Vol. 3 Issue 4
On the cover: Official Journal of the Mexican Association of Hepatology
Bile is primarily secreted in hepatocytes (i.e. the canalicular bile) and subsequently delivered to the intrahepatic bile ducts, where is modified by cholangiocytes (i.e. the ductal bile). Bile formation is the result of the coordinated interactions of membrane-transport systems that generate the vectorial movement of solutes and osmotically driven water molecules. Hepatocytes and cholangiocytes express aquaporins, specialized membrane channel proteins that facilitate the osmotic transport of water. In this review, we provide a summary of what is known on liver AQPs and their significance in canalicular and ductal bile formation under normal and pathological conditions.
In this review, the microarray technology and especially oligonucleotide arrays are exemplified with a practical example taken from the perilipin-/- mice and using the dChip software, available for non-lucrative purposes. It was found that the liver of perilipin-/- mice was healthy and normal, even under high-fat diet when compared with the results published for the scd1-/- mice, which under high-fat diets had a darker liver, suggestive of hepatic steatosis. Scd1 is required for the biosynthesis of monounsaturated fatty acids and plays a key role in the hepatic synthesis of triglycerides and of very-low-density lipoproteins. Both models of obesity resistance share many similar phenotypic antiobesity features, however, the perilipin-/- mice had a significant downregulation of stearoyl CoA desaturases scd1 and scd2 in its white adipose tissue, but a normal level of both genes inside the liver, even under high-fat diet. Here, different microarray methodologies are discussed, and also some of the most recent discoveries and perspectives regarding the use of microarrays, with an emphasis on obesity gene expression, and a personal remark on my findings of increased expression for hemoglobin transcripts and other hemo related genes (hemo-like), and for leukocyte like (leuko-like) genes inside the white adipose tissue of the perilipin-/- mice. In conclusion, microarrays have much to offer in comparative studies such as those in antiobesity, and also they are methodologies adequate for new astounding molecular discoveries.
Background: Despite well known worldwide differences in hepatocellular carcinoma incidence, which reflect different risk profiles, current recommendation of surveillance with ultrasound and alpha-fetoprotein twice-a-year has been restricted to cirrhotic patients. To evaluate the generalizability of this recommendation, we reviewed the clinical charts of hepatocellular carcinoma cases in a Mexican scenario. To evaluate efficiency, we performed a literature based cost-effectiveness analysis. Methods: Charts pertaining to 174 consecutive patients with histologically proven hepatocellular carcinoma, seen at a tertiary health care centre were analysed. A decision tree, based on the surveillance and recall algorithm of the European Association for the Study of the Liver was constructed. Ultrasound and/or alpha-fetoprotein, performed every six or twelve months were the diagnostic alternatives, and accurate diagnoses, direct medical costs and cost-effectiveness ratios were the outcomes of interest. Results: Male:female ratio was 1.2:1, underlying liver disease was secondary to alcohol in 44% and to hepatitis C virus in 26%, documented cirrhosis was present in 42%. Cost-effectiveness ratios for twice-ayear ultrasound and alpha-fetoprotein ranged from $303.09 to $346.22 U.S. dollars per accurate diagnosis, and for annual ultrasound from $115.86 to $116.42 U.S. dollars. Conclusions: Male gender, hepatitis C and cirrhosis were not predominant characteristics in our series. If a hepatocellular carcinoma surveillance program were to be instituted in our setting, or where patient characteristics are similar to ours, it probably should not be restricted to cirrhotic patients. Recommended performance of ultrasound and alpha-fetoprotein every six months is the least cost-effective surveillance strategy. Instead, annual ultrasound optimises diagnoses and costs.
Bile duct injuries occur with a frequency of 1 to 5 per 1000 cases as a result of an increase in the number of procedures performed. Elderly patients have more severe lithiasis- related diseases than the younger population. This fact increases the likelihood of conversion from laparoscopic to open surgery, and the probability of injury. We report the results of bile duct reconstruction after injury in these patients. Setting: A tertiary care academic university hospital. Methods: The files of patients over 65 years of age who had biliary tract reconstruction after iatrogenic injury were retrospectively reviewed. Post operative results, quality of life and failures from the repair were analyzed. Results: 20 patients over the age of 65 were referred for biliary tract reconstructive surgery over a ten year period. Mean age was 71 (65 – 83). Nineteen cases were referred from other hospitals. Fourteen cases (60%) had comorbidities (type 2 diabetes mellitus, systemic hypertension). All patients were treated by means of Roux en Y hepatojejunostomy. No operative morbility was recorded and only one major complication (abdominal collection) was found. Two long term mortalities unrelated to surgery were found. Treatment success (as defined by the Johns Hopkins criteria) was obtained in 17 cases (85%) and only one patient (5%) required reoperation two years after the initial attempt. Conclusions: Elderly patients that survive biliary injury and are reconstructed have long-term results comparable to the younger population; Roux en Y hepatojejunostomy offers the best surgical choice.
Prevalence, modes of transmission, clinical characteristics and outcomes of hepatitis C (HCV) infection vary in different geographical areas. We aim to describe clinical and epidemiological features of Chilean patients infected with hepatitis C virus. An analysis of demographic, epidemiological, clinical and laboratory data of patients referred to a liver clinic and blood donors with chronic hepatitis C was carried out. 147 patients were evaluated, 68 (46%) were male. Median age was 56 years, median infection age was 27 years and median duration of infection was 27 years. 52.5% of the patients were cirrhotic, and estimated risk of progression to cirrhosis was 16% at 20 years from infection. Risk factors for acquisition of the disease among patients were: Blood transfusion 54%, injection drug use 5%, and risky sexual behavior 2%. No factor was identified in 43% of the patients. Twelve of 64 (18.8%) family members tested positive for HCV antibodies. Genotype 1b was predominant (82%), and 52% of patients had high viral load (>850.000 IU/ mL). Liver biopsy was available in 50 patients, showing advanced fibrosis in 54%. These patients were in average 10 years older and tended to have longer duration of infection. Hepatocellular carcinoma was present at the moment of enrollment in 7 patients and developed in 4 more patients during follow up (2.4 years). In conclusion, the natural history and clinical characteristics of HCV infection in Chilean patients is similar to that described elsewhere. The main risk factor was blood transfusion. A significant proportion of patients had advanced liver disease or hepatocellular carcinoma at time of diagnosis.
Acute liver failure is a clinical condition associated with high mortality despite recent technological advances. Supportive devices such as the Molecular Adsorbents Recirculating System (MARS®) provide therapeutic strategies to add time to find an organ for orthotopic liver transplantation or to allow the native liver to recover sufficiently to make transplantation unnecessary. In this series of cases, we discuss our initial experiences with three patients with acute liver failure. One patient had high bilirubin levels caused by Epstein–Barr virus infection and responded well after three MARS sessions. In a second patient, MARS therapy was used to treat acute-onchronic liver failure caused by chronic hepatitis B virus infection that had not been treated previously; because of severe hemodynamic compromise, only one MARS session was performed. The third patient had an initial diagnosis of acute liver failure and cryptogenic hepatitis, and was treated with five MARS sessions as a supportive measure until the definitive diagnosis (metastatic disease) was performed. In all patients, MARS therapy was well tolerated and induced only mild hypokalemia. In conclusion, although MARS therapy was an effective strategy for these cases of liver failure and greatly improved the biochemical variables, its impact on the mortality rate has not yet been determined.