Appeal type: Experimental/Investigational
Decision: Upheld

Physician 1: The patient is a 61-year-old man with a 13-year history of type 2 diabetes mellitus with microvascular disease. He has requested coverage for continuation of hepatic activation therapy. The patient believes hepatic activation has improved his blood sugar control, renal function, and sense of well being. He apparently had a previous course of hepatic activation therapy in 1995, which he says improved his blood sugar control at that time. Prior to beginning hepatic activation, the patients physician had not been able to control the patients blood sugar with small doses of subcutaneous insulin and oral agents. According to his treating physician, the patient had proteinuria and neuropathy. The Health Plan has denied coverage for hepatic activation therapy on the basis that it considered investigational for treatment of the patients medical condition.Review of the submitted medical records does not demonstrate clinically significant biochemical improvement in the patients kidney function after beginning hepatic activation. A serum creatinine taken two weeks after hepatic activation was initiated was elevated at 1.5 mg/dL. In addition, a 24-hour urinary protein was elevated at 266mg and A1c was 7.2%, which would indicate only fair sugar control over the prior two to three months. Creatinine clearance was 89mg/ml, which is normal. Three months after beginning hepatic activation, the patients creatinine was still elevated (1.7mg/dl), he still had proteinuria and his creatinine clearance had actually deteriorated to 65mg/ml. Eight months after beginning hepatic activation his creatinine still remained elevated (1.4mg/dL). There is no further record of creatinine clearance. His blood sugar control actually deteriorated with an A1c of 7.6%, although two months later it had fallen to 6.6%. The long-term efficacy of hepatic activation in controlling blood sugar and decreasing microvascular disease beyond that obtained by modern insulin therapy is unproven. A study by Dalley, et al. initially recruited 90 patients with type 1 diabetes mellitus and moderate to advanced nephropathy. Patients whose blood pressure could not be controlled to values less than 140/90 were excluded. The creatinine clearance declined in both groups as expected. There was no difference in the rate of decline in 71 patients in both groups who completed 12 months of hepatic activation. In addition, 49 patients completed 18 months of hepatic activation, at which time the difference in rate of decline in creatinine clearance became significant. Blood pressure was maintained at less than 140/90, which is above that expected by modern standards. The improvement in A1c was similar in both groups. It is impossible to determine if modern recommendations to control blood pressure would have ameliorated the rate of decline in creatinine clearance in both groups. Hepatic activation is not generally accepted to be in accordance with current standards of diabetes management. There is no evidence that it is better than less cumbersome methods of insulin administration for control of blood sugar or microvascular complications. Furthermore, hepatic activation is not considered a treatment option in the Clinical Practice Recommendations published by the American Diabetes Association or the standards from the American Association of Clinical Endocrinologists. Based upon the information set forth above, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld. (For Summary of Relevant Patient Medical History and Current Condition, please refer to Physician 1). Physician 2: Upon review of the medical literature, there are no randomized, controlled studies of hepatic activation therapy. Thus, there is no independent verification of the efficacy of the requested therapy. In addition, 24-hr urine levels are notoriously variable in individual patients depending upon medications taken, prostate status, etc. Furthermore, the patients treatment for his diabetes has been less than optimal with an A1c above 7% until August 2004. Moreover, treatment for his renal problem has been less than optimal with Captopril 25mg. In light of these findings, and given that the physiologic underpinnings of hepatic activation are unproven and unsupported by independent research, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. As such, the Health Plans denial should be upheld. Physician 3: The relevant scientific literature includes the above-cited study in Endocrine Practice, which was a retrospective study without a real control.  Significantly, creatinine clearance did not decline on average over the course of the study, which would have been expected to occur in such patients. A paper by Dalley, et al. showed that in a multicenter, prospective, controlled study of 49 patients, pulsatile IV insulin therapy over an 18-month period resulted in a decline in creatinine clearance from 7.69 ml/min/yr to 2.21 ml/min/yr. However, the study involved patients with type 1 diabetes and included only 49 patients. While hepatic activation is a potentially promising therapy and might be recommended for patients who have exhausted all other measures at preserving renal function in the setting of type 2 diabetes, at this time there is not valid scientific evidence demonstrating that the expected health benefits from hepatic activation therapy are clinically significant and likely to produce a greater benefit for the patient than other possible alternatives. Furthermore, hepatic activation is not within the current standard of medical practice. Therefore, I have determined that the requested therapy is not likely to be more beneficial for treatment of the patients medical condition than any available standard therapy. The Health Plans denial should be upheld.