Hepatitis: Friman S

Lindh M, Uhnoo I, Bläckberg J, Duberg AS, Friman S, Fischler B, Karlström O, Norkrans G, Reichard O, Sangfeldt P, Söderström A, Sönnerborg A, Weiland O, Wejstål R, Wiström J. · Department of Infectious Diseases, Sahlgrenska University Hospital, Göteborg, Sweden. · Scand J Infect Dis. · Pubmed #18584530 No free full text.

Abstract: The main goal for treatment of chronic hepatitis B is to prevent complications such as liver cirrhosis or hepatocellular carcinoma. Knowledge from population studies of the long-term risk of chronic HBV infection, as well as the recent introduction of pegylated interferon and additional nucleoside analogues has changed the therapeutic situation. Recently, a Swedish expert panel convened to update the national recommendations for treatment. The panel recommends treatment for patients with active HBV infection causing protracted liver inflammation or significant liver fibrosis, verified by liver histology. In general, pegylated interferon alpha-2a is recommended as first-line treatment, in particular for HBeAg-positive patients with HBV genotypes A or B. Among nucleoside analogues, entecavir is the first choice and adefovir or tenofovir can be used as alternatives. Lamivudine monotherapy is not recommended due to the high risk of resistance development. Combinations of nucleoside analogues such as tenofovir and lamivudine or emtricitabine are alternatives for patients with non-response or infection with resistant variants, or as first choice for patients with advanced liver disease. Nucleoside analogue treatment should be monitored to detect primary non-response and virological breakthrough. Special recommendations are given for HBV/HIV coinfected patients, immunosuppressed patients, children, and for treatment before and after liver transplantation. The present guideline is translated from Swedish, where it is published on the MPA and RAV websites (www.mpa.se and www.rav.nu.se) including 7 separate papers based on thorough literature search. The complete reference list can be received from the Medical Products Agency upon request.

Melum E, Friman S, Bjøro K, Rasmussen A, Isoniemi H, Gjertsen H, Bäckman L, Oksanen A, Olausson M, Duraj FF, Ericzon BG. · Department of Medicine, Rikshospitalet-Radiumhospitalet Medical Center, Oslo, Norway. · J Hepatol. · Pubmed #17714825 No free full text.

Abstract: BACKGROUND/AIMS: Liver transplantation (LTX) is the only curative treatment for end-stage liver disease caused by hepatitis C (HCV). Hepatocellular carcinoma (HCC) is common in patients with HCV cirrhosis. METHODS: Two hundred and eighty-two HCV patients listed for LTX in the Nordic countries in a 17-year period were included. For comparison a group of patients with non-viral chronic liver disease (n=1552) was used. RESULTS: Two hundred and fifty-three (90%) patients received a first liver allograft. HCC was found in 38% of the explanted livers. Survival at 1, 3 and 5years was 82%, 69% and 61% vs. 85%, 80% and 76% for the comparison group (p<0.0001), this survival difference was also evident when excluding patients with HCC (p=0.007). HCV patients with HCC had 1, 3 and 5year survival of 73%, 52% and 46% compared with 88%, 80% and 71% for the HCV patients without HCC (p=0.0005). In an intention-to-treat analysis (from time of acceptance to the waiting list) HCV was also associated with an impaired survival. CONCLUSIONS: HCV cirrhosis, which is now also an important indication for LTX in the Nordic countries, and significantly impairs survival following LTX. Concomitant HCC and donor age are the two most important factors contributing to an impaired survival.

Lukes DJ, Herlenius G, Rizell M, Mjörnstedt L, Bäcman L, Olausson M, Friman S. · Department of Surgery and Transplantation, Sahlgrenska University Hospital, Göteborg, Sweden. · Transplant Proc. · Pubmed #17098034 No free full text.

Abstract: PURPOSE: Liver transplantation (OLT) is an established treatment with excellent early outcome. However, the long-term results are hampered by side effects of immunosuppression, cardiovascular morbidity, recurrent disease, and chronic rejection. We analyzed causes of late death (>/=2 years post-OLT) in 679 consecutive primary recipients in our institution. MATERIALS AND METHODS: A total of 679 primary OLT recipients including those retransplanted within 3 months between January 1985 and August 2005 were identified; 460 (67.7%) patients survived >/=2 years. The indications were cholestatic disease (35.1%), postviral (11.4%), alcoholic (12.9%), fulminant hepatic failure (7.0%), cryptogenic (3.1%), autoimmune hepatitis (4.8%), malignancy (7.7%), and others (18.0%). Sixty three patients (9.3%) died >/=2 years post-OLT. For 51 patients, sufficient records were present to establish the cause of death. RESULTS: Four hundred sixty (67.7%) patients survived >/=2 years. Their median age was 58 years with, 43.7% older than 60 and 11.1% older than 70 years. Sixty three patients (9.3%) died at a median time of 69 +/- 4.8 months post-primary OLT; 49.1% died of malignancy and 13.7% of vascular complications and infectious complications respectively. CONCLUSIONS: Late mortality in our material is mainly due to malignant disease. Compared to other published reports on late mortality, the proportion of malignancy, especially recurrent, as cause of late death is higher. This might reflect a more generous approach toward accepting older patients and a higher proportion of patients with various malignant diseases accepted for OLT.

Levy G, Grazi GL, Sanjuan F, Wu Y, Mühlbacher F, Samuel D, Friman S, Jones R, Cantisani G, Villamil F, Cillo U, Clavien PA, Klintmalm G, Otto G, Pollard S, McCormick PA. · University Health Network, Toronto General Hospital, Toronto, ON, Canada. · Liver Transpl. · Pubmed #17004259 links to  free full text

Abstract: The LIS2T study was an open-label, multicenter study in which recipients of a primary liver transplant were randomized to cyclosporine microemulsion (CsA-ME) (Neoral) (n = 250) (monitoring of blood concentration at 2 hours postdose) C2 or tacrolimus (n = 245) (monitoring of trough drug blood level [predose]) C0 to compare efficacy and safety at 3 and 6 months and to evaluate patient status at 12 months. All patients received steroids with or without azathioprine. At 12 months, 85% of CsA-ME patients and 86% of tacrolimus patients survived with a functioning graft (P not significant). Efficacy was similar in deceased- and living-donor recipients. Significantly fewer hepatitis C-positive patients died or lost their graft by 12 months with CsA-ME (5/88, 6%) than with tacrolimus (14/85, 16%) (P < 0.03). Recurrence of hepatitis C virus in liver grafts was similar in each group. Based on biopsies driven by clinical events, the mean time to histological diagnosis of hepatitis C virus recurrence was significantly longer with CsA-ME (100 +/- 50 days) than with tacrolimus (70 +/- 40 days) (P < 0.05). Median serum creatinine at 12 months was 106 mumol/L with CsA-ME and with tacrolimus. More patients who were nondiabetic at baseline received antihyperglycemic therapy in the tacrolimus group at 12 months (13% vs. 5%, P < 0.01). Of patients who were diabetic at baseline, more tacrolimus-treated individuals required anti-diabetic treatment at 12 months (70% vs. 49%, P = 0.02). Treatment for de novo or preexisting hypertension or hyperlipidemia was similar in both groups. In conclusion, the efficacy of CsA-ME monitored by blood concentration at 2 hours postdose and tacrolimus in liver transplant patients is equivalent to 12 months, and renal function is similar. More patients required antidiabetic therapy with tacrolimus regardless of diabetic status at baseline.

Gustafsson BI, Backman L, Friman S, Herlenius G, Lindnér P, Mjornstedt L, Olausson M. · Transplantation and Liver Surgery Unit, Department of Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. · Transplant Proc. · Pubmed #16797326 No free full text.

Abstract: Retransplantation (re-TX) is the only available therapy for irreversible liver graft dysfunction. The outcome of a second procedure depends upon several factors, some of which are not defined at the time of the decision to retransplant. This study is an analysis of all re-TX of the liver performed at our unit between January 1995 and January 2004. Among the 474 liver TX were 55 (11.6%) re-TX in 47 patients. We studied (1) diagnosis at first TX; (2) indication for re-TX and time lapse; (3) donor age and cold ischemia time (CIT); (4) duration of operation, peroperative bleeding, and complications; (5) ICU and ward periods; and (6) patient and graft survivals. Patients who underwent re-TX did not differ from those transplanted once with regard to age, gender, or diagnosis. The indications for re-TX were roughly one-third biliary tract complications/chronic rejection, one-third hepatic artery thrombosis, and one-third others, including primary nonfunction, acute rejection, portal vein thrombosis, sepsis, and B/C hepatitis. The re-TX were "urgent" in 29 and "elective" in 26 cases. Complications were common; about half of the patients were reoperated due to bleeding or biliary problems. To date (May 2004), 15 patients have died (12 "urgent" and 3 "elective"), of whom 5 had well functioning grafts. In summary, liver re-TX is a complicated procedure associated with significant mortality and morbidity, but considering that the actual patient group has a poor prognosis without re-TX, the results are nevertheless encouraging.

Castedal M, Felldin M, Bäckman L, Olausson M, Friman S. · Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. · Transplant Proc. · Pubmed #16298583 No free full text.

Abstract: We present our results of preemptive treatment with pegylated interferon and ribavirin after liver transplantation for hepatitis C cirrhosis. PATIENTS: Between September 2001 and August 2002, four patients were started on combination therapy with pegylated interferon-alpha-2b (1microg/kg weekly) and ribavirin (400-1000 mg/d) 3 to 4 weeks' posttransplant. Treatment was continued for 6 (genotype 3a, 2 patients) or 12 (genotype 1b, 2 patients) months. Virologic and biochemical responses as well as side effects were evaluated. RESULTS: Two patients (genotype 3a) became HCV (hepatitis C virus)-RNA negative after 3 months of therapy and are persistently negative 20 and 14 months after end of therapy. One patient (genotype 1b) became HCV-RNA negative 6 months after start of treatment, but therapy had to be withdrawn after 9 months owing to fatigue and suspicion of angina pectoris. One patient who was later retransplanted because of hepatic artery thrombosis discontinued therapy after 2.5 months owing to anemia, leukopenia, and no signs of HCV-RNA reduction. Interestingly, two of the responders were nonresponders prior to liver transplant. Median ALT levels at start of therapy were 98 U/L (r = 60-126) and 12 months later 40 U/L (r = 24-58) (n = 4). No rejection episode was detected. CONCLUSION: In patients liver-transplanted due to HCV-cirrhosis, combination therapy with pegylated interferon and ribavirin can be effective and safe in the early posttransplant period, thus preventing recurrent hepatitis C.

Friman S. · Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden. · Transplant Proc. · Pubmed #16298582 No free full text.

Abstract: Cirrhosis due to hepatitis C is currently the most common indication for liver transplantation in the United States as well as in Europe. The prognosis for patients transplanted due to hepatitis C has changed over the years. Today there is growing concern as to the prognosis of these patients and how we should treat them. This is an overview of the developments in this field concerning treatment of recurrence and the role of preemptive treatment.

Castedal M, Siewert-Delle A, Olausson M, Friman S. · Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. · Transplant Proc. · Pubmed #12644153 No free full text.

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Cahlin C, Olausson M, Friman S. · Department of Transplantation and Liver Surgery, Sahlgrenska University Hospital, Göteborg, Sweden. · Transplant Proc. · Pubmed #11406214 No free full text.

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Cahlin C, Olausson M, Friman S. · Department of Transplantation and Liver Surgery, Sahlgreńska University Hospital, Göteborg, Sweden. · Transplant Proc. · Pubmed #11406213 No free full text.

This publication has no abstract.