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PubMed1986

Oral zinc therapy normalizes serum uric acid level in Wilson's disease patients.

The authors investigated changes in the serum uric acid (s-UrA) level seen in a Wilson's disease patient who had to undergo oral zinc therapy because of the occurrence of D-penicillamine-induced acute sensitivity reactions, including neutrophilic agranulocytosis, thrombocytopenia, and skin eruptions. Although s-UrA levels were low before oral zinc therapy (mean +/- SD, 1.60 +/- 0.20), they increased (mean +/- SD, 2.63 +/- 0.32) to within normal range (2.8-8.0 mg/dl) after therapy. There were no significant changes in the renal tubular reabsorption of UrA during oral zinc therapy. This therapy also produced an improvement of the decreased cholinesterase (ChE) values usually seen in Wilson's disease. These results suggest that oral zinc therapy can normalize UrA metabolism in Wilson's disease by improving liver dysfunction and increasing UrA synthesis.

Administration, Oral↗
PubMed2002

High alanine aminotransferase is associated with decreased hepatic insulin sensitivity and predicts the development of type 2 diabetes.

It has been proposed that liver dysfunction may contribute to the development of type 2 diabetes. The aim of the present study was to examine whether elevated hepatic enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], or gamma -glutamyltranspeptidase [GGT]) are associated with prospective changes in liver or whole-body insulin sensitivity and/or insulin secretion and whether these elevated enzymes predict the development of type 2 diabetes in Pima Indians. We measured ALT, AST, and GGT in 451 nondiabetic (75-g oral glucose tolerance test) Pima Indians (aged 30 +/- 6 years, body fat 33 +/- 8%, ALT 45 +/- 29 units/l, AST 34 +/- 18 units/l, and GGT 56 +/- 40 units/l [mean +/- SD]) who were characterized for body composition (hydrodensitometry or dual-energy X-ray absorptiometry), whole-body insulin sensitivity (M), and hepatic insulin sensitivity (hepatic glucose output [HGO] during the low-dose insulin infusion of a hyperinsulinemic clamp) and acute insulin response (AIR) (25-g intravenous glucose challenge). Sixty-three subjects developed diabetes over an average follow-up of 6.9 +/- 4.9 years. In 224 subjects, who remained nondiabetic, follow-up measurements of M and AIR were available. At baseline, ALT, AST, and GGT were related to percent body fat (r = 0.16, 0.17, and 0.11, respectively), M (r = -0.32, - 0.28, and -0.24), and HGO (r = 0.27, 0.12, and 0.14; all P < 0.01). In a proportional hazard analysis with adjustment for age, sex, body fat, M, and AIR, higher ALT [relative hazard 90th vs. 10th centiles (95% CI): 1.9 (1.1-3.3), P = 0.02], but not AST or GGT, predicted diabetes. Elevated ALT at baseline was associated prospectively with an increase in HGO (r = 0.21, P = 0.001) but not with changes in M or AIR (both P = 0.1). Higher ALT concentrations were cross-sectionally associated with obesity and whole-body and hepatic insulin resistance and prospectively associated with a decline in hepatic insulin sensitivity and the development of type 2 diabetes. Our findings indicate that high ALT is a marker of risk for type 2 diabetes and suggest a potential role of the liver in the pathogenesis of type 2 diabetes.

Adipose Tissue↗
PubMed1992

[A study on virus localization and microcirculation in the liver in patients with epidemic hemorrhagic fever].

The findings in our clinical study was consistent with those reported by others that a temporary elevation of serum alanine aminotransferase activity is associated with epidemic hemorrhagic fever (EHF). However, the pathogenesis of the concomitant changes in liver function tests is still not clear. To clarify whether EHF virus is cytopathic or not for the liver, percutaneous liver biopsy was done in 19 patients with EHF within 3-12 days after the onset of symptoms. These liver biopsy specimens were examined with immunofluorescence assay and cell cultural technique, showing the presence of active viral replication in liver cells. Electron microscopy observation of the infected liver cells showed that ultrastructural distortions was accompanied by the existence of inclusion bodies of EHF virus in vacuoles of rough endoplasmic reticulum, endotheliocyte and microvilli. These findings strongly suggest that EHF virus may play a causative role in liver injury in patients suffering from EHF and hepatic microcirculation disturbance may be involved in the pathogenesis of EHF-related liver dysfunction as well.

Adolescent↗
PubMed1989

Histidine-rich glycoprotein is elevated in mild liver cirrhosis and decreased in moderate and severe liver cirrhosis.

Histidine-rich glycoprotein (HRG) reduces by complex formation with plasminogen the amount of "free" plasminogen in circulation and is therefore considered an inhibitor of fibrinolysis. We studied the levels of both HRG and plasminogen in patients with different degrees of liver cirrhosis to assess the role of HRG in enhanced fibrinolysis in these patients. In mild (Child A) cirrhosis, HRG levels unexpectedly were significantly increased. The total plasminogen level and the calculated amount of free plasminogen were decreased. In moderate (Child B) cirrhosis, both HRG levels and total plasminogen levels were reduced, resulting in a normal amount of free plasminogen in circulation. In severe (Child C) cirrhosis, HRG level, total plasminogen level, and free plasminogen level were all decreased. Because the HRG level is increased in Child A liver cirrhosis, we suggest that other mechanisms, other than simply a decreased synthetic capacity of the liver, contribute to the changes in HRG levels in patients with liver disease. Because of the reduction of free plasminogen levels in severe liver cirrhosis, we propose that the decrease in HRG levels in liver cirrhosis plays no role in enhanced fibrinolysis in these patients. The increase in the HRG level in Child A liver cirrhosis may be of importance in future studies on familial thrombosis associated with elevated levels of HRG, where mild liver dysfunction should at least be excluded.

Adult↗
PubMed1984

Distribution of cimetidine in postmortem tissues.

The postabsorptive distribution of cimetidine is described. Assays by high pressure liquid chromatography (HPLC) of postmortem samples of cerebrospinal fluid, serum, and solid tissues were used to determine pharmacokinetic parameters as well as mean tissue: serum concentration (T:S) ratios in seven patients with renal and liver dysfunction. Correlations were calculated between the T:S ratio and the volume of distribution, and between the T:S concentration ratio and the time of sampling after death. The highest T:S ratios occurred in the eliminating organs, the liver and kidneys, and the lowest in fat. As the time of autopsy increased after death, the T:S ratios decreased.

Adipose Tissue↗
PubMed1981

Does evidence of reductive halothane biotransformation correlate with hepatic binding of metabolites in obese patients?

Covalent binding of fluorinated anesthetic metabolites was measured using intraoperative liver biopsies obtained from 48 morbidly obese patients randomly assigned to receive N2O-O2 combined with either fentanyl, enflurane, or halothane. No difference in binding was found between anesthetic groups. In addition, preoperative and postoperative levels of serum glutamic oxaloacetic transaminase (SGOT) and serum glutamic pyruvic transaminase (SGPT) did not differ among three groups of patients. However, hepatic organic fluoride binding significantly correlated with peak serum ionic fluoride in patients given halothane (p 0.001, r = 0.68). Thus, the fluorinated metabolites binding assay is a reliable index of reductive halothane metabolism. Possible application of this assay to aid in the diagnosis of postoperative liver dysfunction is suggested.

Adult↗
PubMed2001

Adenosine reverses a preestablished CCl4-induced micronodular cirrhosis through enhancing collagenolytic activity and stimulating hepatocyte cell proliferation in rats.

Cirrhosis is one of the most common causes of mortality worldwide, because hepatic dysfunction constitutes a potentially lethal condition. Having demonstrated the hepatoprotective effect of adenosine against CCl(4)-induced cirrhosis, the present study was aimed at assessing adenosine's effect on an already-established micronodular cirrhosis. Chronic administration of CCl(4) (10 weeks) induced a cirrhotic state, characterized by increased liver fibronectin and collagen types I and III content, enhanced expression of alpha-1 (I) collagen mRNA, portal hypertension, and liver dysfunction. After CCl(4) discontinuation (5 weeks), increased persitance of alpha-1 (I) collagen mRNA expression and deposition, enhanced proline incorporation into collagen and prolyl hydroxylase activity evidenced active fibrogenesis. Several weeks after CCl(4) withdrawal, deposited collagen showed an enhanced type I/III ratio, which was associated with deficient collagenolytic activity in cirrhotic livers. Liver expression of some metalloproteinases (MMPs) and of tissue inhibitors of MMPs (TIMPs) also indicated decreased collagen breakdown in cirrhotic livers. Parameters indicative of oxidative stress (mainly protein oxidation) were persistently augmented. These events were coincident with diminished regenerative capacity of the cirrhotic liver. Intraperitoneal adenosine administration to CCl(4)-induced cirrhotic rats blocked active fibrogenesis and increased the collagen degradation (most probably by decreasing liver TIMPs levels), normalizing collagen-type ratios. In addition, the nucleoside promoted an effective hepatocyte's proliferation in the cirrhotic liver and accelerated normalization of parameters indicative of liver function and oxidative stress. Thus, adenosine readily reversed an experimental cirrhosis through stimulating liver collagenolytic and proliferative capacities, as well as by accelerating functional recovery.

Adenosine↗
PubMed2002

Immunological and virological effects of ribavirin in hepatitis C after liver transplantation.

BACKGROUND: Hepatitis C recurring after liver transplant may cause progressive liver dysfunction, and available treatment regimens are unsatisfactory. A better understanding of the mechanisms of action of drugs currently used to manage hepatitis C would be helpful. METHODS: In a pilot, uncontrolled clinical trial, we treated 12 patients with post-liver transplantation hepatitis C with 1000-1200 mg qd of ribavirin, given as a monotherapy. We measured the transaminases levels, the liver disease grading and staging scores, the intrahepatic interferon-gamma, tumor necrosis factor-alpha, interleukin (IL)-4 and IL-10 mRNA levels, the serum and liver hepatitis C virus (HCV) RNA titers, and the intrahepatic HCV envelope 2 protein staining score before and after 12 weeks of ribavirin monotherapy. RESULTS: Ribavirin induced a significant amelioration of the transaminases levels. This biochemical response was not associated with a distinct change in the intrahepatic T helper 1/T helper 2 cytokine mRNA profile. Furthermore, some histological parameters, such as the portal inflammation and the fibrosis scores, worsened significantly even in the short term. A slight, albeit not significant, decrease of serum HCV RNA level and intrahepatic HCV antigen staining score was observed. Intrahepatic genomic-strand (but not negative-strand) HCV RNA titer decreased significantly (P=0.024). CONCLUSIONS: Contrary to what is suggested by experimental data, administration of ribavirin alone to patients with recurrent hepatitis C after liver transplantation is not accompanied by a specific change of the intrahepatic interferon-gamma, tumor necrosis factor-alpha, IL-4, or IL-10 mRNA transcription profile.

Adult↗
PubMed1997

Chronic hepatitis infected with hepatitis GB virus type C/hepatitis G virus presenting as non-alcoholic steatohepatitis.

A 68-year-old man with moderate liver dysfunction diagnosed with atypical pneumonia showed serum alanine aminotransferase and gamma-glutamyltranspeptidase levels which revealed a sustained abnormality over six months. Hepatitis GB virus type C/hepatitis G virus demonstrated in his serum by reverse transcription-polymerase chain reaction. Liver histology showed steatohepatitis typically observed in alcoholic hepatitis without a remarkable drinking history. This case suggests that hepatitis GB virus type C/hepatitis G virus may induce chronic hepatitis and that there may be cases with chronic hepatitis induced by this virus in patients who have been diagnosed with alcoholic liver disease, even in cases with typical histology of alcoholic hepatitis.

Aged↗
PubMedDate not supplied

Prescribing drugs for patients with liver disease.

BACKGROUND: Adverse reactions to prescribed drugs are a common cause of morbidity in patients receiving medical care. Pre-existing or underlying liver dysfunction is one of the commonest factors that enhance the risk of such adverse events in medical practice. Most textbooks of medicine contain no guidelines on special precautions to be taken in prescribing to a patient with pre-existing liver disease. METHODS: To provide a ready reckoner for modifying drug dosage in liver diseases, a literature search was carried out. All papers related to human studies were reviewed and relevant material extracted for preparing the guidelines. RESULTS: Most adverse drug reactions in the presence of liver disease are related to altered pharmacokinetics, pharmacodynamics and susceptibility to drugs. The influence of hepatic disease on various drugs is highly variable. However, many such adverse events are predictable and preventable. Ideally, drug dosage should be modified with the help of serum drug concentrations, which unfortunately, are not available in most Indian hospitals. Hence, some broad guidelines are presented to assist the treating physician to be aware of the risk of adverse drug reactions and modify drug dosage empirically to avoid such events. CONCLUSION: The altered metabolism of pharmacological agents in patients with liver disease may induce several undesirable effects. A large number of adverse drug reactions can be prevented by modifying drug prescribing habits for patients who have pre-existing liver disease.

Chronic Disease↗
PubMedDate not supplied

Hepatic venous outflow obstruction in Nepal.

Intra hepatic inferior venacaval (IVC) obstruction at the site or just above hepatic vein opening in the IVC, is a common hepatic problem in Nepal. These patients either present as a chronic IVC obstruction with insidious onset or may present with rapid onset disease (acute/subacute disease). The former type may be asymptomatic (20%) or may have features of chronic liver dysfunction. The latter presents with rapid onset ascites. Presence of hepatomegaly with flank/back veins are characteristic clinical features of the disease. The disease is invariably encountered amongst rural poor, alcoholic and in the peripartum period. Ultrasonography, IVC graphy hepatogram and liver biopsies are the usual diagnostic modalities. Twenty four percent of the 126 chronic hepatic IVC disease had associated liver cell cancer at our centre. The aetiology of the disease is unclear. Presently it is believed that local thrombophlebitis in IVC causes such obstruction. Despite, surgical and radiological intervention, the ideal management in such patients is yet to be established. We believe conservative therapy, particularly prevention and early therapy of sepsis in such patients prolongs survival.

Acute Disease↗
PubMed1994

The influence of chronic lobular hepatitis on pharmacokinetics of cefoperazone--a novel galactose single-point method as a measure of residual liver function.

Cefoperazone is a semisynthetic cephalosporin antibiotic containing a piperazine side chain, which results in antipseudomonal activity. Unlike the other cephalosporins, it is mainly cleared by the liver (60-80%) and it may be more sensitive to changes in the liver function and/or plasma protein binding than other cephalosporins, which are not primarily cleared by the liver. In order to study the influence of chronic lobular hepatitis on the pharmacokinetics of cefoperazone, a dose of 1 g of cefoperazone was administered to 11 normal, healthy volunteers and 16 subjects with chronic lobular hepatitis. In each volunteer or patient, a novel galactose single-point (GSP) method, the galactose elimination capacity (GEC) test, and the modified galactose elimination capacity (MGEC) test were also performed as a measure of residual liver function. Cefoperazone was administered intravenously over a period of 3-5 min. Blood and urine samples were collected at appropriate intervals after drug administration and stored at -30 degrees C until high-pressure liquid chromatographic (HPLC) analysis. The cefoperazone hepatic clearance, mean residence time, and renal clearance in hepatitis patients were significantly different from those of normal healthy volunteers, whereas the plasma protein binding was unaltered between the two groups. Urinary excretion of cefoperazone showed a highly significant increase in patients, 23.95 +/- 5.06% and 37.54 +/- 13.61% for normal men and hepatitis patients respectively. Hepatic clearance and fraction excreted in urine significantly correlated with values of GSP and MGEC respectively (p < 0.05). These results suggest (i) cefoperazone kinetics was significantly altered in patients with chronic lobular hepatitis; (ii) GSP, a novel simple, clinically useful quantitative liver function test, can predict the cefoperazone hepatic clearance in patients with liver dysfunction.

Adult↗
PubMed2002

Impairment of activation of hepatocyte growth factor precursor into its mature form in rats with liver cirrhosis.

BACKGROUND: Hepatocyte growth factor (HGF) has a crucial role in liver regeneration following injury. The conversion of an inactive precursor form of HGF (proHGF) into a biologically active form (mature HGF) is essential, as HGF is involved in the recovery of liver damage. Liver regeneration is markedly poor in patients with liver cirrhosis after resection. We hypothesized that impairment of liver regeneration in cirrhosis is in part because of the absence of activation of proHGF to mature HGF. Studies were performed to clarify the molecular form of HGF in the liver of rats with fibrosis/cirrhosis before and after liver resection. METHODS: Rat models of liver fibrosis/cirrhosis were induced by intraperitoneal administration of dimethylnitrosamine, followed by 45% partial hepatectomy or sham operation. HGF was purified from the liver and plasma on a SP-Sepharose column and was analyzed by Western blotting. RESULTS: Production of proHGF in the liver increased in the following order: rats with normal liver, rats with fibrosis, and rats with cirrhosis. However, the levels of proHGF were similar after liver resection in the liver of these groups. A small but significant level of mature HGF was detected before resection in the fibrosis group, but not in the normal and cirrhosis groups. Liver resection increased the levels of mature HGF in the normal and fibrosis groups, but marginally in the cirrhosis group. CONCLUSIONS: These results demonstrate that the conversion of proHGF into mature HGF is impaired after liver resection in liver cirrhosis, while proHGF production is similar in the livers of normal, fibrosis, and cirrhosis groups. Acceleration of the processing of the HGF molecule may contribute to the improvement of liver dysfunction in cirrhosis.

Animals↗
PubMed1993

Plasma activities of hepatic enzymes in patients on anticonvulsant therapy.

The object of the study was to discover the changes in the plasma activities of hepatic enzymes in patients on anticonvulsant drugs. The plasma activities of aspartate transaminase (AST), alkaline phosphatase (ALP), alanine transaminase (ALT) and glutamyltransferase (GGT) were studied in 123 unselected patients on anticonvulsants. The results were compared with 123 control patients not on anticonvulsants matched for age and sex. Patients with known liver disease were excluded. The plasma activities of AST and ALP were similar in the two groups. ALT and GGT were raised in patients on anticonvulsants. No patient developed clinical evidence of liver disease. It was concluded that raised ALT and GGT are not in themselves indications to alter anticonvulsant therapy. Changes in AST and ALP would be more specific markers of liver dysfunction in patients on anticonvulsants.

Adolescent↗
PubMed1970

Red cell survival in biliary cirrhosis.

Studies were carried out on eight patients with primary biliary cirrhosis. Four patients were found to have a haemolytic anaemia; one had Coombs red cell antibodies. Two patients had evidence of splenic sequestration of red cells using the radio-chromium technique. There was a significant correlation between the red cell survival and the bromsulphthalein retention test and the red cell survival and the serum level of bilirubin. It was concluded that the anaemia of cirrhosis of the liver, including primary biliary cirrhosis, may be due to a number of mechanisms and a unifying hypothesis based on the degree of liver dysfunction is suggested.

Aged↗
PubMed1985

[Hemostatic studies on acquired abnormal fibrinogenemia in severe liver diseases and umbilical cord blood].

An abnormal fibrinogen in patients with liver diseases, especially liver cirrhosis and hepatocellular carcinoma was examined. In these patients, delayed polymerization of fibrin monomer, which was useful for detecting abnormal fibrinogen in plasma and also detecting one of liver dysfunctions, was observed. Same results were found by using purified abnormal fibrinogen from these patients. However, according to electrophoretic and immunochemical studies, no difference were shown between purified abnormal fibrinogen and purified normal fibrinogen. The total content of sialic acid in purified abnormal fibrinogen was markedly increased as compared to that in purified normal fibrinogen. When coagulation time was examined by using asialofibrinogen treated with neuraminidase, the prolonged coagulation time was partially normalized even in patients with liver cirrhosis. These findings suggested that sialic acid might affect the polymerization of fibrin monomer. It was reported by Harvey (1978) that an abnormal fibrinogen in liver diseases was similar to the fetal fibrinogen in the content of sialic acid and prolongation of thrombin time. Therefore, purified fibrinogen from umbilical cord blood was also investigated by similar methods. Consequently, it was suggested that a dysfunction of fibrinogen in umbilical cord blood was not related to molecular abnormality, but some inhibitory mechanisms which caused the abnormal pattern of coagulation might be existed.

Fetal Blood↗
PubMed2026

Human Umbilical Cord Mesenchymal Stem Cells in Metabolic Dysfunction-associated Fatty Liver Disease (MAFLD) Therapy: Mechanisms, Clinical Efficacy, and Future Perspectives.

There is currently no approved drug treatment for metabolic dysfunction-related fatty liver disease (MAFLD). Umbilical cord-derived mesenchymal stem cells (UC-MSCs) show therapeutic potential, but their mechanism of action is remains incompletely understood. Different from previous reviews that focused on a single pathway, this article presents three important contributions: First, it constructs an integrated "multi-target synergy network" model, clarifying how UC-MSCs coordinate and regulate the inflammatory, metabolic and fibrotic processes through the interactions between the AMPK/mTOR, Nrf2/HO-1 and TGF-&#x3b2;/Smad pathways; Second, it systematically assesses recent clinical trials (2022-2025), identifying several unaddressed barriers to transformation, including the lack of histological endpoint indicators, batch-to-batch differences, and the absence of dose exploration studies; Third, we integrate the latest developments from 2024 to 2025, particularly mitochondrial transfer (mediated by tunnel nanotubes and accompanied by quantitative efficacy data) and exosome circular RNA networks [Formula: see text], which have not been covered in previous reviews. Based on the above analysis, we also propose specific suggestions for standardized GMP production, mandatory genomic stability testing, and long-term safety registration. This review provides a comprehensive analysis of elaborates on the treatment of MAFLD with UC-MSCs from a mechanistic and translational perspective, based on the extensive updates of relevant literature.

Humans↗