Prevalence of hepatic iron overload and association with hepatocellular cancer in end-stage liver disease: results from the National Hemochromatosis Transplant Registry

Background : It is unclear whether mild to moderate iron overload in liver diseases other than hereditary haemochromatosis (HH) contributes to hepatocellular carcinoma. This study examined the association between hepatic iron grade and hepatocellular carcinoma in patients with end-stage liver disease of diverse aetiologies. Methods : The prevalence of hepatic iron overload and hepatocellular carcinoma was examined in 5224 patients undergoing liver transplantation. Explant pathology reports were reviewed for the underlying pathological diagnosis, presence of hepatocellular carcinoma and degree of iron staining. The distribution of categorical variables was studied using Χ 2 tests. Results : Both iron overload and hepatocellular carcinoma were the least common with biliary cirrhosis (1.8 and 2.8% respectively). Hepatocellular carcinoma was the most common in patients with hepatitis B (16.7%), followed by those with hepatitis C (15.1%) and HH (14.9%). In the overall cohort, any iron overload was significantly associated with hepatocellular carcinoma ( P =0.001), even after adjustment for the underlying aetiology of liver disease. The association between hepatic iron content and hepatocellular carcinoma was the strongest in patients with biliary cirrhosis ( P <0.001) and hepatitis C ( P <0.001). Conclusions : Iron overload is associated with hepatocellular carcinoma in patients with end-stage liver disease, suggesting a possible carcinogenic or cocarcinogenic role for iron in chronic liver disease.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75573/1/j.1478-3231.2007.01596.x.pd

Castleman’s Disease and Posttransplant Lymphoproliferative Disorder after Liver Transplant: 3-Year Follow-Up

A 59-year-old male with a history of hepatitis C cirrhosis and history of hepatitis B exposure presented 8 months after orthotopic liver transplant (LT) with fever, fatigue, myalgia, night sweats, nonproductive cough, and shortness of breath. Bone marrow biopsy for pancytopenia was positive for Epstein-Barr virus (EBV) DNA. Lymph node biopsy for lymphadenopathy on imaging showed human herpes virus 8 (HHV8) associated Castleman’s disease. Treatment included valganciclovir, rituximab, and prednisone taper with eventual discontinuation. Quantitative HHV8 DNA was initially 611,000 DNA copies/mL and was later undetectable at 6 months following treatment and remained undetectable at 3-year follow-up

Randomized, double‐blind, controlled study of glycerol phenylbutyrate in hepatic encephalopathy

Glycerol phenylbutyrate (GPB) lowers ammonia by providing an alternate pathway to urea for waste nitrogen excretion in the form of phenylacetyl glutamine, which is excreted in urine. This randomized, double‐blind, placebo‐controlled phase II trial enrolled 178 patients with cirrhosis, including 59 already taking rifaximin, who had experienced two or more hepatic encephalopathy (HE) events in the previous 6 months. The primary endpoint was the proportion of patients with HE events. Other endpoints included the time to first event, total number of events, HE hospitalizations, symptomatic days, and safety. GPB, at 6 mL orally twice‐daily, significantly reduced the proportion of patients who experienced an HE event (21% versus 36%; P = 0.02), time to first event (hazard ratio [HR] = 0.56; P < 0.05), as well as total events (35 versus 57; P = 0.04), and was associated with fewer HE hospitalizations (13 versus 25; P = 0.06). Among patients not on rifaximin at enrollment, GPB reduced the proportion of patients with an HE event (10% versus 32%; P < 0.01), time to first event (HR = 0.29; P < 0.01), and total events (7 versus 31; P < 0.01). Plasma ammonia was significantly lower in patients on GPB and correlated with HE events when measured either at baseline or during the study. A similar proportion of patients in the GPB (79%) and placebo groups (76%) experienced adverse events. Conclusion: GPB reduced HE events as well as ammonia in patients with cirrhosis and HE and its safety profile was similar to placebo. The findings implicate ammonia in the pathogenesis of HE and suggest that GPB has therapeutic potential in this population. (Clinicaltrials.gov, NCT00999167). (Hepatology 2014;59:1073‐1083