Volume 68 - 2005 - Fasc.1 - Symposium
Longitudinal prospective study on quality of life and psychological distress before and one year after liver transplantation
Background : The impact of liver disease and medical complica- tions on quality of life (QOL) and psychological distress before and after liver transplantation (LT) is a matter of growing inter- est.
Methods : In a longitudinal prospective study, perceived QOL (LEIPAD Quality of Life test) and psychological distress (Brief Symptom Inventory, BSI) were assessed in 25 cirrhotic patients when they were listed for LT and 1, 3, 6 and 12 months after LT. Patients were also evaluated for medical complications and blood levels of immunosuppressive agents.
Results : Overall QOL and psychological distress improved sig- nificantly and rapidly in most domains from the first month and up to a year after LT. Medical complications and immunosup- pressive agents did not correlate with any changes in QOL and psychological distress after LT.
When patients were divided according to liver disease etiology : 1. HCV patients listed for LT had worse QOL levels than the group of patients as a whole or the alcoholic liver disease (ALD) patients ; 2. HCV patients reported a significant improvement in QOL only 6 and 12 months after LT, and still suffered more psy- chological distress 12 months after surgery ; 3. in ALD patients, overall QOL and psychological distress improved significantly at all follow-up points after LT ; 4. HCV patients reported a worse QOL and greater psychological distress 1 and 3 months after LT than the group as a whole or the ALD patients (p < 0.05).
Conclusions : Liver transplantation improves QOL and psycho- logical distress in most recipients, but not in the early stages after LT in patients transplanted for HCV cirrhosis. (Acta gastroenterol. belg., 2005, 68, 19-25).
Genes and metals : a deadly combination
Wilson's disease is an autosomal recessive disease of copper metabolism, with an estimated prevalence of 1:3000O.The most common presentations of WD are liver disease and neurological disturbance. For many years the diagnosis was based on the results of several clinical and biochemical tests, for which several limitations had been reported. In recent years the developments of new techniques in genetic and molecular biology have provided useful tools in the diagnosis of Wilson's disease. However, the presence of several mutations and the fact that most patients are compound heterozygote means that the problem is not completely resolved. Chelators and zinc salts have been largely used in the treatment of WD patients with a favorable outcome, but the debate continues as to the agents of first choice. Liver transplan- tation is a cure for patients with decompensated liver disease but its effect on the neurological outcome is still not clear. (Acta gastro- enterol. belg., 2005, 68, 26-32).
Genetic hemochromatosis update
Hereditary Hemochromatosis is an autosomal recessive disease, characterized by chronic iron overload. It is mainly due to muta- tions of the HFE-1 gene. In the large majority of patients, the sub- stitution of tyrosine for cysteine at amino acid 282 (C282Y) is found at the homozygous state. Since the HFE-1 hemochromatosis identification, several other entities of iron overload have been individualized. In the present article, the frequency, penetrance and pathophysiology of HFE-1 hemochromatosis as well as vari- ous clinical presentations resulting from different mutations affecting different proteins involved in iron metabolism are described. (Acta gastroenterol. belg., 2005, 68, 33-37).
Guidelines for the management of chronic hepatitis C in patients infected after substance use
These guidelines, from the Belgian Association for the Study of the Liver (BASL), contain evidence-based recommendations for the management of chronic hepatitis C (CHC) infection in substance users.
Substance use in Belgium : Prevalence and management
Substance use is emerging in Belgium. The 'typical user' starts at a young age. Polydrug use has become very common. Cannabis and alcohol are the most frequently used substances among the school population. Heroin and cocaine are the most frequently injected drugs.
Sharing of injecting material and paraphernalia is reported to happen in half of the subjects injecting drugs. Substance use causes a lot of adverse organic, social and psychiatric events. Management of substance use consists of information, drug-free treatment and harm reduction, including substitution and mainte- nance programs. The management of care in Belgium differs between the regions. (Acta gastroenterol. belg., 2005, 68, 46-49).
The epidemiology of hepatitis C among injecting drug users in Belgium
In industrialised countries, injecting drug use is currently the most important risk factor for infection with hepatitis C, resulting in high prevalence rates of hepatitis C among injecting drug users. To contain the hepatitis C epidemic major efforts should be done to prevent new infection among injecting drug users. Monitoring infection rates are crucial as it may provide feedback on the effec- tiveness of interventions. In this article the epidemiology of hepati- tis C among injecting drug users in Belgium is briefly reviewed. More specifically the prevalence of anti-HCV antibodies, the prevalence of co-infections, the proportion of chronic HCV carri- ers, the distribution of genotypes and preventive measures among injecting drug users in Belgium are discussed and compared to the situation elsewhere in Western Europe. (Acta gastroenterol. belg., 2005, 68, 50-54).
Treatment of hepatitis C viral infections in substance abusers
Aims : To examine the evidence for excluding chronic hepatitis C (CHC) patients with substance abuse from treatment with inter- feron (IFN) and ribavirin.
Methods : We reviewed clinical trials focussing on the treatment of chronic hepatitis C of patients with substance abuse between 2001 and 2004. Ten clinical trials concerning antiviral treatment in substance abusers were described of which six were controlled ones. There were no randomised trials. There was one controlled multi-centre trial. One trial used pegylated IFN.
Results : In the total group of substance abusers the sustained viral response (SVR) and the adherence was not different from control groups. In former drug users, active drug users and patients taking substitution therapy for opioid dependence the sustained viral response and adherence was not different from control populations. However, non-substituted active drug users seemed more likely to be lost to follow-up. Discontinuation of treatment occurred most frequently during the first 8 weeks of therapy. Neurobehavioural changes leading to depression started in the first 8 weeks of treatment. Although follow-up periods after SVR were short, the currently described re-infection rate occur- ring in active intravenous drug users remains low.
Conclusions : There is no evidence to withhold antiviral treat- ment against HCV in active substance abusers. It seems important to advise to start substitution therapy in non-substituted active drug users, increase substitution therapy dose in substituted patients and treat depression as early as possible. More prospec- tive controlled trials on HCV treatment in active and difficult-to- reach substance users are needed. (Acta gastroenterol. belg., 2005, 68, 55-67).
Hepatitis C, interferon alpha and psychiatric co-morbidity in intravenous drug users (IVDU) : Guidelines for clinical practice
The evidence regarding the co-morbidity of chronic hepatitis C, psychiatric illness and intravenous drug abuse is reviewed from the literature. Also the occurrence and the treatment of psychi- atric side effects during treatment with interferon in patients with a history of drug abuse are reviewed.
There is insufficient evidence for a specific hepatitis C induced depression or fatigue, but a direct link between hepatitis C and cerebral dysfunction is not excluded. Immune system activation rather than drug use may explain cerebral symptoms. In HCV positive substance users anxiety and depression are more preva- lent than in HCV negative substance users.
During treatment with regular or pegylated (PEG) interferon depression is a frequent side effect (ca 30%) and occurs indepen- dently from pre-existing psychiatric disorders or drug abuse. A history of drug abuse per se does not increase the risk of depres- sion as a side effect of interferon treatment. It is extremely impor- tant to monitor symptoms of depression in the early weeks of treatment and to start antidepressant treatment as early as possi- ble. Antidepressants should be continued throughout the interfer- on treatment period.
There are insufficient data to assess these situations in which preventive antidepressant treatment should be started before interferon treatment. Clinical judgement can, however, lead to preventive antidepressant treatment, even at subclinical levels of depression. A cut off score of > 10 on the Beck Depression Inventory before interferon treatment is associated with a higher risk of depression during treatment.
Both selective serotonin reuptake inhibitors and other classes of antidepressants can be used. (Acta gastroenterol. belg., 2005, 68, 68- 80).
Methadone and buprenorphine maintenance therapies for patients with hepati- tis C virus infected after intravenous drug use
Heroin addiction is a chronic relapsing disease that is difficult to cure, but stabilisation and harm reduction can importantly increase the life time expectancy and the quality of life of the patient, his immediate vicinity and society in general. Currently, no proven effective pharmacological interventions are available for cocaine addiction, and treatment has to rely on existing cogni- tive behaviour therapies combined with contingency management strategies. Substitution therapy, however, is effective in caring for heroin addicts. Methadone is a synthetic opioid that counteracts withdrawal symptoms of heroin. Buprenorphine is a derivative of the morphine alkaloid, thebaine, and is a partial opioid agonist at the µ opioid receptor in the nervous system. A substitution treat- ment program effectively reduces and often eliminates heroin injection behaviour, rendering patients more socially stabilised. Reduction in the number of viral co-infections can be observed. Methadone undergoes oxidative biotransformation in the liver, but is also stored in the liver and released into the blood in unchanged form. The usual dose can be continued in patients with stable chronic liver disease, including advanced cirrhosis. In acute liver disease or acute decompensation of chronic liver disease, close clinical observation for signs of narcotic overdose or with- drawal is necessary. A modest alteration in methadone dose may be appropriate for some patients. Buprenorphine can cause liver dysfunction after sublingual and even more after intravenous administration. It is advised to follow the liver function during buprenorphine treatment and to warn the clients for intravenous use of buprenorphine. Neither methadone nor buprenorphine do influence the effect of interferon and ribavirin during the treat- ment of chronic hepatitis C patients. It may be necessary to increase the dosage of methadone during interferon treatment. (Acta gastroenterol. belg., 2005, 68, 81-85).
Therapy of chronic hepatitis C in the setting of HIV co-infection
Hepatitis C virus (HCV) and human immunodeficiency virus (HIV) infections are major health problems world-wide. As both viruses partially share routes of transmission, co-infection is com- mon. This is especially the case in patients infected through intra- venous drug use. It has been shown that HIV accelerates HCV progression to cirrhosis. The influence of HCV infection on the natural history of HIV disease remains highly controversial. It is also known that HCV co-infection increases the risk of hepato- toxicity of Highly Active Antiretroviral Therapy (HAART). These considerations as well as the improved survival of HIV patients due to HAART leads to increasing numbers of patients undergo- ing assessment and treatment of HCV infection. HCV treatment should be considered in stable HIV disease. Recent data indicate that HCV treatment schedules should be similar in co-infected and HCV mono-infected individuals, with pegylated interferon com- bined with ribavirin. For all treatment regimens published, co- infected patients had a lower sustained viral response rate com- pared to HCV mono-infected patients. Similar predictive factors determine the success rate. The effect of prolonging therapy to 12 months in genotype 2/3 and to 18 months in early viral respon- ders with genotypes 1/4 needs to be assessed in further studies. (Acta gastroenterol. belg., 2005, 68, 86-91).
