Hepatic decompensation

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. 

Tipranavir coadministered with ritonavir 200 mg has been associated with reports of clinical hepatitis and hepatic decompensation including some fatalities. Extra vigilance is warranted in patients with chronic hepatitis B or hepatitis C coinfection because these patients have an increased risk of hepatotoxicity. 

Hepatic toxicity Tipranavir coadministered with ritonavir 200 mg has been associated with reports of clinical hepatitis and hepatic decompensation, including some fatalities. 

Hepatic function impairment Patients with chronic hepatitis B or hepatitis C coinfection or elevations in transaminases are at an approximately 2.5-fold risk for developing further transaminase elevations or hepatic decompensation. Carcinogenesis Long-term animal carcinogenicity bioassays with tipranavir and tipranavir/ritonavir are currently in progress. 

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. 

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... 

Hepatic function impairment Chronic hepatitis C patients with cirrhosis may be at risk of hepatic decompensation and death when treated with alfa interferons. 

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

Contraindications Autoimmune hepatitis, decompensated hepatic disease... 

Contraindications Autoimmune hepatitis, creatinine clearance less than 50 ml/min, hemoglobinopathies, hepatic decompensation, hypersensitivity to ribavirin products, pregnancy, significant or unstable cardiac disease... 

Cirrhosis patients are at risk for hepatic decompensation if dehydration or hyponatremia occurs. 

Search for and treat complicating illnesses such as pneumonia, gastrointestinal bleeding, hepatic decompensation, pancreatitis, subdural hematoma, and fractures. 

Contraindications to interferon alfa therapy include hepatic decompensation, autoimmune disease, and history of cardiac arrhythmia. Caution is advised in the setting of psychiatric disease, epilepsy, thyroid disease, ischemic cardiac disease, severe renal insufficiency, and cytopenia. Alfa interferons are abortifacient in primates and should not be administered in pregnancy. Potential drug-drug interactions include increased theophylline levels and increased methadone levels. Co-administration with didanosine is not recommended because of a risk of hepatic failure, and co-administration with zidovudine may exacerbate cytopenias. 

Diagnosis (including the presence or absence of fibrosis, cirrhosis and hepatic decompensation). 

NUCLEOSIDE REVERSE TRANSCRIPTASE INHIBITORS RIBAVIRIN 1. t side-effects, risk of lactic acidosis, peripheral neuropathy, pancreatitis, hepatic decompensation, mitochondrial toxicity and anaemia with didanosine and stavudine 2.1 efficacy of lamivudine 1. Additive side-effects t intracellular activation of didanosine and stavudine 2. J intracellular activation of lamivudine 1. Not recommended. Use with extreme caution monitor lactate, LFTs and amylase closely. Stop co-administration if peripheral neuropathy occurs. Stavudine and didanosine carry a higher risk 2. Monitor HIV RNA levels if they T, review treatment combination... 

Duchini, A., Viernes, M.E., Nyberg, L.M., Hendry, R.M., Rockros, R.J. Hepatic decompensation in patients with cirrhosis during infection with influenza A. Arch. Intern. Med. 2000 160 113-115... 

Janssen HL, Brouwer JT, Nevens F, Sanchez-Tapias JM, Craxi A, Hadziyannis S. Fatal hepatic decompensation associated with interferon alfa. European concerted action on viral hepatitis (Eurohep). BMJ 1993 306(6870) 107-8. 

Liver biopsies performed in patients with chronic HBV infection are classified as chronic persistent hepatitis, chronic active hepatitis, and cirrhosis. Histologic results do not correlate with symptoms and often patients are asymptomatic until the development of cirrhosis. " Cirrhosis is manifested by interlacing strands of fibrous tissue with nodules of regenerating cells resulting in a characteristic small and knobby-appearing liver. This form of injury is irreversible and can be exacerbated by heavy alcohol consumption and concomitant infection with HCV or HIV. Hepatic decompensation as a result of cirrhosis includes ascites, jaundice, variceal bleeding, and hepatic encephalopathy. The 5-year risk of decompensation after the development of cirrhosis is estimated to be 20%. ... 

Hui AY, Chan HL, Leung NW, Hung LC, Chan FK, Sung JJ (2002) Survival and prognostic indicators in patients with hepatitis B virus-related cirrhosis after onset of hepatic decompensation. J Clin Gastroenterol 34 569-572... 

In vitro, ribavirin reduced the intracellular activation and antiretroviral activity of stavudine. However, in a study in 5 HIV-positive patients with hepatitis C, ribavirin 800 mg daily had no statistically significant effect on the pharmacokinetics of stavudine (a 45% increase in AUC), and no effect on intracellular activation of stavudine, when compared with similar patients who received placebo. Similarly, no decrease in antiviral activity of stavudine (as assessed by plasma HIV-RNA levels) has been seen when ribavirin was given with interferon for hepatitis C infection in patients with HIV. " Nevertheless, the UK manufacturers of ribavirin continue to recommend that plasma HIV-RNA levels are closely monitored in patients taking ribavirin with stavudine to ensure continued efficacy. In contrast, based on an analysis of data from the adverse event reporting system of the FDA in the US, (see didanosine above), the UK manufacturers of ribavirin consider that concurrent use of stavudine should be avoided to limit the risk of mitochondrial toxicity. The UK manufacturer of stavudine notes that patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk ofNRTI-associated lactic acidosis. Patients at increased risk should be monitored closely. Similarly, the US manufacturer of stavudine states that patients receiving interferon with or without ribavirin and stavudine should be closely monitored for treatment-associated toxicities, especially hepatic decompensation. ... 

Tenofovir disoproxil fumarate 300 mg daily did not alter the pharmacokinetics of a single 600-mg dose of ribavirin in 22 subjects, and the pharmacokinetics of tenofovir did not appear to be changed by ribavirin when compared with historical data. Note that, there is evidence that HIV-pos-itive patients co-infected with hepatitis C and treated with interferon alfa and ribavirin may be at increased risk of lactic acidosis and hepatic decompensation when receiving any NRTF, (p.805), including tenofovir, and increased monitoring is recommended. ... 

Background. Radiation induced hepatitis was first described in the 1960s [8] and results in various degrees of hepatic decompensation. It is a well recognized complication of external beam radiation that encompasses the liver [9] since it involves the irradiation of normal parenchyma beyond that which can be tolerated (35 Gy when exposed to uniform radiation fields). However, it is a rare complication after microsphere treatment since this technique allows the safe delivery of radioactive particles to liver tumors with healthy liver tissue sparing [10]. Doses greater than 70 Gy to liver tumors can be delivered without involving the normal liver tissue [11]. 

Trientine is a copper chelator, acting primarily by enhancing urinary copper excretion. Trientine is licensed for treatment of Wilson disease and is now generally available. Experience with trientine is not as extensive as with penicillamine. It seems to be as effective as penicillamine, with far fewer side effects. Its efficacy was evaluated in patients with intolerance to penicillamine (Scheinberg et al 1987). Discontinuation of penicillamine resulted in death from hepatic decompensation or fulminant hepatitis in 8 of 11 patients who stopped their own treatment after an average survival of only 2.6 years. In contrast, 12 of 13 patients with intolerance to penicillamine switched to trientine (1-1.5 g/day) were alive at 2-15 years later. The remaining patient was killed accidentally. However, the efficacy of trientine was not compared with penicillamine as initial treatment of Wilson disease. Uncontrolled anecdotal reports and our own experience indicate that trientine is a satisfactory first line treatment for Wilson disease. In the early phase of treatment trientine appears to be more potent to mobilize copper than penicillamine, but cupriuresis diminishes more rapidly than with penicillamine. The cupri-uretic power of trientine may be disappointing but is sufficient to keep the patient clinically well. 

Amiodarone has been associated with steatohepadtis with advanced fibrosis, presenting with hepatic decompensation and portal hypertension, with ascites and recurrent hemorrhage from esophageal varices [42 ]. There was marked histological similarity between amiodarone-induced liver disease and alcoholic and non-alcoholic steatohepatitis. 

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