Hepatic disease pathophysiology

Analysis of BAs in urine, serum, bile and stool is crucial for the diagnosis of inborn errors of BA metabolism. It is also helpful for understanding their pathophysiological role in acquired hepatic diseases and for monitoring the effects of therapy on metabolism. Several different inborn defects affecting BA synthetic pathway, have been described over last 20 years [7]. 

Zambon A, Hokanson JE, Brown BG, Brunzell JD. Evidence for a new pathophysiological mechanism for coronary artery disease regression hepatic lipase-mediated changes in LDL density. Circulation 1999 99 1959-1964. 

Pawlotsky, J. M., 2004, Pathophysiology of hepatitis C virus infection and related liver disease. Trends Microbiol 12, 96-102. 

There is epidemiologic evidence to suggest an increased prevalence of duodenal ulcers in patients with certain chronic diseases, but the pathophysiologic mechanisms of these associations are uncertain. A strong association exists in patients with systemic mastocytosis, multiple endocrine neoplasia type 1, chronic pulmonary diseases, chronic renal failure, kidney stones, hepatic cirrhosis, and ai-antitrypsin deficiency. An association may exist in patients with cystic fibrosis, chronic pancreatitis, Crohn s disease, coronary artery disease, polycythemia vera, and hyperparathyroidism. 

HAV is primarily responsible for acute hepatitis. It is most often linked to sporadic events of contaminated food in the United States and to international travel, and is usually a self-limited disease. HBV and HCV are primarily responsible for the development of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. Immunomodulatory therapy and direct antiviral agents have been developed for both HBV and HCV. These therapeutic modalities require long courses of therapy and are associated with limited success. This chapter will focus on the pathophysiology, clinical course, and management of these three primary causes of viral hepatitis, namely HAV, HBV, and HCV. 

Figure 15.1 Different functions for CAR and PXR in health and disease. In recent years, novel functionsforthexenobiotic-sensing nuclear receptors CAR and PXR beyond hepatic drug metabolism have been found. Potential implications of these findings for various physiological and pathophysiological processes are depicted in this figure. See text for details and references.

Adams RD, Foley JM. The neurological disorder associated with liver disease. In Metabolic and Toxic Diseases of the Nervous System. (H.H. Merritt, and C.C. Hare, eds.)Vol. 32. WiUiams and Wilkins, Baltimore, USA, pp. 198-237, 1953 Ahboucha S, Butterworth RF. The neurosteroid system Implication in the pathophysiology of hepatic encephalopathy. Neurochem. Int., 52, 575-587, 2008 Ahboucha S, Pomier-Layrargues G, Mamer O, Butterworth RF. Increased brain concentrations of a neuroinhibitory steroid in human hepatic encephalopathy. Arm. Neurol, 58, 169-170, 2005 Ahboucha S, Coyne L, Hirakawa R, Butterworth RF, Halliwell RF. An interaction between benzodiazepines and neuroactive steroids at GABA receptors in cultured hippocampal neurons. Neurochem. Int., 48, 703-707, 2006... 

Plasma vitamin A and RBP levels have been investigated in patients with cystic fibrosis of the pancreas (Smith et al., 1972 Knopfle et al., 1975 Palin et al, 1979). Plasma vitamin A and RBP levels have been found to be lower than normal in patients with cystic fibrosis, despite the administration of oral vitamin A supplements adequate to maintain normal hepatic stores. In one study (Smith et al., 1972), the plasma vitamin A transport system was studied in 43 patients with cystic fibrosis receiving oral supplements of vitamin A and in 95 normal control subjects of a similar age range. The mean plasma concentrations of vitamin A and RBP were significantly lower in the patients than in the controls. Moreover, in cystic fibrosis patients each component of the transport system failed to show the normal age-related rise. It is not known whether these abnormalities of the retinol transport system are primary or secondary features of cystic fibrosis the abnormalities may, however, play a role in the pathophysiology of the disease. 

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