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PubMedDate not supplied

Hepatopulmonary syndrome: prevalence and clinical profile.

BACKGROUND: The hepatopulmonary syndrome (HPS) is defined as a triad of liver dysfunction, intrapulmonary vascular dilatations (IPVD) and arterial hypoxemia. There is paucity of Indian studies regarding the prevalence of IPVD and arterial hypoxemia particularly amongst patients with non-cirrhotic portal fibrosis (NCPF) and extrahepatic portal vein obstruction (EHPVO), where liver dysfunction is not a feature. METHODS: All patients with portal hypertension and esophageal varices seen at a tertiary care hospital during 1995-98 were studied. Ultrasonography of abdomen, contrast-enhanced echocardiography (CEE), arterial blood gas analysis and assessment of alveolar-arterial oxygen gradient were done. RESULTS: Of 138 patients with portal hypertension seen during the study period, 88 fulfilled the inclusion and exclusion criteria. These included 63 with cirrhosis, 15 with NCPF and 10 with EHPVO. CEE showed IPVD in 17 (27%) patients with cirrhosis, of which 11 (17.5%) fulfilled the criteria for HPS. IPVD were also noted in 4 (26.6%) cases of NCPF and 3 (30%) of EHPVO, though only 2 (13.3%) and 1 (10%) respectively had elevated alveolar-arterial gradient and liver dysfunction in addition. Age and sex distribution and duration of symptoms were not different in patients with HPS. Patients with HPS had higher incidence of dyspnea, platypnea, clubbing and spider nevi. CONCLUSIONS: Hepatopulmonary syndrome is present in 17.5% of cirrhotics, 13.3% of patients with NCPF and 10% with EHPVO. Patients with HPS had significantly higher incidence of dyspnea, platypnea, clubbing and spider nevi.

Adolescent↗
PubMed2005

Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease.

BACKGROUND/AIMS: In patients with severe acute liver dysfunction, i.v. phylloquinone (vitamin K1) may be given to exclude vitamin K deficiency, rather than impaired hepatic synthesis of coagulation factors alone, as the cause of the coagulopathy. However, there have been no studies of the pharmacokinetics or efficacy of i.v. or oral K1 in such patients. METHODS: 49 adults with severe acute liver disease were randomised double-blind to a single 10 mg dose of i.v. or oral mixed-micellar K(1), or placebo. Serum levels of phylloquinone and undercarboxylated prothrombin (PIVKA-II) were assessed before and after treatment. RESULTS: At admission, 13 patients (27%) had either low serum K1 levels or elevated PIVKA-II concentrations, indicative of subclinical vitamin K deficiency. In the 16 patients who received i.v. K1, there was one (6%) treatment failure (K1 rise <10 ng/ml above baseline), compared with 12 of the 15 (80%) who received oral K1 (P<0.0001). One patient in the placebo group developed overt vitamin K deficiency. CONCLUSIONS: A minority of patients with severe acute liver dysfunction have subclinical vitamin K deficiency at the time of presentation, which is corrected by a single dose of i.v. K1. The intestinal absorption of mixed-micellar K1 is unreliable in adults with severe acute liver dysfunction.

Acute Disease↗
PubMed2002

Concomitant overdosing of other drugs in patients with paracetamol poisoning.

AIMS: Paracetamol is frequently involved in intended self-poisoning, and concomitant overdosing of other drugs is commonly reported. The purpose of the study was to investigate further concomitant drug overdose in patients with paracetamol poisoning and to evaluate its effects on the outcome of the paracetamol intoxication. METHODS: Six hundred and seventy-one consecutive patients admitted with paracetamol poisoning were studied and concomitant drug intake was recorded. The relative risk of hepatic encephalopathy, death or liver transplantation, hepatic dysfunction, liver cell damage, and renal dysfunction associated with concomitant overdosing of other drugs was evaluated by multivariate analysis. RESULTS: Concomitant drug overdose was found in 207 patients (31%, 95% confidence interval [CI] 27, 34%). Concomitant overdosing of benzodiazepines (99 cases), opioid analgesics (38 cases), acetylsalicylic acid (33 cases), and NSAID (32 cases) predominated. Concomitant benzodiazepine overdose was an independent risk factor in the development of hepatic encephalopathy (odds ratio [OR] 1.91; CI 1.00, 3.65) and renal dysfunction (OR 1.81; CI 1.00, 3.22). Concomitant overdosing of opioid analgesics was a protective factor in the development of hepatic encephalopathy (OR 0.26; CI 0.07, 0.96). Concomitant acetylsalicylic acid overdose was a risk factor in the development of hepatic encephalopathy (OR 4.87; CI 1.52, 15.7) and death or liver transplantation (OR 6.04; CI 1.69, 21.6). A tendency towards a more favourable outcome was observed in patients with concomitant NSAID overdose. CONCLUSIONS: Concomitant overdosing of benzodiazepines or analgesics is frequent in patients admitted with paracetamol poisoning. Concomitant benzodiazepine or acetylsalicylic acid overdose was associated with more severe toxicity, whereas concomitant overdosing of opioid analgesics was associated with less toxicity.

Acetaminophen↗
PubMed1994

Inverse correlation between the titre of antibody to hepatitis C virus and the degree of hepatitis C viraemia.

We titrated 277 hepatitis C virus (HCV) antibody-positive serum samples from 235 volunteer blood donors as well as from 42 outpatients of a hospital for elderly people and studied the relation of the titre of HCV antibody to the presence of HCV RNA, of antibody to C100 protein (anti-c100) and of antibody to GOR epitope (anti-GOR). Liver dysfunction was measured also. Of 177 HCV RNA-positive serum samples, 87 were tested for the degree of HCV viraemia by means of a competitive assay. Among the 277 samples, prevalences of HCV RNA, anti-c100, anti-GOR and liver dysfunction were 63.9%, 71.8%, 75.7% and 17.5%, respectively. The prevalence of HCV RNA became higher as the titre of HCV antibody increased. The titre tended to increase with age but the tendency was not statistically significant. The mean titre was higher in females (2(10.4 +/- 1.8)) than in males (2(9.4 +/- 2.2)) (P < 0.01). In the HCV RNA-positive serum samples, the HCV antibody titre was significantly higher in the anti-c100-positive samples than in the negative ones. This difference between the positive and negative samples, however, was not statistically significant for anti-GOR and liver dysfunction. Low degrees of HCV viraemia were accompanied by high titres of HCV antibody while high degrees of HCV viraemia went with low titres of HCV antibody. The study revealed that titres of HCV antibody were higher in females and the degree of HCV viraemia correlated inversely with the titre of HCV antibody.

Adolescent↗
PubMed2006

Minor liver profile dysfunctions in Plasmodium vivax, P. malaria and P. ovale patients and normalization after treatment.

Liver function tests were performed in 61 vivax, 54 malariae and 15 ovale malaria patients who were admitted to Bangkok Hospital for Tropical Diseases between 2001 and 2004. The objective of the study was to evaluate changes in hepatic biochemical indices before and after treatment with artemisinin derivatives. On admission and prior to treatment, hepatic dysfunction was found among the 3 groups. Serum liver function tests and physical examinations were performed weekly during the 28-day follow-up period. Initially elevated serum bilirubin and diminished albumin returned to normal within 2 weeks of treatment. Serum alkaline phosphatase and aminotransferases returned to within normal limits within 3 weeks. We conclude that patients with Plasmodium vivax, P. malariae and P. ovale infections had slightly elevated serum bilirubin, aminotransferase and alkaline phosphatase levels, and hypoalbuminemia. These minor abnormalities returned to normal within a few weeks after treatment with therapies based on artemisinin derivatives.

Adolescent↗
PubMed2000

Toxic metronidazole-induced MRI changes.

OBJECTIVE: To report a case of changes documented by magnetic resonance imaging (MRI) of the head probably due to accumulation of metronidazole in a patient with liver dysfunction. CASE SUMMARY: A 34-year-old Hispanic man with cirrhosis and hepatitis C being treated with metronidazole for Bacteroides fragilis meningitis and bacteremia developed ataxia, disorientation, and peripheral neuropathy. An MRI at the time meningitis was diagnosed was negative. After the patient received > 60 g of metronidazole, an MRI revealed increased signal intensity below, behind, and lateral to the fourth ventricle. Concomitant metronidazole serum concentration was toxic at 35.1 micrograms/mL. DISCUSSION: This is the second reported case of metronidazole-induced MRI changes. Metronidazole is known to accumulate in patients with liver dysfunction and can cause peripheral neuropathy and central nervous system (CNS) dysfunction; these effects may take up to two years to completely resolve. CONCLUSIONS: Metronidazole dosages should be reduced in patients with liver dysfunction to prevent the accumulation of metronidazole, which can lead to CNS dysfunction and peripheral neuropathy.

Adult↗
PubMed2001

Changes of DNA titer and sequence variance of TT virus in hepatic disorders.

TT virus (TTV) has been reported to occur in association with elevated alanine aminotransferase (ALT) levels in patients with posttransfusion hepatitis of unknown etiology. We examined whether the presence, change of DNA titer, or variation in sequence of this virus is associated with acute or chronic liver dysfunction in Japanese. We detected TTV by polymerase chain reaction (PCR) using primers generated from the conserved region of the TTV genome. Direct DNA sequencing of the original N22 region was used to characterize TTV isolates. We detected TTV DNA in 15 (25%) of 60 patients with liver dysfunction. Variants recovered from infected patients formed four genotypes/subtypes, corresponding to G1a, G1b, G2, and G4. Although TTV DNA titers in patients with G2 and G4 were lower than those with G1, TTV was consistently detected regardless of genotype/subtype. TTV infection continued for at least 1 year after normalization of ALT level in patients with acute liver dysfunction. Changes in DNA titer, substitutions of deduced amino acids, and variety of quasispecies of TTV were detected during the observation period, but no significant fluctuation in ALT level was found. We conclude that persistent infection, changes in DNA titer, and variation in sequence of this novel virus are not significantly related to hepatic disorders.

Journal Article↗
PubMed1992

[Activities of antithrombin III and heparin cofactor II in patients with pathologic blood coagulation conditions].

To investigate the physio-pathological functions of HC-II, assays for HC-II and AT-III were performed simultaneously on the samples from patients with DIC, liver dysfunction or renal disease from the three view points of consumption, production and loss of AT-III and HC-II. For the AT-III activity, two kinds of assays were applied: the automatic chromogenic substrate method and a newly developed clotting method which receives no effects from HC-II activity. The activity of HC-II was significantly lower than that of AT-III in patients with either DIC or liver dysfunction. However, no significant difference between HC-II and AT-III activities in patients with either thrombosis or renal disease. There were high correlations between HC-II and AT-III activities were found in the patients with liver dysfunction, suggesting that low activity was due to decreased production of HC-II and AT-III in the liver. It will be necessary that elucidation of the significant functions of HC-II not only in coagulation and hemostasis but also in regulation of local inflammation and invasion of neoplasm is necessary.

Adult↗
PubMed2006

Platelet recruitment in the murine hepatic microvasculature during experimental sepsis: role of neutrophils.

OBJECTIVES: Sepsis is a major clinical problem that often results in the dysfunction or failure of multiple organs, including the liver. While inflammatory cell activation has been implicated as an early critical event in sepsis-induced liver dysfunction, there is growing evidence for the involvement of activated platelets in this pathologic process. METHODS: Intravital microscopy was used in this study to assess the magnitude and time course of platelet adhesion in the liver microcirculation during experimental sepsis and to determine whether the platelet accumulation is linked to leukocyte infiltration. The adhesion of platelets and leukocytes in terminal hepatic venules (THV) and sinusoids was quantified at 2, 4, and 6 h after abdominal sepsis induced by cecal ligation and puncture (CLP). RESULTS: While the rolling and firm adhesion of platelets and leukocytes in THV were not altered in the first 2 h after CLP, platelet recruitment was observed at 4 h and further elevated at 6 h after CLP. Leukocyte adhesion in THV exhibited a similar time course. A similar accumulation of blood cells in sinusoids was noted after CLP. This was accompanied by an increased number of nonperfused sinusoids. CLP-induced leukocyte and platelet recruitment in THV and sinusoids was attenuated in mice rendered neutropenic with anti-neutrophil serum. CONCLUSION: These findings indicate that sepsis is associated with a neutrophil-dependent recruitment of platelets in the liver microcirculation that impairs sinusoidal perfusion and may contribute to the liver dysfunction associated with sepsis.

Animals↗
PubMedDate not supplied

Hepatic resection for hepatocellular carcinoma existing with liver cirrhosis.

BACKGROUND/AIMS: Hepatocellular carcinoma is usually complicated with liver cirrhosis, which makes its treatment difficult. Also a high rate of recurrence exists after surgical resection. However, how the prognosis after surgical treatment is affected by the severity of coexisting cirrhosis has not been clarified. METHODOLOGY: We compared the postoperative longterm courses of hepatocellular carcinoma patients with cirrhosis according to the liver function. All 112 hepatocellular carcinoma patients in this study underwent curative hepatic resection, and were classified into three groups according to the severity of liver dysfunction. The ICG R15' (indocyanine green retention test) normal: < 10%) was used in this study. Patients whose ICG R15' was less than 20% were classified as group I of 62, patients equal to 20% or between 20% and 30% as group II of 24, and patients equal to and more than 30% as group III of 26. RESULTS: In this series, 76 of 112 patients had recurrence (68%). A second hepatic resection was performed in six cases of group I and one case in group II. Fifty-eight of 76 recurrent cases (76%) were treated with transcatheter arterial chemoembolization. A total of eleven cases had no transcatheter arterial chemoembolization in the three groups: 3 cases in group I, 5 cases in group II, and 3 cases in group III; The three cases of group III had no treatment because of extremely poor liver dysfunction, whilst the 8 patients without transcatheter arterial chemoembolization in groups I and II had hepatocellular carcinoma itself and other diseases. The 1-, 3-, and 5-year survival rates after recurrence were 92%, 48%, and 14%, respectively, in group I; 83%, 37%, 12%, respectively, in group II; and 66%, 30%, 0%, respectively, in group III. The prognosis was significantly worse according to the degree of liver dysfunction (p = 0.0206). CONCLUSIONS: The prognosis of hepatocellular carcinoma with liver cirrhosis is affected not only by hepatocellular carcinoma itself, but also by the severity of the coexisting cirrhosis. Moreover, the cirrhotic liver can decline due to surgery. Surgical resection of this disease should be performed after careful patient selection and using a less invasive technique.

Aged↗
PubMed1994

[Results of annual health examination for the aged provided by the law that are predictive of increased mortality risk].

Possible risk factors associated with mortality were studied in a community using data derived from annual mass health examinations for the aged mandated by law. A total of 1,804 adults (685 men and 1,119 women) aged 40 or older in A-town, located on Tsushima Island, Nagasaki Prefecture, Japan who had participated in annual health examinations at least once between 1984 and 1990, were followed for a mean period of 4.9 years. After adjustment for age using Cox proportional hazards models, in men liver dysfunction (aspartate aminotransferase > 40 U/l or alanine aminotransferase > 35 U/l), fasting blood glucose > or = 110 mg/dl and glucosuria, and in women serum creatinine > or = 1.2 mg/dl, fasting blood glucose > or = 110 mg/dl and proteinuria were found to be associated with a significantly increased risk of total mortality. In multivariate analysis using all independent variables that were significantly associated with mortality in age-adjusted bivariate analysis, in men liver dysfunction and hyperglycemia, and in women hypercreatininemia and hyperglycemia, were significant predictors of mortality. These independent variables remained significant or marginally significant predictors of total mortality even after excluding the effects of 3 pancreatic cancer cases with liver dysfunction or hyperglycemia or 12 deaths within the first year of follow-up, being associated with at least two-fold increased hazard rate ratios. From these results, it is recommended that persons with these risk factors be followed intensively and counseled by public health personnel to modify risk factors.

Adult↗
PubMed1998

Pharmacokinetics of anticancer agents in patients with impaired liver function.

This report reviews published information on the clinical pharmacokinetics of antitumour agents in patients with liver dysfunction, associated with primary liver disease or liver metastases. Information was available for anthracyclines and their related compounds, antimetabolites, cyclophosphamide, vinca alkaloids, taxanes and epipodophyllotoxins. Changes in the pharmacokinetic profile or metabolism in patients with mild or severe hepatobiliary dysfunction are described and the relationships between serum levels, parameters employed for measuring hepatic function and toxic or therapeutic effects are examined. Current knowledge of the pharmacokinetics of antineoplastic agents in liver disease is far from complete, mostly obtained in small numbers of non-homogeneous patients often presenting only moderate liver dysfunction, and empirical guidelines for dose assessment are still largely applied in clinical practice. Because of the complex pathophysiological mechanisms of liver insufficiency in cancer patients, there is still doubt whether endogenous markers are useful. Although caution in treating cancer patients with liver insufficiency is compulsory, for most compounds there seems no need to recommend dose reductions for moderate impairment. However, for the tubulin acting agents, vincristine, vinblastine and possibly for paclitaxel and docetaxel, there is strong evidence that dose adjustment is mandatory in order to avoid excessive neutropenia and neurotoxicity.

Anthracyclines↗
PubMed2004

Cancer patients with septic shock: mortality predictors and neutropenia.

GOALS OF WORK: To study outcome and its predictive factors in cancer patients admitted to the ICU with septic shock, and the implications of neutropenia as a risk factor in this advanced stage of systemic inflammatory response. PATIENTS AND METHODS: A prospective consecutive observational cohort study was conducted in 73 adults with cancer and septic shock admitted to the ICU at the Cancer Medical Center associated with the University of Buenos Aires. MAIN RESULTS: The mortality rate from septic shock was 53.4% (95%CI 41.9 to 64.8%). The mean Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission, the mean number of organ dysfunctions on admission or during the ICU stay, liver dysfunction, respiratory dysfunction, and the need for mechanical ventilation were predictive of mortality in a univariate analysis. Neutropenia was not associated with a worse prognosis in terms of mortality (56%) or mean days of ICU stay (6.64 days) in comparison with nonneutropenic patients (52.1% and 6.8 days) in the univariate analysis. In the logistic regression model only the need for mechanical ventilation and liver dysfunction remained independent predictors of mortality. CONCLUSIONS: Septic shock among cancer patients admitted to the ICU has a mortality rate similar to that reported for mixed populations, and it is particularly increased when hepatic or respiratory dysfunction develop. Neutropenia on admission does not seem to modify outcome.

APACHE↗
PubMed2001

[Infection of herpes simplex virus (HSV) and Epstein-Barr virus (EBV) in acute tonsillitis--histopathological assessment by optical and electron microscopic observation of biopsy specimens of tonsils].

Infection with HSV or EBV was studied by measuring serum antiviral antibody titers in adults with acute tonsillitis, and results were compared to light and electron microscopy findings of tonsil biopsy specimens. The clinical and laboratory features of acute tonsillitis caused by HSV or EBV were also studied. Subjiects were 42 patients with acute tonsillitis treated at the Department of Otorhinolaryngology at Tokyo Women's Medical University Daini Hospital between August 1997 and March 2000. They had failed to respond to antimicrobial agents prescribed by a physician, and had severe oropharyngeal mucosal lesions, liver dysfunction, skin eruptions, or cervical lymphadenopathy, with hospitalization required because of impaired food intake due to sore throat or deterioration in general condition. Subjects were 24 men (mean age: 30.8 years) and 18 women (mean age: 28.3 years) aged 16 to 78 years (mean: 29.8 years). A underwent, bacteriological and hematology tests and palatine tonsil biopsy specimens were obtained to examine tissue changes by light microscopy and electron microscopy due to detect HSV antigen by immunohistochemistry and EBV nucleic acids by EBV-encoded small nuclear RNA 1 and 2 (EBER) in situ hybridization (ISH). Among patients, the serum antiviral antibody profile indicated that 4 (9.5%) had acute tonsillitis due to primary HSV infection and 5 (11.9%) had acute tonsillitis due to primary EBV infection. The findings characteristic of acute tonsillitis due to primary HSV infection included stomatitis, skin eruptions, atypical lymphocytes, and liver dysfunction. Findings characteristic of acute tonsillitis due to primary EBV infection included petechiae of the soft palate, an increase of lymphocytes, atypical lymphocytes, and liver dysfunction. At the initial test, serum anti-HSV antibody was positive in 14 patients (33.3%), and more than half had no history of prior infection. Anti-EBNA antibody was positive in 32 (76.2%), and many had been infected previously. It should be noted that a decrease in positive HSV antibody means that acute tonsillitis due to primary HSV infection is not uncommon in adults and is expected to increase steadily. Light microscopy revealed histological changes in 2 patients. HSV antigen was positive in 2 (50%) with acute tonsillitis due to primary HSV infection, while EBER cells were positive in 5 (100%) with acute tonsillitis due to primary EBV infection, so special staining of the tissues was found to be useful. Electron microscopy failed to detect viral particles in ultrathin sections and no differences were seen in morphological changes or tissue damage between patients with positivity for HSV antigen and with EBER-positive cells. Detection of HSV antigen and EBV nucleic acids in pathological specimens from patients with acute tonsillitis requires careful judgment, but is considered useful for making an early diagnosis and for making a diagnosis in patients without an increase of the antiviral antibody titer and in those with reinfection or reactivation. Pathological examination (including special staining) and careful observation of clinical features may help to identify HSV or EBV infection and allow decisions to be made with regard to the therapeutic strategy and prevention of complications.

Acute Disease↗
PubMed1999

Dihydropyrimidine dehydrogenase activity and fluorouracil pharmacokinetics with liver damage induced by bile duct ligation in rats.

Hepatic metabolism is the main determinant in the pharmacokinetics of 5-fluorouracil (5-FU). Its disposition might be affected with liver dysfunction. In the present study, the influence of liver damage induced by bile duct ligation on dihydropyrimidine dehydrogenase (DPD), a rate-limiting enzyme in 5-FU catabolism, CYP2B, and 5-FU pharmacokinetics were compared in male Sprague-Dawley rats. After 3 weeks of the ligation in two different groups of animals for in vitro and pharmacokinetic experiments, significant increases in serum bilirubin level and spleen weight were found in both groups. No significant differences were noted in bilirubin level or spleen weight of the bile duct ligation group between the two experiment groups. In the in vitro experiment, DPD activity and protein levels determined by Western blot analysis in the bile duct ligation group were slightly but significantly greater than those of a sham-operated group, whereas CYP2B activity and protein level were significantly reduced. These findings were supported by mRNA levels of CYP2B and DPD. When 40 mg/kg 5-FU was administered i.v. in the pharmacokinetic experiment, no significant differences in pharmacokinetic parameters were found between the bile duct ligation and sham-operated groups. These results suggested that DPD activity and protein level were maintained and that 5-FU pharmacokinetics was not altered in the presence of liver damage accompanied by a significant reduction in CYP2B activity and protein level, supporting previous clinical studies showing that mild to moderate liver dysfunction does not affect 5-FU disposition.

Animals↗
PubMed1999

Pharmacokinetics of oral etoposide in patients with hepatocellular carcinoma.

Etoposide dosage in patients with liver dysfunction remains controversial. Since etoposide has a hepatic component to its clearance (CL) and shows a high degree of protein binding, hepatic impairment could affect etoposide disposition. However, the empiric recommendation that the dose of etoposide be decreased in such patients may reduce systemic exposure and be detrimental to its antitumor activity. To address these issues we studied the pharmacokinetics (PK) of etoposide in patients with hepatocellular carcinoma (HCC) and underlying cirrhosis (n = 17) treated with daily oral etoposide. Unbound etoposide was obtained by ultrafiltration. Etoposide concentrations (total and free drug) were measured by high-performance liquid chromatography (HPLC) and analyzed by noncompartmental equations. The patients had mild or moderate liver dysfunction. Albuminemia was in the normal range for all the patients. Creatininemia was normal in all but two patients. PK results (mean and range) showed that etoposide disposition was unchanged in patients with liver dysfunction. We found slightly high etoposide bioavailability [F, 61% (17-95%)] and clearance [CL, 1.1 (0.7-2.3)l h(-1) m(-2)] resulting in a normal degree of systemic exposure (AUC(oral) 27 microg h ml(-1)). Normal protein binding [PB 93.2% (84.4-98.1%)] contributed to a normal level of exposure to free drug (AUC(f, oral) 1.9 microg h ml(-1)). The distribution volume [V(SS) 8.4 (6.1-13.2) l/m2] and the effective half-life [t1/2eff, 5.1 (3.0-9.6) h] were normal. Median CL and protein binding did not differ in the seven patients with total bilirubin value of > 1.2 mg/dl as compared with the ten patients with total bilirubin levels of < or = 1.2 mg/dl (1.3 versus 1.01 h(-1) m(-2) and 92.5% versus 93.4%, respectively). In agreement with this PK finding, we observed no clinical evidence of increased toxicity in patients with hyperbilirubinemia as compared with patients with normal bilirubinemia (mean WBC decrease 38% versus 47%). The only case of severe (grade 4) hematological toxicity was observed in one patient with reduced glomerular filtration. Since the pharmacological effects of etoposide correlate with the level of systemic exposure to the free drug, our data suggest that no dose reduction is needed in patients with HCC. It is even possible to increase the dose intensity in patients with favorable PK parameters under appropriate hematological and therapeutic drug monitoring.

Administration, Oral↗
PubMed1995

Severe hepatic involvement without inflammatory changes in systemic lupus erythematosus: report of two cases and review of the literature.

Hepatic diseases in systemic lupus erythematosus (SLE) are not rare, but liver biopsies of those cases are usually reported as chronic hepatitis or steroid-induced steatosis. We describe two unusual patients with active SLE who displayed liver dysfunction without inflammatory changes or associated with drug administration. A liver biopsy in case 1 showed massive hepatic cell damage resulting in acute hepatic failure. In case 2, the liver specimen revealed diffuse fatty degeneration without symptoms specific to liver dysfunction. No inflammatory cell infiltrate was observed in the liver tissue of either patient. After steroid pulse therapy (case 1) and the administration of 60 mg/day of prednisolone (case 2), liver function improved in parallel with the stabilization of the other manifestations of SLE. No other causes for liver damage except for SLE were observed in either case. Therefore it is supposed that the liver impairments in these cases were one manifestation of SLE.

Adult↗
PubMed2004

Renal dysfunction in liver transplantation: the problem and preventive strategies.

Ongoing improvements in survival following liver transplantation have necessitated a re-evaluation of immunosuppression protocols. Corticosteroids and calcineurin inhibitors (CNIs) are the most frequently used immunosuppressive drugs for liver transplantation but are associated with a wide range of adverse effects, such as hypertension, hyperlipidemia and nephrotoxicity. The need for hemodialysis after liver transplantation is associated with poor outcomes. Renal dysfunction in this setting may be caused by pre-existing renal disease, hepatorenal syndrome and/or post-transplant factors, including the use of nephrotoxic drugs, most notably CNIs such as cyclosporine and tacrolimus. The methods that address this problem include the diligent control of metabolic factors (eg, hypertension and hyperlipidemia), therapeutic monitoring of CNIs and withdrawal or reduction of the dosage of CNIs, combined with the use of newer non-nephrotoxic agents. Although there is no clear consensus about the most effective strategy, the optimal long-term immunosuppressive regimen would prevent rejection without causing nephrotoxicity or other significant adverse effects. Recent evidence suggests that the liver is a tolerogenic organ and that some patients may need little, if any, long-term immunosuppression.

Animals↗