Antti Oksanen

Liver Transplantation for Familial Amyloidotic Polyneuropathy (FAP): A Single‐Center Experience Over 16 Years

Orthotopic liver transplantation (LTx) is currently the only available treatment that has been proven to halt the progress of familial amyloidotic polyneuropathy (FAP). The aim of this study was to assess mortality and symptomatic response to LTx for FAP. All 86 FAP patients transplanted at our hospital between April 1990 and November 2005 were included in the study. Five patients underwent retransplantation. The 1‐, 3‐ and 5‐year patient survival rates in patients transplanted during 1996–2005 were 94.6%, 92.3% and 92.3%, respectively, a significant difference from the rates of 76.7%, 66.7% and 66.7%, respectively, during 1990–1995 (p = 0.0003). Multivariate analysis revealed that the age at the time of LTx (≥40 years), duration of the disease (≥7 years) and modified body mass index (mBMI) (<600) were independent prognostic factors for patient survival. A halt in the progress of symptoms was noted in most patients, but only a minority experienced an improvement after LTx. To optimize the posttransplant prognosis, LTx should be performed in the early stages of the disease, and close post‐LTx monitoring of heart function by echocardiography and of heart arrhythmia by Holter ECG is mandatory.

Outcome following liver transplantation for primary sclerosing cholangitis in the Nordic countries

Background: Primary sclerosing cholangitis (PSC) is the most common indication for liver transplantation in the Nordic countries. Because these patients are difficult to evaluate with regard to timing of liver transplantation, it is important to establish predictors of post‐transplant survival. Methods: Data from two groups of patients receiving liver allografts during 1982–2001 were recorded: (a) PSC patients and (b) comparison patients. Outcome following transplantation has been recorded for all patients. Regression analyses have been performed for PSC patients to analyse predictors of patient and graft survival. Results: A total of 245 PSC and 618 comparison patients received a first liver allograft in the period 1982 until the end of the study. The overall 1‐, 3‐ and 5‐year patient survival rates were 82%, 77% and 75%, and 80%, 77% and 74% in the PSC group and comparison group, respectively. Survival following transplantation has increased with time in both the PSC and the comparison group. Recent year of transplantation, no previous hepatobiliary surgery and a lower MELD score were predictors of survival following transplantation for PSC patients. PSC patients had a higher rate of re‐transplantations (13% versus 8%, Pu2005=u20050.01). Predictors of re‐transplantation in PSC patients were an episode of early rejection and vascular thrombosis. Conclusion: In PSC patients, year of transplantation, previous hepatobiliary surgery and MELD score are predictors of survival following transplantation and these patients are more frequently in need of re‐transplantation compared to the comparison group.

Health-related quality of life in patients with different stages of liver disease induced by hepatitis C

Objective. Patients with hepatitis C have been shown to have impaired health-related quality of life (HRQoL). The aim of this study was to determine HRQoL in patients in different stages of hepatitis C virus (HCV) and to compare HRQoL in HCV cirrhosis with non-HCV-induced cirrhosis. Material and methods. Out of 489 consecutive patients who fulfilled the inclusion criteria, 472 (96%) agreed to participate in the study: 158 patients with mild/moderate fibrosis with chronic hepatitis C (CHC group), 76 patients with HCV compensated cirrhosis (CC), 53 patients with HCV decompensated (DC) cirrhosis, 52 non-cirrhotic patients with sustained viral response (SVR), and a control group consisting of 32 patients with non-HCV CC and 101 with non-HCV DC who completed the Short Form-36 (SF-36) and EQ-5D questionnaire. Results. The CHC group had significantly lower SF-36 scores than healthy controls, with the exception of scores for the dimensions physical function and bodily pain. HCV patients with DC had lower scores in all SF-36 dimensions in comparison with those of the CHC group, as well as in physical and mental component summaries (p<0.001). In comparison with the CHC group, the HCV CC group had lower scores on the SF-36 general health dimension (p<0.05) and lower SF-36 physical component summary (PCS) scores (p<0.05). No major differences were seen in patients with HCV- and non-HCV-induced cirrhosis. Conclusions. Impairment in HRQoL in patients with HCV was associated with the severity of liver disease, patients with decompensated cirrhosis exhibiting the highest impairment in HRQoL. The etiology of liver disease does not seem to be important in determining HRQoL in cirrhosis.

Liver Transplantations in the Nordic Countries, 1982-1998: Changes of Indications and Improving Results

BACKGROUNDnLiver transplantation has become an established therapeutic option for patients with life-threatening liver disease. The aim of the present study was to analyse the results of and developments in liver transplantation in the Nordic countries during a 15-year period.nnnMETHODSnData on all patients receiving a liver allograft in the Nordic countries during 1982-98 and waiting list data for all patients listed for a liver transplantation after 1989 were obtained from the Nordic Liver Transplantation Registry.nnnRESULTSnA total of 1485 first liver transplantations were performed during 1982-98. The annual number of first liver transplantations increased steadily up to 1993, thereafter remaining around 150-170 per year. There are major differences between countries both in the number of transplants adjusted to populations performed per year, with more than twice as many performed in Sweden as in Norway, and in the relative distribution of patients in accordance with diagnosis. The number of patients more than 60 years old increased and comprised 13%-14% of the total patient population during 1996-98. Primary biliary cirrhosis, primary sclerosing cholangitis, acute hepatic failure, malignant liver disease, and alcoholic cirrhosis are the five most frequent diagnoses. The over-all 1-year patient survival probability has increased from 66% among patients receiving a transplant in 1982-89 to 83% in 1995-1998. The waiting time remains stable, with a median waiting time of 35 days during 1990-98. The mortality of patients while on the waiting list is 7.4% and is not increasing.nnnCONCLUSIONnResults of liver transplantation in the Nordic countries are very similar to those obtained in other countries. Waiting time and mortality remain low. There are, however, major differences between the countries both as to the number of transplantations performed and as to distribution of diagnoses.

Application of hepatocellular carcinoma surveillance in a European setting. What can we learn from clinical practice

Surveillance for hepatocellular carcinoma (HCC) in patients with cirrhosis is recommended in clinical guidelines. In real‐life management, surveillance rates below 20% have been reported from the United States. We aimed to determine the use of HCC‐surveillance in patients diagnosed with HCC in a European setting, and to identify the reasons for surveillance failures.

Pegylated interferon and ribavirin combination therapy for chronic hepatitis C virus infection in patients with Child-Pugh Class A liver cirrhosis

Objective. Pegylated interferon (peg-IFN) and ribavirin (RBV) treatment is less effective in patients with hepatitis C virus (HCV) and liver cirrhosis than in non-cirrhotic patients. Many patients with advanced liver disease have been excluded from the pivotal randomized controlled studies. The aim of this study was to investigate the efficacy and tolerability of combination therapy in unselected patients with Child-Pugh Class A liver cirrhosis at a Swedish university clinic. Material and methods. The virologic response and adverse events were retrospectively analyzed in 104 patients with HCV-associated Child-Pugh Class A liver cirrhosis who had been treated with peg-IFN and RBV. Results. Overall sustained virologic response (SVR) was achieved in 13% genotype 1-, 60% genotype 2-, and 31% genotype 3-infected patients. In treatment-naïve patients, the corresponding rates were 13%, 82%, and 38%, respectively. In 46% of patients, treatment was discontinued prematurely owing to lack of virologic response in the majority. Conclusions. SVR rates found in our study, in particular for genotype 1 patients (13%), were lower than those generally found in randomized controlled studies. For cirrhotic patients, new treatment alternatives are urgently needed to improve treatment outcome.

Expression of autoantibodies to specific cytochromes P450 in a case of disulfiram hepatitis

BACKGROUND/AIMSnImmunological mechanisms are involved in many adverse drug reactions. In certain forms of drug-induced hepatitis, patients have been reported to express specific autoantibodies to hepatic drug-metabolising enzymes. The alcohol deterrent disulfiram is associated with a low frequency of severe liver toxicity, including hepatitis, but the mechanism of the toxicity is unknown. We investigated whether autoantibodies to cytochrome P450 enzymes were expressed in the serum of a 28-year-old male patient, who developed hepatitis after 7 weeks of disulfiram treatment and in whom possible causes of hepatitis other than disulfiram had been ruled out.nnnMETHODSnPatient serum IgG reactivity was analysed by immunoblotting or ELISA against test antigens consisting of recombinant/purified human or rat liver P450 enzymes, or isolated rat liver microsomes.nnnRESULTSnA significant serum reactivity was found in immunoblotting against human cytochromes P450 1A2 and rat P450 3A1, using serum dilutions of up to 1:900 and 1:2400, respectively. In contrast, the reactivity against cytochromes P450 2E1, 2C9, 2D6, 3A4, and rat liver P450 reductase was either very low or undetectable. ELISA reactivity was low in general, indicating that the P450 epitopes were not surface exposed. Immunoblotting of rat liver microsomes revealed that autoantibodies recognised one major polypeptide corresponding to P450 3A. Autoantibody titres remained stable for at least 6 months after acute hepatitis. A similar reactivity was not found in any of ten control sera.nnnCONCLUSIONSnThe expression of autoantibodies directed against specific cytochromes P450 in a case of disulfiram hepatitis suggests that immunological mechanisms are involved in this adverse drug reaction, and that these P450 proteins should be evaluated as possible diagnostic test antigens in disulfiram hepatotoxicity.

Long-Term Outcome of Liver Transplantation in HIV-1-Positive Patients: 15-Year Follow-Up

Liver transplantation (LT) for patients with human immunodeficiency virus type-1 (HIV-1) infection has been associated with poor outcome. However, after the introduction of the highly active antiretroviral therapy, short-term patient survival after LT has improved significantly. We examined the long-term outcome of HIV-1-positive patients who underwent LT. Medical records were analysed in nine HIV-1-positive LT patients who underwent LT from August 1998 to May 2012. Eight were known to be HIV-1 positive at the time of listing for LT and had end-stage liver disease (ESLD) due to hepatitis C. One patient had primary biliary cirrhosis, and primary HIV-1 infection was found at the date of LT. Seven of the nine patients remain alive to date. So far, three have survived more than 12 years after LT. The overall patient survival rate for both five and 10 years is 77.8%. Four patients experienced acute rejection and six acquired biopsy-confirmed HCV recurrence. HIV-1 replication was effectively blocked during follow-up in all patients. We conclude that long-term survival of HIV-1-positive patients after LT can be achieved. Our study suggests that LT can offer an effective treatment option in selected HIV-1 infected patients with ESLD.