Cirrhosis etiology trends in developing countries: Transition from infectious to metabolic conditions. Report from a multicentric cohort in central Mexico.

Background: Cirrhosis is a public health threat associated with high mortality. Alcoholic Liver Disease (ALD) is the leading cause in Latin America and Metabolic Associated Fatty Liver Disease (MAFLD) in western countries. In Mexico, ALD and chronic Hepatitis C Virus infection (HCV) were the most frequent aetiologies during the past decades. We aimed to describe the trends in the aetiologies of cirrhosis in a middle-income country. Methods: We performed a retrospective cohort study including patients diagnosed with cirrhosis between 2000 and 2019 from six different tertiary care hospitals in central Mexico. We collected information regarding cirrhosis etiology, year of diagnosis, hepatocellular carcinoma development, liver transplantation, and death. We illustrated the change in the tendencies of cirrhosis aetiologies by displaying the proportional incidence of each etiology over time stratified by age and gender, and we compared these proportions over time using chi square tests. Findings: Overall, 4,584 patients were included. In 2019, MAFLD was the most frequent cirrhosis etiology (30%), followed by ALD (24%) and HCV (23%). During the study period, MAFLD became the leading etiology, ALD remained second, and HCV passed from first to fourth. When analysed by gender, ALD was the leading etiology for men and MAFLD for women. The annual incidence of HCC was 3·84 cases/100 persons-year, the median survival after diagnosis was 12·1 years, and seven percent underwent LT. Interpretation: Increased alcohol consumption and the obesity epidemic have caused a transition in the aetiologies of cirrhosis in Mexico. Public health policies must be tailored accordingly to mitigate the burden of alcohol and metabolic conditions in developing countries. Funding: None.

Pocket ultrasound device as a complement to physical examination for ascites evaluation and guided paracentesis.

The pocket ultrasound device (PUD) is a new tool that may be of use in the early detection of ascites. Abdominal ultrasound-guided paracentesis has been reported to decrease the rate of complications due to the procedure, but must be performed in a healthcare setting; this new tool may be a useful on an ambulatory basis. The aim of this study was to determine the diagnostic usefulness of the PUD in the diagnosis of ascites and the safety of guided paracentesis. We conducted a retrospective study that included adult patients suspected of having ascites and in whom an evaluation was performed with the PUD to identify it. Concordance with abdominal ultrasound (AUS) was determined with the Kappa coefficient. Sensitivity (Se), specificity (Sp) and likelihood ratios (LR) were determined and compared with physical examination, AUS, computed tomography and procurement of fluid by paracentesis. Complications resulting from the guided paracentesis were analyzed. 89 participants were included and 40 underwent a paracentesis. The PUD for ascites detection had 95.8 % Se, 81.8 % Sp, 5.27 +LR and 0.05 -LR. It had a concordance with AUS of 0.781 (p < 0.001). Technical problems during the guided paracentesis were present in only two participants (5 %) and three patients (7.5 %) developed minor complications that required no further intervention. There were no severe complications or deaths. This study suggests that the PUD is a reliable tool for ascites detection as a complement to physical examination and appears to be a safe method to perform guided paracentesis.

A genetic variant in the interleukin 28B gene as a major predictor for sustained virologic response in chronic hepatitis C virus infection.

BACKGROUND AND AIMS: The IL28B single nucleotide polymorphism (SNP) rs12979860 is a major predictor of treatment outcomes in hepatitis C virus (HCV) infection, but its distribution widely varies among populations and ethnicities. We undertook this study to investigate the distribution of IL28B SNP rs12979860 in Mexican patients with HCV infection and to assess its usefulness in predicting response to pegylated interferon-alpha and ribavirin (PegIFN-α/RVB) therapy. METHODS: Three hundred and fifty patients with chronic HCV infection were studied. The frequency of sustained virologic response (SVR), non-responders and relapses following a course of standard therapy was longitudinally assessed in 295 of these patients. IL28B SNP rs12979860 was genotyped from genomic DNA using real-time RT-PCR. The number needed to treat (NNT) to achieve a SVR was calculated. RESULTS: Seventy six (22%) patients were CC homozygous, 210 (60%) were heterozygous and 64 (18%) showed TT homozygosity for the IL28B SNP rs12979860. After a standard course of PegIFN-α/RVB, 69% of patients with the CC genotype, 46% of the heterozygous group and 38% of those with the TT genotype (p = 0.001) achieved a SVR. Conversely, the percentage of non-responders was 15, 43, and 48% (p <0.0001), respectively. The NNT to achieve a SVR was strongly influenced by the IL28B rs12979860 genotype and ranged from 2-10. CONCLUSIONS: The IL-28B rs12979860 CC genotype was found in 22% of Mexican patients chronically infected by HCV. Genotyping IL28B SNP rs12979860 is useful to predict the response to a standard regimen with PegIFN-α/RVB, especially in those infected with HCV genotype 1.

Diagnosis and treatment of hepatocellular carcinoma: An update.

Hepatocellular carcinoma (HCC) is one of the most common malignancies leading to high mortality rates in the general population; in cirrhotic patients, it is the primary cause of death. The diagnosis is usually delayed in spite of at-risk population screening recommendations, i.e., patients infected with hepatitis B or C virus. Hepatocarcinogenesis hinges on a great number of genetic and molecular abnormalities that lead to tumor angiogenesis and foster their dissemination potential. The diagnosis is mainly based on imaging studies such as computed tomography and magnetic resonance, in which lesions present a characteristic classical pattern of early arterial enhancement followed by contrast medium "washout" in late venous phase. On occasion, when imaging studies are not conclusive, biopsy of the lesion must be performed to establish the diagnosis. The Barcelona Clinic Liver Cancer staging method is the most frequently used worldwide and recommended by the international guidelines of HCC management. Currently available treatments include tumor resection, liver transplant, sorafenib and loco-regional therapies (alcoholization, radiofrequency ablation, chemoembolization). The prognosis of hepatocarcinoma is determined according to the lesion's stage and in cirrhotic patients, on residual liver function. Curative treatments, such as liver transplant, are sought in patients diagnosed in early stages; patients in more advanced stages, were not greatly benefitted by chemotherapy in terms of survival until the advent of target molecules such as sorafenib.

Mexican consensus on the diagnosis and management of hepatocellular carcinoma.

INTRODUCTION: There has been an increase in the incidence of hepatocellular carcinoma (HCC) worldwide and information on this disease is limited in Mexico. AIMS: To analyze the available evidence on the diagnosis and treatment of HCC in the Mexican population. MATERIAL AND METHODS: The Mexican Association of Hepatology organized a meeting that 24 medical specialists interested in HCC attended. An electronic database search was carried out to identify documents published from 2000 with the keywords «Hepatocellular carcinoma¼ and «Mexico¼, «epidemiology¼, «diagnosis¼, and «treatment¼. RESULTS: The incidence of HCC in Mexico has increased over the last few decades. The mean age of disease presentation is in patients from 60 to 70 years old, and the man:woman ratio appears to be equal. HCC is frequently associated with underlying hepatopathy and the primary cause reported in our country is chronic hepatitis C virus) infection. Surveillance is recommended for high-risk groups in Child-Pugh stages A and B, and for those in stage C if the patient is on a waiting list or regarded as a candidate for liver transplantation. HCC should be evaluated by a multidisciplinary team of experts in the field. CONCLUSIONS: HCC is a neoplasia that is on the rise in Mexico, with epidemiologic characteristics similar to those of other populations. Diagnosis and treatment should be individualized in accordance with these Consensus guidelines.

Re-treatment with highly purified nIFNα in Mexican nonresponder patients with chronic genotype 1 hepatitis C.

BACKGROUND AND AIMS: We undertook this study to evaluate the virological response to and presence of adverse events to natural interferon α (nIFNα; Multiferon®) treatment in previously nonresponsive Mexican patients chronically infected with genotype 1 hepatitis C. METHODS: Thirty-nine patients received a 4-week induction of 5 days/week of 6 MU nIFNα plus weight-based ribavirin followed by 3 MU of nIFNα three times a week for 44 weeks. The relationship between viral response and incidence of adverse events was analyzed. RESULTS: Early viral response (EVR) was age- and sex-dependent, with older male patients being less responsive. Sustained viral response (SVR) was evaluated according to: a) intention to treat analysis, b) 48-week treatment and 24-week follow-up (16 patients), and c) patients with EVR (11 patients). None of the factors was significantly different in groups a) and b); however, in group c) there was a better response with a marked viral load decline in younger patients and in patients aged 50 years and older. Five of 39 (13%) patients who completed treatment presented with an SVR. The most common adverse effect was asthenia in 27% of patients. CONCLUSIONS: nIFNα could be a useful strategy for re-treatment in chronic hepatitis C, genotype 1, in previously nonresponsive patients. Confirmation of these data in a larger population is required.

Trends and projections of hepatitis C virus epidemiology in Latin America.

BACKGROUND AND AIM: The purpose of the present investigation is to provide an analysis of previous works on the epidemiology of the hepatitis C virus (HCV) infection from six countries throughout Latin America, to forecast the future HCV prevalence trends in Argentina, Brazil, Mexico and Puerto Rico, and to outline deficiencies in available data, highlighting the need for further research. METHODS: Data references were identified through indexed journals and non-indexed sources. Overall, 1080 articles were reviewed and 150 were selected based on their relevance to this work. When multiple data sources were available for a key assumption, a systematic process using multi-objective decision analysis (MODA) was used to select the most appropriate sources. When data were missing, analogues were used. Data from other countries with similar risk factors and/or population compositions were used as a proxy to help predict the future trends in prevalence. RESULTS: The review indicates that the dominant genotype is type 1. HCV prevalence in the analysed countries ranges from 1 to 2.3%. The Latin American countries have been very proactive in screening their blood supplies, thus minimizing the risk of transmission through transfusion. This suggests that other risk factors are set to play a major role in continued new infections. The number of diagnosed and treated patients is low, thereby increasing the burden of complications such as liver cirrhosis or hepatocellular carcinoma. The HCV prevalence, according to our modelling is steady or increasing and the number of infected individuals will increase. CONCLUSIONS: The results herein reported should provide a foundation for informed planning efforts to tackle hepatitis.

IFN-stimulated gene expression is a useful potential molecular marker of response to antiviral treatment with Peg-IFNα 2b and ribavirin in patients with hepatitis C virus genotype 1.

BACKGROUND AND AIMS: We undertook this study to determine the baseline gene expression of IFI27, IFIT1, IFI6, ISG15, IRF-1, IRF-3, OAS-2 and CXCL10 and its usefulness as molecular markers of response to antiviral treatment with peg-IFNα 2b/RBV in patients with hepatitis C virus genotype 1 (HCV-1). METHODS: Gene expression was analyzed by RT-PCR in baseline liver biopsies from 42 HCV-1 patients who were treated with Peg-IFNα 2b/RBV for 48 weeks. In addition, we investigated gene expression of these genes in a second liver biopsy obtained 24 weeks post-treatment in sustained viral response (SVR) and relapser patients. RESULTS: Thirteen patients achieved SVR, four were relapsers, four patients with viral response (VR) discontinued the following for 24 weeks post-treatment and 21 patients did not respond to antiviral therapy (NR). All patients with HCV-1 showed gene overexpression in baseline liver tissue, but only IFI27, IFIT1, IFI6, ISG15, and CXCL10 showed differential gene expression, which is inversely related to the response to antiviral therapy. Thus, liver tissue of NR patients showed upregulation of these genes, whereas patients with SVR gene expression level was significantly lower. Furthermore, 24 weeks afterwards treatment, SVR patients showed a significant downregulation of such genes, which was consistent with the RNA-HCV suppression. ISGs (IFI27, IFIT1, IFI6) and chemokine CXCL10 showed the best positive and negative predictive values on SVR to IFN/RBV therapy (range: 70.8-75% and 71.43-82.35%), respectively. CONCLUSIONS: IFI27, IFIT1, IFI6, ISG15, and CXCL10 genes are potential biological markers useful for predicting response to Peg-IFNα 2b/RBV therapy in HCV-1 patients.

Geographical distribution of HCV genotypes in Mexico.

UNLABELLED: Chronic hepatitis C (CHC) is the second cause of endstage liver disease in our country and one of the main indications of liver transplantation. Hepatitis C virus (HCV) genotype is the principal prognostic factor and the determinant of the therapeutic scheme. In our country few data exist regarding the prevalence of HCV infection and genotype distribution in the Mexican Republic has not been determined. The aim of this study was to characterize the prevalence of the different HCV genotypes and to explore their geographical distribution. METHODS: Mexican patients with hepatitis C infection, detected throughout the country between 2003 and 2006, were included. All samples were analyzed by a central laboratory and Hepatitis C genotype was identified by Line Immuno Probe Assay in PCR positive samples (Versant Line Probe Assay Quest Diagnostics Nichols Institute, San Juan Capistrano CA). Data were analyzed according to the four geographical areas in Mexico. RESULTS: One thousand three hundred and ninety CHC patients were included. The most frequent genotype detected was genotype 1 (69%) followed by genotype 2 (21.4%) and genotype 3 (9.2%). Genotype 4 and 5 were infrequent. There was no subject infected with genotype 6. Genotype 1 and 2 exhibit very similar distribution in all geographical areas. Genotype 3 infected patients were more frequent in the North region (52%) compared with other areas:center-western (30%), center (17%), South-South east (1%) (p < 0.001). CONCLUSIONS: The most prevalent HCV genotype in Mexico is genotype 1. Geographical distribution of HCV genotypes in the four geographical areas in Mexico is not homogenous with a greater frequency of genotype3 in the north region. This difference could be related to the global changes of risk factors for HCV infection.

[Manometry and defecography in constipated patients with dyschezia]. / Manometría y defecografía en pacientes constipados con disquecia.

BACKGROUND: Constipation is one of the most frequent disorders in Gastroenterology. Radiologic and physiologic studies are essential to the diagnosis and treatment of constipated patients. OBJECTIVE: We aimed to assess the usefulness of manometry and defecography in constipated patients with suspect of dyssynergic defecation. METHODS: Dyschesic patients referred for anorectal testing, all patients underwent anorectal manometry and defecography. RESULTS: Fifty eight patients consecutive patients referred from 1998 to 2003. According to manometric findings patients were classified in patients without dyssynergia (group I, n = 16) and patients with dyssynergia (group II, n = 42). Group I patients had intussusception (75%), abnormal rectal emptying (56%), rectocele > 2.5 cm (56%), perineal descending (50%) and inadequate opening of the anal canal (38%). Group II patients had inadequate opening of the anal canal (69%), rectocele < 2.5 cm (55%), perineal descending (17%), intussusception (45%) and abnormal rectal emptying (55%). Group I had a higher frequency of perineal descending (p = 0.01) and intussusception (p = 0.044). Group II had a higher frequency of inadequate opening of the anal canal (p = 0.03), and not for inadequate opening of the anorectal angle. CONCLUSIONS: Defecography showed disorders in group I that may contribute to symptomatology, and in group II the inadequate opening of the anal canal suggests the participation of different parts of the external anal sphincter other than puborectalis in the genesis of dyssynergia.

[Hepatitis C and addictions]. / Hepatitis C y adicciones.

Currently, it has been suggested that hepatitis C virus is the major cause of chronic liver disease. In Western countries, approximately 60% of the cases has been related with intravenous drugs. Also it has been suggested an interaction among alcohol and hepatitis C virus that in turn might induce an additive or synergic effects in causing liver injury. This review analyzes the effect of intravenous drugs and alcohol in the course of chronic hepatitis C.