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Purpose: We analyzed the genotype and allele frequency of variable number tandem repeats (VNTR)-thymidylate synthase (TS) and its relationship with the disease evolution in colon cancer patients., Methods: We selected 24 paraffin-embedded colon cancer tissue samples from Mexican patients who received a 5-fluorouracil (5-FU)-based chemotherapy regimen. Tumor tissue was digested with proteinase K and genomic DNA was isolated by the standard method with phenol-chloroform extraction. Polymerase chain reaction (PCR) was performed for TS genotyping of VNTR and the results were evaluated directly in a stained agarose gel., Results: The allele frequency of 2 repeats (2R) was greater (0.66) than 3R (0.34) in metastatic colon cancer (x 2 =10.24; p=0.001)) however, no difference in allelic distribution between 2R (0.54) and 3R (0.46) in non metastatic patients was observed (x 2 =0.640; p=0.424)., Conclusion: Our results suggest that Mexican patients with colon cancer present differences in the allelic distribution, the 2R allele being the most frequent.

Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation. Under certain physiologic or pathologic events bilirubin level rises but according to literature it does not reach out more than 3 mg/dl. We report 2 cases of Gilbert's syndrome, genetically tested, which presented with bilirubin levels above 6 mg/dl without any trigger or coexisting condition. In conclusion, bilirubin levels higher than 6 mg/dL in Gilbert syndrome are rare, hemolytic and other metabolism diseases must be ruled out, and genetic testing may be necessary in some cases.

Hepatitis C is a common cause of end-stage liver disease, and the main indication for liver transplantation in Latin America. Treatment of hepatitis C infected patients improves important long-term outcomes as mortality. Sustained viral response is reached in near 50% of patients with the previous management based in pegylated interferon and ribavirin. Recently new drugs were available increasing sustained viral response significantly, changing the standard of care to triple therapy. This guidelines provides a framework for practitioner in Latin America, to the management of patients with hepatitis C chronic infection.

Background: Liver transplantation is the only curative alternative for patients with end stage liver disease or acute liver failure., Aim: To report the experience of a single transplant center in Mexico., Material and Methods: Fifty-five transplants in 54 adult patients were analyzed between 1999 and 2011 in a single private institution. All grafts were obtained from deceased donor. Surgical technique, donor and recipient demographics, complications, causes of death and overall survival are described. Results were expressed as range and percentages. A Kaplan-Meier survival curve was done to analyze patient and graft survival., Results: Main cause of cirrhosis was hepatitis C virus infection followed by alcohol intake. A 16% of patients developed biliary complications without graft loss, and vascular complications were observed in 15%. Patient survival at one and five years was 83% and 76%, respectively., Conclusions: Complication rates and survival in our center are comparable to those in the United States and Europe.

Background: Tumor necrosis factor alpha (TNF-α) has been involved in the pathogenesis of chronic hepatitis C virus (HCV) infection. Two polymorphisms at positions -308 and -238 in the TNF-α promoter region influence TNF-α expression and these have been linked to a number of infectious diseases., Aim: To analyze the prevalence of the -308 and -238 TNF-α polymorphisms in a group of Mexican HCV-infected patients and in healthy control subjects not related to the patients., Material and Methods: Both polymorphisms were determined in peripheral blood samples from 48 patients with positive anti-HCV antibodies and discernible HCV-RNA levels. Twenty five patients were women and 23 were men. The control group included 100 healthy subjects. Forty-four were women and 56 were men. The polymorphisms were evaluated by polymerase chain reaction amplification (PCR), followed by the Restriction Fragment Length Polymorphism (RFLP) method., Results: The prevalence of the -308 TNF-α polymorphism was found to be 12% in patients with chronic hepatitis C and 20% in control subjects, (P=0.2616); whereas that of the -238 TNF-α polymorphism was found to be 2% and 12% in patients and control subjects, respectively (P=0.061). The TNF-α genotypes were found to be in Hardy-Weinberg equilibrium., Conclusions: No association was found between -308 and -238 TNF-α polymorphisms and chronic hepatitis C in the Mexican group studied. Our data suggest that additional studies increasing the sample size and a control group which has been exposed to an equal risk of infection are required to investigate whether these polymorphisms represent genetic susceptibility for chronic HCV infection.

Background: Inflammatory bowel disease is a chronic and relapsing disorder without any curative medical treatment. Different drugs have been focused to get clinical remission during the flare, maintenance of remission and improving the quality of life of inflammatory bowel disease patients. Recently, new therapeutic agents blocking the tumoral necrosis factor alpha, a pro-inflammatory cytokine have been approved for the use in these kind of patients., Objective: To establish the first Mexican Consensus for the use of anti tumoral necrosis factor alpha agents in the treatment of patients with inflammatory bowel disease., Material and Methods: A group of gastroenterologist and colorectal surgeons from different regions of the country were invited to attend to this meeting. The consensus was divided in 7 sections and a total of 53 items were evaluated for all participants. The Delphi system was used in this consensus and several clinical trials were considered in order to provide recommendations according to evidence based medicine. Finally, conclusions were obtained after discussing all items., Results: This is the first mexican Consensus that provides the recommendations about the use of anti tumoral necrosis factor alpha agents in inflammatory bowel disease patients, Conclusions: It is important to have a deep knowledge about the anti tumoral necrosis factor alpha in the following conditions: indications and contraindications; parameters of clinical efficacy; predicting factors of medical treatment response; strategies for preventing and treating immunogenicity; efficacy and safety as well as the clinical factors for using these agents as first line of therapy (top-down).

Unlabelled: It has been reported that salicylates (sodium salicylate and aspirin) inhibit the replication of flaviviruses, such as Japanese encephalitis virus and dengue virus. Therefore, we considered it important to test whether acetylsalicylic acid (ASA) had anti-hepatitis C virus (HCV) activity. To this end, we examined the effects of ASA on viral replication and protein expression, using an HCV subgenomic replicon cell culture system. We incubated Huh7 replicon cells with 2-8 mM ASA for different times and measured HCV-RNA and protein levels by northern blot, real-time polymerase chain reaction, and western analysis, respectively. We found that ASA had a suppressive effect on HCV-RNA and protein levels (nearly 58%). ASA-dependent inhibition of HCV expression was not mediated by the 5'-internal ribosome entry site or 3'-untranslated regions, as determined by transfection assays using bicistronic constructs containing these regulatory regions. However, we found that HCV-induced cyclooxygenase 2 (COX-2) messenger RNA and protein levels and activity and these effects were down-regulated by ASA, possibly by a nuclear factor kappa B-independent mechanism. We also observed that the ASA-dependent inhibition of viral replication was due in part to inhibition of COX-2 and activation of p38 and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase 1/2 (MEK1/2) mitogen-activated protein kinases (MAPKs). Inhibition of these kinases by SB203580 and U0126, respectively, and by short interfering RNA silencing of p38 and MEK1 MAPK prevented the antiviral effect of ASA. Taken together, our findings suggest that the anti-HCV effect of ASA in the Huh7 replicon cells is due to its inhibitory effect on COX-2 expression, which is mediated in part by the activation of MEK1/2/p38 MAPK., Conclusion: These findings suggest the possibility that ASA could be an excellent adjuvant in the treatment of chronic HCV infection.

Background: Worldwide HCV studies have documented its large genetic variability; HCV has major genetic groups called genotypes that are designated from 1 to 6, as well as > 50 subtypes. This is very important considering that treatment response varies according to genotype. The purpose of this trial was to ascertain prevalence of HCV genotypes in a group of patients from 10 states in Mexico., Methods: This study enrolled patients from 22 hospitals throughout the country. Patients tested positive to hepatitis C antibody and genotyping was preformed by Lipa method. To carry out a comparison, two regions were arbitrarily defined, the northern region embodied the cities of Culiacan, Torreón, Monterrey, Ciudad Obregón, and Tijuana, while the central-southern region embodied Mexico City, Guadalajara, León, Puebla, and Veracruz., Results: The test was performed on a total of 421 patients. The most frequently found genotype was genotype 1, present in 70.55% of cases. The majority (40.1%) corresponded to genotype 1b, 17.81% to 1a, and genotype 2a/2c (11.64%). A total of 29.4% of samples corresponded to genotypes non-1. Genotype 1 was found in 72.34 (northern region) and 70.03% (central-southern) of the two regions, and genotypes non-1 in 27.66 and 29.97%, respectively., Conclusions: We conclude that the most frequent genotype in Mexico is 1b, followed by 1a, and, in third place 1b1a, for a total of 70.55%; the remaining 29.45% had genotypes other than 1.

The mechanisms by which alcohol exacerbates liver injury in patients with hepatitis C are unknown. We used the hepatitis C virus (HCV) subgenomic replicon cell system to evaluate the effect of ethanol on HCV replication and viral protein synthesis. Our results demonstrate that alcohol stimulates HCV replicon expression at both HCV-RNA and protein levels. Furthermore, we observed that ethanol treatment showed an additive effect in cyclooxygenase-2 (COX-2) protein expression and activity already induced by HCV viral proteins, and in turn increased HCV viral expression. Our results suggest that COX-2 activity is involved in ethanol-induced HCV-RNA and NS5A protein expression, because acetylsalicylic acid (ASA), a COX-1/2 inhibitor, blocked this induction and downregulated COX-2 protein expression and activity. Therefore, we suggest that ethanol increases HCV replication expression, at least in part, by upregulating a key cellular regulator of oxidative stress pathway known as COX-2 or its products.

The mechanism by which hepatitis C virus (HCV) causes chronic, progressive liver damage is unknown. Factors other than the virus itself have been implicated. The role of liver steatosis has been recently studied. Hepatic steatosis is a common histologic finding occurring in >50% of patients with chronic hepatitis C. Both host and viral factors have been demonstrated to play an important role in its development. In patients infected with genotype 1, steatosis appears due to co-existence of Non-alchoholic steatohepatitis (NASH) with HCV and associated with increased body mass index (BMI). Some recent observations suggest that steatosis may be of viral origin and related to genotype 3. This fact raises the possibility of a direct effect of specific viral sequences on the pathogenesis of lipid accumulation. Furthermore, hepatic steatosis attributed to genotype 3 correlates directly with serum and intrahepatic titers of HCV RNA. Resolution of steatosis after successful antiviral therapy as well as steatosis being a sign of recurrent HCV infection in patients with genotype 3 add convincing evidence that steatosis is viral-related. The pathogenic mechanism induced by genotype 3 is speculative. Correlation between steatosis, intrahepatic HCV RNA, and core protein expression suggest a direct effect. Further support is provided by the finding that HCV core protein induces steatosis in transgenic mice. Another possibility relates to interaction with hepatic triglyceride turnover. In conclusion, for patients infected with genotype 1 BMI plays a role in the pathogenesis of steatosis, while in those infected with genotype 3 steatosis may be due to a virus-specific cytopathic effect. Regardless of etiology, the contribution of both to liver fibrosis progression appears to be accepted.

Infection with hepatitis C virus (HCV) is a global public health issue. More than 200 million people in the world are infected with HCV. Hepatitis C is considered one of the main causes of chronic hepatitis, cirrhosis, hepatocellular carcinoma and liver transplantation. The identification of the viral genome quickly allowed delineation of genomic organization, and the structure and biochemical characterization of the proteins of HCV. However, it has been difficult to study its life cycle, as well as the development of antiviral agents due to the lack of a system of permissible culture. Numerous attempts have been reported to establish an in vitro system for the study of HCV. Recently, a system of efficient culture was established that allows replication of subgenomic molecules of HCV in a cell line of human hepatoma. In this revision, after a brief description of the molecular biology, means of transmission and clinical characteristics of hepatitis C, some of the experimental models are described that have been developed to date, focusing mainly on the subgenomic replicon system and their use in the development of new antiviral treatments.

Background: In the last decades it has been suggested that the main cause of liver cirrhosis in Mexico is alcohol. Currently in Western countries hepatitis C virus stage liver disease and liver transplantation. In Mexico, we have no data relative to the etiology of liver cirrhosis. The aim of this study was to investigate the main causes of liver cirrhosis in Mexico., Methods: Eight hospitals located in different areas of the country were invited to participate in this study. Those hospitals provide health care to different social classes of the country. The inclusion criteria were the presence of either an histological or a clinical and biochemical diagnosis of liver cirrhosis., Results: A total 1,486 cases were included in this study. The etiology of liver cirrhosis was alcohol in 587 (39.5%), HCV 544 (36.6%), cryptogenic 154 (10.4%), PBC 84 (5.7%), HBV 75 (5.0%) and other 42 (2.8%). There was no statistical difference between alcohol and HCV., Conclusions: We conclude that the main causes of liver cirrhosis in Mexico are alcohol and HCV.

Treatment with polyethylene glycol-modified interferon alfa-2a (peginterferon) alone produces significantly higher sustained antiviral responses than treatment with interferon alfa-2a alone in patients with chronic hepatitis C virus (HCV) infection. We compared the efficacy and safety of peginterferon alfa-2a plus ribavirin, interferon alfa-2b plus ribavirin, and peginterferon alfa-2a alone in the initial treatment of chronic hepatitis C. Thirty-two patients were randomly assigned to treatment, and received at least one dose of medication consisting of 180 microg of peginterferon alfa-2a once weekly plus daily ribavirin (1,000 or 1,200 mg, depending on body weight) (n = 14), weekly peginterferon alfa-2a plus daily placebo (n = 6), or three million units of interferon alfa-2b thrice weekly plus daily ribavirin for 48 weeks (n = 12). More patients who received peginterferon alfa-2a plus ribavirin had a sustained virologic response (defined as the absence of detectable HCV RNA 24 weeks after cessation of therapy) than patients who received interferon alfa-2b plus ribavirin (7/14 vs. 4/12) or peginterferon alfa-2a plus placebo (0/6). The overall safety profiles of the three treatment regimens were similar. In conclusion, for patients with chronic hepatitis C, once-weekly peginterferon alfa-2a plus ribavirin was tolerated as well as interferon alfa-2b plus ribavirin and produced significant improvements in the rate of sustained viral reduction compared with interferon alfa-2b plus ribavirin or peginterferon alfa-2a alone.

There are real concerns about patients with cirrhosis after HCV infection and their outcome because the survival rate after 5 years in the group with descompensated liver disease (Child-Pugh C) is very poor, it's only 50%. Likewise, it's possible that these patients develop another feared complication, hepatocellular carcinoma. This tumor can appear even in patients with compensated cirrhosis. Prevalence varies according to the geographic region. In the occidental countries, prevalence is 7-11% in the 5 year follow-up (1.6-3.2 cases for every 100 persons each year). On the other hand, oriental series report a prevalence of 30% in the 5 year follow-up (6-7 cases for every 100 persons each year). The quality of available information leads us to suggest that therapy with pegylated interferon and ribavirin is clearly indicated for patients with compensated cirrhosis as long as the white cell and platelet counts allow the reduction induced by the therapy. This scheme is contraindicated in cirrhotic patients with a Child-Pugh score of 10 points or more. Available data about therapeutic effect on cirrhosis progression suggest that an effective scheme based on interferon is able to induce a sustained viral response, and is related with a lesser risk of complications secondary to liver failure. The survival rate is better in these patients. Clinical observations suggest that interferon may prevent hepatocellular carcinoma in cirrhotic patients after HCV infection, especially in Oriental countries which have a high incidence of this carcinoma. Because of geographical and racial differences between East and West, it's inadequate to extrapolate information from one of these regions to the other.

Introduction: Adequate intake of folates has been associated to low prevalence of colon cancer. Methylenetetrahydrofolate reductase enzyme (MTHFR) plays an important role in folate metabolism. The role of the 677 mutation at the MTHFR gene in the risk for colorectal cancer remains controversial. A recent report established that this mutation has a high prevalence in the healthy Mexican population., Aims: To analyze the prevalence of 677T MTHFR mutation in patients with colorectal cancer and controls without chronic gastrointestinal disorders., Methods: Seventy-four colorectal cancer, 32 adenomas and 110 normal samples were analyzed. Patients and controls were matched for sex and age. For each sample, DNA isolation, PCR, and mutation detection by restriction enzyme digestion were performed to determine the allele at the 677 position in the MTHFR gene., Results: Genotype 677C/677C was found in 18.7, 20.3, and 30.9% in adenomas, cancer lesions and controls, respectively. Frequencies of the 677C/677T genotype were 59.4, 56.7, and 47.3%, in adenomas, cancer lesions, and controls, respectively. Genotype 677T/677T was found in 21.9, 23.0, and 21.8% in adenomas, cancer lesions, and controls, respectively. The odds ratio between genotypes carrying the mutation (T/T and C/T) and normal genotype (CC) was 1.81 (IC 95% 0.97-3.3), chi 2 = 3.5, p = 0.06., Conclusion: Our results showed that persons who carry the 677T mutation at MTHFR locus have a tendency for an increased risk for colorectal cancer. This study supports the basic concept that low levels of folic acid contribute with the colorectal cancer pathogenesis. Our lack of statistic significance may be due to reduced sample size.

We analysed retrospectively our clinical experience with 36 cases of mucormycosis. They were seen during the last 15 years. The diagnosis suspected on clinical grounds, was confirmed in 31 cases by finding the hyphae in hematoxylin-eosin stained material obtained from aspirated or tissue biopsy or by isolation of the fungus in culture. Rhinocerebral mucormycosis was diagnosed in 22 patients. Diabetes was the underlying disorder in 20 cases, kidney failure in one and myelodysplastic syndrome in one. Nine had stable and 11 unstable diabetes (ketoacidosis in 10 and hyperosmolar coma in 1). The earliest sign was facial edema, followed by proptosis, chemosis and extraocular muscle paresis. They were treated by extensive surgical debridement, insulin and antifungal drugs with 69% of survival rate. The disseminated mucormycosis was diagnosed at the autopsy in 5 cases, acute leukemia was the underlying disease in 2 of them. Pulmonary mucormycosis was diagnosed in 2 cases, cutaneous form in 2, sinuorbital form in 4 and brain abscess in one patient. Eight of these 9 cases survived after therapy. We emphasize the importance of an early diagnosis. This can only be made in the presence of a typical clinical setting confirmed by finding the hyphae in tissue or culture. Antifungal drugs along with treatment of the underlying disorder and aggressive surgical debridement must follow.

Reye's syndrome is considered a disease of the pediatric age. It is characterized by a prodrome of viral illness followed by vomiting and encephalopathy with associated hepatic dysfunction. This syndrome is potentially life-threatening with high morbidity and mortality rates. There are 27 other cases of adult onset Reye's syndrome reported in the literature. We describe a 18-year-old woman who developed varicella and four days later started with vomiting, delirium and in the following day she became comatose. Laboratory tests of liver function and pathology of a liver biopsy proved the diagnosis. The patient survived. A review of the proposed pathogenic mechanisms are presented. Our patient represents case the number 28 in world literature and the first in the mexican literature.

We review the pathogenesis of cholesterol gallstones, which occur in five steps: 1) metabolic; 2) chemical; 3) nucleation, 4) growing and maturation of gallstones; 5) clinical. It is emphasized that in the third step it could occur an arenous precipitate formed by cholesterol crystals, calcium bilirrubinate granules, calcium phosphate, or fatty acids anions and calcium, and mucin, called "biliary sludge", which has been associated with cholecystitis and pancreatitis. We describe the gallbladder motor abnormalities that occur during the lithogenesis and the diagnostic approach through scintigraphy and real time ultrasound. We review the pancreatobiliary dyskinesia, a condition associated with the postcholecystectomy syndrome. This later condition can result from anatomic stenosis or dyskinetic dysfunction of the sphincter of Oddi. Likewise, it is pointed out that at the present time, the manometric evaluation of the sphincter of Oddi is the gold standard in the diagnostic approach of this condition.

Prevalence of gallstone disease in autopsies from Mexico is 14.3%, 8.4% in men and 20.4% in women respectively. Frequency of cholelithiasis has increased remarkably from 12.2% in 1950 to 15.8% in 1980 (p < 0.05). Population of low socioeconomic status is apparently more affected. Obesity is the clinical association more frequently found in the population studied. Cholesterol gallstones showed the highest frequency. Economic cost of this disease is high. We conclude that gallstone disease is a public health problem for our country.