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Acid hydrolases in monocytes from patients with inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis.

A sensitive technique was used to estimate two acid hydrolases--N-acetyl-beta-glucosaminidase (N.A.G.) and beta-glucuronidase (B.G.)--produced by peripheral-blood monocytes. Enzyme levels were measured after in-vitro incubation of monocytes with or without stimulation by zymosan and endotoxin. Compared with controls, enzyme production and release in inflammatory bowel disease, chronic liver disease, and rheumatoid arthritis were markedly raised. It is suggested that various stimuli, including immunological ones, may be responsible for the release of such enzymes from monocytes and that such release may be a factor in the production of the chronic inflammation seen in these disorders.

Acetylglucosaminidase

Protein binding of salicylate and quinidine in plasma from patients with renal failure, chronic liver disease and chronic respiratory insufficiency.

The plasma protein binding of a representative acidic drug, salicylate, and a representative basic drug, quinidine, has been studied in patients with several diseases that are sometimes associated with uraemia or a change in serum albumin level. Decreased plasma protein binding of salicylate was observed in plasma from patients with uraemia and liver disease. Low albumin levels in these patients could only account inpart for the decreased binding. On the other hand, salicylate binding to plasma proteins appeared to be increased in patients with hypoxia. Decreased plasma protein binding of quinidine was observed in some patients with uraemia and in the majority of patients with liver disease.

Adult

Intravenous administration of diazepam in patients with chronic liver disease.

The EEG response and drug kinetics after intravenous infusion of diazepam at 1-0 mg/min until nystagmus, dysarthria, and moderate sedation developed, has been investigated in five normal subjects and 17 patients with chronic liver disease. Diazepam induced adequate premedication with a similar clinical response in all subjects with no adverse reactions. Maximal response was during or within five minutes of infusion. The dose of diazepam required in liver chronic disease was 17-9 +/- 1-4 mg (M +/- SEM) compared with 27 +/- 5-4 mg in controls (p less than 0-01). Dose correlated significantly with serum albumin (p less than 0-05). Baseline mean dominant frequency (MDF) and slow wave index (SWI) significantly correlated with albumin (p less than 0-01). After diazepam, the MDF decreased and SWI increased. The change was greatest at the time of maximal clinical response. It was greater in liverdisease and was greatest in patients with previous hepaticencephalopathy. In spite of reduced dose requirements in liver disease, there was no significant difference in plasma concentration at the end of drug infusion...

Chronic Disease

Recombinant Human Thrombopoietin Reduces the Need for Platelet Transfusion in Patients With Chronic Liver Disease and Thrombocytopenia.

Chronic liver disease (CLD)-related thrombocytopenia can limit the feasibility of invasive procedures. Recombinant human thrombopoietin (rhTPO) has demonstrated a favorable safety profile without hepatotoxicity. We evaluated the efficacy and safety of rhTPO in patients with CLD-related thrombocytopenia who were undergoing elective invasive procedures. In this multicenter, randomized (2:1), double-blind, placebo-controlled phase III trial, 120 adult Chinese patients with CLD-related thrombocytopenia (platelet count <&#x2009;50 &#xd7;&#x2009;109/L) received rhTPO (n =&#x2009;80) or placebo (n =&#x2009;40) once daily for up to 5 or 7&#x2009;days. The primary endpoint was the proportion of patients with sustained platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L from 24 h before invasive procedure to 7&#x2009;days post-procedure, without requiring emergency bleeding management. The primary endpoint was achieved by 85.0% of patients in the rhTPO group versus 12.5% in the placebo group (p&#x2009;<&#x2009;0.0001). Preoperatively, platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L were achieved in 92.5% and 20.0% of patients in the rhTPO and placebo groups, respectively (p&#x2009;<&#x2009;0.0001). Platelet transfusion was avoided in 92.5% of rhTPO-treated patients versus 25.0% of placebo-treated patients (p&#x2009;<&#x2009;0.0001). The median duration of platelet counts &#x2265;&#x2009;50 &#xd7;&#x2009;109/L was significantly longer with rhTPO than with placebo (21.0 vs. 3.0&#x2009;days, p =&#x2009;0.0007). Treatment-related treatment-emergent adverse events (TEAEs) occurred in 12.5% of patients in both the rhTPO and placebo groups. No treatment-related serious adverse events were reported. Overall, rhTPO was effective and well tolerated in patients with CLD-related thrombocytopenia and may represent a viable therapeutic option for those undergoing elective invasive procedures. Trial Registration: www.chinadrugtrials.org.cn: number CTR20230919.

Humans

[Osmolar and mechanic resistance of erythrocytes in chronic liver diseases].

Out of 120 patients with chronic liver diseases (45 liver cirrhosis, 38 chronic hepatitis, 15 fatty degeneration of the liver and 22 stasis liver) the osmotic resistance of the erythrocytes after Hennemann and the mechanic resistance after Schubothe was determined. 24% of the patients had a decreased osmotic resistance of the erythrocytes, even 55% a decreased incubation resistance. 16% of the patients with liver diseases had a decreased mechanic resistance of the erythrocytes. The comparison of the groups of disease and the stages of the diseases resulted in an increased mechanical resistance of the erythrocytes only for the decompensated liver cirrhosis. A positive correlation was the result between the degree of the haemolysis and the spherical index of the erythrocytes.

Chronic Disease

Decreased first-pass metabolism of labetalol in chronic liver disease.

The effect of chronic liver disease on the rate of elimination and extent of "first-pass" metabolism of labetalol was studied. Pharmacokinetic measurements were made after both oral and intravenous administration to seven healthy subjects and to 10 patients with chronic liver disease. Plasma half life was similar in the two groups. Plasma concentrations were considerably higher in the patients than in the healthy subjects after oral administration but similar after intravenous injection. Thus the bioavailability of labetalol was increased in liver disease due to reduced first-pass metabolism. Bioavailability in the group of patients correlated negatively with serum albumin concentration. There were falls in supine heart rate and blood pressure which tended to be greater after oral administration in the patients with liver disease, suggesting an exaggerated response related to the increased bioavailability. Oral dosage requirements of labetalol and possibly other drugs susceptible to first-pass metabolism are reduced in the presence of liver disease.

Administration, Oral

Shwachman-Diamond sydnrome and chronic liver disease.

Clinically inapparent persistent chronic liver disease in a 15-month-old male patient with Shwachman-Diamond syndrome is presented. Cryptic hepatic involvement may be an unrecognized feature of the syndrome and should be evaluated in all cases.

Chronic Disease

[Corelations between thrombocyte count, clinical diagnosis, and liver pathology in chronic liver diseases].

In 1488 cases of chronic liver disease thrombocyte content of peripheral blood, clinical diagnosis and histologic findings of the liver biopsy were correlated. Ranging from fatty infiltration to fatty cirrhosis or from slightly active chronic hepatitis to active postnecrotic cirrhosis, according to the extent of the liver injury a significant decrease of thrombocyte-count was evaluated. In case of non-active liver disease and posthepatitic status a thrombocytopenia also could be found. Cirrhotic transformation or proliferation of the connective tissue mainly in the periportal fields and inflammatory activity showed a significant correlation to the frequency of a thrombocyte decrease. A pathogenetic relation is ascribed to an increased thrombocyte storage in the spleen depending on the extent of the liver injury and the alteration of the portal blood stream up to a portal hypertension. Our results indicate such correlations of liver injury, portal pressure and platelet-pooling to thrombocyte-count even if the causal dependency cannot be proved.

Adult

[Erythrocyte changes during alcoholism and chronic liver diseases].

50 patients with chronic liver disease and/or alcoholism were studied. 28 cases of anemia were found and macrocytes (and target m.), spurr-cells, spherocytes and stomatocytes observed. For each of these abnormalities the authors report the observed incidence and discuss the literature's data about the pathogenesis. A personal research on the influence of the liver's impaired capability of protein synthesis was also carried out. The usefulness of a careful examination of the blood film is finally stressed, in patients with liver disease and to discover alcoholic subjects still "healthy".

Adult

[Immunological indices in chronic liver diseases].

The study aimed at the confrontation of the results from the investigation of the immunoglobulines G, M, and A (IgG, IgM and IgA), the test for spontaneous rosette formation and the determination of Australian antigen (HBsAg) in 110 patients with chronic liver disease (liver steatosis, chronic persisting hepatitis, chronic aggressive hepatitis and liver cirrhosis). The diagnosis was morphologically confirmed and some of the patients were repeatedly examined. No significant interrelations among the three main classes of immunoglobulines were established in the majority of the groups of chronic liver diseases, speaking for the individual information, carried by the separate immunoglobuline classes. Correlation was established between IgG and IgM in chronic active hepatitis. The mean values of IgG and IgM are considerably higher in cases with splenomegaly. IgG is more often increased when the patients are carriers of HBsAg, being in agreement with the contemporary concepts about the differences in immune pathological mechanism in chronic liver diseases, with and without HB5-antigenemia.

Chronic Disease

Glucocorticoid and mineralocorticoid hormones in chronic liver diseases.

In patients with chronic liver disease a dissociation of the two most important partial functions of the adrenal cortex may be observed. A widening of the zona glomerulosa is associated with an increased aldosterone secretion and an atrophy of the zona fasciculata with a decreased cortisol production rate. In acute alcoholic liver damage there are sometimes remarkable special features concerning the adrenal function. The pathogenesis of the altered C21-steroid hormone metabolism is nonuniform and depends upon the etiology of the liver disease. Following factors may play role: 1. Decreased activity of specific hepatic enzymes a)direct enzyme damage b)indirect enzyme activity decreasing processed by deficiency of hydrogen from NADPH 2. Decreased hepatic blood flow 3. Disturbance of intracellular transport of substrates (e.g. cholestasis 4. Changes of transport proteins. 5. Direct or reactive changes of other factors of hormonal feedback systems (hypothalamus-pituitary-adrenal or gonadal-system; renin-angiotensin-aldosterone-system).

Adrenal Cortex

Noninvasive kinetic approach to the estimation of total hepatic blood flow and shunting in chronic liver disease--a hypothesis.

The intact hepatocyte theory of chronic liver disease suggests a relationship between the degree of shunting of total liver blood flow around the functional liver cell mass and the fraction of functional liver cell mass. By defining this relationship we have developed pharmacokinetic equations to permit the estimation of both total hepatic blood flow and the extent to which this blood flow is shunted. The method requires the determination of the systemic (hepatic) clearances of a high (e.g., indocyanine green [ICG]) and a low (e.g., antipyrine [AP]) extraction ratio drug in the same patient. Applying these equations to literature data obtained from patients with moderate or severe chronic liver disease and from patients with a surgical portacaval shunt, we find: (1) a modest decrease in total hepatic blood flow (16%) and a significant degree of shunting (27%) in patients with moderate chronic liver disease; (2) a substantially reduced total hepatic blood (52%) and extensive shunting (72%) in patients with severe chronic liver disease, and (3) a degree of shunting comparable to that estimated in patients with moderate chronic liver disease but a seriously compromised total hepatic blood flow (a reduction of 55% compared to normal) in patients with surgical portacaval shunts.

Antipyrine

[A contribution to the treatment of chronic liver diseases (author's transl)].

89 randomized liver patients (42 with chronic hepatitis, 25 with hepatic cirrhosis, 14 with hepatitis of protracted evolution, 8 with alcohol-toxic adiposis hepatica, stage II) are reported, in whom considerable functionally and histologically identifiable therapeutic results were achieved by combined i.v. and oral treatment with thioctic acid. According to expectation, the most favourable results were found in alcohol-conditioned chronic liver diseases; however, also in chronic active hepatitis, resistant to treatment, a therapy could be promising. The oral therapy with thioctic acid, producing no side effects, is especially suited for the long-term outpatient treatment of chronic hepatitis and hepatic cirrhosis of toxic and posthepatic etiology.

Administration, Oral

A cause of hyperamylasemia associated with chronic liver disease.

The cause of hyperamylasemia associated with chronic liver disease is unclear. In an attempt to identify the tissue of origin of hyperamylasemia in 3 patients with chornic active hepatitis their serum was isoelectrically focused. The isoamylase patterns obtained were compared to those of pancreatic and salivary amylase. The apparent salivary gland origin of the excessive blood amylase in the patients studied was substantiated by radiological demonstration of parotid sialoectasia in one patient and histological evidence of sialoadenitis in another. Further evidence was the coincident isoelectric points of the predominant isoamylase in the sera of the liver disease patients and of patients with parotid inflammatory disease. Hyperamylasemia associated with chronic liver disease may be of salivary gland origin and as such forms part of the spectrum of extrahepatic manifestations of chronic active hepatitis.

Adult

Percutaneous liver biopsy and chronic liver disease in haemophiliacs.

Systematic screening of forty-seven haemophiliacs in Sheffield revealed abnormal liver-function tests in thirty-six (77%), with a tendency for these abnormalities to persist. To assess the importance of these abnormalities, percutaneous liver biopsy was carried out on eight symptom-free patients under factor-VIII cover. A wide spectrum of chronic liver disease was demonstrated, including chronic aggressive hepatitis and cirrhosis. The liver pathology bore no relation to clinical history or to biochemical findings. Hepatitis-B-virus markers were common, but evidence suggests that this is not the only factor contributing to the development of liver disease. The high incidence of chronic liver disease seems to be a recent development and is probably related to factor-concentrate replacement therapy.

Adult