Vol. 4 Issue 2
On the cover: Official Journal of the Mexican Association of Hepatology
Since the excretion of potentially toxic cholephilic organic anions (COAs) produced by the fetus, such as bile acids and biliary pigments, cannot be performed by the fetal liver alone, the placenta and the maternal liver must play a key role collaborating in this function. COAs are transported across the plasma membranes of fetal and maternal hepatocytes and trophoblastic cells via similar carrier proteins. OATPs (organic aniontransporting polypeptides), mainly OATP1B1 and OATP1B3 are involved in COA uptake across the basal membrane of adult hepatocytes and trophoblastic cells. Certain OATPs may also play a role in COA efflux from fetal hepatocytes toward the fetal blood and from the trophoblast to the maternal blood. Either unmodified or biotransformed during their transit across the placenta, COAs are transferred to the maternal blood by MRPs (multidrug resistance-associated proteins), such as MRP1, MRP2 and MRP3. BCRP (breast cancer resistance protein) may also be involved in this step. Under physiological circumstances, fetal COAs are taken up by the maternal liver, which eliminates them across the canalicular membrane via MRP2 and BSEP (bile salt export pump). However, when normal biliary excretion is not possible, the accumulation of COAs, in particular in the fetal liver, placenta and maternal liver trio, induces oxidative stress and apoptosis, which has noxious repercussions on normal fetal development and even challenges pregnancy outcome. Treatment of pregnant rats with ursodeoxycholic acid, even though maternal hypercholanemia is not corrected, prevents oxidative damage and the subsequent deleterious effects on the placenta and fetal liver.
Hepatobiliary transport systems mediate hepatic uptake and biliary excretion of bile acids, bilirubin and other biliary constituents. Hereditary or acquired defects of these transporters may cause or maintain cholestasis and jaundice under various clinical conditions including progressive familial intrahepatic cholestasis (PFIC) 1-3 or its milder forms, benign recurrent intrahepatic cholestasis (BRIC) 1 and 2 , Dubin- Johnson syndrome, drug and inflammation-induced cholestasis and intrahepatic cholestasis of pregnancy. Moreover, induction of alternative efflux pumps for bile acids/bilirubin and phase I/II detoxifying enzymes may counteract hepatic accumulation of potential toxic biliary constituents in cholestasis by providing alternative escape routes. Transcriptional and post-transcriptional regulation of hepatobiliary transporters in health and disease is mediated by multiple factors such as bile acids, proinflammatory cytokines, drugs and hormones. Ligand-activated nuclear receptors (NR) and hepatocyte-enriched transcription factors play a critical role in transcriptional transporter regulation. Many hepatobiliary transporter alterations in cholestatic liver disease can now be explained by ligand binding of accumulating cholephiles to NRs. Moreover, NRmediated actions may be targeted by pharmacological ligands. Understanding the transcriptional mechanisms leading to transporter changes therefore not only represents a key for understanding the pathophysiology of the cholestatic liver disease, but also represents a prerequisite for designing novel therapeutic strategies.
Hepatitis B virus (HBV) and hepatitis C virus (HCV) share modes of transmission and their combined infection is a fairly frequent occurrence particularly in areas where the two viruses are endemic and among subjects with a high risk of parenteral infections. Moreover, the number of coinfected patients is likely higher than is usually thought. In fact, many studies have shown that HBV genomes may also be present in HBsAg- negative patients, particularly in those with HCVrelated chronic hepatitis. This condition is commonly called “occult HBV infection”. Much evidence suggests that coinfection by HBV and HCV may have considerable clinical relevance. In particular, this condition is generally believed to be a factor favouring the progression of liver fibrosis toward cirrhosis and the development of liver cancer, and in case of both overt and occult HBV infection. In spite of its potential clinical impact, however, there is few information about the possible interplay between the two viruses. Here, we concisely reviewed the available data on the virological and clinical features of the dual HBV/HCV infection prospecting the aspects that should be highlighted in the nearest future for improving the knowledge on this important field of the hepatology.
Oxidative stress (OS) is a biological entity quoted as responsible for several pathologies including diabetes. Diabetes mellitus (DM) has been also associated to human cirrhosis. The present work was designed to study the occurrence of OS as well as morphologic alterations in rat livers following induction of DM. Two groups of rats were used: Control and Diabetic. DM was induced in the second group by streptozotocin (STZ) in a single dose of 60 mg/kg, injected i.p. The occurrence of OS was determined in liver homogenates by measuring the hydroperoxide-initiated chemiluminescence and the activity of antioxidant enzymes (superoxide dismutase, catalase and glutathione peroxidase). Liver sinusoids were morphometrically analyzed. In conclusion, livers from the diabetic group did not show evidence of the occurrence of OS, as it would be expected, but dilation of hepatic sinusoids was documented and it was significantly different from control group.
Aims: N-acetyl cysteine (NAC), an anti oxidant and a glutathione precursor, is effective in ameliorating liver injury of Tylenol overdose. There is experimental evidence that it also reduces ischemia reperfusion (I/R) injury. This clinical study was undertaken to study the effect of NAC administered in the donor operation. Methods: 22 patients were randomized to receive NAC (IV & Portal flush) or no NAC (Control Group) during donor operation. Peak AST levels and 1-hour postreperfusion biopsies were used to assess I/R injury. Episodes of acute rejection were recorded together with immunosuppressive drug levels. Results: There were 4 exclusions (re-exploration for post-operative hemorrhage x3, OLT for acute liver failure x1). The two groups (n = 9 each) were matched for recipient and donor ages and sex. Viral hepatitis accounted for cirrhosis in 3 patients in NAC Group and 6 patients in Control Group. Statistically, Cold and warm ischemia times were not significantly different as was the use of blood and blood products in both groups. Serum peak AST levels were similar and postreperfusion biopsy showed moderate to severe reperfusion injury in 3 recipients in the NAC Group and 4 in the Control Group. Excluding ones associated with low Tacrolimus levels (n = 4), there were 6 episodes of acute rejection (2- mild, 4- moderate) in the NAC Group and 5 in the Control Group (3- mild,1- moderate, 1- severe). Conclusion: In this pilot study, NAC administered during donor operation did not show a protective effect on I/R injury or on acute cellular rejectio
Chronic hepatitis C is a major cause of liver-related morbidity and mortality. Epidemiological data regarding this infection in developing countries is scanty. Methods: Prevalence of hepatitis C (HCV) infection was investigated in a random sample of Chilean general adult population older than 20 years of age. Additionally, frequency of HCV infection was assessed in group of native Chilean Amerindians (Mapuche Indians) living in an isolated locality of the Southern Chile. Incidence of HCV infection was estimated using serum samples separated by 7 years (1993-2000). Results: Among 959 subjects, prevalence of anti-HCV antibodies was 1.15% (95% CI 0.48-1.82%) and 0.83% when only RIBA-confirmed cases were considered. Among these subjects, 62.5% had detectable HCV RNA in serum and 40% of them had a history of blood transfusion. Age distribution of cases showed a steadily increasing prevalence with age. Estimated incidence of new HCV infections was 15 per 100,000 subjects per year in the period 1993-2000. No cases were detected among the 145 Mapuche subjects studied. Conclusions: HCV infection is a prevalent disease in the Hispanic population of Chile with a low incidence in the last decade, whereas it was not detected in an isolated Mapuche Indian community. Age distribution of prevalence suggests that the peak of infection in Chile occurred 30 to 50 years ago.
Detection of anti-hepatitis C virus (anti-HCV) antibodies may yield a high frequency of false-positive results in people at low risk. To date, no clinical rule had been developed to predict viremia in HCV-seropositive patients. Therefore, we aimed to generate a prediction rule on the basis of clinical and serologic data, which can be used in outpatient care. We selected 114 seropositive patients without antiviral treatment or hepatitis B coinfection. Subsequently we identified independent predictors of the hepatitis C viremia by logistic regression and selected the quantitative value of the screening test for anti-HCV antibodies with the best performance in detecting viremia. Then, we combined clinical and serologic data to generate different prediction rules. Ratio of immunoassay signal strength of the sample to cut-off (S/CO) >15 had accuracy, positive predictive value (PPV) and positive likelihood ratio (LR+) of 84%, 83%, and 3.7; respectively. The rule compounded of the antecedent of blood transfusion before 1993 and S/CO >15 performed the best in prediction of viremia in all patients, with accuracy, PPV and LR+ of 71%, 88%, and 5.6; respectively. In the group of asymptomatic patients this rule improved in efficacy of prediction, with accuracy, PPV and LR+ of 79%, 91% and 12.8; respectively. In conclusion, a clinical rule is better than S/CO alone in prediction of the hepatitis C viremia. In a patient that meet the rule the probability of having viremia is high, therefore, it can be indicated directly an assay for viral load instead of other supplemental tests, thus, saving time and economic resources.
We describe the case of a 73-year-old woman was admitted to our hospital because of constant abdominal pain in her right upper quadrant and postprandial bloating and fullness for several months. On abdominal x-ray the extrahepatic bile ducts were positive for gas and on ultrasound a gallstone in the duodenum was suspected whereas the gallbladder was not detectable. An upper gastrointestinal endoscopy confirmed a large gallstone that was impacted in the duodenal bulb (“Bouveret’s syndrome”). The gallstone was fragmented employing mechanical lithotripsy and removed. Duodenoscopy revealed a cholecystoduodenal fistula and a second gallstone in the gallbladder. The patient underwent open cholecystectomy with closure of the cholecystoduodenal fistula and made a full recovery. We conclude that in patients with upper abdominal pain and pneumobilia on x-ray the unusual complication of cholelithiasis with an impacted gallstone in the duodenal bulb should be suspected. In those rare cases of Bouveret’s syndrome endoscopic removal of the gallstone should be attempted to minimize the necessary surgical procedure whenever possible.