Hepatic Impairment In Patients Research Articles

ASSESSMENT OF LIVER FUNCTION IMPAIRMENT AND ITS IMPACT ON SYMPTOMATIC COVID-19 INFECTED PATIENTS

It is noted in literature that a significant number of COVID-19 infected patients had abnormal liver enzyme values as the disease progressed. Studies have shown a higher prevalence of hepatic impairment in patients with severe COVID-19. This study was designed to assess the variation of liver function test in COVID-19 patients and their relation to the severity of the illness. The secondary outcome of the study was the length of hospital stay and mortality assessment. This study was conducted at Bahira town international hospital Lahore from September 1, 2020, to September1, 2021. A total of 169 participants were included in the cross-sectional study those who meet the inclusion criteria. In this study we assessed the records of 169diagnosed cases of COVID-19 Infection on RT-PCR, and data were analyzed. They were further divided into two groups. First with abnormal liver function tests (LFT) and second Group consisted of normal LFTs. Liver function tests including total bilirubin, Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, were recorded and liver dysfunction was labeled if any of the parameters were found to be elevated from the normal physiological range. A total of 236 COVID-19 individuals were examined during the one-year duration. Of those, 169 were found to be eligible, but 67 were disqualified because they had a history of hepatitis B and C or previous history of liver disease. The Abnormal liver function tests group included 81 participants whereas second group with normal LFTs had 88 participants. Patients with severe illnesses were more affected by liver malfunction than those with moderate illnesses. Patients with liver dysfunction required a longer stay in the hospital on average than patients with healthy livers did. Patients who had normal LFT at admission had a cure rate of 95.06%, while 4.94% of them passed away, whereas 18.18% of patients passed away in abnormal liver function test. Liver function derangement is frequent in individuals with severe COVID-19, and it can be brought on directly by a virus that damages the bile duct cells or indirectly by a cytokine storm and lead to increased mortality and length of hospital stay.

Interaction between baseline HBV loads and the prognosis of patients with HCC receiving anti-PD-1 in combination with antiangiogenic therapy undergoing concurrent TAF prophylaxis

BackgroundA high baseline hepatitis B virus (HBV) load has always been listed as an exclusion criterion for programmed cell death-1 (PD-1) inhibitor-associated therapy in clinical trials, as the interaction between HBV load and anti-PD-1/PD-L1 therapy with anti HBV therapy remains controversial.MethodsWe retrospectively enrolled 70 unresectable HCC patients who were seropositive for HBsAg and accepted tenofovir alafenamide fumarate (TAF) therapy before anti-PD-1 in combination with an antiangiogenic treatment. Patients were divided into a low HBV DNA group (≤ 2000 IU/ml) and a high HBV DNA group (> 2000 IU/ml) according to the baseline HBV DNA levels. Tumour response and progression-free survival (PFS) were compared, and univariate and multivariate Cox analyses were performed to identify potential risk factors for PFS. The incidences of HBV reactivation and HBV-associated hepatitis were also recorded.Results48 patients were assigned to the low group and the remaining 22 patients were assigned to the high group. The objective response rates (ORRs), disease control rates (DCRs), and PFS between the two groups showed no significant difference (P = 0.761, 0.552, and 0.784, respectively). The results of Cox analyses revealed that there was no relationship between baseline HBV load and PFS. Additionally, HBV reactivation occurred in only 2 patients (2.9%), and no patient experienced HBV-related hepatic impairment when given a continuous TAF treatment.ConclusionsBaseline HBV loads do not affect the prognosis of HCC patients receiving anti-PD-1 in combination with an antiangiogenic therapy, while PD-1 inhibitors do not aggravate HBV reactivation and hepatic impairment in patients simultaneously subjected to TAF prophylaxis.

Stroke, Thrombosis, Bleeding and Addiction to Anticoagulants in the Context of Course Therapy: A Pharmacologic Perspective.

After reading with great interest the article entitled: "Non-vitamin K antagonist oral anticoagulants (NOACs) do not increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation: insights from multi-source medical data" authored by Zhi-Chun Gu et al. and published by Reviews in Cardiovascular Medicine, we would like to add the following thoughts. Oral anticoagulants are generally accepted in patients with non-valvular atrial fibrillation to prevent thrombosis and stroke. Since anticoagulants are taken daily for many months in these patients, we cannot rule out chronic poisoning and the development of liver failure. But another complication is just as likely, that being bleeding. Thus, the determining risk factor for the health of patients with a prolonged course of oral anticoagulants is hypofunctional activity of the blood coagulation system, which remains at the same level throughout the course of treatment. At the same time, it is the activity of the blood coagulation system that is an important and very sensitive link of adaptation to various external and internal factors, including anticoagulants. The fact is that regular and prolonged oral use of anticoagulants is likely to develop and tolerance to them. That is why it is necessary to carefully study the relationship between the dose of oral anticoagulants, the duration of pharmacotherapy and the development of thrombosis (bleeding) in patients with non-valvular atrial fibrillation.

Non-Vitamin K Antagonist Oral Anticoagulants (NOACs) do not Increase the Risk of Hepatic Impairment in Patients with Non-Valvular Atrial Fibrillation: Insights from Multi-Source Medical Data.

There is controversy over whether non-vitamin K antagonist oral anticoagulants (NOACs) use increase the risk of hepatic impairment in patients with non-valvular atrial fibrillation (NVAF). We conducted a comprehensive assessment using multi-source medical data. We first performed a systematic search of the PubMed, Embase, and Cochrane Library databases (through 11 August 2021) for randomised controlled trials (RCTs) and real-world studies (RWSs) that reported hepatic impairment events in patients with NVAF administered NOACs or vitamin K antagonists (VKAs) therapy. The primary outcomes were hepatic impairment identified by diagnostic liver injury (DLI) or abnormal liver enzyme (ALE). The secondary outcome was hepatic failure. Relative risks (RRs) for RCTs and adjusted hazard ratios (aHRs) for RWSs were calculated separately using random-effects models. We also conducted a disproportionality analysis by extracting reports of hepatic impairment associated with NOACs from the Food and Drug Administration Adverse Event Reporting System (FAERS) database. Reporting odds ratios (RORs) were calculated to identify the statistical associations between NOACs and hepatic impairment. Scenario analyses were further performed to eliminate event- and drug-related competition bias. A total of 559,873 patients from five RCTs and four RWSs were included in the pooled analysis. For RCTs, NOACs use was not associated with an increased risk of DLI (RR: 0.96, 95% confidence intervals (CI): 0.73-1.28) or ALE (RR: 0.91, 95% CI: 0.69-1.19) compared with VKAs. The merged results of RWSs also showed a similar risk of DLI (aHR: 0.88, 95% CI: 0.72-1.09) or ALE (aHR: 0.91, 95% CI: 0.82-1.00) between NOACs and VKAs. The results of hepatic failure were in accordance with the primacy outcomes. Analyses of individual NOACs did not significantly affect the results. Insights from the FAERS database failed to detect hepatic impairment signals for overall NOACs agents (ROR: 0.34, 95% CI: 0.32-0.37). Scenario analyses confirmed the primary results. Insights from multi-source medical data confirmed that NOACs use was not associated with an increased risk of hepatic impairment in patients with NVAF.

Analysis of US Food and Drug Administration Oncology Approvals on the Characterization of Hepatic Impairment Effect and Dosing Recommendations.

Patients with cancer and advanced hepatic impairment (HI) (i.e., moderate and severe impairment) are often excluded from first‐in‐patient, phase II, and phase III studies. Thus, dose recommendations for this subgroup of patients are often derived using a combination of dedicated phase I studies conducted in participants without cancer and a population pharmacokinetic (PK) modeling approach. A standardized risk‐based approach to guide the evaluation of HI in patients with cancer is needed. In this review, we evaluated available oncology drug approvals by the US Food and Drug Administration (FDA) from 1999 to 2019, identified strategies utilized by sponsors to characterize the effect of HI on the PK of oncology drugs, and assessed regulatory expectations for each strategy. Finally, we constructed a decision tree that complements current FDA guidance to enable efficient evaluation of the effect of HI on PK and provide guidance for dose recommendations.

Impact of COVID-19 on the care of patients with liver disease: EASL-ESCMID position paper after 6 months of the pandemic.

SummaryDuring the early stages of the coronavirus disease 2019 (COVID-19) pandemic, EASL and ESCMID published a position paper to provide guidance for physicians involved in the care of patients with chronic liver disease. While some healthcare systems are returning to a more normal routine, many countries and healthcare systems have been, or still are, overwhelmed by the pandemic, which is significantly impacting on the care of these patients. In addition, many studies have been published focusing on how COVID-19 may affect the liver and how pre-existing liver diseases might influence the clinical course of COVID-19. While many aspects remain poorly understood, it has become increasingly evident that pre-existing liver diseases and liver injury during the disease course must be kept in mind when caring for patients with COVID-19. This review should serve as an update on the previous position paper, summarising the evidence for liver disease involvement during COVID-19 and providing recommendations on how to return to routine care wherever possible.

SARS-CoV-2 infection of the liver directly contributes to hepatic impairment in patients with COVID-19

Background & AimsLiver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). Whether or not severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection can lead to liver damage per se remains unknown. Herein, we reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with liver enzyme abnormalities.MethodsWe analyzed 156 patients diagnosed with COVID-19 from 2 designated centers in China and compared clinical features between patients with or without elevated aminotransferases. Postmortem liver biopsies were obtained from 2 cases who had elevated aminotransferases. We investigated the patterns of liver impairment by electron microscopy, immunohistochemistry, TUNEL assay and pathological studies.ResultsSixty-four out of 156 (41.0%) patients with COVID-19 had elevated aminotransferases. The median levels of alanine aminotransferase were 50 U/L vs. 19 U/L, respectively, aspartate aminotransferase were 45.5 U/L vs. 24 U/L, respectively in abnormal and normal aminotransferase groups. Liver enzyme abnormalities were associated with disease severity, as well as a series of laboratory tests including higher alveolar-arterial oxygen partial pressure difference, higher gamma-glutamyltransferase, lower albumin, decreased CD4+ T cells and B lymphocytes. Ultrastructural examination identified typical coronavirus particles, characterized by spike structures, in the cytoplasm of hepatocytes in 2 COVID-19 cases. SARS-CoV-2-infected hepatocytes displayed conspicuous mitochondrial swelling, endoplasmic reticulum dilatation and glycogen granule decrease. Histologically, massive hepatic apoptosis and some binuclear hepatocytes were observed. Taken together, both ultrastructural and histological evidence indicated a typical lesion of viral infection. Immunohistochemical results showed scarce CD4+ and CD8+ lymphocytes. No obvious eosinophil infiltration, cholestasis, fibrin deposition, granuloma, massive central necrosis, or interface hepatitis were observed.ConclusionsSARS-CoV-2 infection in the liver directly contributes to hepatic impairment in patients with COVID-19. Hence, a surveillance of viral clearance in liver and long-term outcome of COVID-19 is required.Lay summaryLiver enzyme abnormalities are common in patients with coronavirus disease 2019 (COVID-19). We reported the clinical characteristics and liver pathological manifestations of COVID-19 patients with elevated liver enzymes. Our findings suggested that SARS-CoV-2 infection of the liver is a crucial factor contributing to hepatic impairment in patients with COVID-19.

Non-invasive assessment of liver alterations in Senning and Mustard patients.

Adults with congenital heart disease and ventricular dysfunction are prone to liver congestion, leading to fibrosis or cirrhosis but little is known about the prevalence of liver disease in atrial switch patients. Liver impairment may develop due to increased systemic venous pressures. This prospective study aimed to assess non-invasively hepatic abnormalities in adults who underwent Senning or Mustard procedures. Hepatic involvement was assessed non-invasively clinically by laboratory analysis, hepatic fibrotic markers, sonography, and liver stiffness measurements [transient elastography (TE) and acoustic radiation force impulse imaging (ARFI)]. Overall, 24 adults who had undergone atrial switch operation (13 Senning, 11 Mustard; four female; median age 27.8 years; range 24-45 years) were enrolled. In liver stiffness measurements, only three patients had values within the normal reference. All other patients showed mild, moderate or severe liver fibrosis or cirrhosis, respectively. Using imaging and laboratory analysis, 71% of the subjects had signs of liver fibrosis (46%) or cirrhosis (25%). Non-invasive screening for liver congestion, fibrosis or cirrhosis could be meaningful in targeted screening for hepatic impairment in patients with TGA-ASO. As expert knowledge is essential, patients should be regularly controlled in highly specialised centres with cooperations between congenital cardiologists and hepatologists.

Prevalence and clinical significance of liver function abnormalities in patients with acute heart failure

Liver pathology caused by cardiac dysfunction is relatively well recognized, however, its clinical importance has not been fully evaluated. The aim of this study was to assess the prevalence of liver function tests (LFTs) abnormalities and to identify associated factors mediating hepatic impairment in patients with acute heart failure (AHF). The AHEAD (Acute Heart Failure Database) registry is a database conducted in 9 university hospitals and 5 regional health care facilities in the Czech Republic. From December 2004 to October 2012, the data of 8818 patients were included. The inclusion criteria for the database followed the European guidelines for AHF. Serum activities of all LFTs and total bilirubin were available in 1473 patients at the baseline. In patients with AHF, abnormal LFTs were seen in 76% patients (total bilirubin in 34%, γ-glutamyltransferase in 44%, alkaline phosphatase in 20%, aspartate aminotransferase in 42%, alanine aminotransferase in 35%). Patients with cardiogenic shock were more likely to have LFTs abnormalities compared to mild AHF and pulmonary oedema. LFTs abnormalities were strongly associated with AHF severity (left ventricular ejection fraction and NYHA functional class) and clinical manifestation. While hepatocellular LFTs pattern predominated in left sided forward AHF, cholestatic profile occurred mainly in bilateral and right sided AHF. Additionally, patients with moderate to severe tricuspid regurgitation had significantly higher prevalence of abnormalities in cholestatic LFTs. Defining the LFTs profile typical for AHF plays an important role in management of AHF patients, since it may avoid redundant hepatic investigations and diagnostic misinterpretations.

Hepatic Impairment Induced by Scrub Typhus is Associated with New Onset of Renal Dysfunction

Scrub typhus is a potentially fatal infectious disease caused by Orientia tsutsugamushi. There is little attention given to hepatic impairment in the adults with scrub typhus. This study investigated the incidence and the prognostic implications of hepatic impairment in patients with scrub typhus. We retrospectively reviewed a total of 143 adult patients with scrub typhus who were admitted between January 1999 and December 2010 in Guangdong province, China. The patients were divided into three groups, e.g., normal, mild, and moderate to severe groups based on the elevated serum ALT and/or total bilirubin levels. Furthermore, clinical characteristics and prognosis of the patient groups were compared. 109 patients (76.2%) had abnormal liver function. Among the patients with hepatic impairment 45 cases (31.4%), 54 cases (37.8%), and 10 cases (7.0%) had mild, moderate, and severe hepatic damage, respectively. The moderate to severe hepatic impairment group had higher levels of serum creatinine compared with that of normal hepatic function. The incidence of new onset of renal dysfunction - defined as peak serum creatinine > or = 176 micromol/L during hospital stay with no evidence of renal disease prior hospitalization - was 0% in the mild hepatic impairment group, 8.9% in the moderate hepatic impairment group, and 21.9% in the severe hepatic impairment group, (p = 0.005 for trend). Additionally, the patients with hepatic impairment (n = 109) had higher incidences of episodes of thrombocytopenia (45.9% vs. 8.82%, p < 0.001), hypoalbuminemia (50.5% vs. 11.8%, p < 0.001), new onset of renal dysfunction (16.5% vs. 0.0%, p = 0.011), and electrocardiogram abnormality (28.4% vs. 8.82%, p = 0.019) than the patients without hepatic impairment. The degree of hepatic impairment induced by scrub typhus is associated with new onset of renal dysfunction.

Serum paraoxonase-3 concentration in HIV-infected patients. Evidence for a protective role against oxidation

We investigated the influence of the HIV infection on serum paraoxonase-3 (PON3) concentration and assessed the relationships with lipoprotein-associated abnormalities, immunological response, and accelerated atherosclerosis. We studied 207 HIV-infected patients and 385 healthy volunteers. Serum PON3 was determined by in-house ELISA, and PON3 distribution in lipoproteins was investigated by fast-performance liquid chromatography (FPLC). Polymorphisms of the PON3 promoter were analyzed by the Iplex Gold MassArray(TM) method. PON3 concentrations were increased (about three times) in HIV-infected patients with respect to controls (P < 0.001) and were inversely correlated with oxidized LDL levels (P = 0.038). Long-term use of nonnucleoside reverse transcriptase inhibitor (NNRTI)-based antiretroviral therapy was associated with a decrease of PON3 concentrations. In a multivariate linear regression analysis, these relationships were still strong when the main confounding covariates were considered. PON3 was mainly found in HDL in HIV-infected patients, but a substantial amount of the protein was detected in LDL particles. This study reports for the first time an important increase in serum PON3 concentrations in HIV-infected patients that is associated with their oxidative status and their treatment with NNRTI. Long-term, prospective studies are needed to confirm the possible influence of this enzyme on the course of this disease and its possible utility as an analytical biomarker.

Serum paraoxonase-3 concentration is associated with the severity of hepatic impairment in patients with chronic liver disease

Objectives Research on paraoxonase-3 (PON3) has been hampered by the lack of methods for measurement. This is a pilot study aimed at exploring whether chronic liver impairment is associated with changes in serum PON3 concentrations, and to know whether this measurement may provide useful information to investigate this derangement. Design and methods We studied 110 patients with chronic liver disease (21 minimal changes, 79 chronic hepatitis, 10 cirrhosis) and 356 healthy volunteers. Serum PON3 concentration was determined by ELISA using polyclonal antibodies generated against a synthetic peptide with a sequence specific to PON3. Results Serum PON3 concentrations were increased in patients with chronic hepatitis or cirrhosis and showed significant direct correlations with the degree of periportal abnormalities including fibrosis, and with serum FAS (a marker of antiapoptosis) concentrations. Conclusion These results suggest that PON3 may play a hepatoprotective role against histological alterations and hepatic cell apoptosis leading to liver disease.

Association of hypophosphatemia-occurring sorafenib with prognosis and hepatic impairment in patients with advanced hepatocellular carcinoma.

188 Background: Hypophosphatemia is observed during sorafenib treatment. At the increased metabolic demand of the liver, hypophosphatemia is considered to be associated with a good clinical course. Hypophosphatemia associated with sorafenib treatment may also be a favorable event, but this has not yet been elucidated. The aim of this study was to evaluate the clinical significance of hypophosphatemia developing during sorafenib treatment for advanced hepatocellular carcinoma (HCC). Methods: The data of 41 advanced HCC patients (median age: 68 years, female/male: 4/37, HBs-Ag(+)/HCV-Ab(+):10/22) who received sorafenib treatment (800 mg, daily) for more than 30 days were reviewed. There were 27 and 14 patients with Child-Pugh class A and B. UICC stage II/III/IV was observed in 13/10 /18 patients. Clinical data, including those on the serum level of inorganic phosphate (IP), were collected before and after 30 days of sorafenib treatment. Overall survival time (OS) was calculated from the start of sorafenib treatment. The significance level was set at p&lt;0.05. Results: Mean serum IP level before sorafenib treatment was 3.2mg/dL (range 2.4-4.5). After 30 days treatment, IP level was decreased (mean 2.6mg/dL, range 1.3-3.9), compared to that at pre-treatment (p&lt;0.001). The patients in whom the serum IP was less than 2.4mg/dL at 30 days was assigned to the decreased IP group (N=14, mean IP 2.1mg/dL, range1.3-2.3). The decreased IP group showed a better prognosis (no event of death during the observation time) than the nondecreased IP group (MST 286 days, p=0.024). In the non-decreased IP group, the serum Alb (mean 3.6g/dL) and T.Bil (mean 0.8mg/dL) were worse after 30 days treatment (Alb 3.4g/dL p=0.007, T.Bil 1.1mg/dL p=0.037). However, deterioration of Alb (mean 3.7 vs. 3.6g/dL p=0.505) and T.Bil (mean 0.7 vs. 0.8mg/dL p=0.404) could be avoided in the decrease IP group. Conclusions: Hypophosphatemia occurring during sorafenib treatment for advanced HCC was associated with a favorable prognosis. The serum Alb and T.Bil levels were indicators of liver function and were preserved in patients with decreased serum levels of phosphate. No significant financial relationships to disclose.

S1860 The 13C Breath Test Identifies Decreased Beta-Oxidation and Improved Glucose Tolerance and Hepatic Impairment in Patients With Non Alcoholic Steatohepatitis After an Exercise and Diet Intervention

S1860 The 13C Breath Test Identifies Decreased Beta-Oxidation and Improved Glucose Tolerance and Hepatic Impairment in Patients With Non Alcoholic Steatohepatitis After an Exercise and Diet Intervention

Hepatic Impairment in Patients with SARS Hepatitis

Severe acute respiratory syndrome-associated coronavirus (SARS-CoV), an enveloped coronavirus discovered in March 2003, causes atypical pneumonia and

SARS-associated viral hepatitis caused by a novel coronavirus: Report of three cases

Liver impairment is commonly reported in up to 60% of patients who suffer from severe acute respiratory syndrome (SARS). Here we report the clinical course and liver pathology in three SARS patients with liver impairment. Three patients who fulfilled the World Health Organization case definition of probable SARS and developed marked elevation of alanine aminotransferase were included. Percutaneous liver biopsies were performed. Liver specimens were examined by light and electron microscopy, and immunohistochemistry. Reverse‐transcriptase polymerase chain reaction (RT‐PCR) using enhanced real‐time PCR was applied to look for evidence of SARS‐associated coronavirus infection. Marked accumulation of cells in mitosis was observed in two patients and apoptosis was observed in all three patients. Other common pathologic features included ballooning of hepatocytes and mild to moderate lobular lymphocytic infiltration. No eosinophilic infiltration, granuloma, cholestasis, fibrosis, or fibrin deposition was noted. Immunohistochemical studies revealed 0.5% to 11.4% of nuclei were positive for proliferative antigen Ki‐67. RT‐PCR showed evidence of SARS‐associated coronavirus in the liver tissues, but not in the sera of all 3 patients. However, electron microscopy could not identify viral particles. No giant mitochondria, micro‐ or macro‐vesicular steatosis was observed. In conclusion, hepatic impairment in patients with SARS is due to SARS‐associated coronavirus infection of the liver. The prominence of mitotic activity of hepatocytes is unique and may be due to a hyperproliferative state with or without disruption of cell cycle by the coronavirus. With better knowledge of pathogenesis, specific therapy may be targeted to reduce viral replication and modify the disease course. (Hepatology 2004;39:302–310.)

Quantitative liver function tests define the functional severity of liver disease in early-stage cirrhosis.

Some patients with early-stage cirrhosis preserve hepatic function, whereas others have little hepatic reserve and rapidly deteriorate. The aim of this study was to use quantitative tests of liver function (QLFTs) to define the degree of functional hepatic impairment in patients with early-stage cirrhosis (Child-Pugh score 5-7) and to determine whether the tests predicted subsequent hepatic decompensation. We recruited 10 cirrhotic (Cr) patients and 10 healthy controls (NI), who were well matched for race, age, weight, and gender. Clearances of caffeine (CF) and antipyrine (AP) after oral administration were measured from timed samples of saliva. The clearance of cholate (CA) was measured from serum samples obtained after simultaneous oral ([2,2,4,4-2H]CA) and intravenous ([24-13C]CA) administration. CA shunt was calculated as (Cl i.v./Clo x 100%). CF elimination rate (Cr v NI, mean +/- SD: 0.03 +/- 0.02 v 0.075 +/- 0.018 h-1, P < .0005) and AP clearance (24 +/- 16 v 40 +/- 7 mL/minute, P < .02) were reduced in Cr patients. CA shunt was increased in Cr patients (43 +/- 18 v 18 +/- 7%, P < .002). Five Cr patients decompensated during follow-up and had the worst CA shunts (76%, 66%, 51%, 48%, and 45%). Three subsequently received successful orthotopic liver transplantation, 1 died of hepatoma, and 1 is on the waiting list for transplantation. In conclusion, QLFTs define the degree of functional impairment in early cirrhosis and may identify Cr patients at greatest risk of decompensation who may require transplantation for survival.

Pharmacokinetics of amoxycillin and clavulanic acid in haemodialysis patients following intravenous administration of Augmentin.

1. Serum concentrations of amoxycillin and clavulanic acid were measured in patients with end-stage renal disease (ESRD) following intravenous administration of 1.2 g Augmentin. Augmentin was administered on a non-dialysis day and 2 h prior to a 4 h dialysis session. 2. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for amoxycillin on the non-dialysis day were 14.4 ml min-1, 19.2 h, 14.9 l and 13.6 h, respectively. 3. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for amoxycillin were 77.1 ml min-1, 91.5 ml min-1, 0.64 and 2.30 h, respectively. 4. The mean values of total serum clearance, mean residence time, volume of distribution at steady state, and terminal half-life for clavulanic acid on the non-dialysis day were 43.6 ml min-1, 4.4 h, 11.0 l and 3.05 h, respectively. 5. The mean values of dialysis clearance, total serum clearance during dialysis, fractional drug removal during haemodialysis and half-life during dialysis for clavulanic acid were 92.8 ml min-1, 136 ml min-1, 0.65 and 1.19 h, respectively. 6. The total serum clearance on the non-dialysis day, which represents non-renal clearance, was lower than that in normal subjects for both amoxycillin and clavulanic acid. These data would suggest some degree of hepatic impairment in patients with ESRD.(ABSTRACT TRUNCATED AT 250 WORDS)