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Current Issue

April - June, 2006

Vol. 5 Issue 2

On the cover: Official Journal of the Mexican Association of Hepatology



  • The future of stem cells in liver diseases Maurizio Muraca, Ginevra Galbiati, Maria Teresa Vilei, Aline Sueli Coelho Fabricio, Maddalena Caruso Page 68-76

    Preliminary experience with clinical hepatocyte transplantation during the past decade has provided proof of concept that cell therapy can be effective for the treatment of some liver diseases. Recent progress in cell biology resulting in the isolation and characterization of hepatic stem cells and progenitor cells further increased the expectation for a new approach to the treatment of genetic and chronic liver disease. Several potential sources have been identified of hepatic stem/ progenitor cells exhibiting both differentiation towards the hepatic lineage in vitro and hepatic parenchymal repopulation with liver-specific metabolic activity in liver-injured animal models. However, a few of these results proved to be poorly reproducible in different laboratories, and it was recognized that some initial optimistic conclusions were drawn from incorrect interpretation of experimental data or from insufficient knowledge of the mechanisms involved in tissue regeneration. Moreover, only modest results have emerged so far from ongoing clinical experience involving the use of putative stem cells in liver disease. There is much need for a joined effort to concentrate the resources on a specific cell population, in order to better characterize its function, to assess its safety and to develop better focused clinical trials. In conclusion, while the biological features of stem cells still justify the hope for future clinical applications, hepatic stem cell therapy has still a long way to go from bench to bedside.

  • Post-liver transplantation medical complications Rosalba Moreno, Marina Berenguer Page 77-85

    Liver transplantation (LT) is widely accepted as an effective therapeutic modality for a variety of irreversible acute and chronic liver disease. The success of liver transplantation has increased steadily over the last two decades and several advances have been made since the first human liver transplant. This procedure has become routine with an excellent outcome in terms of both quality and length of survival. The results of liver transplantation have improved due to advances in perioperative technique, a better understanding of the course and prognosis of several liver disease, improved immunosuppressive therapy and more effective postoperative care. Nevertheless, improved tools detecting under immunosuppression, new strategies against viral infections (i.e. cytomegalovirus), and new immunosuppressive drugs will probably even prevent further graft dysfunction in the future. However, complications are common in the early and long term period and contribute to significant morbidity and mortality. One of the major challenges facing the transplant community is the increasing metabolic complications that are now affecting quality of life and long-term survival. Thus, knowledge of complications that emerge during follow up period, early and accurate establishment of diagnosis, and prompt institution of appropriate interventions are essential for optimal patient and graft outcome. This review summarizes available data about medical complications of the early and long term follow up.

  • Beta blockers in portal hypertension. Are they really a good option? Eric López-Méndez, Misael Uribe Page 86-91

    Non-selective beta blockers are very useful drugs in preventing first variceal bleeding and re-bleeding in patients with cirrhosis. These drugs work in two ways: 1) by blocking β1 receptors and reducing cardiac output, and 2) by blocking β2 receptors, producing splanchnic vasoconstriction and reducing portal flow. Consequently, they reduce portal pressure. In primary prophylaxis, beta blockers reduced the bleeding risk from 30 to 15%; in secondary prophylaxis, this risk decreased from 60 to 42% in the first year. Heart rate decrease does not necessary correlate with reduction in hepatic venous pressure gradient (HVPG). When this gradient is reduced to less than 12 mmHg, the patient will not bleed; when this is reduced > 20% from basal values bleeding risk is extremely low, estimated at 9% at 2 years. The only way to know whether the patient has become a responder is to measure the HVPG. Additionally, by means of this method we also can identify the non-responders, who have a higher rate of re-bleeding, between 54 and 64%, and can attempt to utilize a more aggressive therapy, such as adding isosorbide mononitrate to the beta blocker or combining the beta blocker with endoscopic ligation. These options are discussed in the present review.


  • Clinical and virological features of acute HBV-related hepatitis in southern Vietnam Yen-Xuan Thi Nguyen, Dieu-Hien Tran Pham, Nga Ngoc Cao, Lory Saveria Crocè Page 92-96

    Background: Despite the availability of effective vaccines, hepatitis B virus (HBV) infection is still frequent worldwide, and accounts for significant morbidity and mortality. However, data of acute HBeAg negative hepatitis still remain limited. Aims and Methods: To understand clinical pictures of acute HBV hepatitis and its natural evolution, a prospective study was conducted in adult patients. Results: Ninety patients were enrolled between March 2004 and April 2005 at Hospital for Tropical Diseases in Ho Chi Minh city. The prevalence of HBeAg negative was 53%. No significant difference was found in clinical characteristics and laboratory findings between HBeAg positive and negative patients. HBV-DNA was detected in 75% and 88% HBe negative and positive patients, respectively, where the frequency of ALT below 400 U/L was significantly higher in HBeAg negative cases (p = 0.01). Six month follow-up was available in 47 patients. HBsAg positivity was found in 16% of HBeAg negative subjects but only in 4.5% of HBeAg positive cases. Thirty two patients had neither HBsAg nor anti-HBs. Conclusions: The clinical and laboratory feature and the outcome at 6 months of HBV acute hepatitis in Vietnam is similar in HBeAg positive and negative patients.

  • Obesity-related leptin receptor polymorphisms and gallstones disease Nahum Méndez-Sánchez, Luisa Bermejo-Martínez, Norberto C. Chávez-Tapia, Daniel Zamora-Valdés, Karla Sánchez-Lara, Martha H Uribe-Ramos, Guadalupe Ponciano-Rodríguez, Hector A. Baptista-González, Martha H. Ramos, Misael Uribe Page 97-102

    Objective: Investigate the association between polymorphisms in the leptin receptor gene associated with obesity and gallstone disease. Design: We conducted a cross-sectional study, carried out at a tertiary setting. Subjects: We enrolled 97 subjects, comprising 54 subjects with gallstones (cases) and 43 controls (without gallstones). Measurements: Diet was assessed using a validated questionnaire for the Mexican population. Body mass index, waist circumference, serum glucose, insulin, leptin, lipids and lipoproteins levels were measured. Insulin resistance was calculated by HOMA-IR. Genomic DNA was isolated from lymphoblastoid cells, and Q223R and K656N polymorphisms in the leptin receptor gene were typed using polymerase chain reaction. Unconditional univariate logistic regression analysis was conducted to estimate the probability of gallstone disease associated with the polymorphisms as main effect. Results: Cases were different in gender (40.74% males in cases vs 74.41% in controls; p < 0.001), older (49.74 vs 44.83 years; p < 0.05), and had more body fat (32.34% vs 28.14%; p = 0.01). Individuals carrying the polymorphism Q223R exhibited a higher BMI (28.44 ± 6.6 kg/m2 vs 25.94 ± 3.67 kg/m2, p < 0.05) and waist circumference (96.7 ± 16.39 cm vs 89.2 ± 11.05 cm, p < 0.05). In univariate analysis, we did not observe a relation between the presence of a R223 or N656 genotype and gallstone disease in our population (OR = 0.78, 95% CI 0.35-1.73). Conclusion: Obesity-related leptin receptor polymorphisms are not associated with gallstones disease.

  • An experience with covered transjugular intrahepatic portosystemic shunt for refractory ascites from western India Deepak N. Amarapurkar, Sundeep Punamiya, Nikhil D. Patel Page 103-108

    Background: In refractory ascites/hydrothorax (RA), uncovered transjugular intrahepatic portosystemic shunt (TIPS) is shown to be superior to large-volume therapeutic paracentesis (LVP) for long-term control of ascites, but at a cost of increased risk of hepatic encephalopathy (HE). Use of covered TIPS has shown to improve shunt patency rate over uncovered TIPS. This retrospective analysis was performed on patients with RA to assess efficacy of TIPS, both covered and uncovered. Methods: Over 10-year period, patients with RA, patients either required LVP at least 2 times in a month, or were intolerant to LVP, or were unwilling to undergo further LVP, were treated with TIPS (Group-A = 12 patients with uncovered TIPS {Wallstent = 10, Memotherm = 1, SMART = 1}, age = 56.1 ± 4.5 years, male: female = 5:1; Group-B = 11 patients with e-PTFE-covered TIPS {Viatorr = 11}, age = 55.8 ± 5.2 years, male: female = 8:3). They were followed-up with clinical and ultrasonography/ Doppler examination every monthly for 3 months and every 3 monthly thereafter (mean = 9.6 ± 4.2 months). Clinical success (disappearance of ascites at 1-month), technical success (post-TIPS reduction of portosystemic pressure gradient {PPG} < 12 mmHg), appearance of encephalopathy, TIPS-dysfunction (> 50% reduction in flow-velocity, > 50% shunt stenosis or increase in PPG > 12 mmHg in presence of symptoms) and mortality were noted. Data were analyzed using chi-square test and t test. Results: Baseline clinical and biochemical characteristics were similar in both groups. TIPS placement was possible in 11/12 group-A and 11/ 11 group-B patients. Fall in PPG after TIPS was similar in both groups. One patient in group-A was lost followup after the procedure. On comparison of group-A and group-B, clinical success (63.3% and 81.8%), technical success (90.9% and 100%), occurrence of HE (60% and 54.4%) and mortality at 1-year (70% and 63.3%) were not significantly different. TIPS-dysfunction requiring re-intervention was significantly more common in group-A (50%) than group-B (0%). Conclusions: Covered TIPS was superior to uncovered TIPS, because of less TIPS-dysfunction without increasing chances of HE; but failed to offer any survival advantage.

  • Metabolic syndrome, non-alcoholic steatohepatitis (NASH), and hepatocyte growth factor (HGF) Yasemin H. Balaban, Hale Sumer, Halis Simsek, Durdal Us, Gonca Tatar Page 109-114

    Background: Hepatocyte growth factor (HGF) is not only an antiapoptotic and antifibrotic factor of liver, but it is also an adipokine. Serum HGF levels are strongly associated with liver diseases, obesity, insulin resistance (IR), and metabolic syndrome (MS). Non-alcoholic steatohepatitis (NASH) is the hepatic component of MS. To the best of our knowledge, serum HGF levels in patients with NASH have not been previously studied. Our aim was to elucidate the correlation of HGF with the clinical and histopathological parameters of NASH. Methods: The study group consisted of 26 patients (13 men) who had clinical diagnoses of NASH and underwent liver biopsies. Controls were 13 volunteers (3 men) with negative viral autoimmune markers, and with normal levels of serum lipids and liver enzymes. Results: Among the NASH patients, 14 (54%) were overweight and 10 (39%) had grade I-II obesity. All the patients had class 3-4 non-alcoholic fatty liver disease (NAFLD) except for 2 who had class 2 disease. All of the patients had Child’s class A liver disease, and MS was present in 5 (19%) patients and 8 (31%) patients had Homeostasis Model Assessment of Insulin Resistance (HOMA) > 3. Serum HGF levels were similar in NASH patients (1.24 ± 1.09 pg/mL) and controls (0.86 ± 0.22 pg/mL) (p = 0.21). The levels of serum HGF did not differ between the patients with or without MS (1.65 ± 1.48 pg/mL and 1.04 ± 0.80 pg/mL, respectively, p=0.65). HGF was not correlated with the laboratory or histopathological parameters. Conclusions: Serum HGF levels were higher in NASH patients than in the controls, although it was statistically insignificant and a correlation with MS could not be detected in this study.



  • Vanishing bile duct syndrome in a child with toxic epidermal necrolysis: An interplay of unbalanced immune regulatory mechanisms Wikrom Karnsakul, Thaschawee Arkachaisri, Kanit Atisook, Wanee Wisuthsarewong, Yudhtana Sattawatthamrong, Prapun Aanpreung Page 116-119

    Vanishing bile duct syndrome (VBDS) is a rare disorder and requires a liver biopsy for a diagnosis. The condition has not been reported in children with toxic epidermal necrolysis (TEN). The etiology of VBDS in our patient with TEN is most likely from drug hypersensitivity. A high index of suspicion will prompt clinicians to start more specific investigations and treatments. The use of immunosuppressive agents, intravenous immunoglobulin and ursodeoxycholic acid has not been consistently successful in these patients. A new approach with biologic agents such as anti-tumor necrosis factor-α may be a promising therapy and reduce severe adverse outcomes.

  • An unusual cause of bilioenteric anastomotic dysfunction after iatrogenic bile duct injury Miguel Angel Mercado, Daniel Borja-Cacho, Ismael Domínguez, Eduardo Carrillo Maravilla, Norberto Sánchez, Eli Zavaleta-Martínez, Arturo Ramírez-Muciño, Alexandra Barajas-Olivas, Ricardo Arceo-Olaiz Page 120-122

    Roux en Y hepatojejunostomy is the surgery of choice for bile duct repair. Anastomotical dysfunction after reconstruction has several etiopathologies. Besides technical factors, ischemia of the duct is responsible for late obstruction. Bile colonization with secondary stones and sludge can also be identified as a cause. An unusual cause of anastomotical dysfunction secondary to ascaris biliary infestation after biliary reconstruction is reported herein. The patient had intermittent cholangitis and eosinophilia. At operation, the worm was found obstructing the anastomosis.

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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