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®

SEPTEMBER 2003

 

CHRONIC HEPATITIS C VIRUS (HCV) INFECTION

Determination of sustained virologic response (SVR).  The standard definition of a SVR is undetectable serum HCV RNA 24 weeks after the completion of therapy.  Stefan Zeuzem et al determined HCV RNA in 1,441 patients with chronic hepatitis C by polymerase chain reaction (PCR) at 4-week intervals during and after the completion of 48 weeks of treatment with either standard or pegylated interferon a-2a to investigate if sensitive molecular tests permit earlier determination of SVR.  End-of-treatment response and SVR were achieved in 624 and 342 patients, respectively.  Relapse was most frequently discovered at weeks 52 and 56 (4 and 8 weeks post-treatment).  Only 6 patients (2%) became HCV RNA positive between weeks 60 and 72 (12 and 24 weeks post-treatment).  Multivariate analysis failed to identify risk factors predictive of early relapse.  The low relapse rate after week 60 using PCR suggests that 12 weeks of follow-up is sufficient to determine SVR.  (Zeuzem S, et al. J Hepatol 2003;39:106-111)

 

Incidence of HCV in patients with type 2 diabetes.  HCV infection is known to be common among patients with type 2 diabetes.  Shruti Mehta and others performed a prospective analysis of subjects enrolled into the Atherosclerosis Risk in Communities Study (ARIC) to examine if persons who acquired type 2 diabetes were more likely to have antecedent HCV infection.  Among 1,084 adults, 548 subjects developed diabetes over 9 years of follow-up.  The overall prevalence of HCV in this population was 0.8%.  Among subjects categorized as high-risk for diabetes, persons who had HCV infection were >11 times more likely to develop diabetes.  Among subjects categorized as low-risk for diabetes, no increased incidence of diabetes was detected in those with HCV infection.  These findings indicate that HCV infection may increase the risk for the development of type 2 diabetes in those with risk factors for diabetes.  (Mehta SH, et al. Hepatology 2003;38:50-56)

 

Favorable prognostic effect of interferon (IFN) therapy.  Fumio Imazeki and colleagues at Chiba University in Japan analyzed data from 355 chronic HCV patients treated with IFN and 104 chronic HCV patients who were not treated.  Patients were followed for 8.2 ± 2.9 years (range, 7-183 months).  Fourteen percent (15) of patients who were not given IFN died while 9% (33) of IFN-treated patients died during follow-up.  Death was liver related in 67% of cases and due to HCC in 52% of patients.  Multivariate Cox regression analysis identified IFN treatment and SVR to be independently associated with a lower risk for death.  These results suggest that IFN therapy results in a long-term survival benefit in patients with chronic hepatitis C, especially in those who achieve a SVR.  (Imazeki F, et al. Hepatology 2003;38:493-502)

 

HEPATOCELLULAR CARCINOMA (HCC)

HFE C282Y heterozygosity.  Previous studies have suggested that chronic iron overload may contribute to the pathogenesis of HCC. Claus Hellebrand and coworkers at the University of Regensburg in Germany analyzed 137 HCC patients (without a history of hereditary hemochromatosis [HH]), 107 patients with cirrhosis (without HCC), and 126 healthy controls for the C282Y and H63D mutations of the HFE gene.  Heterozygosity for C282Y was found in 17 (12.4%) HCC patients, 4 (3.7%) cirrhotic patients, and 6 (4.8%) healthy controls (p <0.05).  There were no differences observed in the frequency of the H63D mutation in the 3 groups.  C282Y heterozygote HCC patients had higher levels of serum ferritin and transferrin saturation as well as increased stainable intrahepatic iron compared to C282Y wild-type patients.  In an accompanying editorial, George Ioannou and Kris Kowdley relate that this study has several limitations.  Firstly, hepatic iron staining was used to compare iron content instead of quantitative hepatic iron content.  In addition, hepatic iron content in cirrhotic livers with HCC was not compared to the hepatic iron content in cirrhotic livers without HCC to examine whether HCC was independently associated with increased iron stores.  Furthermore, there was a surprisingly low prevalence of C282Y heterozygosity in the control groups.  However, the study by Hellebrand et al. adds to the growing body of evidence indicating a potential role of iron in hepatic carcinogenesis.  Investigation of the effect of iron depletion therapy for cirrhotic patients with mild to moderately increased hepatic iron stores is warranted.  (Hellebrand C, et al. Clin Gastroenterol Hepatol 2003;1:279-284 and Ioannou GN, Kowdley KV. Clin Gastroenterol Hepatol 2003;1:246-248)

 

PRIMARY SCLEROSING CHOLANGITIS (PSC)

Long-term follow-up.  While PSC is increasingly diagnosed in pediatric patients, its long-term prognosis is unknown.  Thus, a longitudinal cohort study was conducted at the Mayo Clinic in Rochester to examine the long-term outcomes of children with PSC.  Fifty-two children were seen over 20 years and were followed for up to 16.7 years.  At presentation, two-thirds of patients were symptomatic, 81% had concomitant inflammatory bowel disease, 35% had overlapping autoimmune hepatitis, and all patients had elevated gamma-glutamyl transpeptidase levels.  During follow-up, one child died and 11 children underwent liver transplantation for end-stage PSC.  The median liver transplantation-free survival time was 12.7 years and overall survival for children with PSC was shorter compared to age- and gender-matched US children (p <0.001).  Multivariate Cox regression analysis identified lower platelet count, splenomegaly, and older age to be predictive of shorter survival.  These data show that PSC decreases survival in children despite current pharmacologic therapy. (Feldstein AE, et al. Hepatology 2003;38:210-217)

 

REVIEW: Management of ascites.  Kevin Moore et al. reviewed guidelines developed by The International Ascites Club at a recent consensus conference for the management of early to refractory ascites.  (Moore KP, et al. Hepatology 2003;38:258-266)

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