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Biomedical subjects

M K Porayko

Publications and source records attributed to M K Porayko.

At least 55 records · Page 3Linked to original sources

Etiology and incidence of unconjugated hyperbilirubinemia after orthotopic liver transplantation.

OBJECTIVES: Gilbert's syndrome, or slow bilirubin glucuronidation phenotype, is a common cause of benign hyperbilirubinemia in the general population. There have been only two previously reported cases of Gilbert's syndrome occurring in patients after liver transplantation. This study was conducted to determine the frequency of Gilbert's syndrome in liver transplant recipients. METHODS: The charts of all patients followed by the Mayo Liver Transplant Clinic for 1 yr or more after transplantation, as of June 1992, were reviewed to identify all patients with a consistent pattern of unconjugated hyperbilirubinemia greater than two times the upper limits of normal and with a normal conjugated bilirubin level. These patients were further evaluated to exclude all other causes of hyperbilirubinemia, including biliary obstruction, rejection, viral infection, cholestatic liver disease, and hemolysis. RESULTS: Five of 229 patients (2.2%) had a consistent pattern of unconjugated hyperbilirubinemia. Only three patients (1.3%) had no other identifiable cause of hyperbilirubinemia. CONCLUSIONS: This study was performed to determine the incidence of unconjugated hyperbilirubinemia and particularly to determine the incidence of Gilbert's disease in liver transplant recipients. The apparently low frequency of Gilbert's after liver transplantation may reflect the masking of the diagnosis by other transplant-associated pathology or donor selection bias because of unexplained hyperbilirubinemia. Post-transplant patients who fit the Gilbert's syndrome profile of unconjugated hyperbilirubinemia should have a postprandial bilirubin drawn as a first step. The awareness of this syndrome may avoid a costly and invasive evaluation in the liver transplant recipient.

Bilirubin↗

Cyclosporine withdrawal for nephrotoxicity in liver transplant recipients does not result in sustained improvement in kidney function and causes cellular and ductopenic rejection.

Twelve consecutive liver transplant recipients with stable allograft function and cyclosporine nephrotoxicity were subjected to cyclosporine withdrawal in an attempt to halt and possibly reverse renal damage. Only patients who met the following criteria were included: (a) triple immunosuppression with cyclosporine, azathioprine and prednisone; (b) stable graft function for at least 1 yr without rejection; and (c) serum creatinine greater than 2.1 mg/dl or renal clearance less than 35 ml/min. Cyclosporine was reduced by 50 mg every 3 wk until discontinuation, prednisone was temporarily increased from 10 to 20 mg/day and azathioprine was maintained at 2 mg/kg/day. Sustained improvement in kidney function in the 12 patients was minimal, with the mean serum creatine level decreasing from 2.5 +/- 0.5 mg/dl (mean +/- S.D.) at study entry to 2.4 +/- 1.2 mg/dl after a mean follow-up of 18 +/- 6 mo. In six patients, histologically confirmed cellular rejection developed after a mean of 5 +/- 6 mo from the time that cyclosporine withdrawal was begun. Two of six patients with rejection responded to bolus steroid therapy and are in stable condition at this writing with low-dose cyclosporine (2.8 and 3.2 mg/kg/day). Two patients initially responded to bolus steroids but later exhibited ductopenic rejection; one responded to treatment with FK 506 and the other died of sepsis. The two remaining patients were steroid unresponsive. One responded to treatment with OKT3 and is now stable on low-dose cyclosporine (2.3 mg/kg/day), but in the other ductopenic rejection developed and the patient died of sepsis during rescue therapy with FK 506.(ABSTRACT TRUNCATED AT 250 WORDS)

Azathioprine↗

Histological evidence for recurrence of primary biliary cirrhosis after liver transplantation.

Whether primary biliary cirrhosis recurs after orthotopic liver transplantation remains a controversial issue. Sixty consecutive patients with primary biliary cirrhosis with at least 1 yr of follow-up after liver transplantation were studied. All patients were treated with triple-drug immunosuppression (cyclosporine, prednisone, azathioprine). Hepatic biochemical parameters and protocol liver biopsy specimens were evaluated 1 wk, 3 wk, 4 mo and yearly after orthotopic liver transplantation and at times of liver dysfunction. Antimitochondrial antibody titers and IgM levels were determined at 4 mo and yearly. At the time of last follow-up, all patients had marked symptomatic improvement compared with their pretransplant condition, and 91% of the patients had normal hepatic biochemical parameters, including serum levels of alkaline phosphatase, bilirubin, ALT and IgM. In addition, all patients had significant decreases in antimitochondrial antibody titer (p = 0.0001) and significant decreases in serum levels of IgM (p = 0.0001). Forty-one of the 60 patients had near-normal liver histological appearance. Of those with abnormal histological appearance, five patients, 2 to 6 yr after orthotopic liver transplantation, had histological features typical of a florid duct lesion, suggesting recurrent primary biliary cirrhosis. All five patients with portal granulomas had normal hepatic biochemical values and were clinically asymptomatic. Two of the five patients had persistent antimitochondrial antibody titers. We consider the documented histological changes highly suggestive of recurrence of primary biliary cirrhosis after liver transplantation but, so far, have no evidence that the condition in these patients is progressive.

Adult↗

Advances in the diagnosis, treatment, and prevention of cytomegalovirus infections after liver transplantation.

CMV is one of the most frequent viral infections after orthotopic liver transplantation. Thus, there should be a high index of clinical suspicion, particularly in liver transplant recipients who have risk factors for the development of CMV disease, including donor CMV seropositivity, the use of antilymphocyte preparations, and retransplantation. The availability of effective antiviral therapy to treat CMV disease has emphasized the importance of an aggressive approach to the early diagnosis and treatment of this viral infection. Ganciclovir has been a major advancement in the treatment of severe CMV disease and has had a major impact on reducing the incidence and severity of CMV disease and its complications in the liver transplant recipient. Furthermore, these antiviral agents are now being evaluated for their prophylactic potential. Indeed, a number of these agents or combinations of these agents have been shown to be effective in reducing the incidence and severity of CMV disease, particularly in the CMV-seropositive transplant recipient; however, the cost-effectiveness of such therapy and its overall impact on long-term graft and patient outcome remain poorly defined at this time. Further investigations will be needed to define the role and importance of prophylactic therapy for the prevention of CMV infection and disease in the liver transplant recipient.

Cytomegalovirus Infections↗

Intravascular volume regulation in cirrhotic patients with functional renal failure.

Central volume expansion is an important component of treating renal dysfunction associated with advanced chronic liver disease. Experiments using HWI in these patients emphasize the importance of increasing central vascular filling as a way to normalize renal function through multiple physiologic mechanisms. However, the desired improvement in renal function is not always obtained with HWI, especially in patients with greater degrees of hepatic dysfunction, central volume depletion, and activation of neurohumoral support systems. This may, in part, be related to reflexive decreases in systemic vascular resistance during immersion. The development of techniques to expand central arterial volume while maintaining systemic vascular resistance and mean arterial pressure may add to the beneficial effects on renal function in cirrhotics. Pneumatic compression of the lower extremities may be one way of achieving the desired circulatory effects. Adjunctive therapy with splanchnic vasoconstrictors may be necessary in patients with marked vasodilation but they often have undesirable intrarenal actions.

Bandages↗

Management of ascites in patients with cirrhosis. What to do when diuretics fail.

Resistant or refractory ascites is unusual in cirrhotic patients who comply with dietary sodium restriction and optimal diuretic therapy. Patients unresponsive to medical therapy often have end-stage liver disease and renal insufficiency, although reversible complicating factors must be excluded. For patients with truly refractory ascites, liver transplantation is the only option that improves chances of survival. When this is not feasible, therapeutic paracentesis is the procedure of choice for intractable ascites. Several surgical shunts have been used, but none have been found to be safer and more effective than large-volume paracentesis.

Ascites↗

Selection and timing of liver transplantation in primary biliary cirrhosis and primary sclerosing cholangitis.

In summary, we answer the three questions we have previously posed: (a) Can liver transplantation prolong survival? Evolving data from several centers indicate that liver transplantation indeed prolongs survival in patients with PBC and PSC as compared with estimated survival using disease-specific risk scores based on the natural history of PBC and PSC. (b) Can we optimize timing of liver transplantation? Although many factors enter into the timing of liver transplantation, including when the patient is actually referred for liver transplantation and the individual desires of the patient to pursue liver transplantation, evidence is growing that having patients with chronic liver diseases like PBC and PSC undergo transplantation a little earlier in the course of the disease rather than waiting until the patients have experienced life-threatening complications or are on life-support measures can indeed improve early postliver transplant survival. In patients with PBC and PSC, the survival risk score, which reflects disease severity, can serve as an objective measurement to assess and evaluate the effect of liver disease severity on transplant outcome. Indeed, a number of studies have strongly suggested that optimal timing of liver transplantation may indeed be important to improve outcome, decrease morbidity and decrease cost. (c) Does the present allocation system in the United States allow for optimal use of our scarce donor organ resource?(ABSTRACT TRUNCATED AT 250 WORDS)

Cholangitis, Sclerosing↗

Role of endoscopic retrograde cholangiopancreatography after orthotopic liver transplantation.

We reviewed the records of 20 liver transplant patients who underwent 28 procedures [endoscopic retrograde cholangiopancreatography (ERCP)] to rule out biliary obstruction, treat bile leaks, dilate and/or stent strictures, or remove stones and debris. Three patients (two with abnormal T-tube cholangiograms and one with hyperbilirubinemia) underwent ERCP to rule out obstruction. Therapeutic ERCP (sphincterotomy with balloon dilatation or stone extraction) was successful in 16 of 17 patients, including seven of nine in whom there was resolution of bile leaks without the use of stents or surgery. Mild pancreatitis occurring in one patient was the only complication experienced that was related to ERCP. We conclude that ERCP is a safe and important modality in the medical management of biliary tract complications after orthotopic liver transplantation.

Adult↗

Initial two-year results of the Oregon Liver Transplantation Program.

During the first 24 months of the Oregon Liver Transplantation Program, which began in October 1988, 94 patients were formally evaluated and 47 adults underwent 54 liver transplantations. Thirty-four percent of patients were veterans. The recipient operation lasted a mean of 7.4 hours (range: 4 to 16 hours). Veno-venous bypass was used routinely at first but selectively later (7 of the last 26 cases), resulting in reduced operating time. Hepatic artery reconstruction was end-to-end anastomosis in 52 cases and iliac conduit in 2. No arterial thrombosis occurred. Biliary reconstruction was choledochocholedochostomy in 83% and choledochojejunostomy in 17%. Biliary complications occurred in 28%. Operative mortality was 2%, and 1-year actual survival was 80%. Patients with hepatitis B fared worse, with four of six dying at a mean of 7.6 months. Overall, the median hospital stay was 30 days. Patients surviving more than 3 months had a mean Karnofsky score of 82%. No significant difference in outcome was noted in patients receiving prophylactic OKT3 monoclonal antibody (used in 45%) versus conventional immunosuppressive therapy. Overall, allograft rejection occurred in 55% of patients. Retransplantation was required in seven patients, three for primary graft nonfunction, two for uncontrolled rejection during induction therapy with OKT3, and two for graft failure secondary to recurrent hepatitis B.

Adolescent↗

Primary sclerosing cholangitis: a progressive disease?

Patients with PSC should be viewed as having a disease that frequently progresses to liver failure if followed long enough. The rate of disease progression is variable and can occur without changes in symptoms or signs. With the advent of ERCP and widespread use of liver tests on routine examinations, the diagnosis of PSC is being made earlier and survival estimates have lengthened. Varying methods of survival analysis have also been responsible for differing opinions regarding the natural history of this disease. Nevertheless, it is probable that with close prospective, long-term follow-up, evidence of disease progression and increased mortality becomes apparent. Challenges for the future include being able to predict accurately the rate of disease progression and timing of liver failure in the individual patient. Preliminary studies using statistical survival modeling have been developed; however, further refinement of these models will be needed prior to application to clinical trials and liver transplantation.

Cholangitis, Sclerosing↗

Impact of malnutrition and its therapy on liver transplantation.

The consequences of malnutrition and impact of nutritional support on the liver transplant patient have not been adequately addressed in clinical research studies. As we have gained experience in assessing patients for transplantation surgery, the risks of malnutrition have been realized. Part of the success of liver transplantation today is related to improved timing of surgery, patient selection, and perioperative management. Malnutrition is one of the adverse risk factors that is potentially reversible and therefore specialized nutritional support techniques should be able to improve postsurgical outcome. However, the performance and interpretation of nutritional research has been impeded by difficulties in separating the effects of liver dysfunction from disturbances secondary to nutritional deficiencies; for example, hypoproteinemia would be a consequence of both. Through the use of multivariate prognostic formulas and development of better nutritional indices for patients with liver disease, it should be possible to identify those patients who will receive the greatest benefit from preoperative and perioperative nutritional support. Furthermore, the kinds of nutritional supplementation having the greatest impact could then be determined.

Diet Therapy↗

Rates of vertebral bone loss before and after liver transplantation in women with primary biliary cirrhosis.

Atraumatic fractures caused by osteoporosis may be a serious complication of primary biliary cirrhosis. Mean (+/- S.D.) bone mineral density in the lumbar spine in 210 ambulatory women with primary biliary cirrhosis was 1.02 +/- 0.19 gm/cm2, 7% lower than that in 139 age-matched normal women (after adjustment for age and body weight) (p less than 0.001). Bone mineral density in the lumbar spine was inversely related to a risk score index of liver disease severity (r = -0.29, p less than 0.001). The mean rate of bone loss in 105 of these 210 women was 2%/yr +/- 4%/yr, twice as great as in the 139 normal women (p less than 0.02). In 20 women with primary biliary cirrhosis followed up after orthotopic liver transplantation, bone mineral density in the lumbar spine decreased at 3 mo (p less than 0.01), and this decrease may have resulted in atraumatic fractures in 13 of them. Bone mineral density in the lumbar spine then increased (p less than 0.01) so that by 12 mo the median bone mineral density in the lumbar spine was similar to that before transplantation and by 24 mo it was 5% above it. Therefore we conclude that the progressive bone loss observed in primary biliary cirrhosis (which is further accentuated immediately after transplantation) may be halted, and the bone mass may be restored toward normal within 2 to 3 yr after orthotopic liver transplantation.

Absorptiometry, Photon↗

Complications of liver biopsy in liver transplant patients: increased sepsis associated with choledochojejunostomy.

We investigated the incidence and types of liver biopsy complications in our first 160 consecutive liver transplantations. A significant complication was identified by the need for therapeutic intervention (for example, hospitalization, transfusion, intravenous fluids, chest tube, surgery or antibiotic therapy). A total of 950 percutaneous hepatic allograft biopsies were performed in 136 patients (mean = 6.9 biopsies/graft; range = 1 to 29). A significant complication was reported after 17 (1.8%) liver biopsies in 13 (9.6%) patients. Bleeding complications occurred in 11 patients and serious infection developed in 6 patients, but all patients recovered with appropriate therapy. Of special interest was that five of six patients with infectious complications had undergone Roux-en-Y choledochojejunostomy as part of the transplantation operation. The incidence of infectious complications related to a series of biopsies was significantly greater in patients who underwent choledochojejunostomy (12.5%) than in patients who underwent duct-to-duct biliary anastomosis (1%) (p less than 0.01). Furthermore, all septic events in patients who underwent choledochojejunostomy were related to enteric organisms. This investigation reaffirms the safety and low incidence of complications related to percutaneous liver biopsy even in this unique patient population. However, we did identify a subgroup of patients with biliary-enteric anastomoses who appear to be at increased risk of septic complications after liver biopsy. Antibiotic prophylaxis at the time of liver biopsy may be appropriate in this high-risk subgroup to decrease the frequency of infectious complications.

Adolescent↗