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In the hepatopulmonary syndrome (HPS), a pulmonary vascular complication of liver disease, severe hypoxemia due to pulmonary vascular dilatation can be extremely debilitating. Determining whether patients with advanced liver disease and HPS should be considered for liver transplantation is difficult. We describe three patients with progressive and severe hypoxemia who underwent successful liver transplantation and had resolution of their arterial hypoxemia. In these patients, the progressive pulmonary deterioration accelerated the need and was considered an indication for liver transplantation rather than being considered an absolute or relative contraindication. In addition, we review the literature on 81 pediatric and adult patients with HPS who underwent liver transplantation and specifically highlight mortality, morbidity, syndrome resolution, and prognostic factors. Posttransplantation mortality (16%) was associated with the severity of hypoxemia (mean arterial oxygen tension [PaO2] in 68 survivors was 54.2 +/- 13.2 mm Hg and in 13 nonsurvivors was 44.7 +/- 7.7 mm Hg; P<0.03). Patients with a pretransplantation PaO2 of 50 mm Hg or lower had significantly more frequent mortality (30%) in comparison with those with a PaO2 greater than 50 mm Hg (4%; P<0.02). Pulmonary recommendations that address the severity of hypoxemia and candidacy for liver transplantation are discussed.

Objective: To report our experience with orthotopic liver transplantation (OLT) for highly selected patients with early-stage hepatocellular carcinoma (HCC)., Design: We retrospectively analyzed the demographic, clinical, pathologic, and survival data on 21 patients with HCC who underwent OLT at the Mayo Clinic between 1985 and 1993., Material and Methods: The 21 patients were categorized into three groups: (1) those with incidental HCC (no evidence of HCC preoperatively), (2) those with a unicentric hepatic lesion without vascular invasion, and (3) those with an increased serum alpha-fetoprotein (AFP) concentration but no detectable mass lesion in the liver., Results: For the seven patients with incidental HCC, the 2-year disease-free survival was 68.5%. For the eight patients with a mass lesion, the 2-year disease-free survival was only 50%. Operative staging revealed more advanced stage disease than had been found on preoperative assessment in five of these eight patients. For the six patients with an increased serum AFP value but no mass lesion, the 2-year disease-free survival was 80%. Tumor recurrence was the major cause of all deaths in this series., Conclusion: Disease-free survival for patients with radiographic early-stage HCC was suboptimal because of understaging of the disease preoperatively. In contrast, our initial experience with OLT for patients with an increased serum AFP value in the absence of a mass lesion in the liver was favorable.

Objective: To characterize the caloric and protein requirements of patients with end-stage liver disease before and for 28 days after liver transplantation., Design: We prospectively assessed 16 adult patients who were scheduled to undergo liver transplantation between December 1989 and September 1990., Material and Methods: Nitrogen balance, 24-hour urinary creatinine, 3-methylhistidine, and resting energy expenditure were determined before transplantation and on days 1, 3, 5, 14, and 28 after transplantation. The investigators were unaware of the results of these measurements, and patients were fed in accordance with a previously established clinical protocol., Results: Resting energy expenditure did not increase from preoperative values; however, urinary nitrogen and 3-methylhistidine increased significantly after liver transplantation, an indication of protein catabolism from a myofibrillar source. A negative nitrogen balance persisted for 28 days post-operatively., Conclusion: We recommend that caloric intake be determined by using the formulation provided by the Harris-Benedict equation at ideal body weight plus 20%. We also recommend that intake of protein be adjusted on the basis of preoperative nutritional assessment, perioperative hepatic and renal function, and results of tests used to measure the adequacy of administered protein. Parenterally or enterally administered protein of more than 1.2 g/kg daily should be well tolerated in most patients who have undergone liver transplantation.

Objective: We conducted a treatment trial to determine the relative toxicity of FK-506 and cyclosporine A (CSA) in liver transplant recipients., Design: Between October 1990 and October 1991, 37 patients were enrolled in an open-labeled, randomized study of two immunosuppressive regimens after liver transplantation., Material and Methods: Of the 23 men and 14 women, 20 received FK-506 plus prednisone, and 17 received CSA plus prednisone and azathioprine. Renal function was assessed before and after transplantation (day 1, month 1, month 4, and month 12) by measurements of serum creatinine (SCr) and glomerular filtration rate (GFR) as determined by urinary iothalamate or creatinine clearance (or both). FK-506 trough plasma levels (enzyme immunoassay) were to be maintained between 0.2 and 5.0 ng/mL, and CSA trough blood levels (whole blood high-performance liquid chromatography) were to be maintained between 250 and 400 ng/mL. Severe nephrotoxicity was defined as sudden decreases in urine output to less than 10 mL/h or rapid increases in SCr (more than 0.5 mg/dL daily) that necessitated withdrawal of study medication for more than 48 hours. Mean patient age and values for SCr and GFR were comparable between the two groups at entry., Results: Both study groups demonstrated a similar deterioration in renal function during a 12-month follow-up, although patients who received FK-506 had a significantly (P < 0.05) lower GFR when measured at 12 months than did patients treated with CSA (45 +/- 4 versus 64 +/- 6 mL/min per body surface area). Mild nephrotoxicity that responded to decreased drug doses was noted in 9 CSA-treated patients (53%) and 10 FK-506-treated patients (50%). Severe nephrotoxicity that necessitated drug withdrawal occurred in only four patients, all of whom were in the FK-506 group. These severe nephrotoxic reactions to FK-506 occurred early after transplantation, often during intravenous administration of the drug, and were not associated with poor liver allograft function or drug levels outside the therapeutic range., Conclusion: Both FK-506 and CSA are significantly nephrotoxic in liver transplant recipients. In this trial, however, we observed an early development of severe nephrotoxic reactions only in some patients who received FK-506.

We retrospectively reviewed the long-term results in 46 patients who survived at least 1 year after liver transplantation. Only one death has occurred, and one patient has required retransplantation. Biochemical liver function tests showed median values in the normal range, except for mild elevation of serum gamma-glutamyltransferase. In patients with primary biliary cirrhosis, these test results were completely normal. A liver biopsy 1 year after transplantation disclosed normal histologic findings in 31 patients (67%). The other patients had either transient (acute rejection) or stable (chronic rejection) abnormalities, except for two patients with progressive graft dysfunction attributable to chronic rejection. A clinically significant vascular anastomotic abnormality was noted in one patient who had hepatic artery thrombosis. Late bile duct complications occurred in 15% of patients, all of whom had a satisfactory outcome after surgical or radiologic intervention. Cyclosporine-related nephrotoxicity and hypertension each occurred in 67% of patients; however, conversion to a low-dose cyclosporine-azathioprine regimen yielded stabilization of renal function after the first postoperative year, and hypertension has been easily controlled medically. Diabetes necessitating insulin treatment developed in three patients. The body weight of the study patients had increased by a median of 6.5 kg at 1 year but stabilized thereafter. Subjective well-being and satisfaction with life were reported by 91% of the patients. Of the 46 patients, 26 were employed, 16 were homemakers, and only 4 did not work, 2 because of transplant-related medical problems. Thus, we conclude that liver transplantation rehabilitates patients with end-stage liver disease and enhances their quality of life.