Liver fibrosis

E. histolytica invades mucosal cells of colonic epithelium, producing the classic flask-shaped ulcer in the submucosa. The trophozoite toxin has a cytocidal effect on cells. If the trophozoite gets into the portal circulation, it will be carried to the liver, where it produces abscess and periportal fibrosis. Liver abscesses are more common in men than women and are rarely seen in children. Amebic ulcerations can affect the perineum and genitalia, and abscesses may occur in the lung and brain. 

Amiodarone Tremor, ataxia, pareslfresia, insomnia, corneal microdeposits, optic neuropathy/neuritis, nausea, vomiting, anorexia, constipation, TdP (<1%), bradycardia or AV block (IV and oral use), pulmonary fibrosis, liver function test abnormalities, hepatitis, hypothyroidism, hyperthyroidism, photosensitivity, bluegray skin discoloration, hypotension (IV use), phlebitis (IV use)... 

Sarin, S.K., Nundy, S. Subclinical encephalopathy after portosystemic shunts in patients with non-cirrhotic portal fibrosis. Liver 1985 5 142-146... 

Strandvik, B., Hnltcrantz, R. Liver function and morphology during long-term fatty acid supplementation in cystic fibrosis. Liver 1994 14 32-36... 

Stage II The periportal stage presents an encroachment of the inflammatory changes on the parenchyma with piecemeal necrosis connective tissue proliferations also break into the lobule (so-called periportal hepatitis + fibrosis). Liver cell necroses are also found sporadically, whereby CD4 cells, CD56-NK cells and lymphocytes are markedly increased. In places, reduction in and fibrosis of bile ducts are already in evidence, (s. fig. 32.13) (335, 349, 384)... 

Delayed portal blood flow Congenital fibrosis Liver cirrhosis Lymphoma Nodular regenerative hyperplasia Retroperitoneal fibrosis Stenoses/strictures ... 

Protein/peptide inhibitors Cystic fibrosis, liver disease, Rice Human a-l-aminotrypsin Particle ... 

Liver Fibrosis Liver fibrosis is a common end result of inflammation and/or necrosis. While the liver does have considerable regenerative capabilities, cytokine release associated with the inflammatory/necrotic process can lead to fibrosis that can have a deleterious effect on hepatic function, not only from the aspect of decreased hepatic functional mass but also from the standpoint of compromising blood supply. Animal models of hepatic fibrosis would be valuable from the standpoint of facilitating the development of noninvasive biomarkers as well as development of interventional agents. 

OA were aborted in 2003 due to the development of mild to moderate liver fibrosis in dogs treated for 9 months with high doses of pralnacasan. This was in spite of recent evidence demonstrating the effectiveness of pralnacasan treatment in the acute dextran sulfate sodium (DSS)-induced colitis model, which resembles Crohn s disease (CD) characteristics, and in transient ischemia induced brain damage. 

Hemmann S, Graf J, Roderfeld M et al (2007) Expression of MMPs and TIMPs in liver fibrosis—a systematic review with special emphasis on anti-fibrotic strategies. J Hepatol 46 955-975... 

Dibutyltin dichloride induced acute pancreatitis and bile duct lesions in rats, depending on dose (6 and 8 mg/kg body weight intravenously) and time (1-24 weeks) (Merkord Hennighausen, 1989 Merkord et al., 1997, 1999 Sparmann et al., 2001). The lesions in the pancreas developed into a pancreatic fibrosis, and the lesions in the liver into liver cirrhosis. A single intravenous administration of dibutyltin dichloride at 4 mg/kg body weight induced a mild interstitial pancreatitis after 2 days (Merkord et al., 2001). Repeated administration of dibutyltin dichloride (4 mg/kg body weight intravenously) to rats at intervals of 3 weeks induced acute interstitial pancreatitis and, after 9-12 weeks, a pancreatic fibrosis and liver lesions (intrahepatic bile duct hyperplasia) (Merkord et al, 2001). 

The main treatment objective is the sustained suppression of HBV DNA to reduce hepatic necroinflammation and progression of liver fibrosis. Furthermore, seroconversion to anti-HBe should be pmsued in HBeAg positive mdividuals, as it has been shown that seroconversion in these individuals is associated with improved outcome. Seroconversion to anti-HBs is rarely observed during antiviral therapy, mdi-cating that eradication of HBV is a ramer unlikely event with me currently available antiviral treatment. 

Detailed sub-analyses of a variety of clinical trials have provided information about host and viral factors influencing the virologic response in the treatment of chronic hepatitis C. The most important factors include the HCV genotype, HCV RNA concentration at baseline, age, weight, gender, ethnicity, liver enzymes, and stage of fibrosis (Mihm et al. 2006 Pawlotsky 2005). 

Tsukamoto, H., Gaal, K. and French, S.W. (1990). Insights into the pathogenesis of alcoholic liver necrosis and fibrosis, status report. Hepatology 12, 599-608. 

Sinusoidal damage from cirrhosis is the most common cause of portal hypertension. The sinusoids are porous vessels within the liver that surround radiating rows of hepatocytes, the basic functional cells of the liver (Fig. 19-2). Progressive destruction of hepatocytes and an increase in fibroblasts and connective tissue surrounding the hepatocytes culminate in cirrhosis. Fibrosis and regenerative nodules of scar tissue... 

Wilson s disease is another autosomal recessive disease leading to cirrhosis. Protein abnormalities result in excessive copper deposition in body tissues. The faulty protein is responsible for facilitating copper excretion in the bile, so copper accumulates in hepatic tissue. High copper levels within hepatocytes are toxic, and fibrosis and cirrhosis may develop in untreated patients. Those with Wilson s disease usually present with symptoms of liver or neurologic disease while still in their teens. 

Liver biopsy Mild inflammation and minimal fibrosis (grade 1, stage 1 disease) that is consistent with chronic hepatitis C... 

The incidence of liver complications associated with PN ranges from approximately 7% to 84%, and end-stage liver disease develops in as many as 15% to 40% of adult patients on long-term PN.35 Patients often develop a mild increase in liver enzymes within 1 to 2 weeks of initiating PN, but this generally resolves when PN is discontinued. Severe liver complications include hepatic steatosis (fat deposition in liver), steatohepatitis (a severe form of liver disease characterized by hepatic inflammation that may progress rapidly to liver fibrosis and cirrhosis), cholestasis, and cholelithiasis.35... 

Cirrhosis Widespread disruption of normal liver structure by fibrosis and the formation of regenerative nodules that is caused by any of various chronic progressive conditions affecting the liver. 

Steatohepatitis A severe form of liver disease caused by fat deposition in the liver, characterized by hepatic inflammation that may rapidly progress to liver fibrosis and cirrhosis. 

Findings from studies of schistosomiasis-induced liver fibrosis, as well as other models of pulmonary, kidney, and liver fibrosis, strongly support the role of CD4+ Th2 cells in the progression of fibrosis (4). In this regard, analyses of gene and protein expression after stimulation by Thl (vs. Th2) cytokines indicates that IL-4 is found at increased concentrations in the bronchoalveolar lavage (BAL) fluid of patients with idiopathic pulmonary fibrosis, as well as in the peripheral blood mononuclear cells of those afflicted with periportal fibrosis (10,53-56). 

Marra F. Chemokines in liver inflammation and fibrosis. Front Biosci 2002 7 dl899-dl914. 

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