Editorial Board: Emmet B. Keeffe, MD (Chair); M. Eric Gershwin, MD;

Ira S. Goldman, MD; John L. Gollan, MD, PhD; Kris V. Kowdley, MD;

Paul Martin, MD; Marion G. Peters, MD

HEPATOLOGY WATCH®

MARCH 2004

HEPATOCELLULAR CARCINOMA (HCC)

Correlation of tumor recurrence with HBV genotype.  HBV carriers have an estimated 100-fold increased risk for developing HCC compared to an uninfected population. Surgery is a potentially curative therapy for HCC, but tumor recurrence following resection of HCC is a major limiting factor.  Jin-De Chen and colleagues at the National Taiwan University Hospital tested stored serum samples from 62 patients with HBV-related HCC who had undergone curative-intent surgery to investigate the influence of HBV genotype on the rate of tumor recurrence.  Sixty (96.8%) patients were found to have been infected with either genotype B or C.  With a mean follow-up of 26.3 ± 9.8 months, patients with genotype B had a lower tumor recurrence rate than patients with genotype C (22% vs. 46%; p = 0.04).  Cox regression analysis showed that multiplicity of hepatic tumor was independently associated with tumor recurrence (p = 0.02) and that genotype C and age were associated with borderline significance (p = 0.06) for predicting recurrence.  These data suggest that HBV patients with genotype C may have a greater rate of tumor recurrence following surgical resection of HCC.  Larger multicenter studies are needed to confirm these interesting observations.  (Chen J-D, et al. Clin Gastroenterol Hepatol 2004;2:64-71)

 

Cancer risk in patients with hereditary hemochromatosis (HH).  Maria Elmberg and others performed a population-based cohort study of 1,847 Swedish patients with HH and 5,973 of their first-degree relatives utilizing health and census registries.  Among those with HH there were 62 patients with HCC and 128 patients with nonhepatobiliary cancers.  The HH patients were at a 20-fold risk of HCC (standard incidence rate [SIR] of 21; 95% CI: 16-22) and an almost unaltered risk for other cancers (SIR, 1.2; 95% CI: 1.0-1.4).  The absolute risk of developing HCC at 10 years was 6% for men and 1.5% for women.  First degree relatives were at a modest increased risk of hepatobiliary cancer (SIR, 1.5; 95% CI: 1.0-2.4) and an unaltered risk of other cancers.  These findings indicate that patients with HH (especially men) in Sweden are at an increased risk for HCC. (Elmberg M, et al. Gastroenterology 2003;125:1733-1741)

 

INSULIN RESISTANCE AND NONALCOHOLIC STEATOHEPATITIS (NASH)

Metabolic markers of insulin resistance.  Insulin resistance occurs more commonly in overweight individuals and is associated with increased risk for type 2 diabetes mellitus and cardiovascular disease.  Tracey McLaughlin and colleagues performed a cross-sectional study that included 258 nondiabetic, normotensive overweight volunteers to evaluate the ability of metabolic markers to identify a subset of individuals who are insulin resistant. Overweight was defined as a body mass index >25 kg/m2 and insulin resistance was defined as being in the top tertile of steady-state plasma glucose concentrations.  Plasma triglyceride concentration, the ratio of triglyceride to high-density lipoprotein cholesterol concentrations, and insulin concentration were found to be the most useful metabolic markers for insulin resistance.  The ability of these measurements to identify insulin-resistant individuals was similar to that of criteria proposed by the Adult Treatment Panel III to diagnose the metabolic syndrome (sensitivity, 52%, and specificity, 85%).  This investigation showed that these 3 simple metabolic markers can help identify overweight individuals who are insulin resistant and at an increased risk for various adverse outcomes.  (McLaughlin T, et al. Ann Intern Med 2003;139:802-809)

 

Pilot study of pioglitazone.  Kittichai Promrat et al. conducted a pilot study of pioglitazone treatment for 48 weeks in 18 nondiabetic patients with NASH to evaluate the role of insulin-sensitizing therapy.  By 48 weeks, serum ALT levels had normalized in 72% of patients.  Glucose and free fatty acid sensitivity to insulin had improved uniformly and hepatic fat content and size had decreased by magnetic resonance imaging.  In addition, histological improvement occurred in two-thirds of patients.  Pioglitazone was well tolerated.  The main side effects were weight gain and increased adiposity.  These encouraging preliminary results warrant further study of insulin-sensitizing agents for the treatment of NASH.  (Promrat K, et al. Hepatology 2004;39:188-196)

 

TRANSPLANTATION

Results of the first year of the new liver allocation plan.  The Organ Procurement and Transplantation Network (OPTN) administered by the United Network for Organ Sharing (UNOS) recently changed the liver allocation policy in the US to a continuous disease severity scale that de-emphasized waiting time.  Richard Freeman and associates from OPTN/UNOS evaluated outcomes during the first year of this new liver allocation plan (2/27/02 - 2/26/03) compared to those during the year prior to its implementation (2/27/01 - 2/26/02).  They observed a 12% reduction in new liver transplant waiting list registrations during the first year of the new plan.  The new plan has also been associated with a 3.5% decrease in waiting list death rate (p = 0.076) and a 10.2% increase in cadaveric transplants (p <0.001).  These results were evenly distributed across demographic and medical strata.  Early patient and graft survival rates remain unchanged.  These findings demonstrated that the new system has resulted in reduced registrations and improved transplantation rates without increasing mortality rates.  (Freeman RB, et al. Liver Transpl 2004;10:7-15)

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