Cholestasis liver disease

There is very little evidence relating to the role of ROMs in cholestatic liver disease. Serum selenium and glutathione peroxidase activity are decreased in humans with intrahepatic cholestasis of pregnancy (Kauppila et al., 1987). Low levels of vitamin E have been reported in patients with primary biliary cirrhosis, and in children with Alagille s syndrome or biliary atresia (Knight et al., 1986 Jeffrey etal., 1987 Lemonnier etal., 1987 Babin etal., 1988 Kaplan et al., 1988 Sokol etal., 1989). Serum levels of Mn-SOD are increased in patients with all stages of primary biliary cirrhosis compared with patients with other forms of chronic liver disease, although whether this causes or results from the disease process is unclear (Ono etal., 1991). 

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... 

Alkaline phosphatase levels and GGT are elevated in plasma with obstructive disorders that disrupt the flow of bile from hepatocytes to the bile ducts or from the biliary tree to the intestines in condition such as primary biliary cirrhosis, sclerosing cholangitis, drug-induced cholestasis, gallstone disease, and autoimmune cholestatic liver disease. 

Oral testosterone-replacement regimens can cause hepatotoxicity, ranging from mildly elevated hepatic transaminases to serious liver diseases (e.g., peliosis hepatitis, hepatocellular and intrahepatic cholestasis, and benign or malignant tumors). 

This is an autosomal dominant hereditary disorder characterised by a progressive loss of the bile ducts within the liver and narrowing of the bile ducts outside the liver. It is also associated with congenital heart disease, and in particnlar pulmonary stenosis. Symptoms are related to chronic cholestasis and include jaundice, pruritus, pale loose stools and poor growth within the first three months of life. The majority of children have a benign course and many cases go undetected however, there is an overall mortality of 20-30% due to progressive liver disease with the development of cirrhosis, cardiac disease or intercnrrent infection. 

Table 4.3 summarises the potential extent of change in each individual LFT for an example patient with compensated chronic liver disease, decompensated chronic liver disease, hepatitis, hyperacute liver failure and cholestasis. This is a snapshot of the changes that may occur in these conditions however, if each patient s results were observed over time a range of results would be seen. 

A biopsy is often required to make a diagnosis of most types of liver disease. A specimen of liver can be used to identify fibrosis, cirrhosis, cholestasis and hepatitis, both acute and chronic, and tumours. Biochemical measurements can also be taken from a biopsy specimen to determine iron and copper content, virology, microbiology and haematology (e.g. increased numbers of eosinophils in a drug-induced cause). The biopsy can give an indication of the extent of the liver damage. See Chapter 3 for slides of liver biopsies. 

Herbal medicines are becoming more and more popular, and indeed some herbal products may be considered to benefit people with liver disease, e.g. Silybum marianum (milk thistle), Picrorhiza kurroa, Phyllanthus, etc. Herbal hepatotoxicity is increasingly being recognised, for example, with kava kava, black cohosh, and many traditional Chinese remedies. The range of liver injury includes minor transaminase elevations, acute and chronic hepatitis, steatosis, cholestasis, zonal or diffuse hepatic necrosis, veno-occlusive disease and acute liver failure. In addition to the potential for hepatotoxicity, herb-drug interactions may affect the safety and efficacy of concurrent medical therapy [15]. 

In another trial the pharmacokinetics of a single dose of naproxen was studied in 11 patients with liver disease (four severe hepatitis with cholestasis two extrahepatic cholestasis one chronic alcoholic cirrhosis two active chronic hepatitis, with and without symptoms one asymptomatic PBC and one asymptomatic hepatic cirrhosis). In two of the seven patients with cholestasis, a significant delay in absorption occurred. In most of the patients studied there was a significant decrease in elimination, increasing the half-life from around 14 hours to 20 hours [41]. 

The use of HRT is generally cautioned in liver disease because of concern over its potential to provoke or worsen cholestasis. This is based on early experience with oral contraceptive pills that contained higher doses of the less degradable synthetic oestrogen ethinylestradiol. However, several studies have demonstrated the safety and efficacy of HRT in patients with chronic liver disease, in particular those with PBC and viral hepatitis. HRT may be particularly beneficial in patients with PBC owing to the high prevalence of osteoporosis in this population. 

This chronic cholestatic liver disease affects 1 in 4000 people in the United Kingdom. Pruritus is a common early symptom, and can be helped by colestyramine. Qu-onic cholestasis leads to malabsorption of fat-soluble vitamins, particularly vitamin D, and deficiency of which must be corrected to avoid osteomalacea. 

Elevation of y-GT is found in cholestasis, liver cirrhosis, viral hepatitis, fatty liver, porphyria, toxic liver damage, pancreatitis and pancreatic cancer, myocardial infarction, nephrotic syndrome, diabetes mellitus, right heart failure, obesity, nicotine abuse, and brain tumours. There is a good correlation of y-GT with CEA in colon cancer, involving a metastatic spread to the liver - an increase in y-GT in neoplastic disease is likewise supportive of the diagnosis of hepatic metastases. 

Elevation of 5 -NU is found in cholestasis, biliary diseases and liver tumours (in 80-90% of metastases). It not only precedes, but also persists longer than AP. The... 

There are chronic autoimmune-associated liver diseases with and without cholestasis which are negative in virus serology. With the help of selected autoantibodies, a detailed laboratory diagnosis can be achieved. (124,126,129, 130, 133, 134) (s. tabs. 5.19-5.21 33.1) (see chapter 33)... 

In classifying cholestasis, the cause, localization and duration of the disease as well as the involvement of bilirubin metabolism must be considered. Laboratory parameters of liver cell damage (increased activity of GPT, GOT and GDH) may be attributed to the underlying liver disease, but can also appear subsequently during the course of cholestasis-related hepatocellular damage, (s. tab. 13.1)... 

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