Iron reduction as an adjuvant to interferon therapy in patients with chronic hepatitis C who have previously not responded to interferon: A multicenter, prospective, randomized, controlled trial

Adrian M. Di Bisceglie, Herbert L. Bonkovsky, Sanjiv Chopra, Stephen Flamm, Rajender K. Reddy, Norman Grace, Paul Killenberg, Christine Hunt, Carlo Tamburro, Anthony S. Tavill, Roy Ferguson, Edward Krawitt, Barbara Banner, Bruce R. Bacon – 30 December 2003 – Hepatic iron concentration has consistently been observed as being directly correlated with the response to interferon therapy in chronic hepatitis C virus (HCV).

High‐lose and long‐term therapy with interferon‐alfa inhibits tumor growth and recurrence in nude mice bearing human hepatocellular carcinoma xenografts with high metastatic potential

Lu Wang, Zhao‐You Tang, Lun‐Xiu Qin, Xiao‐Feng Wu, Hui‐Chuan Sun, Qiong Xue, Sheng‐Long Ye – 30 December 2003 – Postoperative recurrence of human hepatocellular carcinoma (HCC) is the major issue that must be addressed to further improve prognosis. This study was undertaken to investigate the effects of interferon‐alfa‐1b (IFN‐α‐1b) on recurrent tumor and metastasis after curative resection in nude mice bearing an HCC xenograft with high metastatic potential. Tumor tissues from LCI‐D20, a metastatic model of HCC in nude mice, were orthotopically implanted in 105 nude mice.

Mrp2 is essential for estradiol‐17β(β‐D ‐glucuronide)–induced cholestasis in rats

Liyue Huang, Johan W. Smit, Dirk K. Meijer, Mary Vore – 30 December 2003 – The present study evaluates the roles of the multidrug resistance‐1 P‐glycoprotein, Mdr1a/1b, the bile salt export pump (Bsep), and the multidrug resistance‐associated protein‐2 (Mrp2) in mediating cholestasis induced by estradiol‐17β(β‐d ‐glucuronide) (E2 17G). Administration of [3H]E2 17G (18 nmol/g body weight) gave a similar degree of cholestasis and biliary excretion of E2 17G‐equivalents in wild‐type and Mdr1a‐/‐/1b‐/‐ mice.

Low frequency of cirrhosis in a hepatitis C (genotype 1b) single‐source outbreak in germany: A 20‐year multicenter study

Manfred Wiese, Frieder Berr, Michael Lafrenz, Heiner Porst, Ute Oesen – 30 December 2003 – From August 1978 until March 1979, 14 batches of anti‐D immune globulin contaminated with hepatitis C virus (HCV) genotype 1b (20,000‐480,000 copies/dose) from a single erythrocyte donor had been administered for prophylaxis of rhesus isoimmunization throughout East Germany. All 2,867 women involved had been recalled after January 12, 1979 for repeated screening of alanine transaminase (ALT). They were prospectively followed in regional centers.

Results of surgical and nonsurgical treatment for small‐sized hepatocellular carcinomas: A retrospective and nationwide survey in Japan

Shigeki Arii, Yoshio Yamaoka, Syunji Futagawa, Kyoichi Inoue, Kenichi Kobayashi, Masamichi Kojiro, Masatoshi Makuuchi, Yasuni Nakamura, Kiwamu Okita, Ryusaku Yamada – 30 December 2003 – Hepatic resection (HX), percutaneous ethanol injection (PEI), and transcatheter arterial embolization (TCAE) have all been used in the treatment of patients with small‐sized hepatocellular carcinomas (HCCs). However, the indications for these therapeutic modalities remain unclear.

Impaired protein maturation of the conjugate export pump multidrug resistance protein 2 as a consequence of a deletion mutation in dubin‐johnson syndrome

Verena Keitel, Jürgen Kartenbeck, Anne T. Nies, Herbert Spring, Manuela Brom, Dietrich Keppler – 30 December 2003 – The Dubin‐Johnson syndrome is an inherited disorder characterized by conjugated hyperbilirubinemia. The deficient hepatobiliary transport of anionic conjugates is caused by the absence of a functional multidrug‐resistance protein 2 (MRP2, symbol ABCC2) from the apical (canalicular) membrane of hepatocytes. Mechanisms underlying this deficiency may include rapid degradation of mutated MRP2 messenger RNA (mRNA) or impaired MRP2 protein maturation and trafficking.

Different costimulation signals used by CD4+ and CD8+ cells that independently initiate rejection of allogenic hepatocytes in mice

Donghong Gao, Jiashun Li, Charles G. Orosz, Ginny L. Bumgardner – 30 December 2003 – The current study evaluated the role of CD40/CD40 ligand (CD40L) and CD28/B7 costimulation signals during alloimmune responses independently mediated by CD4+ or CD8+ T cells. Allogeneic hepatocytes were transplanted into CD8 or CD4 knock out (KO) mice under cover of costimulatory blockade. Rejection of FVB/N (H‐2q) hepatocytes occurred by day 10 posttransplant in untreated CD8 or CD4 KO (H‐2b) mice.

Silymarin in the treatment of patients with primary biliary cirrhosis with a suboptimal response to ursodeoxycholic acid

Paul Angulo, Tushar Patel, Roberta A. Jorgensen, Terry M. Therneau, Keith D. Lindor – 30 December 2003 – Ursodeoxycholic acid (UDCA) is a safe and effective medical therapy for most patients with primary biliary cirrhosis (PBC), but some patients show an incomplete response. Silymarin is a potent antioxidant with immunomodulatory and antifibrotic properties. The aim of this study was to evaluate the safety and assess the efficacy of silymarin in patients with PBC who had shown a suboptimal response to UDCA.

Prevalence of obesity and diabetes in patients with cryptogenic cirrhosis: A case‐control study

Asma Poonawala, Satheesh P. Nair, Paul J. Thuluvath – 30 December 2003 – It has recently been suggested that nonalcoholic steatohepatitis (NASH) is an under‐recognized cause of cryptogenic cirrhosis (CC) on the basis of higher prevalence of obesity and type II diabetes among these patients. To test this hypothesis, we studied 65 consecutive patients with advanced cirrhosis (Child‐Pugh Score ≥ 7) of undetermined etiology (CC) from our active waiting list for liver transplantation in January 1993, 1996, and 1999.

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