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Current Issue

July - September, 2006

Vol. 5 Issue 3

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

HEPATOLOGY HIGHLIGHTS

CONCISE REVIEW

  • Cirrhotic cardiomyopathy Waleed Al Hamoudi, Samuel S. Lee Page 132-139

    Liver cirrhosis is associated with a wide range of cardiovascular abnormalities. These abnormalities include hyperdynamic circulation characterized by an increase in cardiac output and a decrease in peripheral vascular resistance. Despite the increased cardiac output, impaired ventricular contractility in response to both physiological and pharmacological stimuli has been described. Other cardiac abnormalities include structural changes including enlargement or hypertrophy of different cardiac chambers and electrophysiological changes such as QT prolongation. This constellation of cardiac abnormalities is termed cirrhotic cardiomyopathy. The pathogenic mechanisms of cirrhotic cardiomyopathy are multifactorial and include cardiomyocyte plasma membrane physico-chemical changes, attenuated stimulatory pathways, and enhanced activity of inhibitory systems. Accumulating evidence suggests that cirrhotic cardiomyopathy plays a major role in the pathogenesis of cardiac dysfunction following liver transplantation or transjugular intrahepatic portosystemic shunt placement. Recent research also strongly suggests that cirrhotic cardiomyopathy contributes to the pathogenesis of hepatorenal syndrome, especially following infections such as spontaneous bacterial peritonitis. Treatment of this syndrome remains largely empirical. Successful liver transplantation is thought to improve all the organ-related hemodynamic dysfunctions, including hepatopulmonary syndrome, cerebral hypoperfusion, hepatorenal syndrome, and cirrhotic cardiomyopathy. The prolonged QT interval normalizes following liver transplantation. Thus, liver transplantation appears to be the ultimate treatment for the cardiovascular complications of cirrhosis.

  • Genetic predisposition of cholesterol gallstone disease Alejandro Hernández-Nazará, Fátima Curiel-López, Erika Martínez-López, Zamira Hernández-Nazará, Arturo Panduro Page 140-149

    Gallstone disease (GSD) is the result of the interaction between genetic and environmental factors and it is a major disease cause of surgery with high costs to health systems. Worldwide prevalence varies according to the ethnic population suggesting that high prevalence of GSD in certain ethnic groups is due to the presence of genetic factors implicated in different metabolic pathways. However, environmental factors play a determinant role in gene expression. This review summarizes the genes involved in biliary salt and cholesterol synthesis, lipids transport and the Lith genes. Future studies should be focused on the study of interactions between genetic and environmental factors which could be specific for each population.

ORIGINAL ARTICLES

  • Differential diagnosis of acute liver failure in India Amarapurkar Deepak N, Nikhil D Patel Page 150-156

    Background: Acute liver failure (ALF) is a condition with rapid deterioration of liver function resulting in hepatic encephalopathy and/or coagulopathy in patients with previously normal liver. Complicated forms of certain infectious diseases like falciparum malaria, leptospirosis, dengue fever, ricketsial fever, typhoid fever, haemophagocytosis, herpes simplex virus, cytomegalovirus, tuberculosis or amoebic liver abscess can present with altered mentation and/or bleeding manifestations in presence of jaundice and mimic ALF due to acute viral hepatitis (AVH). Methods: We describe our experience in last 2 years with 28 patients of ALF due to above mentioned conditions (ALF-ID) and compared them with 28 patients with ALF due to AVH (ALF-AVH). Results: In ALF-ID, typhoid fever was present in 1, haemophagocytosis in 1, ricketsial infection in 4 (scrub typhus = 2, endemic typhus = 2), amoebic liver abscess in 4, leptospirosis in 5, dengue fever in 5 and falciparum malaria in 8 patients. In ALF-AVH, hepatitis E and B co-infection was responsible in 1, hepatitis A and E co-infection in 1 and hepatitis E, B and C co-infection in 1, hepatitis E in 18, hepatitis A in 2 and hepatitis B in 5 patients. Differentiation of various forms of ALF-ID from ALF-AVH depends on various clinical, haematological and biochemical parameters, in addition to specific diagnostic tests. Patients with ALF-AVH had mortality rate of 50% (14/28) and ALF-ID had mortality rate of 25% (7/28). Conclusions: In developing countries, ALF-mimicking infections should be looked for in differential diagnosis of ALF. Early identification and treatment of these infections is important in reducing mortality.

  • Early experience of Budd-Chiari syndrome treatment with transjugular intrahepatic portosystemic shunt Eric López-Méndez, Norberto C Chávez-Tapia, Lourdes Avila Escobedo, Tatiana Cabrera-Aleksandrova, Misael Uribe Page 157-160

    The Budd–Chiari syndrome is a heterogeneous group of disorders characterized by obstruction of hepatic venous outflow at any level from the small hepatic veins to the junction of the inferior vena cava with the right atrium. We present two cases of Budd– Chiari syndrome with severe ascites associated with polycythemia vera in first case and protein C deficiency in the second, in both cases transjugular intrahepatic portosystemic shunt were placed, with excellent control of symptoms, no mortality were observed, and just one episode of pulmonary venous thrombosis was observed. To our knowledge this is the first time that transjugular intrahepatic portosystemic shunt are used and reported in Budd–Chiari syndrome in Mexico.

EDITORIAL

IMAGES IN HEPATOLOGY

CASE REPORTS

  • Nodular regenerative hyperplasia associated to aplastic anemia: A case report and literature review María S. González-Huezo, Luis M. Villela, María del Carmen Zepeda-Florencio, Claudia S. Carrillo-Ponce, Ricardo J. Mondragón-Sánchez Page 166-169

    Introduction: Nodular regenerative hyperplasia (NRH) is a rare condition is associated to immune, neoplastic, vascular disorders, and certain drugs and toxins. Portal hypertension is the main complication. Aim: To report the case of a woman with NRH and aplastic anemia, association not previously described. Case: A 31- year-old hispanic female presented with pancitopenia and cholestasis. Bone marrow biopsy: aplastic anemia. Abdominal ultrasound revealed multiple liver nodules, without hepato-splenomegaly. No abnormalities were noted in hepatic vessels. Antimitochondrial (AMAs) were positive. Coagulation tests were normal. Liver biopsy: hepatocite nodules with central atrophy and sinusoidal dilatation in the absence of significant fibrosis. No arteritis, thrombosis or bile duct damage was found. Discussion: Pathogenesis of NRH remains unclear. The most accepted theory was developed by Wanless 24 years ago, and reinforced in 1997. It states that alterations in hepatic blood flow (portal obliterative venopathy) originate a specific response, initially consisting of apoptosis secondary to acute ischemia, with ensuing parenchymal atrophy and surrounding areas of liver regeneration and chronic ischemia. The common pathologic mechanism of all the diseases associated with NRH involves liver blood-flow abnormalities secondary to microthromboses, vascular congestion, or vasculitis. In the current case we were unable to document evidence of liver flow abnormalities. Noteworthy, there are previous descriptions of the association of NRH with primary biliary cirrhosis, and this patient was AMA positive, but without bile duct damage in liver biopsy. Conclusions: We cannot sustain Wanless' theory, and this is the first description of the association of NRH with aplastic anemia.

  • Lymphocytic interstitial pneumonitis (LIP) - The liver and the lung A Koulaouzidis, A Karagiannidis, S Prados, D Pattenshetty, A DeRamon, WC Tan Page 170-171

    Chronic liver disease may involve the lung through abnormal communications between the portal and pulmonary veins or by changes in the lungs caused by similar biochemical abnormalities to those in liver parenchyma. Lymphocytic interstitial pneumonitis(LIP) is more common in women and is associated with autoimmune diseases. Chest x-ray findings include reticular or reticulonodular opacities while computed tomography (CT) usually shows subpleural fibrosis (predominately in basal areas), ground-glass attenuation, traction bronchiectases and pulmonary parenchymal cysts.

  • Choroidal neovascularization with interferon associated retinopathy: Case report and review of literature Salem M. Bazarah, Rusty Ritenour, Sunil T. Patel, Geri Hirsch, Kevork M. Peltekian, Alan F. Cruess Page 172-176

    We report a case of new interferon-associated ocular complication during treatment with combination of pegylated interferon plus ribavirin for chronic hepatitis C infection. Our patient developed choroidal neovascularization in addition to the classic interferon associated retinopathy. Choroidal neovascularization has not been reported before in association with interferon induced retinopathy. We describe our management to control the ocular symptoms and the retinal lesions with one year follow up. We also provide literature report on the natural history, the pathophysiology and the variable characteristics of interferon associated retinopathy versus hepatitis C related ophthalmopathy.

  • Primary biliary cirrhosis associated pustular vasculitis A Koulaouzidis, S Campbell, A Bharati, N Leonard, R Azurdia Page 177-178

    The association between primary biliary cirrhosis (PBC) and cutaneous vasculitides is well recognized. Pustular skin lesions though, have been described in association with hepatobiliary diseases other than PBC. Once the more common infective pustular rashes have been excluded, the differential diagnoses for a pustular skin rash are acute generalized exanthematous pustulosis (AGEP), Sweet's Syndrome (SS), pyoderma gangrenosum (PG) and pustular vasculitis (PV). We present a case of pustular vasculitis associated with PBC.

  • Hepatoblastoma in adult age. A case report and literature review José M. Remes-Troche, Aldo Montaño-Loza, Judith Meza-Junco, Jorge García-Leiva, Aldo Torre-Delgadillo Page 179-181

    Hepatoblastoma (HB) rarely occurs in adults. We report herein the unusual case of a 19-year-old, otherwise healthy woman with no history of liver disease who presented with upper abdominal pain and hepatomegaly. Tests for hepatitis B virus (HBV), hepatitis C virus (HCV) were negative, and AFP was normal. There was no evidence of liver cirrhosis. A welldemarcated solid mass of 14 cm in diameter, which was lobulated and partly necrotic, was detected in the liver by computed tomography (CT). At surgical exploration a large liver mass was detected occupying the entire right lobe. A right trisegmentectomy was performed with tumor grossly resected with microscopic residual disease (i.e positive margins). On microscopic examination the tumor was composed mainly of two components which were intermingled: epithelial and mesenchymal elements. The epithelial component was formed of small embryonal cells, grouped into nodules, scattered in cellular mesenchymal tissue. The diagnosis was mixed hepatoblastoma. The patient received 4 cycles of systemic chemotherapy with cisplatinum and adriamycin. Post-chemotherapy evaluation revealed recurrence of the hepatoblastoma in the remaining liver. She died 6 months later.

SYMPOSIUM LIVER & PRENANGCY

  • Effect of Pregnancy on Pre-existing Liver Disease Physiological Changes During Pregnancy Angel García Alonso L Page 184-186

    The pregnant woman experiences physiological changes to support fetal growth and development. Particularly the physiological changes of the liver are the results of the increment of estrogens and progesterone during the pregnancy, and also the hemodynamics changes. (hemodilution). Telangiectasia may appear in up to 60% of normal pregnancies. Liver function test (LFT) abnormalities occurs in 3% of the pregnancies, and the Preeclampsia is the most frequent cause. Most of the articles agree that in normal pregnancy the LFT are either normal or slightly increase o decrease but within normal range. Thus, an increase in serum ALT, AST and GGT activities and serum bilirubin and total bile acid concentration during pregnancy may be pathologic and should prompt further evaluation. In the same way the serum albumin levels is significantly low and the serum alkaline phosphatase concentrations are considerably higher and are a normal component of the pregnancy , and if they are within normal range, do not usually indicate the presence of liver disease. The prothrombine time and the partial prothrombine time remain unchanged during pregnancy and serum fibrinogen increase in late pregnancy. Most of the articles related to plasma lipids in pregnancy agree that cholesterol. Triglyceride and lipoprotein increase during pregnancy. Use of gestational age of the pregnancy are the best guide to the differential diagnosis of liver disease in the pregnancy.

  • Pregnancy and autoimmune hepatitis Misael Uribe, Norberto C. Chávez Tapia, Nahum Méndez-Sánchez Page 187-189

    Autoimmune hepatitis is a rare condition that is more common among women than men. An association between pregnancy and autoimmune hepatitis is rare. This clinical scenario requires the gastroenterologist and hepatologist to have a profound knowledge of clinical course counseling and medical management. The prognosis in well-controlled and closely monitored patients is good. In this review, we discuss the most important aspects of autoimmune hepatitis and pregnancy as part of the Symposium on Liver and Pregnancy, co-sponsored by the Mexican Association of Hepatology and the Mexican Association of Gynecologists and Obstetrics.

  • Effect of pregnancy on pre-existing liver disease: Chronic viral hepatitis Silvia Sookoian Page 190-197

    Women with viral chronic hepatitis generally do quite well during pregnancy, providing that they have not progressed to decompensated cirrhosis. As a general rule, a stable liver equals a safe pregnancy. However, concern is about how pre-existing chronic liver disease may affect the pregnancy and the unborn baby. This review plans to answer some key questions regarding this issue in order to provide to healthcare professionals updated information of the current knowledge in this field. Besides, a synopsis of the following subject matters are reviewed, for instance, the main risk factors associated with vertical transmission of HBV and HCV in pregnant women chronically infected, the influence of pregnancy on HBV and HCV viral load and the effect of pregnancy on the clinical course of chronic hepatitis. Lastly, it is included a list of recommendations to decrease vertical transmission rates of chronic viral hepatitis as well as some information for the reproduction team.

  • Primary biliary cirrhosis Mary Eugenia Rinella Page 198-200

    Primary biliary cirrhosis (PBC) is a chronic, cholestatic liver disease that is characterized by progressive immune mediated destruction of the intrahepatic bile ducts. Over time, fibrosis extends out of the portal tracts and progresses to cirrhosis. Neither the etiology nor the pathogenesis are well understood; however, most of the current evidence suggests that it is an autoimmune condition that may be triggered by environmental stimuli in genetically predisposed individuals. Since the precise mechanisms involved in the pathogenesis of PBC have not been elucidated, curative therapy has not been identified and the focus has been on preventing disease progression. Ursodeoxycholic acid (UDCA), the only approved therapy for PBC, improves histology and retards disease progression. Future studies will likely combine UDCA with anti-inflammatory, immunosuppressive, immunomodulatory or antimicrobial agents. Once the etiology and pathogenesis of PBC are better delineated, more definitive therapy can be designed with curative intent.

  • Intrahepatic cholestasis of pregnancy: A past and present riddle Marco Arrese, Humberto Reyes Page 202-205

    Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy- specific disorders that occurs mainly in the third trimester of pregnancy and is characterized by pruritus and elevated bile acid levels. ICP is regarded as a benign disease with no meaningful consequences to the mother but associated to an increased perinatal risk with increased rates of fetal morbidity and mortality. The pathogenesis of disease is unknown but likely involves a genetic hypersensitivity to estrogen or estrogen metabolites. Mutations or polymorphisms of some hepatobiliary transport proteins may contribute to disease pathogenesis or severity. Treatment is focused on a) reducing symptoms in the mother and b) to provide an adequate obstetric management in order to prevent fetal distress. Currently, only Ursodeoxycholic acid treatment has been proven to be useful and should be considered mainly in patients with severe pruritus or complications in previous pregnancies

  • Focal nodular hyperplasia and hepatic adenoma: A Review Javier Lizardi-Cervera, Lorena Cuéllar-Gamboa, Daniel Motola-Kuba Page 206-211

    Focal Nodular Hyperplasia (FNH) and Hepatic Adenoma (HA) are a benign tumors of the liver. The association with the use of oral contraception in women in middle age has been mentioned. This benign liver tumors are relatively rare lesions and are usually unrelated to subjective symptoms. They are increasingly being diagnosed as a result of the widespread use of ultrasound, computed tomography and magnetic resonance in the evaluation of patients with non-specific abdominal symptoms.

  • Pregnancy after liver transplantation Mary Eugenia Rinella Page 212-215

    Although the transplant community has begun to gather experience in pregnancy after liver transplant, much remains to be learned about the effects of pregnancy on mother and child. Most women with end stage liver disease have amenorrhea or are unable to conceive due to medical complications. Liver transplantation offers such patients the opportunity to have children. Since libido and fertility can return fairly rapidly, it is important to discuss birth control in the early post transplant period. It is recommended that pregnancy be delayed for 1 and preferably 2 years post-transplant as pregnancies within the first year are associated with higher rates of premature birth and cellular rejection. The current evidence suggests that pregnancy is safe after transplant, however it requires close follow-up by a team of experienced physicians.

  • Cholestasis during pregnancy: Rare hepatic diseases unmasked by pregnancy Marco Arrese Page 216-218

    The occurrence of cholestasis during pregnancy may be due to several disorders. These include pregnancyspecific diseases, like intrahepatic cholestasis of pregnancy (ICP), as well as to other causes such as oligosymptomatic choledocolitiasis, viral hepatitis and other underlying liver disorders like primary biliary cirrhosis. In recent years, the discovery of mutations in hepatobiliary transporters genes responsible of some rare forms of genetic cholestasis have led to the study of this mutations in pregnant women with cholestasis. Thus, mutations in the hepatic phospholipid transporter (MDR3, ABCB4), in the aminophospholipid transporter ATP8B1 and in the bile salt export pump (BSEP, ABCB11) have been found in patients diagnosed as ICP. However, patients included in these studies belong to a heterogeneous population, which may not represent true cases of ICP since some reports include patients diagnosed in the first trimester of pregnancy, with elevated serum levels of gamma-glutamyl transpeptidase and clear evidence of chronic liver disease. Thus, consideration must be given to the possibility of other rare underlying hepatic disorders may be unmasked during pregnancy with cholestasis as its first manifestation.

  • Pregnancy and portal hypertension a pathology view of physiologic changes Eric López-Méndez, Lourdes Ávila-Escobedo Page 219-223

    The coexistent of pregnancy and liver disease represent a complex clinical situation, besides the liver complications that present in pregnancy with a previous health liver, like intrahepatic cholestasis of pregnancy, acute fatty liver of pregnancy or HELLP syndrome with bleeding disorders and viral hepatitis, the previous liver damage with portal hypertension associated represent a clear stated of hemodynamic changes which increased risk of variceal bleeding. The portal hypertension syndrome has a splanchnic blood flow increase. During pregnancy an hypervolemic stated developed as consequence there is an increased in portal flow that contributed to more portal pressure transmitted to the collaterals veins which increase variceal bleeding risk in this group of patients. The present review will focus on treatment options to prevent variceal bleeding in this clinical situation.

  • Hepatic hematoma and hepatic rupture in pregnancy Jorge Luis Poo, Julieta Góngora Page 224-226

    Hepatic perforation is an unusual complication of woman pregnancy associated with a poor outcome. A comprehensive review of epidemiology, clinical spectrum, diagnostic methods and therapeutic options is presented in this short paper.

  • Pregnancy and gallbladder disease Nahum Méndez-Sánchez, Norberto C. Chávez Tapia, Misael Uribe Page 227-230

    Gallbladder disease is a highly prevalent disease in western countries as a consequence of several genetic, biochemical, and environmental factors. Females are a highrisk group, and pregnancy increases this risk considerably. In fact, gallbladder diseases are the second most common indication for nonobstetric surgical intervention in pregnancy. In this review, we discuss the most important aspects of gallbladder disease and pregnancy as part of the Symposium on Liver and Pregnancy, co-sponsored by the Mexican Association of Hepatology and the Mexican Association of Gynecologists and Obstetrics.

  • Liver disease during pregnancy: acute viral hepatitis Silvia Sookoian Page 231-236

    Acute viral hepatitis is the most common cause of jaundice in pregnancy. The course of most viral hepatitis infections (e.g., hepatitis A, B, C and D) is unaffected by pregnancy, however, a more severe course of viral hepatitis in pregnancy has been observed in patients with hepatitis E. Notwithstanding, opinions differ over the maternal and fetal outcome of pregnancy associated with viral hepatitis. While some authors reported that acute viral hepatitis carries a high risk for both mother and fetus others conclude that non-fulminant viral hepatitis did not influence the course of pregnancy or fetal well-being. Rate of transmission of the virus during pregnancy depends on the virus. For instance, intra-utero transmission of hepatitis A virus is very rare, but perinatal transmission could occur. Conversely sixty percent of pregnant women who acquire acute HBV infections at or near delivery will transmit the HBV virus to their offspring and mother to child transmission of hepatitis E virus infection was established between 33.3 and 50%. Breast-feeding is not contra-indicated in women infected with the hepatitis A, E or C. However, for acute hepatitis B, with appropriate immunoprophylaxis, including hepatitis B immune globulin and hepatitis B vaccine, breast-feeding of infants of HBV infected mother's poses no additional risk for the transmission of the hepatitis B virus. Finally, whether live or inactivated vaccines are used, vaccination of pregnant women should be considered on the basis of risks versus benefits. Pregnant women who think they may have been exposed to hepatitis B may be given and hepatitis B immunoglobulin (ideally within 72 hours of exposure), as well as the hepatitis B vaccine.

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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