Alström Syndrome Patient with Liver Cirrhosis (Complicated with Portal Hypertension), His

Management and Fetal Cell Transplantation.

Gocha Shatirishvili, M.D., Georgian-German Clinic for Oncology, Tbilisi, Georgia

Connoly et al. in 1991 first proposed that liver dysfunction could be a previously undescribed systemic manifestation of Alström Syndrome. We report a 37-year-old Alström Syndrome patient with complicated liver cirrhosis. In 1999 liver dysfunction first was manifested by bleeding from esophageal varices. Patient was infected with hepatitis B virus after blood transfusion that apparently accelerated already existing liver disorder. Varices were documented by esophagogastroscopy. By abdominal ultrasonography there was no liver enlargement or ascites identified, portal and splenic veins were dilated and spleen was slightly enlarged. Varices were found between liver and stomach. Serum albumin level was slightly decreased, ALT and AST were slightly and creatinine was moderately elevated. Doppler study showed low blood flow velocity in portal vein (11,7 cm/sec). Moderate portal hypertension was diagnosed. After computed tomography examination liver cirrhosis was suspected and liver biopsy recommended, but not performed. After three months bleeding recurred and stopped with the Blakemore balloon tamponade. After this hospitalization patient takes daily 80 mg nadolol and phosphatidylcholine for 6 months yearly. The use of isosorbide mononitrate was discontinued because of hypotension. In 1999 recovery from acute Hepatitis B was documented. Anti-HAV and anti-HCV were negative. Gastroscopy revealed varices in the middle and distal esophagus (II degree). Rubber band legation was performed successfully. Since 1999 every 3-4 months measurements for serum ALT, AST, albumin, bilirubin, GGT, alkaline phoshatase, creatinine, ammonia, thromboplastin time, hematologic evaluation, abdominal ultrasonography with Doppler study are performed, esophagogastroscopy 1-2 times yearly. Hyperammonemia - 123 µmol/l (despite high level of ammonia, no signs of encephalopathy was revealed) is treated successfully with lactulose 30 ml daily. Liver was never enlarged. Parenchymal echo texture was normal in 1999, small nodular in 2000 and small and middle nodular in 2002. Spleen every time was enlarged (121 mm to 164 mm) and splenic vein dilated. Portal vein dilatation was revealed only once-in 1999, ascites was never detected, the portal blood average flow velocity was low-11,8 cm/s in 1999, 6,6 cm/s in 2002. Volume flow in the portal vein was low (max. 586 ml/min in 2000 and min. 395 ml/min in 2001). Patient is estimated with Child-Pugh scores. We recommend for patient vaccination against HAV and HBV, avoidance of alcohol, caution in use of hepatotoxic medicines, weight reduction. In 2002 we transplanted patient with fetal liver and neural cells. There were several considerations: 1. The some encouraging results after fetal liver cells transplantation in a variety of inborn errors of metabolism (Touraine, 1991) - most patients were in good condition and displayed objective criteria of partial improvement, their disease was stabilized for some time after each transplant. Fetal liver transplantation was repeated to maintain the clinical result. 2. Use of stem cells as a possible carrier of normal ALMS1 protein. 3. Several liver disorders, including liver cirrhosis, were treated with the liver fetal cells transplantation. Fetal tissue was obtained after legal elective abortion (fetal age 8-12 weeks). Donor’s and patient’s HLA-antigens were not tested. Patient’s blood group was O(Rh+), donor’s- A(Rh+). No myeloablative preparation was performed. After one week Patient described improvement of his emotional and physical condition. Low platelet count before transplantation was normalized after one week and so remains until today. After two months ALT, AST, bilirubin, alkaline phosphatase and GGT were also normalized. This effect continued for three months. After six month by Doppler study volume flow in the portal vein was 758 ml/min (the highest value ever measured). Spleen until now remains enlarged. In December 2002 the transplantation was repeated. Viability of the fetal liver cells in the host is monitored by serum alpha-fetoprotein measurements.