Hepatic Injury Due to Combined Choline-Deprivation and Thioacetamide Administration: An Experimental Approach to Liver Diseases

Background

The induction of prolonged choline-deprivation (CD) in rats receiving thioacetamide (TAA) is an experimental approach of mild hepatotoxicity that could resemble commonly presented cases in clinical practice (in which states of malnutrition and/or alcoholism are complicated by the development of other liver-associated diseases).

Aim

The present study aimed to investigate the time-dependent effects of a 30-, a 60- and a 90-day dietary CD and/or TAA administration on the adult rat liver histopathology and the serum markers of hepatic functional integrity.

Methods

Rats were divided into four main groups: (a) control, (b) CD, (c) TAA and (d) CD?+?TAA. Dietary CD was provoked through the administration of choline-deficient diet, while TAA administration was performed ad libitum through the drinking water (300?mg/l of drinking water).

Results

Histological examination of the CD?+?TAA liver sections revealed micro- and macro-vesicular steatosis with degeneration and primary fibrosis at day 30, to extensive steatosis and fibrosis at day 90. Steatosis was mostly of the macrovesicular type, involving all zones of the lobule, while inflammatory infiltrate consisted of foci of acute and chronic inflammatory cells randomly distributed in the lobule. These changes were accompanied by gradually increasing mitotic activity, as well as by a constantly high alpha-smooth muscle actin immunohistochemical staining. The determination of hepatocellular injury markers such as the serum enzyme levels?? of alanine aminotransferase and aspartate aminotransferase demonstrated a decrease at day 30 (they returned to control levels at days 60 and 90). However, the determination of those serum enzymes used for the assessment of cholestatic liver injury (gamma-glutamyltransferase, alkaline phosphatase) revealed a constant (time-independent) statistically-significant increase versus control values.

Conclusions

Long-term combined dietary CD and TAA administration could be a more realistic experimental approach to human liver diseases involving severe steatosis, fibrosis, stellate cell activation and significant regenerative hepatocellular response.     

Hepatic Necrosis Due to Marsilid

In the patient reported here severe jaundice and death resulted from treatment with iproniazide ("marsilid") given for only three days.     

Effect of Granulocyte Colony-Stimulating-Factor Administration on Tissue Regeneration Due to Thioacetamide-Induced Liver Injury in Rats

It has been shown recently that granulocytecolony-stimulating factor (G-CSF) accelerates andenhances the hepatocyte proliferative capacity ofpartially hepatectomized rats. In the present study, weinvestigated the effect of G-CSF administration in a ratmodel of liver injury and regeneration, induced bythioacetamide (TAA) injection. TAA (300 mg/kg bodyweight) was injected intraperitoneally in male Wistarrats, and this was followed by administration ofeither saline (group A) or G-CSF at a dose of 150g/kg body weight (group B), 24 hr later. The animalswere killed at different time points after TAA treatment and the rate of tritiated thymidineincorporation into hepatic DNA, the activity of theenzyme thymidine kinase (EC 2.7.1.21) in the liver, andthe assessment of the mitotic index of hepatocytes, wereemployed to estimate liver regeneration. Theadministration of TAA caused severe hepatic injury,recognized histopathologically and by the raisedactivities of the serum hepatic enzymes aspartate andalanine aminotransferases. The hepatic injury, which peaked 36 hr afterTAA injection, was followed by a regenerative process ofhepatocytes presenting peaks at time points of 48 and 60hr (group A). The administration of G-CSF 24 hr after the injection of TAA (group B) causeda statistically significantly increase in the hepatocyteproliferation indices examined (P < 0.001), comparedto those found in group A at the same time points. It was concluded that G-CSFadministration enhanced the hepatocyte proliferativecapacity in this model of liver injury induced by TAAadministration.     

Hepatic Portal Venous Gas Due to Endoscopic Sphincterotomy

This report describes a patient with sickle cell disease and cholelithiasis with choledocholithiasis who developed benign hepatic portal venous gas following endoscopic sphincterotomy. The portal venous gas was rapidly absorbed without untoward sequelae.     

Multiple Hepatic Abscesses Due to Yersinia enterocolitica Infection Secondary to Primary Haemochromatosis

A case of hepatic abscesses due to Yersinia enterocolitica in an immunocompetent male is presented. Reexamination after 3 months showed that the patient had primary haemochromatosis. Treatment with repeated phlebotomies was instituted. Two years after the patient was first admitted to hospital, 17.2 g iron had been removed and all haematological and biochemical parameters had returned to normal. Genetic analysis of the patients' two sons showed that one was positive for the chromosome defect found in primary haemochromatosis; further investigation is under progress. A study of the literature showed that prior to this case only 45 cases of hepatic abscess secondary to Yersinia enterocolitica have been registered. Of the 45 reported cases, 64% had underlying haemochromatosis and 29% had diabetes mellitus. The overall mortality was 31%. Mortality before 1987 was 60% (n = 20) and since 1987 it has been 8% (n = 25).     

Long-term Follow-up of a Patient with Portal Hypertension and Hepatic Failure Due to Hepatic Hydatid Disease

We observed liver failure with a presumed etiology of echinococcosis in an 89-year-old woman. Our patient had been born and then resided on Rebun Island until she was 12 years old. At 46 years old, she had been referred to our hospital due to right abdominal pain. Ultrasound had revealed multilocular cysts in the right lobe of the liver. At 84 years old, the hepatic cyst occupied nearly the entire liver with ring-shaped calcification along the cyst wall. The patient was diagnosed with decompensated cirrhosis and hepatic hydatid disease based on typical imaging and the long-term natural clinical course.     

Fatal Upper Gastrointestinal Bleeding Due to Hepatic Artery Pseudoaneurysm Diagnosed by Endoscopy

We report a case of fatal gastrointestinal bleeding due to hepatic artery pseudoaneurysm diagnosed by means of endoscopy in a 66-year-old male who had undergone laparoscopic cholecystectomy the previous month. We think that the image is of remarkable interest and rarity.     

Next-Generation Airbags and the Possibility of Negative Outcomes Due to Thoracic Injury

Airbags have been shown to decrease morbidity and mortality associated with motor vehicle accidents when used in conjunction with seat belts. Airbag deployment alone however, has recently been implicated as a cause of significant thoracic injuries to unrestrained drivers. Resulting injuries include major cardiovascular and pulmonary complications. Airbags provide safety to occupants of cars and reduce mortality by 25%-30%. When not used in accordance with international standards, however, they can cause serious injury. We searched online databases from 1970 to January 2013 and included 17 retrospective studies, 12 systematic review articles, 18 case reports, 5 prospective studies, 1 lab study, 3 cohort studies, and 1 meta-analysis. Outcomes included clinical/functional response, left ventricular remodelling, hospitalizations, and mortality. Physicians must maintain a high index of suspicion for injury when evaluating drivers who were not wearing seat belts when airbags deployed, regardless of the speed of the collision, because increased risk of thoracic injury with airbags has been described in the literature. Our review indicates that even new technology, specifically the side air bag, has been associated with a risk of thoracic injury. Considering that regulations are a driving force for airbag technology, further research and scrutiny by medical teams is needed to consider the effects of airbag technology advancements on morbidity and mortality rates of car accidents, to help in guiding further improvement, and to help lawmakers in implementing rules that protect the safety of occupants.