Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023890 (cirrhosis)
 42,195 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The purpose of this paper is to report findings in post-MTX liver biopsies from 160 psoriatics treated with Methotrexate (MTX) in single biopsy and B. 68 patients with serial biopsies. At the time of liver biopsy the 92 patients had received a mehosis and six patients had fibrosis. Comparing these 7 patients with patients having normal liver histology (13 patients) revealed no statistically significant difference in cumulative doses of MTX, but a statistically significant higher admitted alcohol intake during MTX therapy (p less than 0.002) and an older age (p less than 0.01) in the patients with cirrhosis or fibrosis. in the 68 patients MTX had accumulated to a mean dose of 3940 mg (range 32k-8355 mg) at the time the latest liver biopsies were taken. Among the latest liver biopsies were 14 cirrhosis (21 per cent, 95 per cent confidence limits: 12-32 per cent) and 16 fibrosis (24 per cent, 95 per cent confidence limits: 14-35 per cent). The 14 patients with cirrhosis when compared to patients with normal histology (9 patients), had taken an equal total dose of MTX at the latest liver biopsy, but had consumed a statistically significant higher amount of alcohol (p less than 0.05) during MTX therapy and also tended to be older (p less than 0.006). Comparison of a material A and B indicates that the prevalence of cirrhosis and fibrosis among MTX treated psoriatics increases rapidly beyond a cumultative dose of two to four grams of MTX. No MTX treated psoriatics should thus be allowed to pass this dosage range without having a liver biopsy performed.
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PMID:Liver biopsies from psoriatics related to methotrexate therapy. 3. Findings in post-methotrexate liver biopsies from 160 psoriatics. 89 89

Serial liver biopsies before and after Methotrexate therapy were performed in each of eight patients with severe, recalcitrant psoriasis treated for years with Methotrexate in a single, weekly, oral dose not exceeding 25 mg per dose. A total of 31 liver biopsies was studied. The study revealed liver damage commencing with small foci of piecemeal necrosis, followed by the destruction of the limiting plate and the occurrence of stellate periportal fibrosis. Eventually, partial and then whole fibrous septa developed between portal tracts and between portal tracts and central veins, with resultant distortions of the lobular architecture. In two patients with an admitted daily alcoholic intake, additional findings were seen, including alcoholic hepatitis, centrilobular fibrosis and development of partial and whole fibrous septa between the central vein area, and portal tracts adding to the number of septa running between the portal tracts and central veins which split up the lobules. The following conclusions seem probable: 1) Methotrexate therapy in psoriatics may cause development of fibrosis or cirrhosis; 2) the morphological changes during this development follow a consistent pattern; and 3) the pathogenesis of the development of fibrosis and cirrhosis is mixed in some cases, being dependent on both alcoholic and Methotrexate intake.
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PMID:Morphogenesis of fibrosis and cirrhosis in methotrexate-treated patients with psoriasis. 92 Aug 71

A prospective study was started in 1969 to describe morphological features of liver biopsies from patients with severe psoriasis. Among 123 patients evaluated for possible MTX therapy, liver biopsies disclosed pathological histology (maninly fatty change and/or non-specific reactive hepatitis) in 51 per cent. The incidence of pathological liver histology did not statistically correlate with psoriasis parameters such as duration and extent. However, statistically significant correlations (p less than 0.0001) were found between the frequency of pathological liver histology and other factors such as age, obesity, and daily alcholic intake. Comparison of liver histology with SGOT value at the time of liver biopsy showed that while the diagnostic specificy of this test high (1.00), the diagnostic was low (0.17). Normal values of SGOT should not be relied upon to indicate all types of liver pathology. A "risk index" indicating the probability of pathological liver histology was developed. It is calculated as follows: two times the height (cm) minus weight (kg) minus age (years) minus 50 (in case of daily alcoholic intake) minus 50 (in case of elevated SGOT). To elucidate liver histology and particularly to rule out fibrosis and cirrhosis, a liver biopsy should be performed in every psoriatic patient with a low score in the risk index prior to beginning MTX therapy.
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PMID:Liver biopsies from psoriatics related to methotrexate therapy. 1. Findings in 123 consecutive non-methotrexate treated patients. 127 90

Eightyeight patients with severe, recalcitrant psoriasis had liver biopsies performed before and after Methotrexate (MTX) therapy. MTX was given for an average of 26 months as a single, weekly, oral dose of 25 mg maximum. The mean cumulative dose was 1733 mg (range 175-4590 mg). A statistically significant increase in the number of pathological post-MTX liver biopsies was found (p less than 0.0001). Of the 88 patients 6 developed cirrhosis and another 5 developed fibrosis, in all 12.5 per cent, during MTX therapy (95 per cent confidence limits for cirrhosis: 3-14 per cent). There was no statistically significant correlation between the number of pathological post-MTX liver biopsy findings in the 88 patients and the following variables one by one: cumulative dose of MTX, duration of MTX therapy and admitted alcoholic intake during MTX therapy. Cirrhosis and fibrosis did not develop statistically more frequently from pathological than normal pre-MTX liver histology (p = 0.062). The liver damage appeared to be due to a multifactorial interaction of straining factors on the liver during MTX therapy. A multifactorial index comprising: cumulative dose of MTX, admitted alcoholic intake during MTX therapy, age, obesity and, if available, pre-MTX liver histology gave an estimate of the probability of developing cirrhosis or fibrosis during treatment of psoriasis with weekly, oral doses of MTX. For use of MTX therapy in psoriasis the following precautions are suggested: MTX therapy should be used only in disabling cases; a pre-MTX liver biopsy and repeat liver biopsies at regular intervals of 1/2-1 year should be performed, alcohol should be prohibited and frequent inquiries should be made about the patient's alcoholic intake; and strong reliance should not be placed on the SGOT as an indicator of abnormal liver histology.
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PMID:Liver biopsies from psoriatics related to methotrexate therapy. 2. Findings before and after methotexate therapy in 88 patients. A blind study. 127 91

Methotrexate is an effective and convenient treatment for severe psoriasis whose use is limited by the development of hepatic fibrosis and cirrhosis in a small number of patients. The mechanism of hepatotoxicity is unknown, but it is believed to be the result of intracellular polyglutamation and prolonged retention of methotrexate within the cell. Piritrexim isethionate is a lipid-soluble antifolate that has a mechanism of action similar to that of methotrexate. Since it is not polyglutamated, piritrexim could be effective in the treatment of psoriasis without the associated long-term hepatotoxicity. A 12-week phase I/II clinical trial of severe chronic plaque psoriasis assessed the safety and efficacy of oral piritrexim therapy. Based on experience gained from oncologic trials, each patient received a twice-daily dosage for 5 consecutive days every 2 weeks. Dosages ranged from 25 to 100 mg twice a day. Improvement in both lesion scores and percentage of body involvement was significant at a dose of 50 mg or more twice daily. Fifteen of 19 patients who completed 12 weeks of therapy demonstrated greater than 50% improvement in lesion scores. Improvement was limited by recrudescence of lesions over the 9-day rest period. Adverse experiences were minimal and dose related. Piritrexim is efficacious in the treatment of psoriasis.
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PMID:Treatment of psoriasis with piritrexim, a lipid-soluble folate antagonist. 200 83

Methotrexate is by far the most widely used cytotoxic drug in psoriasis. Treatment requires normal kidney, liver and bone-marrow function, and pregnancy and alcohol abuse are absolute contraindications. Serious toxic reactions are recognized, but can be avoided if the drug is used correctly. The most important side-effects are haematopoietic and hepatotoxic. It is well established that long-term methotrexate can induce liver damage which, in a number of patients, may lead to fibrosis or cirrhosis. Recent studies have, however, documented that the methotrexate-induced liver cirrhosis is not aggressive. Interaction can occur with a number of drugs; serious problems in particular may arise with concomitant use of sulphonamides and salicylates. The recommended guidelines for methotrexate use in psoriasis should be followed and patients given clear instructions.
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PMID:Methotrexate side-effects. 185 36

Methotrexate has been used for many years to treat refractory psoriasis. Three cases of methotrexate-induced cirrhosis requiring orthotopic liver transplantation are presented to emphasize the importance of strict adherence to published criteria for patient selection, monitoring of cumulative drug dosages, and the performance of serial liver biopsies. Each patient had been treated with long-term methotrexate therapy (cumulative doses far in excess of 1.5 g) without undergoing serial liver biopsies, contrary to well-established treatment guidelines. Caution must be exercised in using methotrexate as a steroid-sparing agent in the treatment of inflammatory diseases because of its potential to cause severe hepatotoxic effects with long-term usage and cumulative doses above 1.5 g. Patients easily become psychologically dependent on the drug, and physicians need to guard against the false sense of security engendered by normal results on liver function studies.
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PMID:Methotrexate-induced cirrhosis requiring liver transplantation in three patients with psoriasis. A word of caution in light of the expanding use of this 'steroid-sparing' agent. 232 35

Methotrexate is an effective agent for the treatment of rheumatoid arthritis. It is now widely prescribed for patients who have not tolerated or responded to gold compounds or penicillamine. Minor adverse reactions are common, and fatal pulmonary toxicity or cirrhosis can occur. The drug does not produce disease remissions, but continued administration helps reduce pain, stiffness and swelling. Within the past year, the Food and Drug Administration has approved methotrexate for use in treating rheumatoid arthritis.
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PMID:Methotrexate in the treatment of rheumatoid arthritis. 267 14

Methotrexate-induced hepatotoxicity is well recognised in the treatment of leukaemia, psoriasis and rheumatoid arthritis. The pathological lesions are non-specific, consisting of fatty change, nuclear pleomorphism, hepatocyte necrosis, portal chronic inflammatory infiltrate, fibrosis and cirrhosis. The mechanism of liver injury is poorly understood; intracellular accumulation of methotrexate polyglutamate and consequent folate depletion are suspected to play a role. Early studies in psoriasis clearly established a relationship of the hepatic injury with the frequency of methotrexate administration. With weekly low dose therapy, however, consensus is lacking regarding the incidence of hepatotoxicity because studies have had disparate control groups, used variable dosage regimens and often failed to document pre-existing liver disease or categorised patients at risk, i.e. elderly patients, alcoholics and obese diabetics. Moreover, current methods of assessing the degree of hepatic injury are subjective, relying on interpretation by an experienced histopathologist. Preliminary evidence suggests less frequent and less severe hepatotoxicity occurs in patients with rheumatoid arthritis, probably as a result of lower methotrexate doses and better patient selection. Nevertheless, until the risk of serious liver disease is better defined it is recommended that patients have a pretreatment liver biopsy, a follow-up biopsy after a cumulative dose of 1500 mg, and then biopsies approximately every 2 years in the absence of other evidence of liver disease or risk factors.
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PMID:Hepatotoxicity of methotrexate in rheumatic diseases. 304 Dec 45

Thirty patients with psoriasis or other nonmalignant diseases had liver biopsies done before treatment with low-dose methotrexate, 15 mg/week, and then at one- to two-year intervals as long as they continued the methotrexate. All patients were symptomatically improved on this regimen. The 15 patients who had normal liver biopsies at the start of the study had normal biopsies after methotrexate. Fifteen others had minor hepatic histologic abnormalities before treatment. Eleven patients had fatty infiltration. Ten showed no significant change after treatment while one had increased fat and portal fibrosis on a fourth liver biopsy done seven years after MTX was begun. This last patient, a former alcohol abuser, continued methotrexate and showed no further worsening at 8 years. The remaining four had portal fibrosis before treatment. One patient had less fibrosis after methotrexate, two patients slightly more fibrosis, and one a marked increase in portal fibrosis. No patient developed cirrhosis or clinical liver disease. Our results suggest that in the absence of alcohol consumption, low-dose weekly methotrexate treatment rarely causes clinically significant liver damage.
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PMID:Low incidence of hepatotoxicity associated with long-term, low-dose oral methotrexate in treatment of refractory psoriasis, psoriatic arthritis, and rheumatoid arthritis. An acceptable risk/benefit ratio. 396 57


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