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Current Issue

January March, 2005

Vol. 4 Issue 1

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

EDITORIAL

CONCISE REVIEW

  • Current concepts in autoimmune hepatitis Albert J. Czaja Page 6-24

    Autoimmune hepatitis has a global occurrence, diverse clinical phenotype, and evolving treatment options. The goals of this report are to review the codified diagnostic criteria, spectrum of clinical presentations, proposed pathogenic mechanisms, conventional treatment strategies, and promising interventions. The literature published in English from 1980-2005 was reviewed and an updated current perspective provided. Autoimmune hepatitis affects all ages, may be asymptomatic, frequently has an acute onset, and can present as fulminant hepatitis. Perivenular (zone 3) necrosis is within the histological spectrum. Autoimmune hepatitis can recur or develop de novo after liver transplantation. CD4+ T-helper cells and natural killer T cells have been implicated in the pathogenesis, and molecular mimicry may break self-tolerance. DRB1*0301 and DRB1*0401 are the susceptibility alleles among white North Americans and northern Europeans, whereas diverse alleles of HLA DR4 have been associated with the disease in Japan, mainland China, and Mexico. DRB1*1301 is associated with autoimmune hepatitis in South American children, and it may predispose to an indigenous etiologic agent. Antibodies to soluble liver antigen/liver pancreas may have prognostic importance, and cyclosporine and mycophenolate mofetil must be assessed by clinical trial before incorporation into management algorithms. Sitespecific interventions are feasible, and they require a confident experimental animal model for evaluation. Variant syndromes lack diagnostic and therapeutic guidelines. In conclusion, autoimmune hepatitis must be considered in all patients with acute and chronic liver disease and those with allograft dysfunction after transplantation. New immunosuppressive agents and site-specific interventions promise to improve care.

  • Effect of cold preservation/reperfusion on glycogen content of liver. Concise review Alejandra B. Quintana, Edgardo E. Guibert, Joaquín V. Rodríguez Page 25-31

    Livers cold preserved during variable periods of ischemia suffer functional, morphological and hemodynamic alteration, which are exacerbated when they are reperfused. One important injury is glycogen depletion during cold ischemia/ reperfusion. How liver can restore their energy during reperfusion is related with the preservation time, nutritional status of the donor, and the preservation solution used. However, there are some treatments that help livers to preserve their energy storage. These procedures used drugs or metabolites, which are added to the liver to maintain their glycogen storage during preservation, time and allow the organ to restore its energy during reperfusion. There are several publications where the nutritional status of the donor was studied. There is controversy about the quality or the donor organ. Some authors say that fasted animals are better donors because this condition reduced hepatic injuries; others think that fed animals provide the necessary glycogen (energy) to improve liver preservation, reducing morphological and functional damages. Many others are convinced that nutritional status of the donor is not relevant because hepatic injuries will occurred even though the donor was fed or not. The preservation solution has an important role in reducing liver damages during cold ischemia/reperfusion and in restoring liver energy storage. Storage in HLR (histidine, lactobionate and raffinose) solution facilitated the resuscitation of energetic status and preserved adenine nucleotide levels significantly greater than Marshall's citrate or Bretschneider's histidine-based solution (HTK). University of Wisconsin (UW) proved to be suitable for energy recovery during reperfusion. In conclusion, the aim of this review is to present studies performed by different authors where they analyzed preservation/reperfusion injuries, how the liver restores its energy storage during reperfusion time, different strategies to avoid glycogen depletion during cold ischemia/reperfusion, the efficacy of preservation solutions and the effect of nutritional status of the donor to prevent functional alteration of the liver during cold preservation.

  • Alcoholic liver disease. An update Nahum Méndez-Sánchez, Paloma Almeda-Valdés, Misael Uribe Page 32-42

    The prevalence and incidence of alcoholic liver disease are constantly evolving. Alcoholic liver disease has a wide clinical spectrum. It may progress to cirrhosis and to end-stage liver disease requiring liver transplantation. The histological manifestations range from steatosis without inflammation to liver cell injury and ultimately to fibrosis and cirrhosis. In some cases, the histological manifestation is steatohepatitis, morphologically characterized by inflammation and necrosis. Currently, although there are no specific tests to establish a diagnosis of steatohepatitis, some serological, radiological, or laboratory tests may be useful. Liver biopsy is useful in confirming a suspected diagnosis and in assessing the extent of parenchymal damage. This review synthesizes the main aspects of the epidemiology, pathogenesis, morphological characteristics, diagnosis, treatment, and prognosis of alcoholic liver disease.

ORIGINAL ARTICLES

  • Hepatitis G virus RNA positivity among the voluntary blood donors: a summary Viroj Wiwanitkit Page 43-46

    Hepatitis virus infection is an increasing problem. Millions of humans all over the world are infected. Viral hepatitis is accepted as a significant public health problem with several life altering complications. Recently, new viruses have been identified for their association with hepatitis. Hepatitis G virus (HGV) is a single stranded RNA virus which represents a newly discovered virus belonging to the flavivirus family. Epidemiological data indicate that the virus is transmitted via blood/blood products, sexually and vertically from infected mothers to children. There are some previous reports on the prevalence of HGV infection among the blood/blood products. The purpose of this study is to summarize the prevalence of HGV infection, defined as HGV RNA positivity, among the voluntary blood donors in the previous reports. Due to this study, there have been at least 30 reports. Of 13,610 documented voluntary donors, there are 649 cases with HGV RNA positivity. The summative percentage for HGV RNA positivity is 4.8%: 4.5% in Caucasian, 3.4 % in Asian and 17.2% in Negroid. There is no significant association between ethnicity of donors and prevalence of HGV RNA positivity (p > 0.05). The HGV infection seems to distribute in all ethnicities all over the world, implying the global importance of this hepatitis virus infection. Screening for HGV RNA might be an important test in blood bank process in the future.

  • Histological spectrum of liver in HIV - Autopsy study Anjali D Amarapurkar, NA Sangle Page 47-51

    Introduction: Liver abnormalities are common in HIV positive patients. They are usually part of generalized process and rarely produce significant liver failure. Aim: To evaluate histological spectrum of liver disease in HIV positive patients and to ascertain if any pathologic features are widespread among HIV infection. Material & methods: Autopsy data from year 1991 to 2003 consisting of 60 HIV positive patients were evaluated. Demographic profile, clinical and laboratory data were obtained from hospital records. Macroscopic findings of all organs at autopsy were noted. Histological features of liver were studied in detail using routine H & E., Ziehl-Neelson stain for acid fast bacilli and other special stains such as PAS and GMS for fungal infection were done whenever indicated. Results: Patients were in age group 19 to 55 years with mean age of 32.1 year; male to female ratio was 4:1. Evidence of tuberculosis either pulmonary or extrapulmonary was found in 35 (58.3%) cases. On histological examination of liver, tubercular granulomas were seen in 19 (31.6%) cases of disseminated tuberculosis. Granulomas were typical caseating epitheloid cell type in 14 (73.6%) and in 5 cases granulomas were not typical. Acid fast bacilli were demonstrated in 4 (6.6%) cases, all of which showed presence of granulomas. Other histological findings were sinusoidal and centrivenular congestion in 14 (23.3%), extensive fatty change 6 (10%), portal inflammation resembling chronic hepatitis 5 (8.3%), focal necrosis 2 (3.3%), Kupffer cell hyperplasia 1 (1.6%) and metastasis from known case of adenocarcinoma of pancreas 1 (1.6%). Associated hepatitis C and B infections were seen in 4 (6.6%) and 1 (1.6%) respectively. Opportunistic infection was seen in only 1 (1.6%) case with disseminated cryptococcosis involving liver. In remaining 6 (10%) liver histology was normal. Considering cause of death, 58.3% patients died due to disseminated tuberculosis. Patients with associated hepatitis B & C infection died due to liver cirrhosis and the remaining died of miscellaneous conditions, which were not related to HIV infection. Conclusion: Histopathological findings of the liver in HIV positive patients were mainly non specific. Tuberculosis was the commonest infection noted. There was no significant mortality observed specifically related to liver involvement in these patients.

  • Trends in liver disease prevalence in Mexico from 2005 to 2050 through mortality data Nahum Méndez-Sánchez, Antonio R. Villa, Norberto C. Chávez-Tapia, Guadalupe Ponciano Rodriguez, Paloma Almeda-Valdés, Daniela González, Misael Uribe Page 52-55

    Background and Aims. The epidemiology of liver cirrhosis differs across sex, ethnic groups, and geographic regions. In 2000, chronic liver disease was the fifth leading cause of death in Mexico. Accurate knowledge of the demographics of liver disease is essential in formulating health-care policies. Our main aim was to project the trends in liver disease prevalence in Mexico from 2005 to 2050 based on mortality data. Methods. Data on national mortality reported for the year 2002 in Mexico were analyzed. Specific-cause mortality rates were calculated for a selected age population (> 25 years old) and classified by sex and projected year (2005–2050). The following codes of the International Classification of Diseases for liver diseases were included: non-alcoholic chronic liver disease and cirrhosis, alcoholic liver disease, liver cancer, and acute and chronic hepatitis B and C infection. The projected prevalence of a chronic liver disease was estimated using the following equation: P = (ID × T) / [(ID × T) + 1], where P = prevalence, ID = incidence density (mortality rate multiplied by 2), T = median survival with the disease (= 20 years). Results: Nearly two million cases of chronic liver disease are expected. Alcohol-related liver diseases remain the most important causes of chronic liver disease, accounting for 996,255 cases in 2050. An emergent syndrome is non-alcoholic liver disease, which will be more important that infectious liver diseases (823,366 vs 46,992 expected cases, respectively). Hepatocellular carcinoma will be the third leading cause of liver disease. Conclusions: Chronic liver disease will be an important cause of morbidity and mortality in the future. Preventive strategies are necessary, particularly those related to obesity and alcohol consumption, to avoid catastrophic consequences.

  • Combination of Peginterferon (omega)-2b (12 kDa) and Lamivudine in difficult-to-treat chronic hepatitis B-an Indian experience Deepak N. Amarapurkar, Nikhil D. Patel Page 56-59

    Introduction: Treatment strategies for chronic hepatitis B (CHB) using either interferon or Lamivudine can achieve sustained response in 30-40 % in HBeAg positive CHB. Retreatment of treatment failure in CHB and treatment of HBeAg negative patients pose major therapeutic challenge. Because of success story of Peginterferon in hepatitis C and some preliminary data in CHB, we undertook this open-labeled prospective study to study the response of Peginterferon ?-2b (PegIFN) and Lamivudine combination in patients of CHB. Materials and methods: Following 4 groups of patients of CHB with persistently elevated transaminases were treated with Lamivudine 100 mg PO daily and PegIFN 1.5 ?g/ kg SC once a week- 1) HBeAg negative treatment naïve patients- for 12 months 2) HBeAg negative patients who were nonresponsive to at least two treatment regimensfor 12 months, 3) HBeAg positive treatment naïve patients- for 6 months 4) HBeAg positive patients who were treatment failure at least with two regimens- for 6 months. Patients were tested for LFT, HBeAg, antiHBe, quantitative HBVDNA (only in HBeAg negative CHB) and liver biopsy when possible at inclusion. During treatment period, LFT was tested at monthly interval and HBeAg, antiHBe and HBVDNA (in HBeAg negative CHB) at 3 monthly intervals. End of treatment response (EOR) was assessed at end of treatment period and sustained response (SR) at 6 months post treatment. Treatment response was defined in HBeAg positive patients with normalization of enzymes and disappearances of HBeAg & in antiHBe positive patients with normalization of enzymes and loss of detectable HBVDNA. Results: Total 25 patients with CHB were included in this study with mean age of 37.9 ± 4.6 years (range 20-56) and male: female= 11.5:1. 1) In HBeAg negative treatment naïve patients, 4/6 patients achieved EOR (66.6%), whereas in 3/6 patients (50%) had SR. 2) In HBeAg negative treatment failure group, 4/5 patients had EOR (80%) and 3/5 patients achieved SR (60%), of which 1 patient lost HBsAg. 3) In HBeAg positive treatment naïve patients, 4/5 patients achieved EOR (80%) and 3/5 patients obtained SR (60%). One patient in this group lost HBsAg. 4) In HBeAg positive treatment failure group, 5/9 patients achieved EOR (55.5%), whereas 3/9 patients (33.3%) obtained SR. Conclusion: Overall, in difficult-to-treat patients (considering groups 1, 2 & 4- total 20 patients) with combination of PegIFN and Lamivudine, EOR was seen in 13 patients (65%), SR was obtained in 9 patients (45%) and loss of HBsAg was seen in 1 patient (5%).

IMAGES IN HEPATOLOGY

  • Hepatic angiosarcoma Nahum Méndez-Sánchez, Ernesto Roldán-Valadéz, Daniel Motola-Kuba, Paloma Almeda-Valdés, Misael Uribe Page 60-61

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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