Liver decompensation

Ascites, jaundice, variceal bleeding, and hepatic encephalopathy can manifest with liver decompensation. 

VecchiM, FolliC, Donato MF, Formenti S, Arosio E, deFranchisR. High rate of positive anti-tissue transglutaminase antibodies in chronic liver disease. Role of liver decompensation and of the antigen source. Scand J Gastroenterol 2003 38 50-54. 

In chronic liver disease, PT may increase over a period of weeks or months to values up to about 30 seconds as the liver decompensates. In patients with acute liver failure the values may increase to over 100 seconds within a few hours. 

The encephalopathy score gives an indication of how severe the liver impairment is. A score of 1 shows early signs of liver decompensation a score of 4 implies end-stage Uver failure with very little function remaining. 

Sykia A, Gigi E, Sinakos E, Bibashi E, Bellou A, Raptopoulou-Gigi M. Severe autoimmune hemolytic anemia complicated with liver decompensation and invasive aspergillosis in a patient with chronic hepatitis C during treatment with peg-interferon-a and ribavirin. J Gastrointestin Liver Dis 2009 18(1) 118-9. 

Ascites is the accumulation of fluid in the peritoneal space and is often one of the first signs of decompensated liver disease. Ascites is the most common complication of cirrhosis and portends a dire prognosis.14... 

While there are no FDA-approved treatments for hepatitis D, interferon has been shown to be effective.46 48 Various doses have been evaluated, with the most effective treatment being 9 million units three times weekly.47 Seventy-one percent of patients who were treated with this regimen for 48 weeks had normalized ALT levels.47 Adverse effects and monitoring parameters for interferon therapy are similar to treatment for hepatitis C. In some situations, patients infected with hepatitis D who develop hepatic decompensation and ESLD may need to undergo liver transplantation. 

Contraindications to treatment include autoimmune hepatitis, decompensated liver disease, women who are pregnant or patients whose female partners are pregnant, hemoglobinopathies, creatinine clearance <50 mL/ min, hemodialysis, or ischemic cardiovascular or cerebrovascular disease. 

Factors that may decrease theophylline clearance and lead to reduced dosage requirements include advanced age, bacterial or viral pneumonia, heart failure, liver dysfunction, hypoxemia from acute decompensation, and use of drugs such as cimetidine, macrolides, and fluoroquinolone antibiotics. 

Decompensated liver disease is complicated by jaundice, refractory ascites, bacterial peritonitis, coagulopathy, and variceal bleeding and may require liver transplantation. The number of liver transplants for decompensated cirrhosis doubled from 1990 to 2004, when 5845 cadaveric (orthotopic) liver transplants were performed (65). 

Hepatic function impairment Zaleplon is metabolized primarily by the liver and undergoes significant presystemic metabolism. Consequently, the oral clearance of zaleplon was reduced by 70% and 87% in compensated and decompensated cirrhotic patients, respectively. 

Liver function impairment - In patients with progressive ALT increases above baseline values, reduce the dose of peginterferon alfa-2a to 135 meg. Immediately discontinue therapy if ALT increases are progressive despite dose reduction or are accompanied by increased bilirubin or evidence of hepatic decompensation. 

Peginterferon alfa-2b Hypersensitivity to peginterferon alfa-2b or any component of the product autoimmune hepatitis decompensated liver disease. 

Peginterferon alfa-2a treatment results in more sustained responses than simple interferon alpha, although relapse is not uncommon. Such treatment should generally be avoided in those receiving immunosuppressants and those with decompensated liver disease. Lamivudine, a reverse transscriptase inhibitor is often used in initial treatment and in decompensated liver disease. 

The most common adverse effects of lamivudine seen at doses used to treat HBV are mild they include headache, malaise, fatigue, fever, insomnia, diarrhea, and upper respiratory infections. Elevated alanine aminotransferase (ALT), serum lipase, and creatine kinase may also occur. The safety and efficacy of lamivudine in patients with decompensated liver disease have not been established. Dosage adjustment is required in individuals with renal impairment. Coadministration of trimethoprim-sulfamethoxazole decreases the renal clearance of lamivudine. 

Dosage in liver impairment 100 mg q6h (200 mg q 12h with extended-release). Dosage in cardiomyopathy, cardiac decompensation No loading dose 100 mg q6-8h with gradual dosage adjustments. 

Azizov KhA (1998) Surgical treatment of the patients with a liver cirrhosis in conditions portal hypertension decompensation with ascite syndrome. MD Thesis (in Russian) Tashkent, Uzbekistan, p 45... 

Perrillo, R., C. Tamburro, P. Regenstein, et al., Low-dose titratable interferon alfa in decompensated liver disease caused by chronic infection with hepatitis B virus. Gastroenterology, 1995.109 908-16. 

Oral bioavailability of adefovir dipivoxil is about 59% and is unaffected by meals it is rapidly and completely hydrolyzed to the parent compound by intestinal and blood esterases. Protein binding is low (< 5%). The intracellular half-life of the diphosphate is prolonged, ranging from 5 to 18 hours in various cells this makes once-daily dosing feasible. Adefovir is excreted by a combination of glomerular filtration and active tubular secretion and reguires dose adjustment for renal dysfunction however, it may be administered to patients with decompensated liver disease. 

The pharmacokinetics of lamivudine are described earlier in this chapter (see section, Nucleoside and Nucleotide Reverse Transcriptase Inhibitors). The more prolonged intracellular half-life in HBV cell lines (17-19 hours) than in HIV-infected cell lines (10.5-15.5 hours) allows for lower doses and less ffeguent administration. Lamivudine can be safely administered to patients with decompensated liver disease. 

Peg Interferon Alfa-2b (PEG-Intron) [Antiviral/ Immunomodulator] WARNING Can cause or aggravate fatal or life-threatening neuropsychiatric, autoimmune, ischemic, and infectious disorders. Monitor pts closely Uses Rx Hep C Action Immune modulation Dose 1 mcg/kg/wk SQ 1.5 mcg/kg/wk combined w/ ribavirin Caution [C, X if used w/ ribavirin /-] w/ Hx psychiatric Contra Autoimmune Hep, decompensated liver Dz, hemoglobinopathy Disp Vials 50, 80, 120, 150 mcg/0.5 mL Reclipen 50, 80,120,150 mcg/5 mL reconstitute w/ 0.7 mL w/ sterile water SE Depression, insomnia, suicidal behavior, GI upset, neutropenia, thrombocytopenia, alopecia, pruritus Interactions T Myelosuppression W/ antineoplastics T effects OF doxorubicin, theophylline T neurotox W/ vinblastine EMS See Peg Interferon Alfa-2a may cause flu-like Sxs... 

Typical side effects are constitutional in nature, including a flu-like syndrome within 6 hours after dosing in more than 30% of patients that tends to resolve upon continued administration. Other potential adverse effects include thrombocytopenia, granulocytopenia, elevation in serum aminotransferase levels, induction of autoantibodies, nausea, fatigue, headache, arthralgias, rash, alopecia, anorexia, hypotension, and edema. Severe neuropsychiatric side effects may occur. Absolute contraindications to therapy are psychosis, severe depression, neutropenia, thrombocytopenia, symptomatic heart disease, decompensated cirrhosis, uncontrolled seizures, and a history of organ transplantation (other than liver). Alfa interferons are abortifacient in primates and should not be administered in pregnancy. 

OTC deficiency is the most common urea cycle defect.As it is X linked, affected boys typically have severe disease with neonatal presentation as described in this chapter. The disease in women who carry an OTC mutation on one X chromosome ranges from severe early-onset disease to complete absence of symptoms. Furthermore, affected women may decompensate in the context of a metabolic stress such as an infection or following parturition. OTC-deficient patients have low plasma citrulline and high urine orotic acid. Confirmation of the diagnosis requires mutation analysis or a liver biopsy for enzymology. The carrier status of women is most accurately determined by mutation analysis. 

A 43-year-old woman was admitted to hospital in December feeling unwell with a two-week history of urinary symptoms. She had decompensated cirrhosis of her liver on ultrasound and was taking pentoxifylline (oxpentifylline, Trental), co-amoxiclav, omeprazole and thiamine. She was jaundiced and confused with respiratory failure limiting speech to partial sentences. There was a marked deterioration in liver function overnight and she went into acute renal failure. 

Hemoglobinopathy (such as thalassemia major and sickle-ceU anemia) Decompensated liver disease Autoimmune diseases Renal function impairment... 

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