Liver disease patient response

Although as many as 20% of patients with chronic hepatitis C may be coinfected with HGV/GB V-C, coinfection does not appear to influence the severity of liver disease or response to interferon-a therapy (Martinot et al., 1997). 

Martinot, M, etal, (1997). Influence of hepatitis G virus infection on the severity of liver disease and response to interferon-a in patients with chronic hepatitis C. Ann. Intern. Med. 126,874-881. 

Intestinal transplantation is combined with liver transplantation in 46% of cases, because of terminal liver failure (93). Of 78 patients who had received parenteral nutrition for more than 2 years n — 66) and/ or had short bowel syndrome and could not be weaned from parenteral nutrition (n = 12), 58 developed chronic cholestasis and 37 developed one or more severe liver complication (serum bilirubin concentration 60 pmol/l, factor V (proaccelerin) 50%, portal hypertension, encephalopathy, ascites, bleeding from the gastrointestinal tract, or histological findings consisting of extensive fibrosis and cirrhosis) after 6 (3-132) months and 17 (2-155) months respectively. Liver disease was responsible for deaths in 6.5% of the patients (22% of deaths). 

The use of the flame photometric detector in the sulfur-sensitive mode (attributed to the emission of S2 spectral species at 394 nm) is exemplified in measuring the sulfur-containing volatiles in physiological fluids [110], or breath of liver-disease patients [111]. A word of caution concerns the fact that co-eluting non-sulfur compounds may result in a diminished or quenched response of the measured species [112]. Hence, the need for maximum solute separation. The detector is responsive to nanogram amounts of sulfur-containing compounds, but the response increases with the square of sulfur content [112]. Merits of the flame photometric detector in the detection of phosphorus compounds is somewhat overshadowed by a similar capability of the thermionic detector. 

Worldwide, 15 million HBsAg carriers are also infected with hepatitis D/delta virus (HDV) (Gaeta et al. 2000). This situation represents a major therapentic challenge, as most of these patients have advanced liver disease, inclnding cirrhosis in 60-70% of cases, and hepatocellular carcinoma (Fattovich et al. 2000 Saracco et al. 1987). No specific HDV inhibitors have been developed, and IFN-a-based treatment is more difficnlt in HBV-HDV infection than in HBV monoinfection. HDV RNA levels in sernm can be nsed to monitor treatment efficacy. The endpoint of therapy is HDV RNA clearance and ALT normalization, and this is sometimes achieved after the end of treatment. A snstained response can lead to HBsAg clearance from serum. 

Another common liver disease, alcoholic liver damage produced by moderate to heavy alcoholic intake, is also reflected by an elevation of the serum GOT and GPT activities. The serim glutamyl transferase activity is reported to be a sensitive index of alcoholic intake and can serve to monitor persons on alcoholic withdrawal programs (60). The LD-5 isoenzyme arises mainly from liver tissue, but has a short half-life (61), which is about 1/5 and 1/2 of the half life of the transaminases, GPT and GOT respectively. Some authors consider that a normal LD-5 isoenzyme activity in a jaundiced patient is sufficient evidence to exclude primary liver disease and that obstruction is probably responsible for the jaundice (62). In hemolytic jaundice the LDH-1 and 2 isoenzymes are elevated. 

Methotrexate, an antimetabolite, is indicated for moderate to severe psoriasis. It is particularly beneficial for psoriatic arthritis. It is also indicated for patients refractory to topical or UV therapy. Methotrexate can be administered orally, subcutaneously, or intramuscularly. The starting dose is 7.5 to 15 mg per week, increased incrementally by 2.5 mg every 2 to 4 weeks until response maximal doses are approximately 25 mg/wk. Adverse effects include nausea, vomiting, mucosal ulceration, stomatitis, malaise, headache, macrocytic anemia, and hepatic and pulmonary toxicity. Nausea and macrocytic anemia can be ameliorated by giving oral folic acid 1 to 5 mg/day. Methotrexate should be avoided in patients with active infections and in those with liver disease. It is contraindicated in pregnancy because it is teratogenic. 

Mutchnick, M.G. and Lee, H.H., Impaired lymphocyte proliferative response to mitogen in alcoholic patients. Absence of a relation to liver disease activity, Alcohol Clin. Exp. Res., 12, 155, 1988. 

Whole and partial liver transplants have become the treatments of choice for patients with imminent liver failure. Advances in surgical techniques and immune suppression are responsible for this progress. Treatments for liver diseases were unknown in the 1960s. Despite our improved knowledge of the function and physiology of the liver, one of every 10 individuals in the U.S. has been or will be diagnosed with liver disease. Hepatitis C virus (HCV) is a public health problem approximately 170 million people are infected worldwide, and 8,000 to 10,000 deaths per year... 

Other potential adverse responses include malignancy (e.g., lymphoma), liver disease, heart failure, lupuslike disease, irritation around the injection site, and demyelinating disorders that mimic multiple sclerosis.34,70 88 The incidence of these adverse effects, however, seems to be fairly low. For the most part, these drugs provide an acceptable risk-to-benefit ratio for most people with rheumatoid arthritis. Patients should, however, be screened carefully for any risk factors before beginning drug therapy, and should likewise be monitored periodically for any potential adverse reactions to these drugs. 

Ropinirole, another nonergoline derivative, is a relatively pure D2 receptor agonist that is effective as monotherapy in patients with mild disease and as a means of smoothing the response to levodopa in patients with more advanced disease and response fluctuations. It is introduced in a dose of 0.25 mg three times daily, and the total daily dose is then increased by 0.75 mg at weekly intervals until the fourth week and by 1.5 mg thereafter. In most instances, a dose of between 2 and 8 mg three times daily is necessary. Ropinirole is metabolized by CYP1A2 drugs metabolized by the liver may significantly reduce its clearance. 

Aldehyde-protein adducts and hydroxyl radicals also stimulate immunological responses directed against the specific modifications of proteins. High antibody titres have been observed from patients with severe alcoholic liver disease, particularly IgA and IgG autoantibodies. Such antibodies have considerable specificity towards aldehyde-lysine residues. Alcohol consumption markedly increases the hepatic output of very low-density lipoprotein (VLDL), but decreases the low-density lipoprotein (LDL) levels and apolipoprotein B. Ethylation of apo-B-lysine renders LDL immunogenic and accelerates its clearance. Alcoholics have been shown to develop acetaldehyde adducts in apo-B-containing lipoproteins, particularly VLDL. 

Regardless of whether the pharmacokinetics of a drug is altered or not, the response to sedative drugs may be increased in patients with liver disease, perhaps as a result of increased end-organ sensitivity. Opioids should therefore be used cautiously, ensuring the patient is closely monitored. 

Monitor for clinical efficacy and toxicity. Warn patients to report t drowsiness, malaise and anorexia. Measure amylase and lipase if toxicity is suspected. Tramadol causes less respiratory depression than other opiates, but need to monitor BP and blood counts and advise patients to report wheezing, loss of appetite and fainting attacks. Need to consider reducing dose. Methadone may cause Q-T prolongation the CSM has recommended that patients with heart and liver disease on methadone should be carefully monitored for heart conduction abnormalities such as Q-T prolongation on ECG, which may lead to sudden death. Also need to monitor patients on more than 100 mg methadone daily, and thus t plasma concentrations necessitates close monitoring of cardiac and respiratory function 2. Recommended that a small test dose (one-quarter of the usual dose) be administered initially to assess response... 

The relationship between drug concentration and response also can be altered in patients with advanced liver disease. Of greatest concern is the fact that customary doses of sedatives may precipitate the disorientation and coma that are characteristic of portal-systemic or hepatic encephalopathy. Experimental hepatic encephalopathy is associated with increased y-aminobutyric acid-mediated inhibitory neurotransmission, and there has been some success in using the benzodiazepine antagonist flumazenil to reverse this syndrome (50). This provides a theoretical basis for the finding that brain hypersensitivity, as well as impaired drug elimination, is responsible for the exaggerated sedative response to diazepam that is exhibited by some patients with chronic liver disease (51). Bakti et al. (52) conducted a particularly well-controlled... 

Patients with severe liver disease characteristically show abnormal end-organ response to drugs. For example ... 

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