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Current Issue

October - December, 2011

Vol. 10 Issue 4

On the cover: Liver biopsy showing a pattern of hepatic sinusoidal dilatation with presence of a cystic blood filled space in liver parenchyma and related ultrasonography of the internal carotid artery showing the typical halo sign of inflammatory arteritis.

FROM THE EDITOR

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • Pre operative cardio pulmonary assessment of the liver transplant candidate Graciela Martinez-Palli, Andres Cardenas Page 421-433

    Given the severe shortage of liver donors, a carefully evaluation and selection of patients who are likely to obtain a significant survival benefit from liver transplantation (LT) is imperative in order to attain successful outcomes. Cardiovascular and respiratory events remain one of the leading causes of non-graft-related death in LT. A variety of pre-existing cardiac and pulmonary disorders are commonly identified in LT recipients, more so than in the general population. Uncertainties regarding the optimal assessment of cardiovascular and respiratory function in potential transplant candidates have produced a wide variation in the clinical care of tjis population. There is still no consensus on which assessment algorithm confers the best outcomes. Once the diagnosis has been established, the prognosis should be estimated for risk stratification and to confirm the candidacy for LT. Additionally, the challenge remains in knowing how cardiac or respiratory derangements in candidates affect the long-term outcome after LT and which is the magnitude of risk that we as physicians are willing to accept. This article discusses the cardiac and pulmonary aspects of liver disease that may impact recipient selection. Relevant literature focused upon the most common entities in this field is presented in this review.

ORIGINAL ARTICLES

Clinical Studies

Viral Hepatitis
  • Evolution of hepatitis B virus during long-term therapy in patients with chronic hepatitis B Elisabete Arrese, Miren Basaras, Sonia Blanco, Pablo Ruiz, Ramón Cisterna Page 434-440

    Background. Long-term lamivudine (LAM), adefovir (ADV) and entecavir (ETV) treatment induce the emergence of drug-resistant hepatitis B virus (HBV) in patients with chronic hepatitis B infection. Aim. To evaluate the LAM, ADV and ETV resistance mutations detected in our patient group. Materials and methods. Twenty patients who had received at least two years of treatment with nucleoside/tide analogues were enrolled in this study. Patients with detectable HBV DNA were analyzed in order to detect resistance mutations and in this group of patients treatment was change. Results. Three patients developed LAM resistance mutations (2 presented rtM204I and one rtL180M+rtM204V/I) and one patient showed rtN236T ADV resistance mutation. During ADV and LAM treatment, one patient developed ADV plus LAM resistance mutations (rtI163V+rtL180M+rtA181V+rtN236T), in this case, HBV strains harbouring polymerase mutations did not develop LAM associated rtM204V/I primary mutation. In addition, ETV resistance mutations (rtL180M+rtT184A+rtS202G+rtM204V) were detected in one patient. Conclusions. These findings suggest that monotherapy resulted in a limited virological response and combination strategies including potent antiviral agents should be recommended for patients with resistant mutations.

  • The role of hepatitis B immunoglobulin in hepatitis B related liver transplantation: Canadian Transplant Centre Position Paper Mark Levstik, Philip Wong, Erica D. Greanya, Eric M. Yoshida Page 441-444

    Introduction. Hepatitis B virus (HBV) related liver transplant (LT) recipients face a high risk of HBV reinfection in the absence of continuous post-operative HBV prophylaxis. Combination HBV prophylaxis with hepatitis B immune globulin (HBIg) and nucleos(t)ide anti-viral agents prevents HBV recurrence in 90 to 100% of patients who undergo transplantation for hepatitis B and is considered the standard of care in Canada. Post liver transplant HBV prophylaxis protocols vary with regard to the dosing, duration and routes of HBIg administration. All Canadian transplant centres managing liver transplant patients were surveyed as to their HBV transplant protocols. Results. Results of the survey showed that the majority of the Canadian transplant centres use an oral antiviral in combination with long term or indefinite HBIg for prevention of HBV recurrence post liver transplantation. Studies were done to test new protocols using lower HBIg doses given intramuscularly or subcutaneously alone or in combination with antiviral agents. Conclusion. Long term HBIg administration post transplantation in combination with antiviral agents is an integral part of Canadian HBV related liver transplant protocol.

  • No association of promoter variations of HMOX1 and UGT1A1 genes with liver injury in chronic hepatitis C Petr Urbánek, Martin Lenícek, Lucie Muchová, Iva Subhanová, Ladislav Dušek, Nikola Kaspríková, Petr Hrabal, Radan Bruha, Libor Vítek Page 445-451

    Background. Heme oxygenase-1 (HMOX1) and bilirubin UDP-glucuronosyltransferase (UGT1A1), both enzymes involved in bilirubin homeostasis, play an important role inoxidative stress defense. Objective. To assess the effect of promotervariations of HMOX1 and UGT1A1 genes on the progression of fibrosis in patients chronically infected with the hepatitis C virus (HCV). Material and methods. The study was performed on146 chronic HCV infection patients, plus 146 age- and sex-matched healthy subjects. The (GT)n and (TA)n dinucleotide variations in HMOX1 and UGT1A1 gene promoters, respectively, were determined by fragment analysis in all subjects. Results. No differences were found in the frequencies of each particular allele of both genes, between HCV patients and a control group (p > 0.05). Furthermore, no association was detected (p > 0.05) between either the HMOX1 or the UGT1A1 promoter variants and the individual histological stages of liver disease in the HCV positive patients. Finally, no differences in the HMOX1 and UGT1A1 genotype prevalence rates were found between pre-cirrhotic and cirrhotic patients (p > 0.05). Conclusion. Based on our data, microsatellite variations in the HMOX1 and UGT1A1 genes are not likely to protect from progression of liver disease in patients with chronic hepatitis C.

  • Genetic variation in Interleukin-28B predicts SVR in hepatitis C genotype 1 Argentine patients treated with PEG IFN and ribavirin Ezequiel Ridruejo, Ángela Solano, Sebastián Marciano, Omar Galdame, Raúl Adrover, Daniel Cocozzella, Dreanina Delettieres, Alfredo Martínez, Adrián Gadano, Oscar G. Mandó, Marcelo O. Silva Page 452-457

    Background and aims. Genetic variations in the interleukin 28B (IL28B) gene have been associated with viral response to PEG-interferon-α/ribavirin (PR) therapy in hepatitis C virus (HCV) genotype 1 infected patients from North America, Europe and Asia. The importance of these IL28B variants for Argentine patients remains unknown. Material and methods. IL28B host genotypes (rs8099917 and rs12979860) were determined in a population of Argentine patients with European ancestry. Results were analyzed looking for their association with sustained virologic response (SVR) to PR therapy and compared with other baseline hosts' biochemical, histological and virological predictors of response. Results. We studied 102 patients, 60% were men, and 40% of them were rs8099917 TT and 18% rs12979860 CC. Mean baseline serum HCV RNA was 1.673.092 IU/mL and mean F score was: 2.10 ± 1.18 (21% cirrhotic). SVR rate was higher in rs8099917 TT genotypes (55%) when compared to GT/GG (25%) (p = 0.002) and in rs1512979860 CC (64%) than in CT/TT (30%) (p = 0.004). The univariate analysis showed that rs8099917 TT (OR 3.7; 95 %CI 1.5-8.7; p = 0.002), rs12979860 CC (OR 4.6; 95%CI 1.5-13.7; p = 0.006), low viral load (OR 4.6; 95% CI 1.7-12.6; p = 0.002) and F0-2 (OR 8.5; 95% CI 2.3-30.6; p = 0.001) were significantly associated with SVR. In the multivariate analysis, rs12979860 CC, rs8099917 TT, viral load < 400.000 IU/mL and F0-2 were associated with SVR rates (p = 0.029, p = 0.012, p = 0.013 and p = 0.004, respectively). Conclusion. IL28B host genotypes should be added to baseline predictors of response to PR therapy in Latin American patients with European ancestry.

  • Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin Guillermo Cabrera Álvarez, Diana Gómez-Galicia, Lourdes Rodríguez-Fragoso, Vicente Madrid-Marina, Luis Cañedo Dorantes, Miguel Sánchez-Alemán, Nahum Méndez-Sánchez, Jorge Reyes-Esparza Page 458-468

    Background. Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV. Objective. The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV. Material and methods. We included patients whose platelets were < 90,000/mm3 and who were undergoing antiviral treatment. Danazol (300-600 mg/day) was administered during and until the end of antiviral therapy [7.6 months (2 to 11 months)]. The monitoring was performed through platelet analysis and liver function tests. A viral load test was done at the beginning and end of treatment. Fortynine patients receiving a combined therapy of PEG-INF, ribavirin and Danazol increased their platelet levels to 121,081/mm3 (46,000-216,000/mm3); 10.6% of patients gained > 100,000 platelets/mm3, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol. Conclusion. Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.

  • Impact of Fibroscan® on management of chronic viral hepatitis in clinical practice Dietje Fransen van de Putte, Renske Blom, Hanneke van Soest, Marco Mundt, Claudia Verveer, Joop Arends, Robert E. de Knegt, Eveline Mauser-Bunschoten, Karel van Erpecum Page 469-476

    Background. Liver stiffness measurement (LSM) using Fibroscan® is an increasingly popular non-invasive method for quantifying liver fibrosis in patients with chronic viral hepatitis. We aimed to explore potential impact of Fibroscan® on clinical management. Material and methods. 133 patients with chronic hepatitis B (HBV, n = 75) or C (HCV, n = 58) underwent Fibroscan® measurement. LSM results were compared with liver biopsy results, ultrasound, and APRI-scores, and the impact of LSM on clinical management was evaluated. Results. LSM results indicated fibrosis stage F0-F1 in 84 patients (63%), F2 in 28 (21%), F3 in 8 (6%), and F4 in 13 patients (10%). Nineteen patients had liver biopsies within one year of LSM. In ten patients, LSM and biopsy showed the same fibrosis stage, in 8 there was one stage difference, and in 1 three stages difference. Ultrasound only showed cirrhosis in three patients, who all exhibited advanced cirrhosis at LSM. There was a statistically significant, but weak correlation between LSM results and APRI scores (r = 0.31, pvalue < 0.001). LSM results changed clinical management in 39% of patients (55 cases): in 15 patients antiviral treatment was indicated, in 21 patients surveillance for hepatocellular carcinoma was indicated, and 19 successfully treated hepatitis C patients could be discharged from clinical follow-up in absence of severe fibrosis or cirrhosis. Conclusion. LSM appears to be a valuable non-invasive tool to manage patients with chronic viral hepatitis in clinical practice.

Liver transplantation
  • Do older patients utilize excess health care resources after liver transplantation? Neil Shankar, Mamoun AlBasheer, Paul Marotta, William Wall, Vivian McAlister, Natasha Chandok Page 477-481

    Introduction. Liver transplantation is a highly effective treatment for end-stage liver disease. However, there is debate over the practice of liver transplantation in older recipients (age ≥ 60 years) given the relative shortage of donor grafts, worse post-transplantation survival, and concern that that older patients may utilize excess resources postoperatively, thus threatening the economic feasibility of the procedure. Aim. To determine if patients ≥ 60 years of age utilize more health resources following liver transplantation compared with younger patients. Material and methods. Consecutive adult patients who underwent primary liver transplantation (n = 208) at a single center were studied over a 2.5-year period. Data were collected on clinico-demographic characteristics and resource utilization. Descriptive statistics, including means, standard deviations, or frequencies were obtained for baseline variables. Patients were stratified into 2 groups: age ≥ 60 years (n = 51) and < 60 years (n = 157). The Chi-Square Test, Mantel-Haenszel Test, 2-sample test and odds ratios were calculated to ascertain associations between age and resource utilization parameters. Regression analyses were adjusted for model for end-stage liver disease score, location before surgery, diabetes mellitus, donor age, cold ischemia time, albumin, and diagnosis of hepatitis C. Results. Recipients ≥ 60 years of age have similar lengths of hospitalization, re-operative rates, need for consultative services and readmission rates following liver transplantation, but have longer lengths of stay in the intensive care (hazard ratio 1.97, p = 0.03). Conclusion. Overall, liver transplant recipients ≥ 60 years of age utilize comparable resources following LT vs. younger recipients. Our findings have implications on cost-containment policies for liver transplantation.

  • Should donation after cardiac death liver grafts be used for retransplantation? Dana K. Perry, Darrin L. Willingham, Lena Sibulesky, Ilynn G. Bulatao, Justin H. Nguyen, C. Burcin Taner Page 482-485

    Introduction. Donation after cardiac death (DCD) donors provide an important source of livers that has been used to expand the donor pool. As a consequence of increased numbers of OLT, allograft failure due to early and late complications and disease recurrence are more commonly encountered. The only life saving treatment for patients with liver allograft failure is liver re-transplantation (LR). The use of DCD liver grafts for LR is controversial. Material and methods. Between February 1998 and June 2008, 10 patients underwent LR with DCD allografts. Five (50%) patients had no post operative complications. The 30 day, 1 year, and 3 year patient survival are 80, 60, and 60%, respectively. When DCD grafts are used for sick patients with high MELD scores for LR, the patient and graft survivals are prohibitively low. Conclusion. We do not recommend utilization of DCD liver grafts for LR if a candidate recipient has moderate to high MELD score.

Non alcoholic fatty liver disease (NAFLD)
  • Decrease of aminotransferase levels in obese women is related to body weight reduction, irrespective of type of diet Heriberto Rodríguez-Hernández, Miriam Cervantes Huerta, Martha Rodriguez Moran, Fernando Guerrero-Romero Page 486-492

    Objective. To evaluate the efficacy of low carbohydrate diet (LCD) as compared with low fat diet (LFD) to decrease aminotransferase levels in obese women with nonalcoholic fatty liver disease. Material and methods. A total of 59 women were randomly enrolled in a non-controlled clinical intervention study to receive either LCD or LFD during six months. Apparently healthy non-pregnant obese women aged 20 to 65 years were eligible to participate. Previous diagnosis of hepatic disease, serum creatinine level ≥ 1.5 mg/dL, severe life-limiting medical illness, pregnancy, active participation in other dietary program, use of weight loss drugs, or alcohol consumption ≥ 30 g per day were exclusion criteria. Results. A total of 31 obese women who received LCD were compared with 28 women allocated in the LFD group. There were 3 (LCD group) and 2 (LFD group) women with lost of follow-up. No differences in the proportion of type 2 diabetes, hypertension and hyperlipidemia were noted between women in the LCD and LFD groups. At end of follow-up, there were not significant statistical differences in the anthropometric and biochemical characteristics between women in both groups. The weight loss was 5.7 and 5.5% for women in the LCD LFD groups. Although the decrease of AST (31.7 and 22.4%) and ALT (41 and 33.3%) levels was more elevated in the women of LCD group, as compared with the LFD group, there were not significant statistical differences. Conclusions. Our results show that weight loss, irrespective of the type of diet, reduces aminotransferase levels in obese women with NAFLD.

  • Plasminogen activator inhibitor type 1 serum levels and 4G/5G gene polymorphism in morbidly obese Hispanic patients with non-alcoholic fatty liver disease Alberto Espino, Andrea Villagrán, Valeska Vollrath, Paulina Hanckes, Roberto Salas, Andrea Farah, Nancy Solís, Margarita Pizarro, Alex Escalona, Camilo Boza, Gustavo Pérez, Gonzalo Carrasco, Oslando Padilla, _ Francisco Miquel Page 493-501

    Background. The plasminogen activator inhibitor type-1 (PAI-1) has been implicated in the regulation of fibrinolysis and extracellular matrix components. The single base pair guanine insertion/deletion polymorphism (4G/5G) within the promoter region of the PAI-1 gene influences PAI-1 synthesis and may modulate hepatic fibrogenesis. Aim. To evaluate the influence of PAI-1 serum levels and 4G/5G polymorphism on the risk of liver fibrosis associated to non-alcoholic fatty liver disease (NAFLD) in morbidly obese patients. Material and methods. Case-control study of 50 obese patients undergoing bariatric surgery and 71 non-obese subjects matched by age and sex. Anthropometric and biochemical measurements were performed, including PAI-1 serum levels. Genomic DNA was obtained to assess the presence of 4G/5G polymorphism. Results. BMI, insulinemia, triglycerides, HOMA-IR, hypertension and diabetes were significantly higher in obese patients compared to control subjects. PAI-1 serum levels observed in obese patients were significantly lower (10.63 ± 4.82) compared to controls (14.26 ± 11.4; p < 0.05). No differences were observed in the PAI-1 4G/5G promoter genotypes frequencies (p = 0.12). No differences were observed in PAI-1 plasma levels among obese patients with liver fibrosis (10.64 ± 4.35) compared to patients without liver fibrosis (10.61 ± 5.2; p = 0.985). PAI-1 4G/5G promoter genotypes frequencies were similar in patients with or without liver fibrosis associated to NASH (p = 0.6). Conclusions. Morbidly obese patients had significantly lower PAI-1 serum levels with similar PAI-1 4G/5G genotypes frequencies compared to non-obese subjects. The frequency of 4G/5G genotypes in Chilean Hispanic healthy subjects was similar to that described in other populations. No association was found between PAI-1 serum levels or 4G/5G genotype with liver fibrosis in obese patients.

Miscellaneous
  • Alcohol use among patients with HIV infection Maurizio Bonacini Page 502-507

    Objective. To evaluate alcohol use in patients with HIV infection, assess ethnic and social associations, and describe outcomes. Material and methods. Design: cohort study. Setting: Academic HIV-Liver Clinic. Patients: 431 HIV-infected patients (371 men, 60 women); 249 patients with HIV/HCV coinfection, 115 HIV alone, and 67 with HIV/HBV. Intervention: alcohol use was estimated at first interview and reported as the estimated average lifetime consumption in grams/day. Outcome measures: laboratory values, liver fibrosis, decompensation and mortality. Results. Twenty-two percent of patients in the entire cohort had high risk lifetime average alcohol consumption, defined as ≥ 50 mg/day. Fifty-six percent of patients had quit all alcohol when first evaluated, but follow-up showed that 26% continued high risk consumption. By univariate analysis high alcohol consumption was associated with Latino ethnicity, injection drug use (IDU) and hepatitis C (HCV) coinfection. Multivariable analysis showed only IDU to be independently associated with high alcohol consumption (RR = 4.1, p = 0.0005). There were no significant differences in laboratory values, including CD4 cell counts, except for a trend towards higher transaminases and liver fibrosis scores, between high and low alcohol users. All-cause mortality was statistically higher in the high (37%) vs. low (25%, p = 0.03) alcohol use group, and was associated with both IDU (RR = 2.2, p = 0.04) and the amount of alcohol consumed (RR = 1.1, p = 0.04). Liver decompensation and mortality were both higher in the high use group but of borderline significance. Using an ordinal grouping, we found a strong correlation (R = 0.88) between alcohol consumption and the percentage of liver death over total deaths, with lowest mortality rates found in those use of 10 g/day or less. Conclusions. Unsafe use of alcohol is prevalent in HIVinfected patients and stoppage is not universal. There is a significant impact on all-cause mortality and a trend towards higher liver morbidity and mortality. IDU is significantly and independently associated with high ethanol intake. Practitioners should strongly recommend that HIV patients minimize alcohol use.

  • Differential diagnosis of malignant epithelial tumours in the liver: an immunohistochemical study on liver biopsy material Najla Al-Muhannadi, Naseem Ansari, Urmil Brahmi, Ali Abdel Satir Page 508-515

    Introduction. A variety of primary and secondary malignant tumours may present in the liver. In clinical practice the most commonly encountered hepatic tumours are primary hepatocellular carcinoma, metastatic carcinoma and primary cholangiocarcinoma, each with its separate prognostic and management implications. When these tumours are poorly differentiated and the biopsy size is limited to a needle core, the distinction can be extremely difficult. Material and methods. All liver tumours reported between 1994 and 2004 were examined. Slides from each case were tested separately with each of nine antibodies (HepPar1, CD10, MOC31, Villin, pCEA, mCEA, CK7, CK19, and CK20). Results. Liver biopsy tissue from 53 patients was examined in this retrospective study. The 53 liver biopsies were classified thus: hepatocellular carcinoma (n = 23); metastatic adenocarcinoma (n = 15); cholangiocarcinoma (n = 5); metastatic small cell carcinoma (n = 7); liver cell dysplasia (n = 1); carcinoid (n = 1); and unclassified (n = 1). Sensitivity and specificity values for different antibodies in relation to their positive staining of specific tumours was as follows: HepPar1 for HCC-81.8% and 100%; MOC31 for MA-73.3% and 92.1%; MOC31 for MA and CC as a combined group-65% and 100%; pCEA (canalicular) for HCC-82.6% and 83.3%; mCEA for MA-93.3% and 75.6%; CK7 for CC-100% and 68%; CK19 for MA and CC as a combined group-90% and 86.3%. Conclusions. An antibody panel consisting of HepPar1, pCEA, CK19 and CK7 together with either MOC31 or mCEA is recommended for use in the differential diagnosis of HCC, MA and CC.

Basic studies

  • Alteration of AP-endonuclease1 expression in curcumin-treated fibrotic rats Ahmad R. Bassiouny, Amira Zaky, Faten Fawky, Kamal M. Kandeel Page 516-530

    Background. Apurinic/apyrimidinic endonuclease1/ redox factor-1 (APE1/Ref-1) is a multifunctional protein involved in DNA base excision repair and redox regulation of many transcription factors. It is an important pro-survival protein activated in response to oxidative stress. Increased level of this essential redox sensitive protein correlates closely with cellular survival against oxidative insults. Curcumin (diferuloylmethane) a naturally occurring compound derived from turmeric has attracted interest because of its anti-inflammatory, anti-oxidative, and chemopreventive activities. Material and methods. The current study evaluates the in vivo role of curcumin in protecting and treating liver injury and fibrogenesis caused by carbon tetrachloride (CCl4) in rats. It also addresses the possible involvement of the multifunctional protein APE1 in hepatoprotection. Analysis of APE1 expression was performed at mRNA and protein levels by reverse transcriptase (RT)-PCR and western blotting respectively. Profile of HSCs-activation related genes were assayed by RT-PCR and pro-inflammatory cytokines levels were determined by enzyme-linked immune assays. Results. Here we show that oral administration of curcumin was accompanied by a robust increase in APE1 protein and mRNA levels, and improved the histological architecture of rat liver. In addition, curcumin attenuated oxidative stress by increasing the content of hepatic glutathione within normal values, leading to the reduction in the level of lipid hydroperoxide. Curcumin remarkably suppressed inflammation by reducing levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), nuclear factor-kappa B (NF-κB) and interleukin-6 (IL-6). It also inhibited hepatic stellate cells (HSCs) activation by elevating the level of PPARγ and reducing the abundance of transforming growth factor-β (TGF-β). We found that oral administration of curcumin at 200 mg/kg dose not only protected against CCl4-induced hepatic injury, but also resulted in more than two-fold induction of APE1 protein expression in CCl4-induced rat group. Conclusions. It can be concluded that curcumin reduced markers of liver damage in rats treated with CCl4, with concomitant elevation in APE1 protein level indicating a possible protective effect with unknown mechanism. The induction of DNA repair enzymes may be an important and novel strategy for hepatic protection against oxidative injury.

  • Glutamine prevents gastric oxidative stress in an animal model of portal hypertension gastropathy Camila Marques, José L. Mauriz, Douglas Simonetto, Claudio A. Marroni, María J. Tuñon, Javier González-Gallego, Norma P. Marroni Page 531-539

    Background and rationale. Portal hypertension (PHI) is a clinical syndrome characterized by increases of the blood flow and/or of the vascular resistance in the portal system. A direct consequence of PHI can appearance different lesions on the gastric mucosa and submucosa, cumulatively termed portal hypertensive gastropathy (PHG). Aims. To investigate the effects of glutamine on oxidative stress in an experimental model of PHG induced by partial portal vein ligation (PPVL). Material and methods. Portal pressure, transaminase and alkaline phosphatase activity were quantified. Gastric tissue damage was assessed by histological analysis. Oxidative stress was measured by quantification of cytosolic concentration of thiobarbituric acid reactive substances (TBARS), hydroperoxide-initiated chemiluminescence (QL), and nitric oxide (NO) production. Moreover, activities of the antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT) were analyzed. Results. Transaminase and alkaline phosphatase activities were not significantly modified by PPVL, indicating absence of liver injury. Histological analysis of gastric sections showed a lost of normal architecture, with edema and vasodilatation. TBARS, QL, and NO production were significantly increased in PPVL animals. A reduction of SOD activity was found. Glutamine administration markedly alleviated histological abnormalities and oxidative stress, normalized SOD activity, and blocked NO overproduction. Conclusions. Our results confirm that the use of molecules with antioxidant capacity can provide protection of the gastric tissue in portal hypertension. Glutamine treatment can be useful to reduce the oxidative damage induced by PHI on gastric tissue.

  • Protective effect of Thymic Humoral Factor on porcine serum-induced hepatic fibrosis and liver damage in Wistar rats Ulises Osuna-Martínez, Jorge Alberto Reyes-Esparza, Vera L. Petricevich, Rogelio Hernández-Pando, Lourdes Rodríguez-Fragoso Page 540-551

    Introduction. Immunomodulatory drugs have been reported to have anti-inflammatory and anti-fibrotic properties. Thymic Humoral Factor (THF), a peptide produced in the thymus, causes a potent immunomodulatory effect on different components of the immune system. Objective. To evaluate the effect of THF on different stages of liver damage and fibrosis induced in rats through the administration of porcine serum (PS). Material and methods. PS-induced liver fibrosis models serve as a primarily immunological mechanism in the development of liver damage and fibrosis. Results. The intraperitoneal administration of THF in rats with PS-induced liver damage produced a reduction of ALT and AST after 60 days. Histopathological changes in liver sections showed an improved histological appearance and lower % of fibrosis after 60 days in liver damaged rats that received THF treatment. Serum IL-6 levels were visibly reduced by THF administration after 60 days and in comparison with rats that did not receive the treatment. This was due to an increment in serum IL-10 levels caused by the administration of THF, which appears to reduce the inflammatory process by decreasing immune response. Conclusion. THF had beneficial effects in combating liver damage and fibrosis processes in an autoimmune model of PS-induced liver fibrosis in rats.

EDITORIAL

IMAGES IN HEPATOLOGY

  • Takayasu arteritis associated with hepatic sinusoidal dilatation Cécile Durant, Jérome Martin, Baptiste Hervier, Jérome Gournay, Mohamed Hamidou Page 559-561

    Hepatic sinusoidal dilatation (HSD) is a pathological entity that is characterized by peliosis hepatis (PH) like lesions, with vascular lesions that consist of multiple cyst-like, blood-filled cavities within the liver. To the best of our knowledge, neither PH nor HSD have been associated with systemic vasculitis. We describe herein two cases of idiopathic HSD associated with Takayasu arteritis (TA), diagnosed at an early stage of vasculitis. The same endothelial target in HSD and TA, and the favorable outcome of HSD with treatment of TA, suggest a pathogenic link between the two diseases.

CASE REPORTS

  • Recurrent liver failure caused by IgG4 associated cholangitis Jacob N. Clendenon, Jaime Aranda-Michel, Murli Krishna, C. Burcin Taner, Darrin L. Willingham Page 562-564

    Immunoglobulin G4 associated cholangitis (IAC) is an autoimmune disease associated with autoimmune pancreatitis (AIP). It presents with clinical and radiographic findings similar to primary sclerosing cholangitis (PSC). IAC commonly has a faster, more progressive onset of symptoms and it is more common to see obstructive jaundice in IAC patients compared to those with PSC. One of the hallmarks of IAC is its responsiveness to steroid therapy. Current recommendations for treatment of AIP demonstrate excellent remission of the disease and associated symptoms with initiation of steroid therapy followed by steroid tapering. If untreated, it can progress to irreversible liver failure. This report describes a 59 year-old female with undiagnosed IAC who previously had undergone a pancreaticoduodenectomy for a suspected pancreatic cancer and later developed liver failure from presumed PSC. The patient underwent an uncomplicated liver transplantation at our institution, but experienced allograft failure within five years due to progressive and irreversible bile duct injury. Radiology and histology suggested recurrence of PSC, but the diagnosis of IAC was suspected based on her past history and confirmed when IgG4 positive cells were found within the intrahepatic bile duct walls on a liver biopsy. A successful liver retransplantation was performed and the patient is currently on triple immunosuppressive therapy. Our experience in this case and review of the current literature regarding IAC management suggest that patients with suspected or recurrent PSC with atypical features including history of pancreatitis should undergo testing for IAC as this entity is highly responsive to steroid therapy.

  • Cholestasis as the initial presentation of relapsing polychondritis Renata Cristina Teixeira Pinto Viana, Lígia da Rosa, Maria Beatriz Cacese Shiozawa, Janaína L. Narciso-Schiavon, Esther Buzaglo Dantas-Corrêa, Leonardo de Lucca Schiavon Page 565-567

    Relapsing polychondritis is an immune-mediated disease associated with inflammation in cartilaginous structures and other tissues throughout the body, particularly the ears, nose, eyes, joints, and respiratory tract. Although association with other conditions is seen in about one-third of the cases, liver involvement is not usually observed in those patients. We described a case of liver involvement in relapsing polychondritis, presenting with a predominantly cholestatic pattern. Other conditions associated with abnormal liver tests were excluded and the patient showed a prompt response to steroid therapy. We discuss the spectrum of the liver involvement in relapsing and review the literature.

  • Hepatotoxicity from ingestion of wild mushrooms of the genus Amanita section Phalloideae collected in Mexico City: two case reports Jorge Méndez-Navarro, Nayeli X. Ortiz-Olvera, Margarita Villegas-Ríos, Luis J. Méndez-Tovar, Karin L. Andersson, Rosalba Moreno Alcantar, Víctor E. Gallardo-Cabrera, Sergio Félix, Carlos Galván, Gilka Vargas, Luz M. Gómez, Margarita Dehesa-Violante Page 568-574

    We present two cases of acute liver injury resulting from consumption of wild mushrooms. The first case was a male who developed acute hepatitis after ingestion of diverse mushrooms including Amanita species. His clinical course was favorable with complete recovery of liver function. The second case was a male who developed acute liver failure (ALF) after ingestion of Amanita bisporigera. He required MARS therapy as a bridge to liver transplantation but transplantation was not performed because he succumbed to multiorgan failure. There are few trials demonstrating the efficacy of the different treatments for mushroom poisoning. These cases demonstrate that the consumption of wild mushrooms without proper knowledge of toxic species represents a serious and under recognized health problem.

LETTER TO EDITOR

LIVER NEWS ELSEWHERE

  • Hepatitis A virus infection in high-risk subjects Tonatiuh Barrientos-Gutiérrez, Diana Brizuela-Alcántara, Norberto C. Chávez-Tapia Page 578-579

    Background & Aims. Several outbreaks of hepatitis A affecting homosexual men have been reported in Europe. However, the prevalence of HIV infection in patients affected by hepatitis A has not been extensively studied and hepatitis A is not considered as an indicator disease for routine HIV testing. Methods. We retrospectively analyzed all adult cases of acute hepatitis A, reported by the National Institute of Infectious Disease ''L. Spallanzani'', Rome-Italy, in 2002–2008. Data on HIV infection were obtained by chart review and cross-linkage with laboratory. Information on exposure to risk factors were collected from the standard questionnaire of the Local Health Unit. Results. We analyzed a total of 473 cases of hepatitis A, 368 (77.2%) males that accounted for 75% of all reported cases in Rome, aged 25–64 years (same gender distribution). During the study period, we diagnosed a high proportion of cases among male individuals (78%). Among the male patients, HIV serology was available for 203/368 (55.2%). The overall HIV prevalence was 15.2% (56/368); it was significantly associated with same gender sex and was significantly higher than that observed among patients with hepatitis B (4.0%). Conclusions. We found a high HIV prevalence, associated with same gender sex, among adult male patients diagnosed with hepatitis A in the period 2002–2008, except for 2006. Our data suggest that in a low incidence area for hepatitis A, with a constant high proportion of cases among male individuals, all individuals with acute hepatitis A should be routinely offered an HIV test.

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The Official Journal of the Mexican Association of Hepatology, the Latin-American Association for the Study of the Liver and the Canadian Association for the Study of the Liver

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