Biomedical subjects
Publications and source records attributed to Kaushik Agarwal.
A 55-year-old Caucasian male developed a well characterized autoimmune hepatitis after completing treatment with pegylated interferon and ribavirin for recurrent hepatitis C. We hypothesize that pegylated interferon triggered a severe form of immune-mediated hepatitis.
Studies have suggested that the use of hepatitis C virus (HCV)-positive (HCV+) donor allografts has no impact on survival. However, no studies have examined the effect that HCV+ donor histology has upon recipient and graft survival. We evaluated the clinical outcome and impact of histological features in HCV patients transplanted using HCV+ livers. We reviewed all patients transplanted for HCV at our institution from 1988 to 2004; 39 received HCV+ allografts and 580 received HCV-negative (HCV-) allografts. Survival curves compared graft and patient survival. Each HCV+ allograft was stringently matched to a control of HCV- graft recipients. No significant difference in survival was noted between recipients of HCV+ livers and controls. Patients receiving HCV+ allografts from older donors (age > or =50 yr) had higher rates of graft failure (hazard ratio, 2.74) and death rates (hazard ratio, 2.63) compared to HCV- allograft recipients receiving similarly-aged older donor livers. Matched case-control analysis revealed that recipients of HCV+ allografts had more severe fibrosis post-liver transplantation than recipients of HCV- livers (P = 0.008). More advanced fibrosis was observed in HCV+ grafts from older donors compared to HCV+ grafts from younger donors (P = 0.012). In conclusion, recipients of HCV+ grafts from older donors have higher rates of death and graft failure, and develop more extensive fibrosis than HCV- graft recipients from older donors. Recipients of HCV+ grafts, regardless of donor age, develop more advanced liver fibrosis than recipients of HCV- grafts.
BACKGROUND: Survival in HIV infection has improved dramatically in the last decade due to antiretroviral therapy (ART). Due to shared routes of transmission, HCV is found in approximately 30% of HIV infected patients. HCV infection has emerged as a major issue in this population as manifest by a major increase in liver-related mortality. ART-associated hepatotoxicity has been demonstrated to occur more frequently in co-infected individuals and may be severe or fatal in some instances. Thus treatment of HCV has become a priority in HIV infected individuals. OBJECTIVES: The main aims of this review are to summarise and illustrate the current evidence based management of anti-HCV therapy in HIV-infected patients. METHODS: A systematic review of the literature was performed using Pubmed and Medline searches. CONCLUSION: All HIV-infected patients should be screened for HCV infection via anti-HCV antibody and HCV RNA polymerase chain reaction. If HCV infection is present, treatment should be considered in those patients with evidence of liver inflammation and fibrosis. Recent studies have demonstrated the safety and efficacy of anti-HCV therapy in HIV-infected individuals with pegylated interferon and ribavirin combination therapy. HCV genotype is predictive of response to therapy and increasing the duration of therapy to 48 weeks has proven to be more effective in patients with genotypes 2 and 3. HCV treatment with interferon based therapy is associated with many unique side effects and toxicities in this population of which the clinician must be aware.
Alcoholic hepatitis (AH) is a common disease associated with significant morbidity and mortality. Most often the diagnosis is suggested by a history of heavy alcohol excess in a patient with features of hepatic decompensation. In its purest form, AH is a histologic diagnosis of acute hepatic inflammation in response to alcohol. The primary objective of treatment for AH is to support long-term alcohol abstinence and to achieve adequate nutrition with lifestyle modification; goal setting and education are integral to long-term medical management. Severity at presentation (calculated by way of the Maddrey score) determines outcome. Patients with AH represent a heterogeneous group with regard to severity and pathogenesis, with various therapeutic interventions assessed in patients with severe AH. To date, corticosteroids have been studied most, and despite remaining controversial, warrant a place in the treatment of selected patients. Recent advances in unraveling the aspects of disease pathogenesis in AH have raised the possibility of targeted therapies, such as anti-tumor necrosis factor-a monoclonals and pentoxifylline. Orthotopic liver transplantation is not recommended for patients with severe acute AH, as most have an unclear long-term prognosis in the context of ongoing excess alcohol ingestion at presentation.
Azathioprine and 6-mercaptopurine (6 MP) are commonly used as immunosuppression postsolid organ transplantation. Recently, a better understanding of the metabolism of these drugs has developed. 6 Mercaptopurine is metabolized by thiopurine methyl transferase (TPMT) which is under the control of a common genetic polymorphism. Genetic testing and measurement of levels of 6 MP metabolites allow identification of patients at risk of toxicity. We report two cases of cholestatic hepatocellular injury associated with 6 MP toxicity occurring after orthotopic liver transplantation. Cholestasis developed after the introduction of 6 MP. Patients underwent extensive investigation and 6 MP toxicity was considered only after all other causes had been excluded. Thiopurine methyl transferase alleles identified on genetic testing were normal as were the 6 thioguanine levels. However, 6-methyl mercaptopurine levels were significantly elevated into the toxic range. Cholestasis resolved within a few weeks of drug withdrawal. 6 Mercaptopurine hepatotoxicity can present with a variety of clinical, biochemical and histological manifestations post OLT and should be considered as a cause of liver enzyme elevation. Monitoring of 6 MP metabolite levels in addition to TPMT allele testing is useful to prevent 6 MP toxicity and to help guide therapy.
Hepatitis C virus (HCV) is the most common chronic infection in the United States, affecting almost 3.9 million Americans. The most effective treatment for chronic HCV infection is combination antiviral therapy with peginterferon and ribavirin. However, combination therapy is also associated with significant adverse effects and is contraindicated in certain patient populations. Hematological adverse effects are common and are a frequent cause of dose reduction and interruption or discontinuation of therapy. Currently there are no approved treatments for the hematological adverse events associated with HCV therapy. However, emerging data suggest that utilization of hematopoietic growth factors can provide a useful adjunct to treatment and optimize sustained virologic response rates.
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) frequently co-exist due to shared routes of transmission. In the past, the impact of HCV on overall morbidity and mortality of coinfected patients was minimal due to the poor prognosis of HIV. However, since the introduction of highly active antiretroviral therapy (HAART), HCV has become a significant pathogen in this population. HIV clearly exacerbates HCV infection and accelerates progression to cirrhosis, end-stage liver disease, and hepatocellular carcinoma. There is debate over whether HCV influences the natural history of HIV. Given the high prevalence of coinfection and the accelerated liver damage, HCV treatment has become a priority in these patients. There are new data on pegylated interferon (PEG-IFN) and ribavirin (RBV) therapy for HCV in coinfected patients. The therapy is well tolerated and safe, although it appears to be slightly less effective than in monoinfected patients. The risk of HAART-related hepatotoxicity is greater in coinfected patients and therefore requires special consideration and close monitoring.