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A 58-year-old man presented with jaundice 6 months after aortic valve replacement. Although non-A, non-B hepatitis was initially suspected, the final diagnosis of phenprocoumon (Marcoumar)-induced hepatitis progressing to cirrhosis was based on recurrence of jaundice after re-exposure to the drug, improvement after withdrawal and centrilobular necrosis with eosinophilic infiltration in the liver biopsy. Antibodies to hepatitis C virus were absent. The aortic valve was replaced by a bioprosthesis to eliminate the need for life-long anticoagulation.

To the Editor: Lamivudine is a registered nucleoside analogue which has been found to suppress hepatitis B virus (HBV) replication. In chronic HBV carriers the decrease in serum HBV DNA levels is followed by improvement in liver histology [1]. The emergence of viral resistance however may compromise this. A 54-year-old woman with treatment naive chronic HBV infection (biopsy stage cirrhose, HBeAg negative, HBV DNA 1.53 E7 geq/ml (Digene Hybrid Capture II assay), ALT 48 IU/l (normal ,31 IU/l) was treated with Lamivudine therapy for 95 weeks. Six weeks before therapy no variant viruses could be found. After 77 weeks of treatment HBV DNA-level levels increased 1.48 E7 geq/ml. Ten weeks later the ALT level increased to 106 IU/l. DNA sequence analyses were performed (Inno Lipa HBVDR, Innogenetics Ghent Belgium) starting from week 89. Analyses of the YMDD motif of the HBV polymerase gene showed a methionine-toisoleucine substitution; rtM204I (YIDD variant). After 95 weeks of treatment with Lamivudine treatment was ceased. HBV DNA level at that time was 2.85 E8 geq/ml and ALT level 44 IU/l. Patient was closely monitored and HBV DNA, ALT and DNA sequence analyses were repeated (Fig. 1). Although Lamivudine was withdrawn, while at week 18 post-dosing a mixture of wild type virus and YIDD variants were detected, at week 41 post-dosing a mixture of wild type-virus, YIDD and YVDD (rtM204V), was still detectable. Mutant detection dropped below the 5% range of the assay detection limit at week 54 post-dosing. Viral resistance to Lamivudine with the emergence of YMDD variants during long-term Lamivudine therapy is well described and considered to be a problem for future optimal therapy [2–4]. Also described is replacement of variant viruses by wild type virus 3–6 months after cessation of Lamivudine therapy [2,3]. This is however the first report of persistence of YMDD variants for at least 41 weeks. Our Letters to the Editor 304

chronic HBV (CHB) has been demonstrated. While the effect on viral suppression is clear, cases of renal dysfunction in patients receiving TDF have been reported. We analyzed TDF’s effect on renal function in patients with CHB in three large randomized clinical trials in patients mono-infected with HBV. Methods: Changes in renal parameters were evaluated in all patients in Gilead studies 102, 103 and 106 receiving TDF through 144 weeks. Baseline and on-treatment renal function was evaluated based on serum creatinine and estimated glomerular filtration rate (eGFR) by Cockcroft-Gault (CG). Renal events were defined as either a confirmed increase in serum creatinine by ≥0.5mg/dL from baseline, or a confirmed eGFR

1023 HEPATOCELLULAR CARCINOMA IN THE NETHERLANDS: CHANGES IN INCIDENCE, TREATMENT AND SURVIVAL DURING THE LAST TWO DECADES C.D.M. Witjes, S.A.W. van den Akker, O. Visser, H.E. Karim-Kos, E. de Vries, J.N.M. Ijzermans, R.A. de Man, J.-W. Coebergh, C. Verhoef. Hepatobiliary and Transplantation Surgery, Public Health, Erasmus MC, Rotterdam, Amsterdam Cancer Registry, Comprehensive Cancer Centre Amsterdam, Amsterdam, HepatoGastroenterology, Surgical Oncology, Erasmus MC, Rotterdam, The Netherlands E-mail: c.witjes@erasmusmc.nl

1023 HEPATOCELLULAR CARCINOMA IN THE NETHERLANDS: CHANGES IN INCIDENCE, TREATMENT AND SURVIVAL DURING THE LAST TWO DECADES C.D.M. Witjes, S.A.W. van den Akker, O. Visser, H.E. Karim-Kos, E. de Vries, J.N.M. Ijzermans, R.A. de Man, J.-W. Coebergh, C. Verhoef. Hepatobiliary and Transplantation Surgery, Public Health, Erasmus MC, Rotterdam, Amsterdam Cancer Registry, Comprehensive Cancer Centre Amsterdam, Amsterdam, HepatoGastroenterology, Surgical Oncology, Erasmus MC, Rotterdam, The Netherlands E-mail: c.witjes@erasmusmc.nl

Background: Despite its benign nature, hepatocellular adenomas (HA) have a potential for malignant degeneration or spontaneous rupture and bleeding. Therefore, surgical resection is the treatment of choice in selected patients. However, radio frequency ablation (RFA) could offer a viable alternative, and might prevent these patients from undergoing major hepatic surgery with associated morbidity and costs. Aim: To investigate the safety and efficacy of RFA for the treatment of HA. Methods: From 2000 to 2009, 168 patients diagnosed with HA in a tertiary hepato-biliary centre were included in a database. For patients undergoing RFA, clinicopathologic data with regard to diagnosis, treatment and outcome were collected. RFA was considered successful if no residual HA tissue was visualized on contrast enhanced CT or MRI 4–6 weeks post-RFA. Results: Of 61 patients undergoing treatment for HA, 17 patients (28%) underwent RFA. Mean age was 29 years. All patients were female with a history of hormonal contraceptive use. Nine patients (53%) had multiple HA, with a median number of 2 lesions (range 1–10) per patient. Median size of the largest HA at the time of RFA was 3.9 cm (range 1.5–6.7). 39 lesions were ablated in 25 sessions (open n=5, percutaneous n =20). Complete remission was acquired in eight patients after one (n =4) or two (n =4) RFAsessions. Another five patients (29%) had radiological evidence of residual HA tissue (≤15mm) bordering the thermal lesion, but due to low clinical importance no further treatment was administered. All of these lesions have remained stable or regressed during followup. Four patients are currently awaiting further therapy or followup. Post-operatively, one patient developed a liver abscess requiring re-intervention and one patient suffered from amajor but reversible complication related to concomitant hemi-hepatectomy. Median hospital stay was 7 days in the open group and 2 days in the percutaneous group. Conclusion: HA can be safely treated using both open and percutaneous RFA. However, often multiple sessions are required and signs of residual adenoma persist in some patients despite repetitive treatment. RFA might be especially beneficial for patients not amenable for surgery or those that would require major hepatic resection otherwise.

based format that includes discussion of history, physical examination and test results. In these case-based learning clinics, partners rapidly gain deep domain expertise in HCV as they collaborate with university specialists in hepatology, psychiatry and substance abuse in co-managing their patients. Results: Since June of 2003, 185 HCV knowledge network clinics have been conducted with 2640 case presentations of HCV patients. Of 327 patients treated via Project ECHO, 63.5% were members of a minority (Hispanic in 53.2%, Native American in 4.4%, and African American in 2.0%). Cirrhosis was present in 24.1% and depression in 41.4%. Genotype 1 was found in 61.1%, while the average log viral load was 5.94 ± 0.94. Early Virological Response was seen in 82/96 (85%), 61/74 (82%) and 105/ 113 (93%) of university, prison and rural patients. Significant adverse events (SAE) occurred in 24 (11.8%). Compared to patients without SAE, those with events were significantly older (48.7 ± 6.9 vs 43.6 ± 9.3 years; P=0.002); had lower serum albumin (3.69 ± 0.58 vs 4.08 ± 0.49 gm/dl; P=0.009), and platelet count (156 ± 75 vs 190 ± 81 x1000; P=0.047); and more likely to have cirrhosis of liver (50.0% vs 21.0%; P=0.002), and report a history of depression (66.7% vs 38.1%; P=0.008). Logistic regression showed that cirrhosis of liver [adjusted odds ratio (OR) 4.59; 95% confidence interval (CI) 1.66 12.7), depression (OR 4.77; 95% CI 1.66 13.7), were independent determinants of SAE (Hosmer-Lemeshow P= 0.927; ROC area 0.742). No differences in genotype distribution, SAE or response to treatment were found across sites. Conclusions: HCV treatment delivered to patients in rural areas and prisons using the Project ECHO model is as safe and effective as a university HCV clinic.

INTRAVENOUS MONOCLONAL ANTI-HBS (m-anti-HBs) IN CHRONIC HEPATITIS B (HBV) PATIENTS TREATED WITH LAMIVUDINE A.B. van Nunen l, R.A. de Man I, R.A. Heijtink 2, S.W. Schalm l 1Dept. of Hepatogastroenterology, University Hospital Rotterdam, The Netherlands. 2Dept. of Virology, University Hospital Rotterdam, The Netherlands. M-anti-HBs is a human monoclonal antibody, which recogniscs the stable adeterminant of HBsAg. The binding of m-anli-I-IBs to HBsAg is 200-fold higher than of HBIg, Anti-FIBs has been used successfully for virus neutralisation following liver transplantation. Furthermore it may have some immunostimulatory effects. We evaluated the safety and efficacy of m-anti-FIBs in lamivudine-treated chronic I-IBV patients during maximal virus suppression. Methods: Nine patients were included (7~. 2~). At screening 6/9 were HBV DNA negative by PCR, in 3 patients I-IBV DNA was detectable only by quantitative PCR techniques (QPCR), median (range) trealment with lamivudine was 35 (10-53) weeks. ALT was slightly devat~ in one patient. Patients received 8 gifts of m-anti-HBs over 2 weeks in a dose escalating way (20-20-40-40-80-80 mR) to reduc© possible side-effects due to the formation of insoluble immun¢complexes. Follow-up was 2 weeks. Neutralisation of HBsAg was mimick~ in an "inhibition in solution assay" CHeijtink et al). HBsAg and anti-FIBs were measured quantitatively by an experimental EIA. Results: In 2 patients a m-anti-HBs-related anaphylantie reaction occurred leading to withdrawal of therapy in 1 patient. This patient was excluded from further analysis of eftieany. In vitro m-anti-ttBs antibodies were partially effective in neutralisation of HBsAg. Depending on the monoelonsi antibody used at the solid phase a maximum percentage inhibition around 800 was obtained. During treatment HBsAg significantly declined. Median (range) HBsAg levels dropped from 2,24 (0,49-19,84) p.8/ml to 0,65 (0,01-14,08) Ixg/ml at end of foUow up (EFLD (Wilcoxon signed rank, p 90% decline was observed at EFU. M-anti-FIBs was still detectable at EFU in all patients varying between 0,04 and 8,8 lag/ml. One month after the EFU in all patients m-anti-HBs was undeteetable, two months later HBsAg had returned to pretreatment levels again. Conclusions: In 2/9 patients a SAE oceurred, leading to withdrawal of therapy in 1 patient. M-anti-HBs was only partially effective in binding HBsAg in this neutralisation assay. HBsAg declined significantly during therapy with m-enti-HBs and anti-HBs levels remained detectable until EFU. However no long-term effects were observed. Viral hepatitis: clinical aspects