Hepatic fibrosis

Hereditary hemochromatosis is an autosomal recessive disease of increased intestinal iron absorption and deposition in hepatic, cardiac, and pancreatic tissue. Hepatic iron overload results in the development of fibrosis, hepatic scarring, cirrhosis, and hepatocellular carcinoma. Hemochromatosis can also be caused by repeated blood transfusions, but this mechanism rarely leads to cirrhosis. 

Beagle dog inhalation "CeCl, AMAD t.5-2,4 ion a, 1.6-2.1 13-16 mos 70 life span (in progress) death, bone marrow aplasia and pancytopenia, radiation pneumonitis, pulmonary fibrosis, hepatic necrosis 11/48 Yes pulmonary adenoma, bronchtogenic adenocarcinoma 3/48 Yes he man- Yes giocarcinoma osteosarcoma, 6/48 leukemia 3/34 (primary) Benjamin et al. (1972b 1976c) Merickel et al. (1978)... 

PO loading dose 400 mg tid x 15-30 days, then 200-400 mg qd (5-10 mg/l ) pneurrwnitis when dose >400 mg/d elevation of digoxin level, prolongation of prothrombin time (70-100%) with warfarin pultrwnary fibrosis, hepatitis, ocular opacities proarrhythmic monitor thyroid and liver function... 

J. P. Iredale, R. C. Benyon, J. Pickering, M. McCullen, M. Northrop, S. Pawley, C. Hovell, and M. J. P. Arthur, Mechanisms of spontaneous resolution of rat liver fibrosis—Hepatic stellate cell apoptosis and reduced hepatic expression of metalloproteinase inhibitors, J. Clin. Invest. 702 538-549 (1998). 

Amiodarone CNS, corneal microdeposits/blurred vision, optic neuropathy/neuritis, Gl, aggravation of underlying ventricular arrhythmias, torsade de pointes, bradycardia or AV block, bruising without thrombocytopenia, pulmonary fibrosis, hepatitis, hypothyroidism, hyperthyroidism, photosensitivity, blue-gray skin discoloration, myopathy, hypotension and phlebitis (IV use)... 

With chronic use, amiodarone may cause ventricular arrhythmias (mono-morphic or polymorphic ventricular tachycardia see p 14) or bradyanhyth-mias (sinus arrest, AV block). Amiodarone may cause pneumonitis or pulmonary fibrosis, hepatitis, photosensitivity dermatitis, comeal deposits, hypothyroidism or hyperthyroidism, tremor, ataxia, and peripheral neuropathy. 

Percutaneous Hver biopsy after each 1.5 g of total accumulated methotrexate dosage to detect hepatic fibrosis or cirrhosis not rehably predicted by semm aminotransferase tests are recommended (1,50). Concurrent use of NSAIDs may increase toxicity of methotrexate, although toxicity may be avoided if the dmgs are separated by 12 h. 

IFN-y exhibits antiviral activity against HBV in vitro (Parvez et al. 2006). In addition, IFN-y was fonnd to rednce hepatic fibrosis by 63% after 9 months, compared to 24% in nntreated controls (Weng et al. 2005). 

Earci P, Roskams T, Chessa L, Peddis G, Mazzoleni AP, Scioscia R, Serra G, Lai ME, Loy M, Caruso L, Desmet V, PurceU RH, Balestrieri A (2004) Long-term benefit of interferon alpha therapy of chronic hepatitis D regression of advanced hepatic fibrosis. Gastroenterology 126 1740-1749... 

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). 

Iron overload is known to be toxic and potentially fatal. The major pathological effects of hepatic iron overload are fibrosis and cirrhosis, and hepatocellular carcinoma (Bonkovsky, 1991). The role of free radicals in the pathology of hepatic iron overload has been the subject of a detailed review recently (Bacon and Britton, 1990). 

Hepatobiliary disease occurs due to bile duct obstruction from abnormal bile composition and flow. Hepatomegaly, splenomegaly, and cholecystitis may be present. Hepatic steatosis may also be present due to effects of malnutrition. The progression from cholestasis (impaired bile flow) to portal fibrosis and to focal and multilobar cirrhosis, esophageal varices, and portal hypertension takes several years. Many patients are compensated and asymptomatic but maybe susceptible to acute decompensation in the event of extrinsic hepatic insult from viruses, medications, or other factors.7... 

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. 

Only 10% to 15% of patients have acute hepatitis C that resolves without any further sequelae.10 In more than 85% of cases, hepatitis C develops into a chronic disease. Approximately 70% of chronic HCV cases progress to mild, moderate, or severe hepatitis. While the natural history of the progression to cirrhosis is not clear, it is estimated that 10% to 20% of cases may take up to 20 to 40 years from the time of exposure to advance from fibrosis to cirrhosis.10 Fifteen to twenty percent of patients infected with HCV develop complications associated with cirrhosis. Once cirrhosis is confirmed, the rate of developing hepatocellular carcinoma increases to 1% to 4% per year.10 The estimated death rate from HCV infection is 1.8 deaths per 100,000 persons per year.12,15... 

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... 

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. 

Kanno K, Tazuma S, Nishioka T, Hyogo H, Chayama K. Angiotensin II participates in hepatic inflammation and fibrosis through MCP-1 expression. Dig Dis Sci 2005 50(5) 942-948. 

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