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Statins are relatively safe first-line agents to use in the setting of dyslipidemia associated with immunosuppressive therapy in subjects undergoing liver transplantation, and also in HIV-infected patients with dyslipidemia due to antiretroviral drugs, especially ritonavir-boosted protease inhibitors. Rosuvastatin, a new statin, has demonstrated higher potency than previously released statins and is not extensively metabolized by the liver P450 system; therefore, the probability of deleterious pharmacokinetic interactions with commonly used immunosuppressants and antiretroviral drugs is reduced. We present the first case of severe rhabdomyolysis in a liver transplant patient receiving rosuvastatin for the treatment of immunosuppressive therapy-related grade IV dyslipidemia, an HIV-infected subject on protease inhibitor-sparing HAART, that resolved after rosuvastatin withdrawal, probably related to interactions between calcineurin inhibitors and hepatic rosuvastatin uptake transporters such as organic anion transporting polypeptides (OATPs)., (Copyright © 2011 American Association for the Study of Liver Diseases.)

Syncytial giant cell hepatitis (SGCH) among adult human immunodeficiency virus (HIV)-infected patients has been rarely described. Most cases have been reported in subjects coinfected with the hepatitis C virus (HCV), but its prevalence and outcome remain unknown. We performed a retrospective analysis of all cases of SGCH among 332 liver biopsies from HIV-infected patients seen at a tertiary center in Madrid, Spain, between 1984 and March 2004. Two hundred fifty specimens were obtained from HCV-coinfected patients. There were 2 cases of SGCH, leading to an observed overall prevalence of 0.6% (0.8% when considering only HCV-coinfected patients). In addition to histological changes secondary to chronic hepatitis C, the liver cords were replaced by syncytial giant cells with up to 30 nuclei. There was no histological evidence of measles (among paramyxoviruses) or herpes viruses group infections. In patient 1, there was a progressive clinical worsening after a 3-month course of prednisone, leading to liver failure and death. His postmortem liver biopsy showed more abundant giant hepatocytes accompanied with the development of a histologic pattern of severe fibrosing cholestatic hepatitis. The second patient received a prolonged course of pegylated interferon-alpha-2b and ribavirin with clearance of syncytial giant hepatocytes despite HCV-RNA persistence. SGCH is a rare histological finding among HIV-infected patients with chronic hepatitis C. Specific treatment with pegylated interferon and ribavirin can lead to histological resolution and biochemical improvement, even in the absence of HCV-RNA clearance.

Background/aims: Differences in HCV-RNA clearance during therapy might explain the lower efficacy of peg-IFN/RBV in HIV/HCV-coinfection. There are limited data on HCV-RNA clearance and treatment outcomes in liver transplanted (LT) patients., Methods: To assess the rates of SVR and baseline predictors of failure after 48 weeks of weight-adjusted peg-IFN-alpha-2b/RBV in 120 patients with HCV genotype 1: 61 HCV-monoinfected, 40 HIV-coinfected and 19 LT-patients. Viral clearance was evaluated in patients completing 24 weeks of therapy (n=112, 93%)., Results: SVR was significantly lower in HIV-coinfection than in HCV-monoinfection or LT (18 vs. 39 vs. 42%, P<0.02). By multivariate analysis, HIV-coinfection (OR 3.048, 95% CI 1.133-8.196; P=0.027), baseline HCV-RNA over 800,000 IU/ml (OR 2.800; 95% CI 1.121-6.993, P=0.027) and higher AST values (OR 1.009; 95% CI 1.001-1.018; P=0.028) were significantly associated to failure. Despite similar baseline HCV load (5.67 vs. 5.75 vs. 5.90 log10 IU/ml), HIV-coinfection showed significantly lower HCV-RNA decreases than HCV-monoinfection at weeks 4 (P=0.015), 12 (P=0.015) and 24 (P=0.0003), and than LT at weeks 12 (P=0.003) and 24 (P=0.023). 36/60 subjects (60%) reaching EVR by week 12 obtained SVR vs. 3/60 (5%) who did not., Conclusions: HIV-coinfection was independently associated to treatment failure, and led to a significantly slower HCV-RNA clearance.

Liver transplantation is being evaluated as a therapeutic option for human immunodeficiency virus (HIV)-infected patients with end-stage liver disease, but experience is still scarce. We describe the outcome of 4 HIV-infected patients who underwent liver transplantation in our hospital between July 2002 and April 2003. HIV-infected liver transplant recipients meet the same standard criteria for transplantation as do HIV-negative candidates. In addition, HIV infected persons are required to have a CD4 T-cell count greater than 100/mL (CD4 T-cells are targets for HIV infection). Immunosuppressive regimens, perioperative surgical prophylaxis, and prophylaxis for opportunistic infections are standard in the Liver Transplantation Unit in our hospital. Four patients, including 3 former intravenous drug users, received a liver transplant (2 from deceased donors and 2 from living donors), with a median follow-up of 510 days. Three patients (75%) are alive, with 1 death occurring 17 months posttransplantation in a patient who developed fibrosing cholestatic hepatitis. Rejection occurred in 1 patient, and was managed with no complications. Hepatitis C virus (HCV) recurrence occurred in 3 patients. HIV-infection has remained under control with antiretroviral treatment. A combination of 3 nucleoside analogs was used in 3 patients, with no need for drug adjustments. No opportunistic infections or other significant infectious complications developed. In conclusion, orthotopic liver transplantation seems a safe therapeutic option in the short term for HIV-infected persons with end stage liver disease, including patients with a history of drug abuse. If indicated, an antiretroviral regimen consisting of 3 nucleosides could be used to avoid interactions with immunosuppressive drugs.

Partial splenic embolization (PSE), a non-surgical treatment for hypersplenism, has also been reported to improve hepatic function. As severe thrombocytopaenia or leukopaenia contraindicate the use of combined therapy with pegylated interferons (PEG-IFNs) and ribavirin (RBV) in HCV-related cirrhosis, we evaluated, from July 2002 to October 2003, the safety and effectiveness of PSE as a procedure to allow therapy for HCV in three Child-Pugh class B cirrhotic patients with hypersplenism and HIV co-infection. HCV genotypes were 1b (n=2) and 3a (n=1). Severe thrombocytopaenia (in all) and leukopaenia (in two) precluded therapy for HCV. PSE was successfully performed in all with a mean infarcted area of 80%, leading to a significant increase in platelet and leukocyte counts that allowed therapy with weight-adjusted RBV and PEG-IFN-alpha-2b (patients 1 and 3) or 180 microg of PEG-IFN-alpha-2a (patient 2) 8 weeks after the procedure. Moderate pain, well controlled with conservative measures, followed PSE in 100% of cases, but during follow-up (mean 422 days) there were no infectious complications or liver decompensation episodes. Although preliminary, these results suggest the potential role of PSE in HIV/HCV-cirrhotic subjects with hypersplenism as a procedure to allow the use of combined PEG-IFN and RBV.

Background: Nucleoside analogues may induce mitochondrial toxicity, particularly didanosine. Ribavirin increases didanosine exposure, which might be clinically relevant when coadministered in HIV/HCV-coinfected patients., Objective: To evaluate, among 89 patients receiving highly active antiretroviral therapy (HAART) and therapy for chronic hepatitis C, clinically relevant mitochondrial toxicity in those treated with concomitant ribavirin and didanosine (n=35, 39%)., Methods: From January 2000 to July 2002 longitudinal analysis of the incidence and clinical course of didanosine-related hyperamylasaemia, pancreatitis, hyperlactataemia/lactic acidosis or neuropathy. Risk factors were evaluated using univariate and multivariate Cox's proportional hazards model., Results: Among 35 patients who received concomitant didanosine (400 mg/day in 86%) and ribavirin (> or = 10 mg/kg/day in 91%), 20 (57%) developed one or more adverse events after a mean of 87 days. Most frequent laboratory abnormalities were hyperamylasaemia (18 patients, 51%) and hyperlactataemia (eight patients, 23%). Acute pancreatitis and symptomatic hyperlactataemia developed in 10 (28%) and six (17%) patients, respectively. Two patients (6%) with pancreatitis and severe lactic acidosis died; the other patients recovered uneventfully despite continuation of anti-HCV therapy in 83% after didanosine withdrawal in 40%. In the Cox's model higher baseline amylase levels (HR: 1.04, 95% CI: 1.02-1.06, P=0.001) and three nucleoside reverse transcriptase inhibitor-based HAART (HR: 5.3, 95% CI: 1.73-16.24, P=0.003) were significantly associated to toxicity., Conclusions: The coadministration of didanosine and ribavirin should be avoided in HIV/HCV-coinfected patients, due to a high rate of clinically significant toxicity, particularly in triple nucleoside-based HAART. Amylase levels should be strictly monitored, especially if elevated at baseline.

Background: Hepatitis C virus (HCV) and HIV coinfection constitutes an important epidemiological and clinical problem. We evaluated the safety and efficacy of Pegylated interferon alpha2b (Peg-IFN) and a fixed dose of ribavirin in the treatment of chronic hepatitis C in HIV coinfection., Methods: Open, prospective study in HCV-HIV coinfected patients with persistently elevated alanine aminotransferase (ALT) levels and a liver biopsy showing either portal or bridging fibrosis. Therapy included Peg-IFN (50 micro g weekly) with ribavirin 800 mg for 48 weeks. The primary end point was sustained virological response (SVR). Univariate and multivariate analyses were performed to determine factors associated with response., Results: By intent-to-treat analysis, 11 of 35 patients (31%) reached SVR. SVR was significantly better for genotypes 2/3 than for genotype 1 (54% versus 21%; P < 0.05). By multivariate logistic regression analysis, only a non-1 genotype was an independent factor for SVR [odds ratio (OR), 6; 95% confidence interval (CI), 1.1-31.7; P < 0.005]. A decrease of at least 1.5 log10 HCV RNA at week 12 of therapy was highly predictive of SVR (OR, 49.9; 95% CI, 4.9-508.2; P < 0.001). Most patients developed adverse events, although only six patients (17%) discontinued treatment due to toxicity., Conclusions: The combination of low doses of Peg-IFN plus a fixed dose of ribavirin resulted in a rate of SVR similar to that obtained with higher doses of the drugs in HIV-infected patients and lower than those obtained in non-HIV patients. Response at week 12 may be useful to help guide therapy in HCV-HIV co-infected patients.