Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Asociación Mexicana de Hepatología A.C. Clinical guideline on hepatitis B. / Asociación Mexicana de Hepatología A.C. Guía Clínica de Hepatitis B.

Hepatitis B virus (HBV) infection continues to be a worldwide public health problem. In Mexico, at least three million adults are estimated to have acquired hepatitis B (total hepatitis B core antibody [anti-HBc]-positive), and of those, 300,000 active carriers (hepatitis B surface antigen [HBsAg]-positive) could require treatment. Because HBV is preventable through vaccination, its universal application should be emphasized. HBV infection is a major risk factor for developing hepatocellular carcinoma. Semi-annual liver ultrasound and serum alpha-fetoprotein testing favor early detection of that cancer and should be carried out in all patients with chronic HBV infection, regardless of the presence of advanced fibrosis or cirrhosis. Currently, nucleoside/nucleotide analogues that have a high barrier to resistance are the first-line therapies.

Differences in the presentation and treatment of primary liver tumors at a hepatology center and an oncology center.

INTRODUCTION AND AIMS: Primary liver cancer is a public health problem in Mexico and the world. Liver transplantation (LT) is the ideal treatment for early hepatocellular carcinoma (HCC). Our aim was to evaluate the characteristics of patients with HCC and cholangiocarcinoma (CC) at two centers and identify transplantation candidates. MATERIALS AND METHODS: A retrospective observational study was conducted at the Hepatology Center (HC) and the University Center Against Cancer (UCAC), within the time frame of 2012-2018. HCC or intrahepatic CC was confirmed in 109 patients. Staging classifications, transplant selection models, and a predictive model for post-LT recurrence were applied to the HCC patients. RESULTS: Of the total population, 93% (n=102) presented with cirrhosis, 86% (n=94) had HCC (HC: 58%, UCAC: 42%), and 14% (n=15) had intrahepatic CC (HC: 40%, UCAC: 60%). Of the HC patients with HCC, Okuda I-II, BCLC A-B, and AFP levels <100ng/m predominated, whereas Okuda II-III, BCLC C-D, and AFP levels >1000ng/mL predominated in the UCAC patients. Half of the HC population with HCC met the criteria for LT, in contrast to 23% of the UCAC patients. Fifteen patients were evaluated for LT, and at present, six have undergone transplantation. CONCLUSIONS: The most frequent primary liver tumor was HCC. Patients from the HC presented with earlier-stage disease and a high number of them met the criteria for LT. Only patients from the HC underwent transplantation.

Differences in the presentation and treatment of primary liver tumors at a hepatology center and an oncology center. / Diferencias de la presentación y tratamiento en las neoplasias primarias de hígado en un centro de hepatología y un centro oncológico.

INTRODUCTION AND AIMS: Primary liver cancer is a public health problem in Mexico and the world. Liver transplantation (LT) is the ideal treatment for early hepatocellular carcinoma (HCC). Our aim was to evaluate the characteristics of patients with HCC and cholangiocarcinoma (CC) at two centers and identify transplantation candidates. MATERIALS AND METHODS: A retrospective observational study was conducted at the Hepatology Center (HC) and the University Center Against Cancer (UCAC), within the time frame of 2012-2018. HCC or intrahepatic CC was confirmed in 109 patients. Staging classifications, transplant selection models, and a predictive model for post-LT recurrence were applied to the HCC patients. RESULTS: Of the total population, 93% (n = 102) presented with cirrhosis, 86% (n = 94) had HCC (HC: 58%, UCAC: 42%), and 14% (n = 15) had intrahepatic CC (HC: 40%, UCAC: 60%). Of the HC patients with HCC, Okuda I-II, BCLC A-B, and AFP levels < 100 ng/m predominated, whereas Okuda II-III, BCLC C-D, and AFP levels > 1,000 ng/mL predominated in the UCAC patients. Half of the HC population with HCC met the criteria for LT, in contrast to 23% of the UCAC patients. Fifteen patients were evaluated for LT, and at present, six have undergone transplantation. CONCLUSIONS: The most frequent primary liver tumor was HCC. Patients from the HC presented with earlier-stage disease and a high number of them met the criteria for LT. Only patients from the HC underwent transplantation.

Sofosbuvir-velpatasvir in Mexican patients with hepatitis C: A retrospective review. / Sofosbuvir-velpatasvir en pacientes mexicanos con hepatitis C: una revisión retrospectiva.

INTRODUCTION: The sofosbuvir-velpatasvir (SOF/VEL) combination is a direct-acting antiviral therapy that is authorized and available in Mexico, making the performance of a real-world multicenter study that evaluates the sustained virologic response at 12 weeks post-treatment a relevant undertaking. METHODS: A retrospective review of the case records of 241 patients seen at 20 hospitals in Mexico was conducted to assess hepatitis C treatment with the SOF/VEL combination (n = 231) and the sofosbuvir/velpatasvir/ribavirin (SOF/VEL/RBV) combination (n = 10). The primary efficacy endpoint was the percentage of patients that achieved SVR at 12 weeks after the end of treatment. RESULTS: Overall SVR was 98.8% (95% CI 97.35-100%). Only three patients did not achieve SVR, two of whom had cirrhosis and a history of previous treatment with peg-IFN. Of the subgroups analyzed, all the patients with HIV coinfection, three patients with genotype 3, and the patients treated with the SOF/VEL/RBV combination achieved SVR. The subgroups with the lower success rates were patients that were treatment-experienced (96.8%) and patients with F1 fibrosis (95.5%). The most frequent adverse events were fatigue, headache, and insomnia. No serious adverse events were reported. CONCLUSION: Treatments with SOF/VEL and SOF/VEL/RBV were highly safe and effective, results coinciding with those of other international real-world studies.

Attenuation of pro-inflammatory cytokines and oxidative stress by misoprostol in renal ischemia/reperfusion in rats.

The ischemia/reperfusion (I/R) process alters metabolic pathways, releasing reactive oxygen species and pro-inflammatory cytokines that cause tissue necrosis and activate cellular apoptotic pathways. Misoprostol (MSP) is a prostaglandin E1 analog that has demonstrated a cytoprotective role in the I/R process. The study objective was to evaluate the effects of MSP on the regulation of pro-inflammatory and oxidative stress mediators in an I/R-induced acute kidney injury rat model. Wistar rats were divided into 3 groups. Sham and I/R were given 1 mL/day of physiological solution; MSP+I/R was given intragastric MSP (300 µg/kg) for 3 days. For I/R and MSP+IR, the renal hilum was clamped for 45 min, followed by 15 h of reperfusion. Renal function tests, pro-inflammatory cytokines, mediators of oxidative stress, and histological analysis were evaluated. Pro-inflammatory cytokine activity was significantly attenuated in the MSP+I/R group. However, there was no statistically significant difference between Sham and MSP. Regarding antioxidant activity, MSP+I/R showed a significant decrease in these mediators compared with Sham and I/R. Histologically, scarce medullary necrosis was observed with a preserved renal cortex in the MSP group.

Effects of melatonin on the acute inflammatory response associated with endoscopic retrograde cholangiopancreatography: A randomized, double-blind, placebo-controlled trial. / Efectos de la melatonina en la respuesta inflamatoria aguda asociada con la colangiopancreatografía retrógrada endoscópica: un ensayo clínico aleatorizado, doble ciego y controlado con placebo.

INTRODUCTION: Endoscopic retrograde cholangiopancreatography (ERCP) is associated with an acute inflammatory response and melatonin has a variety of immunomodulatory and antioxidant effects studied experimentally in pancreatobiliary pathology. AIMS: The aim of our study was to evaluate the effects of peri-procedural administration of melatonin on the inflammatory response and lipid peroxidation associated with ERCP. METHODS: In this proof-of-concept clinical trial, 37 patients with a high probability of choledocholithiasis were randomized to receive peri-procedure (ERCP) melatonin or placebo. We measured the serum concentration of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), lipid peroxidation, amylase, and liver function tests 24h before and after the procedure. RESULTS: We found no pre-procedure or post-procedure differences between the melatonin group or the placebo group (P>.05) in the serum concentrations of TNF-alpha (melatonin: 153.8 vs. 149.4ng/m; placebo: 103.5 vs. 107.3ng/ml), IL-6 (melatonin: 131.8 vs. 133.3ng/ml; placebo: 177.8 vs. 197.8ng/ml), or VEGF (melatonin: 157.3 vs. 157.8pg/ml; placebo: 97.3 vs. 97.8pg/ml), or in relation to lipid peroxidation (melatonin: 39.2 vs. 72.3µg/ml; placebo: 66.4 vs. 90.5µg/ml). After ERCP, a significant decrease in the AST, ALT, and total bilirubin levels was found only in the melatonin group (P<.05). The administration of melatonin was safe and tolerable. CONCLUSIONS: Melatonin is safe and tolerable in patients undergoing ERCP, but it does not appear to affect inflammatory cytokine concentrations or lipid peroxidation.

Bupropion reduces the inflammatory response and intestinal injury due to ischemia-reperfusion.

Intestinal ischemia-reperfusion (I/R) causes severe organ failure and intense inflammatory responses, which are mediated in part by the cytokine tumor necrosis factor-alpha (TNF-alpha). Bupropion is an antidepressant known to inhibit TNF-alpha production. We sought to examine the protective effects of bupropion on intestinal I/R injury in 15 male Sprague-Dawley rats that were randomized to sham surgery, 45 minutes of intestinal ischemia followed by 180 minutes reperfusion, or bupropion (100 mg/kg) before the intestinal I/R injury. To evaluate the systemic inflammatory response induced by intestinal I/R, we measured serum levels of TNF-alpha, interleukins-1 and -6, lipid peroxidation, and transaminases. Histologic analysis evaluated intestinal injury using the Chiu muscosal injury score. After I/R, Chiu score in control animals was 3.6 ± 1.2 vs 2.6 ± 0.53 in animals that received bupropion (P < .05). Bupropion pretreatment reduced intestinal. I/R injury and blunted serum elevations of TNF-alpha (0.96 ± 1.1 ng/mL vs 0.09 ± 0.06 ng/mL, P < .05) and interleukin-1 (0.53 ± 0.24 ng/mL vs 0.2 ± 0.11 ng/mL, P < .05). Bupropion in reduced intestinal I/R injury through immunomodulatory machanisms that involve inflammatory cytokines such as TNF-alpha.

[Cytokines expression in peripheral blood cells of patients with orthotopic liver transplant: preliminary results]. / Expresión de citocinas en células de sangre periférica de pacientes con trasplante hepático ortotópico: resultados preliminares.

BACKGROUND: Cytokines are important in immune and inflammation response in liver transplantation. Determination of cytokine expression may lead to early detection of risk of rejection and infection in patients with this treatment. OBJECTIVE: To evaluate the expression of interleukin- 1beta (IL-1ß), interleukin-6 (IL-6), interleukin-8 (IL- 8), tumor necrosis factor-alpha (TNF-α), transforming growth factor-beta (TGF-ß) and granulocyte macrophage colony stimulating factor (GMCSF) in peripheral blood mononuclear cells in patients who received an orthotopic liver transplantation (OLT). METHODS: Fourteen patient who underwent OLT due to cirrhosis were analyzed before and after (at 24, 48, 72 hours, 7, 15 and 30 days) transplantation. Peripheral blood cells were tested for IL-1ß, IL-6, IL-8, TNF-α, TGF-ß and GM-CSF using semiquantitative reverse transcriptase-polymerase chain reaction (Roche Kit). RESULTS: No patient present acute rejection, and 11 of them had bacterial infections, 1 to 19 days after OTL. The cytokines IL-6 and TNF-α showed no expression in any phases studied and IL-1ß only in 21% in the first phase post-transplant. Sixty percent of patients who presented bacterial infections express GM-CSF. TGF-b was the most frequently expressed cytokine. CONCLUSIONS: Cytokines expression in the evaluated patients did not follow a defined pattern according to etiology. Increasing the size of the sample is deemed important to establish the implication of the diverse cytokines in liver transplantation.

[Orthotopic liver transplantation. Experience in the University Hospital of Monterrey, N.L]. / Trasplante hepático ortotpico. Experiencia en el Hospital Universitario de Monterrey, N.L.

INTRODUCTION: Several programs of organ and tissues transplantation have been developed for over a decade at the University Hospital. OBJECTIVE: To describe long term complications and survival in the liver transplant program at the University Hospital, UANL. MATERIAL AND METHODS: The long term complications and survival were analyzed in the liver transplant program at the University Hospital Dr. José Eleuterio González in the period between 1991 and 2011. RESULTS: Ninety six liver transplants were performed during this period, four of them received one re-transplant and one patient received 2 retransplants. Most common long term complications were metabolic 62%, bony 31% and infectious 28%. Median survival was 78 months. CONCLUSIONS: Liver transplant program at the University Hospital UANL has grown, being the most active in the state of Nuevo Leon, with 1-, 5- and 10-years survival of 66.1, 53.3 and 46.2%, respectively.

Effects of thalidomide and pentoxyphylline over local and remote organ injury after intestinal ischemia/reperfusion.

OBJECTIVE: We investigated the effects of thalidomide alone or in combination with pentoxyphylline upon intestinal ischemia/reperfusion (I/R) injury in the rat. MATERIALS AND METHODS: Twenty male Wistar rats were randomized into 5 groups: sham-operated (SHAM), control (CTL), thalidomide (400 mg/kg) treatment (THAL), pentoxyphylline (50 mg/kg) treatment and a combination group (THAL + POX). I/R was induced by clamping the superior mesenteric artery for 45 minutes, followed by 120 minutes of reperfusion. We measured serum concentrations of aspartate-aminotransferase (AST), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-alpha as well as lipid peroxidation and antioxidant status. Intestinal samples were morphologically analyzed, and dry to wet (W/D) ratios calculated in intestinal, lung and liver samples, as a measurement of tissue edema. RESULTS: Serum concentrations of AST, LDH, and TNF-alpha were increased after I/R in the CTL compared with the SHAM group (P < .05). Lipid peroxidation was also increased, and antioxidant capacity in serum, decreased (P < .05). The W/D ratio was elevated in all tissue samples as well (P < .05). Both thalidomide and pentoxyphylline effectively reduced AST, LDH, TNF-alpha, and lipid peroxidation levels, as well as attenuated tissue edema and intestinal injury induced by I/R (P < .05). Combination treatment showed only modest additive effects on lung W/D ratio and TNF-alpha levels. CONCLUSION: Both drugs protected the intestine, lungs, and liver against intestinal I/R injury, probably by inhibition of TNF-alpha and lipid peroxidation. However, combination treatment showed small, additive effects.

[Prevalence of hepatitis D in a population of Northeast Mexico and its relationship with other viruses]. / Prevalencia de hepatitis D en una población del Noreste de México y su relación con otros virus.

BACKGROUND: There are few reports in Mexico on the prevalence of infection by virus D. OBJECTIVE: The aim of the present study was to study the hepatitis D virus infection prevalence in patients entering to the University Hospital. METHODS: Seventy three HBsAg positive patients sera were studied. There were 38 patients with acute hepatitis, 28 patients with chronic liver disease and 7 were asymptomatic HBsAg carriers. Serological markers for hepatitis viruses B, D and C were detected by means of ELISA test (Abbott). RESULTS: Anti-HDV was detected in 3 cases (4%). The first two cases were men with acute hepatitis B. Both had a coinfection by viruses B and D, however IgM anticore could not be demonstrated in the first case, this patient developed hepatic cirrhosis within 13 months, in addition he had a concurrent infection by hepatitis C virus with a positive second generation ELISA antibody. The second case recovered from the acute hepatitis. The third case was a female nurse with acute hepatitis and a coinfection by viruses B and D who recovered from the acute attack. Antibody to hepatitis C was present in 3 out of 22 patients with chronic liver disease (13.6%), one of them having an hepatocellular carcinoma. CONCLUSIONS: Our results coincide with the previously reported low incidence of hepatitis D and represent the first report in Mexico of concurrent infections by viruses B-C and B-D-C.

An aflatoxin-associated mutational hotspot at codon 249 in the p53 tumor suppressor gene occurs in hepatocellular carcinomas from Mexico.

The p53 tumor suppressor gene is commonly mutated in human hepatocellular carcinoma (HCC). The most frequent mutation in HCC in populations exposed to a high dietary intake of aflatoxin B1 (AFB1) is an AGGarg-->AGTser missense mutation in codon 249 of the p53 gene. We analyzed HCCs from Monterrey, Mexico, for the codon 249ser hotspot mutation. We also analyzed the serum AFB1-albumin adduct levels of the donors and family members to measure the current AFB1 exposure in this population. Moreover, the presence of hepatitis B and/or C viral infection (HBV or HCV) was analyzed serologically in the patients. Tumor cells were microdissected from tissue sections and exon 7 p53 sequences were amplified by polymerase chain reaction from genomic DNA and sequenced directly. The serological tests for anti-p53 antibodies, HBV or HCV were done by ELISA. Immunohistochemical analysis of p53 protein was done using a polyclonal rabbit antiserum (CM-1). Eight of 21 cases were positive by p53 immunohistochemistry. Of the 16 cases sequenced for exon 7 of p53 three codon 249 AGGarg-->AGTser mutations were found. Serum antibodies recognizing p53 protein were found in one of 18 patients. Positive serology for HBV and/or HCV was found in 12 of 20 cases. The serum AFB1-albumin adduct levels in this population ranged from 0.54 to 4.64 pmol aflatoxin/mg albumin. These results indicate that dietary AFB1 and hepatitis viruses are etiological agents in the molecular pathogenesis of HCC in this geographic region of Mexico.