Lars Wikström

World-wide survey of liver transplantation in patients with familial amyloidotic polyneuropathy

The First International Workshop on liver transplantation in patients with familial amyloid polyneuropathy (FAP) was held at Huddinge Hospital in Stockholm, Sweden, September 10–11, 1993. Information was presented on 64 liver transplant recipients treated at 15 centers in 10 countries. Twenty-two patients had a follow-up time of more than 12 months, the longest follow-up was 41 months. Fifty-three patients had survived the procedure, while 11 had died within 8 months after the operation. The 1 and 2 year actuarial patient survival rate was 67 per cent. In most of the 22 patients surviving more than 1 year, the neurological symptoms had stabilized and the beneficial effect was most apparent as regards symptoms from the autonomic nervous system. There was consensus among the participants at the Workshop that liver transplantation for FAP is a worthwhile procedure and that such transplantation activities should continue. Transplantation should preferably be performed before the symptoms become severe and whi...

Discordant penetrance of the trait for familial amyloidotic polyneuropathy in two pairs of monozygotic twins.

Background.  Familial amyloidotic polyneuropathy (FAP) is caused by mutated transthyretin in which valine at position 30 is substituted by methionine (ATTR Val30Met). FAP is inherited as an autosomal dominant trait with variable penetrance.

Discordant symptoms in monozygotic twins with familial amyloidotic polyneuropathy (FAP) (TTR Met 30)

Two monozygotic twin brothers, 55 years of age, are carriers of the TTR Met 30 gene. Twin no. 1 had onset of typical FAP symptoms seven years ago, while twin no. 2 is absolutely healthy. The twins have the same educational background, are working in the same industry and are living in the same area. The progress of symptoms in twin no. 1 was rather rapid with polyneuropathy, gastrointestinal and heart symptoms. Liver transplantation was per-formed in twin no. 1 in 1993, with a successful result. The discordance of FAP symptoms in identical twins might indicate that environmental factors are of importance for the onset of FAP symptoms. The possible importance of environmental factors is indicated by a population study made in the same area. The TTR Met 30 gene carrier frequency is 1.6 per cent, while the frequency of FAP patients in the same area is only 0.05 per cent, indicating a gene penetrance of only about 5 per cent. To our knowledge this is the first report of discordant symptoms in monozygotic twin...

The long-term impact of liver transplantation on kidney function in familial amyloidotic polyneuropathy patients

The aim of the study is to evaluate the long‐term kidney function after liver transplantation (LTx) in familial amyloidotic polyneuropathy (FAP) Portuguese type patients and compare the findings with patients transplanted for chronic liver disease of other origin. We analysed the medical records of 32 FAP patients who underwent transplantation between 1990 and 1999 with a follow‐up of more than 1 year after LTx. The control group consisted of 61 patients who had undergone LTx for chronic liver disease. Kidney function was measured by the glomerular filtration rate (GFR), serum creatinine and urea. There were no differences between the groups in creatinine and urea levels during the follow‐up. However, during the first year after transplantation, the increase in creatinine and urea was significantly higher in the control group (P < 0.01). The decline in GFR after transplantation was also more pronounced in the controls (P < 0.01). Initially after LTx, kidney function deteriorated in both FAP and control patients, but the deterioration was more pronounced in the controls. The decline of the FAP patients’ kidney function after LTx was not more pronounced than that observed in control patients, although many FAP patients’ kidney function was impaired before the procedure, suggesting that LTx may halt the progression of kidney damage caused by amyloid deposition.

Scavenger treatment of free radical injury in familial amyloidotic polyneuropathy: a study on Swedish transplanted and non-transplanted patients

Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.Since oxidative stress has been implicated in amyloid diseases, a study of scavenger treatment of hereditary transthyretin amyloidosis was undertaken on 23 familial amyloidotic polyneuropathy (FAP) patients. Nine patients had undergone a liver transplantation for the disease. Twenty patients completed the 6-month study period of scavenger treatment (vitamin C, 1 g, three times daily, vitamin E, 0.1 g, three times daily and acetylcysteine, 0.2 g three times daily). They were evaluated clinically and by immunohistochemical measurement of hydroxynonenal (HNE), a product of lipid peroxidation, in biopsy specimens. For non-transplanted patients, no improvement was found for HNE in relation to the amyloid content in biopsy specimens, whereas a tendency to a decreased amount was noted for transplanted patients. Clinically, no differences were found for non-transplanted patients, but an increased nutritional status, measured by a modified body mass index (mBMI) was noted for transplanted patients. In summary, scavenger treatment with the drugs and doses used in the present study appears to be unable to decrease lipid peroxidation in amyloid-rich tissue in non-transplanted FAP patients. For transplanted patients, lipid peroxidation tended to decrease, and the nutritional status measured by mBMI improved, even though the findings may be explained by liver transplantation alone, scavenger treatment may facilitate recovery after transplantation.

L-threo-DOPS treatment of orthostatic hypotension in Swedish patients with familial amyloidotic polyneuropathy (TTR-met30)

L-threo-DOPS is a synthetic precursor to norepinephrine (NE). In order to study its efficacy and dosage, we carried out an open pilot study in ten patients with orthostatic hypotension and a confirmed diagnosis of familial amyloidoticpolyneuropathy (FAP). The initial dosage was 200 mg of L-threo-DOPS daily, with a weekly increment of 100 mg, until a maintenance dose was reached. Ten patients were treated for 12 weeks and five of them for 24 weeks. The blood pressure (BP) and pulse rate were monitored weekly. Before treatment, after four and 12 weeks, the patients underwent clinical and laboratory examinations. Nine patients completed the study. There was a rise in mean BP values in all measurements. After 12 weeks of treatment the rise in mean systolic BP values were statistically significant (p < 0,01) in all measurements in upright position. When treatment was withdrawn BP fell to almost the same levels as before and when treatment was restarted (five patients), there was again a rise in mean BP values....