uses the best available scientific evidence, and recommendations from experts of international organizations. The FOP proposal focuses on the contents of energy, nutrients, ingredients and components that if consumed in excess on the diet, can be harmful to people's health, such as added sugars, sodium, total fat, saturated fat and energy. The academic expert group recommends the implementation of a FOP that provides an easy way to quickly assess the quality of a product. It is essential that this FOP provides direct, simple, visible and easily understandable information.

La Secretaría de Salud solicitó al Instituto Nacional de Salud Pública la conformación de un grupo de expertos académicos en etiquetado de alimentos y bebidas, independientes y libres de conflictos de interés, que tuvieran la encomienda de emitir una postura para contribuir al desarrollo de un sistema de etiquetado frontal para productos industrializados que proporcione información útil para facilitar la decisión de compra. La postura utiliza la mejor evidencia científica disponible y recomendaciones de expertos convocados por organismos internacionales. Así, la propuesta de etiquetado frontal se centra en el contenido de energía, nutrimentos, ingredientes y componentes cuyo exceso en la dieta puede ser perjudicial para la salud, como azúcares añadidos, sodio, grasas totales, grasas saturadas y energía. El grupo recomienda implementar un etiquetado frontal que, de forma sencilla, permita evaluar de manera rápida la calidad de un producto al momento de realizar una compra; por ello, es indispensable que éste proporcione información directa, sencilla, visible y fácil de entender.

Heading Toward the Elimination of Hepatitis C Virus.

Chronic hepatitis C is often asymptomatic and may progress over the years to cirrhosis and hepatocellular carcinoma. Although the prevalence and incident cases are decreasing, the peak mortality of hepatitis C virus (HCV)-related complications is ahead of us in most countries. The economic impact of this burden is enormous. Scaling up the identification of new opportunities to facilitate the road toward HCV elimination includes increasing screening, awareness, and the number of prescribing physicians. Screening should occur within the context of linkage-to-care and patient retention across the care continuum. Awareness and access to treatment in different countries are not systematic as countries have diverse healthcare organizations so that treatment eligibility and availability criteria vary significantly. The simplicity of oral regimens with direct-acting antiviral drugs that are effective across HCV genotypes expands the number of physicians who can prescribe them with accessible treatment models. The ultimate aim is the elimination of HCV by 2030.

Electrolyte and Acid-Base Disturbances in End-Stage Liver Disease: A Physiopathological Approach.

Electrolyte and acid-base disturbances are frequent in patients with end-stage liver disease; the underlying physiopathological mechanisms are often complex and represent a diagnostic and therapeutic challenge to the physician. Usually, these disorders do not develop in compensated cirrhotic patients, but with the onset of the classic complications of cirrhosis such as ascites, renal failure, spontaneous bacterial peritonitis and variceal bleeding, multiple electrolyte, and acid-base disturbances emerge. Hyponatremia parallels ascites formation and is a well-known trigger of hepatic encephalopathy; its management in this particular population poses a risky challenge due to the high susceptibility of cirrhotic patients to osmotic demyelination. Hypokalemia is common in the setting of cirrhosis: multiple potassium wasting mechanisms both inherent to the disease and resulting from its management make these patients particularly susceptible to potassium depletion even in the setting of normokalemia. Acid-base disturbances range from classical respiratory alkalosis to high anion gap metabolic acidosis, almost comprising the full acid-base spectrum. Because most electrolyte and acid-base disturbances are managed in terms of their underlying trigger factors, a systematic physiopathological approach to their diagnosis and treatment is required.

The Expression of PNPLA3 Polymorphism could be the Key for Severe Liver Disease in NAFLD in Hispanic Population.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) encompasses: fatty liver (SS), steatohepatitis (NASH) with or without fibrosis and cirrhosis. Patatine-like phosphatas in domain 3 (PNPLA3; adiponutrin; SNP rs738409 C/G, M148I) shows anabolic and catabolic activities on lipid metabolism and significant association to fatty liver content; however, I148M demographics and ethnics, as its role with NAFLD have not been fully elucidated. MATERIAL AND METHODS: PNPLA3 genotyping from peripheral blood DNA by polymerase chain reaction (PCR) and direct sequencing, 211 patients diagnosed with NAFLD including SS, NASH and fibrosis spectrum. RESULTS: Eighty nine per cent showed the G risk allele [CC: 23 (10.5%), GC: 73 (34.7%), GG 115 (54.7%)], the allele frequency was 77%, NASH (71%), SS (80%) and fibrosis (73%). GG genotype carriers showed 3.8 times (CI 95%: 3.03 - 4.79) of increased risk of steatohepatitis and 2.3 times more (CI 95%: 1.77 ~ 3.23) risk of having liver fibrosis (CC). PNPLA3 (GC, GG) conditioned higher probability of low levels of HDL cholesterol (p < 0.010), SS even in normal weight (p < 0.007), insulin resistance by HOMA (p < 0.029), NAFLD fibrosis score showed > 0.675 (p < 0.001) and altered serum alanine aminotransferase (p < 0.05). CONCLUSION: PNPLA3 expression in Hispanics could be decisive in NAFLD pathogenesis, it's highly prevalent and it's a key to condition and determine the spectrum associated, SS, NASH and fibrosis.

Chronic Hepatitis C Treatment with Direct-Acting Antiviral Agents in a Real-Life Setting.

BACKGROUND: In clinical trials, new oral direct-acting antiviral agent therapies have demonstrated a high sustained virological response rate in patients with hepatitis C virus infection. We aimed to analyze the efficacy and safety data from direct-acting antiviral agent interferon-free therapy in hepatitis C virus infection in a study performed in five different clinical settings in Mexico City; four private practice sites and one academic medical center in a real-world scenario. METHODS: Eighty-one patients were treated with seven different direct-acting antiviral agent regimens, in which the end of treatment, sustained virological response at 12 weeks post-treatment, and adverse effects were evaluated. At their discretion, attending physicians selected the treatment regimens and durations. RESULTS: In total, 70.4% of the patients were female and the mean age was 60.7 years; 74.1% had blood transfusion as a risk factor. The most common genotype was 1b (70.4%). The fibrosis stage was F3 or F4 in 55.5% of patients; liver cirrhosis was present in 44%. The overall end of treatment response was 98.8%, and the rate of sustained virological response was 96%, independent of the regimen. Three patients did not achieve sustained virological response; they had cirrhosis and were treatment-experienced, and two had hepatocarcinoma. Non-significant adverse effects during treatment were documented. CONCLUSIONS: In this real-life setting in Mexico, a rate of 96% of sustained virological response to direct-acting antiviral agents was achieved in an older population of patients with advanced fibrosis. This study provides data that may be useful in guiding health professionals and authorities in the development of health policies.

Editorial.

Effective communication sometimes requires a common language. This is particularly true in science, where communication among health professionals and scientists across national boundaries has become critical because of the rapidity with which new knowledge is acquired. In the modern era, where multinationalism in key medical and scientific discoveries is increasingly common, the language is undoubtedly English. In fact, more than three-quarters of scientific papers today are published in English.

Hepatitis C screening in the general population.

BACKGROUND: A significant number of patients infected with hepatitis C virus remain unaware of their infection, as this is a silent disease for many years. Patients are frequently detected at advance stages of the disease. OBJECTIVE: To identify the prevalence and viremic stage of hepatitis C among a general population cohort. METHODS: Anti-hepatitis C virus detection and viral RNA were offered without cost to individuals who voluntarily considered it relevant to be examined, as part of the World Hepatitis Day annually from 2007-2014. RESULTS: A total of 32,945 individuals were analyzed; 57% were female and 43% male. Of them, 75.7% were between 21-50 years old. In 59%, the sample was obtained at their work place and in 41% at the facilities of 12 private laboratories. Anti-hepatitis C virus was positive in 194 patients (0.58%), of which 129 (66%) were confirmed positive by polymerase chain reaction. The overall prevalence of viremic cases in the sample was 0.39%. CONCLUSIONS: Adequate estimation of the prevalence of anti-hepatitis C virus and viremic population, not only among high-risk groups but also in the general population, is central to the allocation of resources in an effort to reduce the consequences of the disease.

The quest for universal health coverage: achieving social protection for all in Mexico.

Mexico is reaching universal health coverage in 2012. A national health insurance programme called Seguro Popular, introduced in 2003, is providing access to a package of comprehensive health services with financial protection for more than 50 million Mexicans previously excluded from insurance. Universal coverage in Mexico is synonymous with social protection of health. This report analyses the road to universal coverage along three dimensions of protection: against health risks, for patients through quality assurance of health care, and against the financial consequences of disease and injury. We present a conceptual discussion of the transition from labour-based social security to social protection of health, which implies access to effective health care as a universal right based on citizenship, the ethical basis of the Mexican reform. We discuss the conditions that prompted the reform, as well as its design and inception, and we describe the 9-year, evidence-driven implementation process, including updates and improvements to the original programme. The core of the report concentrates on the effects and impacts of the reform, based on analysis of all published and publically available scientific literature and new data. Evidence indicates that Seguro Popular is improving access to health services and reducing the prevalence of catastrophic and impoverishing health expenditures, especially for the poor. Recent studies also show improvement in effective coverage. This research then addresses persistent challenges, including the need to translate financial resources into more effective, equitable and responsive health services. A next generation of reforms will be required and these include systemic measures to complete the reorganisation of the health system by functions. The paper concludes with a discussion of the implications of the Mexican quest to achieve universal health coverage and its relevance for other low-income and middle-income countries.

Liver exhibits thermal variations according to the stage of fibrosis progression: A novel use of modulated-differential scanning calorimetry for research in hepatology.

AIM: Liver fibrosis results in a disproportion of the hepatic composition and architecture, characterized by a progressive accumulation of fibrillar proteins at the liver parenchyma. Modulated-differential scanning calorimetry (mDSC) is an experimental methodology able to determine the specific thermal signature from any biological substance, based on the variation in heat flow and heat capacity. As these physicochemical properties are directly influenced by compositional and structural changes, we decided to study the thermal behavior of the liver during fibrosis using mDSC. METHODS: Liver fibrosis was induced in rats by bile duct ligation or carbon tetrachloride administration. Degree of liver fibrosis was determined by histological examination using the Masson-trichrome stain, accompanied by hepatic expression of α-smooth muscle actin. The thermal analysis was performed in a modulated-differential scanning calorimeter using 20 mg of fresh liver mass. RESULTS: The liver showed a characteristic thermal signature in control animals, which progressively differed among mild (F1), moderate (F2) and advanced (F3-F4) liver fibrosis. For heat flow, the hepatic thermal signature from F3-F4 rats exhibited significant differences when compared with F1, F2 and controls. In terms of heat capacity, liver specimens provided a specific thermal signature for each stage of disease, characterized by a transition temperature onset at 95°C for controls, whereas in F1, F2 and F3-F4 animals this temperature significantly decreased to 93°C, 84°C and 75°C, respectively. CONCLUSION: Because the liver shows a differential thermal signature according to the degree of fibrosis, mDSC could be a novel tool in the study of liver fibrosis progression.

Cost-effectiveness of truncated therapy for hepatitis C based on rapid virologic response.

BACKGROUND: Shortened courses of treatment with pegylated interferon alfa and ribavirin for patients with hepatitis C virus infection who experience rapid virologic response can be effective in appropriately selected patients. The cost-effectiveness of truncated therapy is not known. OBJECTIVE: To assess the cost-effectiveness of response-guided therapy versus standard-duration therapy on the basis of best available evidence. METHODS: We developed a decision model for chronic hepatitis C virus infection representing two treatment strategies: 1) standard-duration therapy with pegylated interferon alfa and ribavirin for 48 weeks in patients with genotype 1 or 4 and for 24 weeks in patients with genotype 2 or 3 and 2) truncated therapy (i.e., 50% decrease in treatment duration) in patients with rapid virologic response. Patients for whom truncated therapy failed began standard-duration therapy guided by genotype. We used a Markov model to estimate lifetime costs and quality-adjusted life-years. RESULTS: In the base-case analysis, mean lifetime costs were $46,623 ± $2,483 with standard-duration therapy and $42,354 ± $2,489 with truncated therapy. Mean lifetime quality-adjusted life-years were similar between the groups (17.1 ± 0.7 with standard therapy; 17.2 ± 0.7 with truncated therapy). Across model simulations, the probability of truncated therapy being economically dominant (i.e., both cost saving and more effective) was 78.6%. The results were consistent when we stratified the data by genotype. In one-way sensitivity analyses, the results were sensitive only to changes in treatment efficacy. CONCLUSION: Truncated therapy based on rapid virologic response is likely to be cost saving for treatment-naive patients with chronic hepatitis C virus infection. Cost-effectiveness varied with small changes in relative treatment efficacy.