Degree Of Liver Impairment Research Articles

Relationship between Bi Ventricular Systolic Function and Different Degrees of Liver Impairment

Relationship between Bi Ventricular Systolic Function and Different Degrees of Liver Impairment

A Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-986263 in Participants With Varying Degrees of Liver Impairment

A Single-dose Study to Evaluate the Pharmacokinetics, Safety, and Tolerability of BMS-986263 in Participants With Varying Degrees of Liver Impairment

Physiological and prescribing tips for managing liver impairment

This article gives prescribing and dosage tips for health professionals caring for patients with liver impairment. Most patients will not know that they have any degree of liver impairment, therefore an assessment of liver function is essential. The Child-Pugh scoring tool, which indicates the level of liver impairment, will be discussed.

Hepatitis C in the era of direct-acting antivirals: real-world costs of untreated chronic hepatitis C; a cross-sectional study.

BackgroundRecent advances in Hepatitis C therapeutics offer the possibility of cure but will be expensive. The cost of treatment may be partially offset by the avoidance of advanced liver disease. We performed a micro-costing study of the ambulatory healthcare utilisation of patients with Hepatitis C supplemented with inpatient diagnosis related group costs.MethodsThe staff utilisation costs associated with a Hepatitis C ambulatory visit were measured and combined with the costs of investigations to establish a mean cost per consultation. An annualised estimate of cost was produced by multiplying this by the number of consultations accessed, stratified by degree of liver impairment. Inpatient costs were established by identifying the number of inpatient episodes and multiplying by Irish diagnosis related group costs. Non-parametric bootstrapping was performed to derive mean and 95%CI values.ResultsTwo hundred and twenty-five patients were identified. The cost of an outpatient medical review was €136 (€3.60 SD). The cost of a Hepatitis C nursing review was €128 (€7.30 SD). The annual mean costs of care were as follows (95%CI): Mild €398 (€336, €482), Moderate €417(€335, €503), Compensated cirrhosis €1790 (€990, €3164), Decompensated cirrhosis €8302 (€3945, €14,637), Transplantation Year 1 €137,176 (€136,024, €138,306), Transplantation after Year 1 €5337 (€4942, €5799), Hepatocellular carcinoma €21,992 (€15,222, €29,467), Sustained virological response €44 (€16, €73).ConclusionsThe direct medical cost associated with Hepatitis C care in Ireland is substantial and increases exponentially with progression of liver disease. The follow-up costs of patients with a sustained virological response in this cohort were low in comparison to patients with chronic infection.Electronic supplementary materialThe online version of this article (doi:10.1186/s12879-015-1208-1) contains supplementary material, which is available to authorized users.

A multicenter prospective study of infections related morbidity and mortality in cirrhosis of liver.

Infections are a common and serious complication among patients with cirrhosis. We assessed the epidemiology, risk factors, and clinical consequences of bacterial infections in cirrhotic patients. In this multicenter prospective study, all patients with cirrhosis of liver with different infections were analyzed. Infections were classified as community-acquired (CA), healthcare-associated (HCA), or hospital-acquired (HA). Site of infection and characteristics of bacteria were recorded; effect on liver function and 30-day survival were evaluated. One hundred and six out of 420 (25%) patients with cirrhosis of liver had infection. Infection rate among indoor patients was 37.5% (92/245) and among outdoor patients was 8% (14/175). Out of 106 patients, CA, HCA, and HA were seen in 19.8%, 50%, and 30.2%, respectively. Spontaneous bacterial peritonitis (31.1%), urinary tract infections (22.6%), and pneumonia and cellulitis (11.3% each) were common infections. Gram-negative bacteria (54%) were more common than Gram-positive cocci (46%). Multidrug resistant (MDR) organisms were seen in 41.7% of patients. Most of the MDR organisms were seen in HCA and HA patients. The degree of liver impairment was significantly more severe in patients with infection. Independent predictor of infection was high Child-Turcott-Pugh (CTP) class (p = 0.006, Child B vs. A (odds ratio (OR) 3.04 95% CI = 1.63 to 5.68) and Child C vs. A (OR 4.17 95% CI = 2.12 to 8.19). Overall in-hospital mortality was 7.6%. Patients with infection had increased mortality at 30-day follow up compared to those without infection (23.5% vs. 2.2%; p<0.001). Infections are one of the important causes of morbidity and mortality in patients with cirrhosis of liver. The most frequent infections are HCA and HA. Infection predisposes to deterioration of liver function and increases mortality. Cirrhotic patients should be monitored closely for infections especially those with Child class B and C.

Review article: prescribing medications in patients with cirrhosis – a practical guide

Most drugs have not been well studied in cirrhosis; recommendations on safe use are based largely on experience and/or expert opinion, with dosing recommendations often based on pharmacokinetic (PK) changes. To provide a practical approach to prescribing medications for cirrhotic patients. An indexed MEDLINE search was conducted using keywords cirrhosis, drug-induced liver injury, pharmacodynamics (PDs), PKs, drug disposition and adverse drug reactions. Unpublished information from the Food and Drug Administration and industry was also reviewed. Most medications have not been adequately studied in cirrhosis, and specific prescribing information is often lacking. Lower doses are generally recommended based on PK changes, but data are limited in terms of correlating PD effects with the degree of liver impairment. Very few drugs have been documented to have their hepatotoxicity potential enhanced by cirrhosis; most of these involve antituberculosis or antiretroviral agents used for HIV or viral hepatitis. Paracetamol can be used safely when prescribed in relatively small doses (2-3g or less/day) for short durations, and is recommended as first-line treatment of pain. In contrast, NSAIDs should be used cautiously (or not at all) in advanced cirrhosis. Proton pump inhibitors have been linked to an increased risk of spontaneous bacterial peritonitis (SBP) in cirrhosis and should be used with care. Most drugs can be used safely in cirrhosis, including those that are potentially hepatotoxic, but lower doses or reduced dosing frequency is often recommended, due to altered PKs. Drugs that can precipitate renal failure, gastrointestinal bleeding, SBP and encephalopathy should be identified and avoided.

Influence of different degrees of liver impairment on the pharmacokinetics of clazosentan

Clazosentan is a selective endothelin A receptor antagonist, formulated for parenteral use, which is in clinical development for the treatment of aneurysmal subarachnoid haemorrhage. The human ADME study showed that most of clazosentan is excreted via the biliary route. The pharmacokinetics (PK) of clazosentan are similar in healthy subjects and those with severe renal impairment. The results of the present study showed that there was an increase in the exposure to clazosentan with increasing severity of liver impairment. Changes in PK in subjects with mild liver impairment compared with healthy subjects are unlikely to be clinically relevant. There are significant differences in the PK parameters of clazosentan in subjects with moderate and severe liver impairment compared with healthy subjects. The results of this study will allow confident dosing of clazosentan in individuals with moderate and severe liver impairment. AIM To investigate the effect of mild, moderate and severe liver impairment on the pharmacokinetics (PK), tolerability and safety of clazosentan, an intravenous endothelin receptor antagonist. Healthy subjects with normal liver function (n= 8), subjects with mild (Child Pugh A, n= 8), and with moderate (Child-Pugh B, n= 8) liver impairment received a continuous intravenous infusion of 1 mg h(-1) and subjects with severe liver impairment (Child Pugh C, n= 8) received a continuous intravenous infusion of 0.5 mg h(-1) clazosentan for a duration of 6 h. The pharmacokinetic (PK) parameters of clazosentan were determined by both model-independent and model-dependent methods. Mean plasma concentrations of clazosentan increased with increasing severity of liver impairment. Geometric means of area under the plasma concentration-time curve from 0 to infinity (AUC((0,∞)) ) were 1.41- (90% CI 1.04, 1.90), 2.37- (90% CI 1.75, 3.19), and 3.79- (90% CI 2.81, 5.11) fold higher in subjects with mild, moderate and severe liver impairment, respectively, compared with healthy subjects. Similar results were obtained by non-compartmental and two-compartmental analysis. A significant positive correlation between clazosentan AUC((0,∞)) and Child-Pugh score (r= 0.83), bilirubin (r= 0.78) and prothrombin time (r= 0.62), and a significant negative correlation with albumin concentrationl (r= 0.71) was observed. Administration of clazosentan was well tolerated in all groups. The increase in exposure to clazosentan in Child-Pugh A patients is not expected to be clinically relevant and no dose adjustment for these patients is proposed. It is recommended to reduce the dose of clazosentan to half in Child-Pugh B and to one fourth in Child-Pugh C patients.

Human serum albumin

Human serum albumin

Lyso-thermosensitive liposomal doxorubicin: a novel approach to enhance efficacy of thermal ablation of liver cancer

Background: Hepatocellular carcinoma (HCC) is the fourth leading cause of cancer death worldwide. No more than 30% of HCC patients receive curative treatment. Factors limiting curative therapy include tumor size and degree of liver impairment. Objective: To develop a cure for medium (3.1 – 5.0 cm) and large ( > 5 cm) tumors in seriously impaired livers. Method: Combine radiofrequency ablation (RFA) with lyso-thermosensitive liposomal doxorubicin (LTLD). Results/conclusions: RFA is used safely in patients with medium/large tumors and severe liver impairment; unclear tumor margins limit its curative efficacy. LTLD concentrates in the liver, where the anti-HCC chemotherapeutic, doxorubicin, is released into tumor margins by hyperthermia. RFA/LTLD can treat Child-Pugh class A-B patients with tumors up to 7 cm, a substantial increase in curable patients.

Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the Eurotransplant allocation system

Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor-related variables were evaluated in 226 patients listed primarily for HCC in Belgium, a region where the allocation system is patient-driven, priority being given to sicker patients, based on the Child-Turcotte-Pugh (CTP) score. Intention-to-treat and posttransplantation survival rates at 4 years were 56.5 and 66%, respectively, and overall HCC recurrence rate was 10%. The most significant predictors of failure to receive a transplant in due time were baseline CTP score equal to or above 9 (relative risk [RR] 4.1; confidence interval [CI]: 1.7-9.9) and alpha fetoprotein above 100 ng/mL (RR 3.0; CI: 1.2-7.1). Independent predictors of posttransplantation mortality were age equal to or above 50 years (RR 2.5; CI: 1.0-3.7) and United Network for Organ Sharing pathological tumor nodule metastasis above the Milan criteria (RR 2.1; CI: 1.0-5.9). Predictors of recurrence (10%) were alpha fetoprotein above 100 ng/mL (RR 3.2; CI:1.1-10) and vascular involvement of the tumor on the explant (RR 3.6; CI: 1.1-11.3). Assessing the value of the pretransplantation staging by imaging compared to explant pathology revealed 34% accuracy, absence of carcinoma in 8.3%, overstaging in 36.2%, and understaging in 10.4%. Allocation rules for HCC should consider not only tumor characteristics but also the degree of liver impairment. Patients older than 50 years with a stage above the Milan criteria at transplantation have a poorer prognosis after transplantation.

Amprenavir and ritonavir plasma concentrations in HIV-infected patients treated with fosamprenavir/ritonavir with various degrees of liver impairment

The purpose of this study was to evaluate the steady-state pharmacokinetics of amprenavir and ritonavir in HIV-infected patients with different degrees of hepatic impairment. HIV-positive patients receiving fosamprenavir/ritonavir (700/100 mg twice daily) were included. Patients were classified into three groups: (i) chronic hepatitis; (ii) liver cirrhosis; (iii) normal liver function. Serial blood samples for steady-state amprenavir and ritonavir pharmacokinetics (>14 days on treatment) were collected in the fasting state before the morning dose (C(trough)) and then 1, 2, 3, 4, 6, 8, 10 and 12 h after drug intake. Amprenavir and ritonavir plasma concentrations were determined by HPLC. Twenty-one HIV-infected patients were included. Seven had chronic hepatitis, eight had liver cirrhosis and six patients were in the control group. Amprenavir AUC(0-12), AUC(0-infinity), C(max) and C(ss) were increased by 50% to 60% in the cirrhotic group when compared with controls, whereas CL/F was decreased by 40%. Patients with chronic hepatitis showed a significant increase in AUC(0-12), C(max) and C(ss) values when compared with controls. Ritonavir pharmacokinetics was different only in cirrhotic patients when compared with controls. Liver function parameters at weeks 4, 12 and 24 were not different from baseline in any of the groups. Overall, a significant correlation between amprenavir AUC(0-12) and total bilirubin values on the day of pharmacokinetic analysis was found (r = 0.64, P = 0.003). On the basis of these data and also of data available in the literature, it seems reasonable to adapt the dose of fosamprenavir and/or ritonavir exclusively in the presence of adverse events, possibly related to protease inhibitors (i.e. liver toxicity), in subjects with high drug plasma levels. Therapeutic drug monitoring is advised in the management of these patients.

Vinflunine in patients with advanced unresectable hepatocellular carcinoma and liver impairment

15023 Background: In patients (pts) with advanced hepatocellular carcinoma (HCC) and liver cirrhosis, systemic chemotherapy has most commonly been associated with a very low response rate and high toxicity leading to death from liver failure. Vinflunine (VFL) is a new microtubule inhibitor of the vinca alkaloid class which has demonstrated clinical activity in several tumour types. Methods: A phase I trial was designed to determine VFL dose adjustments in cancer pts with various degrees of liver dysfunction. A high number of pts with HCC and concomitant liver cirrhosis (Child-Pugh grades A and B) were included in the study (18/30 pts). Therefore, a subgroup analysis was carried out in order to determine the safety profile of VFL in these pts (NCI-CTC version 2.0) and to estimate its anti-tumour activity (WHO criteria). Results: Eighteen pts (15 males) of median age 60.7 [26.4–75.3] years with advanced stage and unresectable HCC were treated with VFL. All these pts were outside Milan criteria and ineligible for liver transplantation. Thirteen pts had been previously treated by chemotherapy. The WHO performance status was 0: 11 pts, 1: 5 pts, 2: 2 pts. They received a median number of 4 cycles [1.0–31.0] of different doses of VFL according to the severity of the underlying liver impairment 320 mg/m2 (3 pts), or 250 mg/m2 (6 pts) or 200 mg/m2 (9 pts). One partial response (PR) was observed while 11 pts (61.1%) had stable disease (SD) yielding a disease control rate (PR + SD) of 66.7%. The median progression free survival was 3.4 months [95% confidence interval (CI): 2.6–6.0]. Haematological toxicity: grades (G) 3 anaemia = 4 pts, G3/4 neutropenia = 11 pts, G3 thrombocytopenia = 7 pts, no febrile neutropenia. Other G3 toxicities included G3 abdominal pain (2 pts), constipation (3 pts), neutropenic infection (1 pt). Six pts experienced G3 (5 pts) or 4 (1 pt) fatigue. Conclusions: Vinflunine can be given safely at 320 mg/m2 or 250 mg/m2 or 200 mg/m2 in pts with unresectable advanced HCC with different degrees of liver impairment. The disease control rate is promising (66.7%). No significant financial relationships to disclose.

MELD score to predict outcome in adult patients with non‐acetaminophen‐induced acute liver failure

A model for end stage liver disease (MELD) score >30 was proposed as an excellent predictor of mortality in patients with non-acetaminophen-induced acute liver failure (ALF). We analyzed the prognostic value of MELD score in our patients with ALF who were prospectively registered in our database since 1990. Overall, 106 patients met the criteria of ALF. Excluding seven patients with acetaminophen etiology, 99 patients (42+/-15 years, 40M/59F) were studied. Causes were cryptogenic (n=38), viral (n=29), drugs (n=20) and miscellaneous (n=12). Of these, 37% (n=37) survived with medical management alone (group I), 16% (n=16) died (group II) and 46% (n=46) underwent liver transplantation (group III). The strongest predictors of poor outcome were advanced encephalopathy, cryptogenic/drug-induced/hepatitis B etiology and a high MELD score. At the time of diagnosis, King's College Hospital criteria and MELD score >30 had similar high negative predictive value (92% and 91%, respectively) and low positive predictive value (52% and 56%, respectively). The predictive values improved only slightly during follow-up. The best cut-off point for MELD score to discriminate between survivors and nonsurvivors was >35, with a sensitivity and specificity of 86% and 75%, respectively. MELD score, which mostly takes into consideration the degree of liver impairment, has a similar prognostic value as King's College Hospital criteria to predict outcome in adult patients with nonacetaminophen-induced ALF. Overall, all current scores miss accuracy and therefore there is a clear need for factors that can better predict the regeneration of the liver in this setting.

30 Outcome of patients with hepatocellular carcinoma listed for liver transplantation within the eurotransplant allocation system

Although hepatocellular carcinoma (HCC) has become a recognized indication for liver transplantation, the rules governing priority and access to the waiting list are not well defined. Patient- and tumor-related variables were evaluated in 226 patients listed primarily for HCC in Belgium, a region where the allocation system is patient-driven, priority being given to sicker patients, based on the Child-Turcotte-Pugh (CTP) score, Intention-to-treat and posttransplantation survival rates at 4 years were 56.5 and 66%, respectively, and overall HCC recurrence rate was 10%. The most significant predictors of failure to receive a transplant in due time were baseline CTP score equal to or above 9 (relative risk [RR] 4.1; confidence interval [Cl]: 1.7-9.9) and a fetoprotein above 100 ng/mL (RR 3.0; Cl: 1.2-7.1). Independent predictors of posttransplantation mortality were age equal to or above 50 years (RR 2.5; Cl: 1.0-3.7) and United Network for Organ Sharing pathological tumor nodule metastasis above the Milan criteria (RR 2.1; Cl: 1.0-5.9). Predictors of recurrence (10%) were a fetoprotein above 100 ng/mL (RR 3.2; Cl:1.1-10) and vascular involvement of the tumor on the explant (RR 3.6; Cl: 1.1-11.3). Assessing the value of the pretransplantation staging by imaging compared to explant pathology revealed 34% accuracy, absence of carcinoma in 8.3%, overstaging in 36.2%, and understaging in 10.4%. Allocation rules for HCC should consider not only tumor characteristics but also the degree of liver impairment. Patients older than 50 years with a stage above the Milan criteria at transplantation have a poorer prognosis after transplantation.

Heat shock protein 27 expression in patients with chronic liver damage

The aim of this study was to evaluate a possible relationship between lymphomonocyte expression of heat shock proteins (HSP) 60/27 and plasma levels of pro-inflammatory cytokines (tumor necrosis factor- α and interleukin-6) and markers of antioxidant/oxidative status [glutathione (GSH), α glutathione- S-transferase activity ( αGST), malonyldialdeyde (MDA), 4-hydroxinonenal (4-HNE), and S-nitrosothiols (S-NO)] in patients with chronic liver diseases. Entered into the study were 47 subjects: 10 healthy controls, 16 patients with HCV-related chronic hepatitis (CH), and 16 patients with HCV-related and 5 with alcohol-related liver cirrhosis (10 Child A and 11 Child B+C). HSP60 was clearly expressed only in 5% of patients and lowly in the control group. HSP27 was clearly expressed in 46.7% of CH and 71.4% of cirrhotic patients but was lowly present in healthy subjects. A significant difference was found between patients with a low expression of HSP27 (negative patients) and those with a high HSP27 expression (positive patients) of plasma levels both of antioxidants (GSH, p < 0.05 ), and of markers of enhanced production of free radicals and cytokines ( αGST, TNF- α and IL-6, p < 0.05 ; MDA, 4-HNE and S-NO, p < 0.01 ) as well as for alcohol use and degree of liver impairment. The present data are the first showing that, particularly in conditions of enhanced oxidative stress, lymphomonocytes from liver disease patients present an increased expression of HSP27.

Natural history of hepatocellular carcinoma

The natural history of hepatocellular carcinoma is variable. In many patients the tumor has a long-lasting subclinical incubation period and often grows as a solitary mass to a size at which it can be detected by ultrasound. In other patients, however, the onset of the tumor is multinodal with great variations in the growth rates. Prognostication of patients with hepatocellular carcinoma takes into account the size and number of tumor nodes and their relation to the portal veins, and the degree of liver impairment.

Increased Homocysteine in Liver Cirrhosis: A Result of Renal Impairment?

In their recent publication, Ferre et al. (1) investigated homocysteine concentrations in 76 patients with liver cirrhosis. The majority of these patients suffered from alcoholic liver disease (63%). The authors described significantly increased homocysteine in nonabstaining alcoholic patients with cirrhosis. Furthermore, the homocysteine concentrations were inversely correlated with the severity of the liver disease (Child–Pugh score) and with the folate concentrations in these patients. The authors proposed that the homocysteine concentration was influenced by alcohol intake and by the degree of liver impairment. The authors conclude that nonnutritional factors may affect homocysteine concentrations. Hyperhomocysteinemia also occurs in patients with decreased renal function, but the investigators provided no information about the renal function of these patients. Renal function is considerably reduced in patients with compensated cirrhosis (2). An inverse relationship between the glomerular filtration rate (GFR) and plasma homocysteine has been noted, and declining renal function is associated with higher plasma homocysteine concentrations (3). We studied 23 patients with liver cirrhosis (median age, 54 years; range, 20–68 years; 16 males, … [↵][1]bAddress correspondence to this author at: Centre de Recerca Biomedica, Hospital Universitari de Sant Joan, C/. Sant Joan s/n, 43201-Reus, Catalunya, Spain. Fax 34-977-312569; e-mail jcamps{at}grupsgs.com. [1]: #xref-corresp-2-1

Pantoprazole in patients with varying degree of liver impairment in comparison to heal thy controls

The aim of this open study with parallel group design was to investigate the pharmacokinetics of pantoprazole in patients with varying degree of liver impairment in comparison to a control group of healthy volunteers. Patients with liver cirrhosis Child A or B were divided by use of the I4C-aminopyrine breath test into two groups: moderate (N=8, 65-98 kg, 36-60 years) and severe (N=8, 64-89 kg, 31-57 years) liver impairment. A control group (N=8, 71-88 kg, 44-51 years) of healthy subjects was also included. Each subject was given a single oral dose of 20 mg pantoprazole. Serum concentrations were measured by HPLC. AUC, tvz and Cma x were calculated. Pantoprazole was well tolerated. No adverse events occurred. Median (N=8 each group) pharmacokinetic characteristics were:

Predictors of the cost of liver transplantation.

Orthotopic liver transplantation (OLT) is a highly effective but costly therapy for end-stage liver disease. However, there are limited data on the demographic and clinical variables that affect cost. We undertook a preliminary study using multiple regression techniques to analyze factors that influence the cost of OLT. Patient and demographic data, including laboratory values and charges for all liver transplantations performed between June 1992 and June 1993 were analyzed (n = 111). Linear regression with standard and log-transformed values was performed by using STATA software (Stata Corporation College Station, TX). Independent variables included in the analyses were age, sex, United Network for Organ Sharing (UNOS) status, primary versus retransplantation, liver-kidney transplantation, and laboratory parameters of both liver (aspartate aminotransferase, AST; alkaline phosphatase; bilirubin; albumin; and prothrombin time) and kidney (blood urea nitrogen, BUN; creatinine) function. An F-to-remove strategy was employed with a significance level set at P = .05. The full model with 12 variables explained 37% of the total variation in charges. When one excludes variables that did not have a significant impact on cost, the remaining significant variables were BUN and UNOS status 1. The final model was Charges (US$) = 3,407 x BUN + 74,474 x status 1 + 102,662. This model accounted for 29% of the total variability with BUN accounting for the vast majority (26%). Renal function is the most important predictor of cost of OLT (P < .001). UNOS status 1 further increases cost, but other hospitalized patients have similar costs when one controls for other clinical variables. The degree of liver impairment is less important in predicting cost.

Pancreatic β-cell function in cirrhotic patients with and without overt diabetes. C-peptide response to glucagon and to meal

To study the role of pancreatic β-cell function in glucose intolerance and frank diabetes that sometimes develops in cirrhosis, the C-peptide response to a bolus IV injection of 1 mg of glucagon was measured in nine controls and in two groups of patients with cirrhosis. The first group comprised nine subjects with normal or high-normal fasting plasma glucose and no glycosuria; five of them had impaired glucose tolerance. The second group consisted of eight cirrhotics in whom frank diabetes had developed six to 48 months after the diagnosis of cirrhosis. They were characterized by fasting plasma glucose > 140 mg/dL and permanent glycosuria. No differences in the degree of liver impairment or portal-systemic shunting were observed between the two groups. Plasma glucose response to glucagon was similarly reduced in cirrhotic subjects. Basal C-peptide was high normal in patients with cirrhosis, and significantly increased in nondiabetic subjects. By contrast peak C-peptide levels and total C-peptide responses to glucagon were low normal in cirrhotics and significantly reduced in patients with cirrhosis and diabetes. In 14 patients the C-peptide response to a standard meal was also measured. It was significantly reduced in patients with cirrhosis and diabetes (six cases), as compared to cirrhotic subjects without diabetes. Peak C-peptide after IV glucagon significantly correlated with peak C-peptide after the meal ( r = .927), or total C-peptide response to meal ( r = .871). Impaired insulin secretion may add to insulin resistance in patients with liver cirrhosis, leading to the development of frank diabetes, characterized by fasting hyperglycemia and glycosuria.