Review article: the burden of hepatic encephalopathy.

Hepatic encephalopathy, a challenging complication of advanced liver disease, occurs in approximately 30-45% of patients with cirrhosis and 10-50% of patients with transjugular intrahepatic portosystemic shunt, while minimal hepatic encephalopathy affects approximately 20-60% of patients with liver disease. Although the total direct and indirect costs of hepatic encephalopathy have not been formally quantified, data from the Healthcare Cost and Utilization Project suggest that hepatic encephalopathy-related hospitalizations are associated with substantial costs. In 2003, there were over 40 000 patients hospitalized in the United States for a primary diagnosis of hepatic encephalopathy, resulting in total charges of approximately $932 million. Furthermore, trends over the past 10 years suggest that the burden of hepatic encephalopathy is increasing, as indicated by increases in hospital admissions and higher charges per stay. Because of inconsistencies in coding for hepatic encephalopathy, the prevalence and cost data from this data source are believed to significantly underestimate the true burden of hepatic encephalopathy. In addition, expenditures for physician fees and out-patient care, as well as indirect costs attributable to lost work days and decreased productivity, have not been quantified. Thus, there is need for future studies to more accurately define the burden of hepatic encephalopathy, including minimal hepatic encephalopathy.

Sirolimus-induced hyperlipidaemia in liver transplant recipients is not dose-dependent.

BACKGROUND: Sirolimus is a potent immunosuppressive medication that acts by inhibiting T-cell proliferation. It has been used in kidney transplantation because of its lack of nephrotoxicity. It is now being investigated in liver transplantation, but there are concerns about safety and long-term side effects such as dyslipidaemia. Hypertriglyceridaemia is a common adverse event seen with sirolimus use, and often does not respond to dose reduction or anti-lipemic drugs. METHOD: We report six patients who have developed significant hyperlipidaemia while receiving sirolimus, in spite of therapeutic trough levels. CONCLUSION: All six patients showed either resolution or improvement in lipid levels with discontinuation of sirolimus.

Bone to total alkaline phosphatase ratios improve sensitivity and specificity of bone alkaline phosphatase immunoassays.

OBJECTIVES: Evaluate the ability of two bone alkaline phosphatase (ALPB) immunoassays (Ostase, Hybritech Inc and Alkphase-B, Metra Biosystems) to clinically differentiate between osseous and non-osseous ALP sources. DESIGN AND METHODS: Specimens from patients with either liver or bone disease (Paget's disease or metastatic cancer) were analyzed by both methods. RESULTS: There was a good correlation between these two assays. Values for ALPB, whether determined as a concentration by the Ostase assay or as an activity by the Alkphase-B assay, were similar for subjects with liver disease or bone disease. However, total ALP (ALPT) activity was higher in liver disease compared to bone. When ALPB was expressed in relation to ALPT, ratios were significantly greater in subjects with bone disease than in those with liver disease. ALPB/ALPT ratios improved the specificity of the Ostase assay from 52% to 86% and the Alkphase-B assay from 58% to 74%. CONCLUSIONS: These two ALPB assays have good analytical performance and their clinical utility can be enhanced by expressing ALPB values in relation to ALPT activity.

Review article: the role of rapid virological response in determining treatment duration for chronic hepatitis C.

BACKGROUND: For patients with chronic hepatitis C, attaining rapid virological response (RVR) is highly predictive of attaining SVR. AIM: To consider the predictive value of RVR in terms of SVR and relapse. METHODS: Data were collected from published clinical trials to define the predictive value of RVR for SVR and evaluate the proposed continuum linking RVR to relapse. RESULTS: These data support a 24-week regimen among genotype (G)1 patients who attain RVR with positive predictive values (PPVs) of 77.8% and 85.7% in patients with G1 infection treated for 24 and 48 weeks. Conversely, failure to attain RVR among G1 patients should not be viewed as a criterion for extending treatment duration beyond 48 weeks: negative predictive values (NPVs) were 60.9% and 52.7% in G1 patients without RVR treated for 48 and 72 weeks. Among G2/3 patients, RVR has a high PPV; however, the NPV varied with treatment duration indicating that a 24-week treatment regimen is warranted in G2/3 patients who fail to attain RVR. CONCLUSIONS: The present analysis confirms RVR as a strong predictor of SVR that can be used to tailor treatment duration, but which also should be appreciated in the context of treatment duration and regimen.

Intramuscular hepatitis B immune globulin combined with lamivudine for prophylaxis against hepatitis B recurrence after liver transplantation.

Immunoprophylaxis using intravenous (IV) hepatitis B immune globulin (HBIG) decreases the recurrence of hepatitis B virus (HBV) infection after orthotopic liver transplantation (OLT). However, IV HBIG is expensive, has significant side effects, and is inconvenient to administer. An alternative approach for prophylaxis using intramuscular (IM) HBIG and oral lamivudine was prospectively evaluated in this study. Ten consecutive patients with cirrhosis with HBV infection who underwent OLT were included in this study. Nine of 10 patients received lamivudine, 150 mg/d, for an average duration of 8.6 months before OLT. Two of 10 patients with detectable HBV DNA at the time of OLT received 10,000 U (45 mL) of IV HBIG daily for 7 consecutive days, followed by 5 mL of IM HBIG weekly for the next 3 weeks, then every 3 weeks. The other 8 patients were HBV DNA negative at OLT and received one dose of IV HBIG (45 mL) during surgery, followed by 5 mL of IM HBIG weekly for 4 weeks, then every 3 weeks. All patients received lamivudine, 150 mg/d, after OLT. During a mean follow-up of 15.6 months, 9 of 10 patients achieved a protective hepatitis B surface antibody (HBsAb) titer greater than 200 IU/L and had no evidence of HBV recurrence. One patient failed to develop an adequate HBsAb titer and developed histological and virological evidence of recurrence. One patient died unrelated to HBV recurrence. Our preliminary data suggest that this combination prophylaxis with IM HBIG and lamivudine is effective and potentially cost saving.

Liver transplantation in patients with severe portopulmonary hypertension treated with preoperative chronic intravenous epoprostenol.

Portopulmonary hypertension (PPHTN) is no longer an absolute contraindication to orthotopic liver transplantation (OLT). The pre-OLT management of patients with PPHTN requires early diagnosis and chronic therapy with intravenous epoprostenol to decrease pulmonary vascular resistance (PVR). Close follow-up is necessary to reassess pulmonary artery pressures (PAPs) and evaluate right ventricular (RV) function. This assists in the optimal timing of OLT. Successful management also necessitates reassessment of pulmonary artery hemodynamics just before OLT, with clearly defined parameters used to determine whether to proceed. Even with the intraoperative and postoperative availability of potent pulmonary vasodilators, clinical management may be suboptimal in reducing PAP. Adequate reduction in PVR and improvement in RV function in response to chronic epoprostenol therapy may facilitate successful OLT. We present a case report and review the limited experience with this treatment.