Child-Pugh score

Variceal bleeding Pharmacologic prophylaxis fever, anorexia, malaise, fatigue) Child-Pugh score, Appropriate reduction in... 

Population PK screening in Phase II and Phase III is useful in assessing the impact of altered hepatic function (as a covariate) in PKs, if those patients are not excluded from Phase II and III trials, and if there is sufficient PK information collected about the patients to characterize them reasonably well. If a population PK approach is used, patients in Phase II and III studies are assessed for encephalopathy, ascites, serum bilirubin, serum albumin, and prothrombin time (which are components of the Child-Pugh score) or a similar group of measures of hepatic function. The population PK study, then, would include the following features ... 

Hepatic function Impairment A dosage reduction is recommended for patients with moderate hepatic insufficiency. There is no clinical experience in patients with severe hepatic insufficiency (Child-Pugh score greater than 9). 

Capsules - Use with caution in patients with moderate or severe hepatic impairment. Patients with Child-Pugh scores ranging from 5 to 8 should receive a reduced dose of amprenavir capsules of 450 mg twice daily, and patients with a Child-Pugh score ranging from 9 to 12 should receive a reduced dose of amprenavir capsules of 300 mg twice daily. 

Dose adjustment in hepatic Impairment The recommended dose of abacavir in patients with mild hepatic impairment (Child-Pugh score 5 to 6) is 200 mg twice daily. To enable dose reduction, use abacavir oral solution (10 ml twice daily) to treat these patients. The safety, efficacy, and pharmacokinetic properties of abacavir have not been established in patients with moderate to severe hepatic impairment therefore, abacavir is contraindicated in these patients. 

Moderate or severe hepatic impairment (Child-Pugh score greater than 6). 

Hepatic function impairment Reduce fosamprenavir dose to 700 mg twice daily, in patients with mild or moderate hepatic impairment (Child-Pugh score ranging from 5 to 8) receiving fosamprenavir without concurrent ritonavir. Do not use fosamprenavir in patients with severe hepatic impairment (Child-Pugh score ranging from 9 to 12). 

Hepatic decompensation (Child-Pugh score greater than 6 class B and C) in cirrhotic chronic hepatitis C monoinfected patients before or during treatment, or... 

Hepatic decompensation with Child-Pugh score greater than or equal to 6 in... 

Dosage in hepatic impairment Dosage and frequency are modified based on the Child-Pugh score. 

Child-Pugh Score Capsules Oral Solution... 

Patients with hepatic impairment 12 patients with hepatic impairment with a Child-Pugh score > 5 and < 14. 

Plots of pharmacokinetic parameters (Cmax, AUC of XYZ123 and XZY456, CLR of XYZ123) versus Child-Pugh score and treatment day were drawn. 

Thus, a multiple dose study was performed in which all healthy and hepatic impaired individuals, received the same dose. It was the aim to include 12 patients with various and well distributed degrees of hepatic impairment (according to the Child-Pugh score) and 12 pair-matched (based on demographic characteristics) healthy subjects, in order to have 10 patients and 10 subjects evaluable. The pharmacokinetics of XYZ123 in plasma (total and unbound) and in urine was assessed after the first dose and at steady state after the seventh dose. The pharmacokinetics in plasma of its main metabolite XYZ456 was also assessed. 

Table 19 Child Pugh score and grade of hepatic impairment...

The demographic characteristics were similar in both groups (Table 18). The median Child-Pugh score of patients with hepatic impairment was 7 with a range of 5-11 (Table 19). 

Figure 10 indicates that in patients with hepatic impairment there was no trend towards any relationships between XYZ456 pharmacokinetic parameters and the Child-Pugh score. 

MELD/PELD/Child-Pugh scores are not designed to provide information on likely drug handling in a patient, but they are often used as surrogate markers in clinical trials. If available, they may give an indication of how far advanced the liver disease is overall. 

Alcoholic liver disease Child-Pugh score C/MELD score 25... 

Trotter, J.F., Suhocki, P.W., Rockey, D.C. Transjugular intrahepatic portosystemic shunt (TIPS) in patients with refractory ascites effect on body weight and Child-Pugh score. Amer. J. Gastroenterol. 1998 93 1891-1894... 

Salerno F, Merli M, Cazzaniga M, Valeriano V, Rossi P, Lovaria A, et al. MELD score is better than Child-Pugh score in predicting 3-month survival of patients undergoing transjugular intrahepatic portosystemic shunt. J Hepatol 2002 36 494-500. 

The only other commonly used alternative is the Maddrey Discriminant Function (MDF) which was developed to assess acute alcoholic hepatitis. This is more easily calculated than the Child-Pugh score as ... 

Hepatic impairment In moderate liver dysfunction (ChUd-Pugh score 7-9), maximiun dose is 16 mg/day. Use is not recommended in severe liver dysfunction (Child-Pugh score 10-15). 

These proteins are markers of hepatic synthetic activity and are therefore used to estimate the level of functioning hepatocytes in cirrhosis. They are employed in the Child-Pugh scoring system for liver disease. Albumin levels can be affected by a number of factors, including the patient s nutritional status, acute illnesses, which result in redistribution of albumin, and protein losses from renal and intestinal sources. 

The development of the TIPS provided a major improvement in the management of refractory or severe cases of esophagogastric variceal bleeding and other complications of portal hypertension. The TIPS procedure involves the placement of one or more stents between the hepatic vein and the portal vein (Fig. 37-6). This procedure is widely used because it provides an effective decompressive shunt without laparotomy, and can be employed regardless of Child-Pugh score. Survival rates with TIPS in patients refractory to endoscopic treatment are comparable to rates achieved with portacaval... 

Variceal bleeding Pharmacologic prophylaxis Endoscopy, vasoactive drug therapy (octreotide), sclerotherapy, volume resuscitation, pharmacologic prophylaxis Child-Pugh score, endoscopy, CBC CBC, evidence of overt bleeding Appropriate reduction in heart rate and portal pressure Acute control acute bleed Chronic variceal obliteration, reduce portal pressures... 

Acid-base balance Of 16 patients with hepatic cirrhosis and chronic hepatitis B infection, five developed lactic acidosis after 4—240 days of treatment with entecavir all five had highly impaired liver function [13 ]. One patient died, but in the other four the lactic acidosis resolved after withdrawal of entecavir. The serum lactate concentrations were not increased in the other 11 patients, who all had less severe liver impairment. Child-Pugh scores did not correlate with the development of lactic acidosis, but MELD (Model for End-Stage Liver Disease) scores did, as did serum bilirubin, creatinine, and international normalized ratio (INR). The authors suggested that entecavir should be used cautiously in patients with severely impaired liver function. 

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