Abnormal Liver Function Studies Research Articles

Hematophagocytic Lymphohistiocytosis Presenting as Acute Liver Failure

INTRODUCTION: Hematophagocytic lymphohistiocytosis (HLH) is an exceedingly rare autoimmune disorder seen more within the pediatric population and only a handful of cases reported in adults. HLH is characterized by massive inflammation and tissue destruction secondary to the unregulated activity of macrophages and cytotoxic T lymphocytes. Herein we present a rare case of HLH in an adult. CASE PRESENTATION: A 25-year-old African American female with no significant past medical or social history presented with fevers, night sweats, and chills. Physical exam revealed a temperature of 103.1 F and diffuse non-tender generalized lymphadenopathy. Laboratory data revealed leukopenia (WBC 1.43 X 103), neutropenia (0.29/mcL), thrombocytopenia (78 X 103), and abnormal liver function studies with AST 3629 U/L, ALT 1647 U/L, total bilirubin 21, normal alkaline phosphatase, INR 2.0, platelet count 45 X 103, and INR 2.0. The ferritin level resulted >40,000 ng/mL. Ceruloplasmin, ammonia, ethanol, acetaminophen levels, and hepatitis serology were normal. ANA was noted to be 1:160 in a speckled pattern and her subsequent extractable nuclear antigen panel was positive for smooth muscle ribonucleprotein antigens. Liver biopsy showed hepatic parenchyma with Kupffer cell hyperplasia with hemophagocytosis. Ultimately the patient was diagnosed with secondary HLH due to rheumatological process and was started on high dose steroids which resulted in near resolution of her liver chemistries.Figure 1Figure 2DISCUSSION: HLH is associated with a very poor prognosis and life span of only few months if left untreated. Mortality is due to rapidly progressive multi-organ failure. Since it is such a rare disorder patients typically undergo lengthy work up before the correct diagnosis can be reached at which point their prognosis is dismal. To allow for rapid detection, a low index of suspicion for HLH should exist in a patient who meets a majority of the clinical criteria set forth by the histiocyte society in 2004, which include hyperferritinemia, hepatosplenomegaly, cytopenia, and hypertriglyceridemia or hypofibrinogenemia, decreased NK activity, and high IL-2 levels. In the case of high suspicion, treatment should be initiated promptly, as these patients deteriorate rapidly. Treatment should focus on suppressing the immune system and targeting the underlying trigger.

Contemporary Experience with Cholecystectomy: Establishing ‘Benchmarks’ Two Decades after the Introduction of Laparoscopic Cholecystectomy

With quality and public reporting of increasing importance, benchmarks are anticipated to grow in relevance. We studied cholecystectomy in a practice in an urban tertiary care hospital. A total of 1083 cholecystectomies were performed in 2008 and 2009. Laparoscopic cholecystectomy was performed in 97.8 per cent of patients with a 2.2 per cent conversion rate. A planned open procedure was performed in only 2.2 per cent of patients. Approximately half of procedures were urgent and performed during an acute hospitalization. Most patients (74%) were female and most patients were overweight or obese (64.8%). Ages into the tenth decade of life were represented. Comorbidities included hypertension, 28.7 per cent; coronary disease, 15.6 per cent; diabetes mellitus, 13.4 per cent; gastroesophageal reflux disease, 10.7 per cent; and asthma, 5.5 per cent. Of female patients, 98 (12.2%) were postpartum and five (0.6%) were pregnant. Of 137 patients without gallstones, 59.1 per cent had biliary dyskinesia and 27 per cent had acalculous cholecystitis. Preoperative magnetic resonance cholangiopancreatography and endoscopic retrograde cholangiopancreatography (ERCP) were performed in most patients with suspected choledocholithiasis. Intraoperative cholangiograms were performed in 6.9 per cent of patients, 3.3 per cent for abnormal liver function studies. Postoperative ERCP was used in most patients with positive intraoperative cholangiograms. All-cause mortality was 0.8 per cent and attributable mortality was 0.2 per cent. Complications occurred in 7.5 per cent of patients, including retained common bile duct stones in 1.1 per cent, bile duct leak in 0.3 per cent, and common bile duct injury in 0.1 per cent.

Amebic Liver Abscess: Fourteen Years Later

Purpose: A 41 year old Mexican American male presented to the hospital with fevers, chills, and headaches for two days. He denied any history of GI or liver disease. He used occasional NSAIDs for pain. He immigrated to the United States from Mexico 14 years ago and has not traveled outside of the country since immigration. He denied recent or remote contact with anyone with GI or liver disorders. Physical exam revealed a febrile male, with icteric sclera and hepatomegaly. Pertinent initial lab tests include neutrophilic leukocytosis and abnormal liver function studies (Total Bili 4.4, Direct Bili 1.8, ALT 261, AST 286 and Alk phos 261). Abdominal Ultrasound showed a 4 x 5 cm heterogeneous hypoechoic mass within the right hepatic lobe. MRI of the liver confirmed the peripherally enhancing lesion with areas of low signal intensity, suspicious for abscess. He was started empirically on metronidazole and levofloxacin. Within 48 hours, he was afebrile, LFT had normalized and leukocytosis improved. CT-guided FNA and core needle biopsy were obtained. The aspirate was thick and maroon colored and showed necrotic debris and inflammatory cells with eosinophilic infiltrate consistent with an abscess or inflammatory process. H&E and trichrome stain revealed structures suspicious for vegetative forms of amoeba. Serum amebiasis antibody test was positive. CT scan, obtained 13 days after MRI, showed a mild decrease in size of the abscess. He was asymptomatic on follow-up, three weeks after discharge. We present an unusual case of amebic liver abscess in a Mexican American male, who has not resided in an endemic area in 14 years. Approximately 10 percent of the world's population has amebiasis. Although prevalent worldwide, amebiasis is rare in the U.S. Hepatic abscess is the most common extraintestinal manifestation associated with invasive amebiasis. Patients with an amebic liver abscess typically present with RUQ pain and fever. Aspiration should be performed if imaging and serological studies are inconclusive. The mainstay of therapy is metronidazole followed by a luminal agent to ensure eradication. Awareness that amebic infections can occur without recent travel to endemic areas may lead to early diagnosis and treatment thereby reducing morbidity and mortality associated with this condition.Figure: No Caption available.

Necrotizing Enterocolitis in the Asphyxiated Full-Term Infant

Five full term infants with necrotizing enterocolitis, confirmed histologically, presented in the first five days of life. All passed grossly bloody stools and three mucosal casts. Severe perinatal asphyxia with accompanying secondary hyperammonemia was present in all, and abnormal liver function studies were present in three. An awareness of the clinical characteristics of these infants may lead to their early identification and conservative management.

Eosinophilic fasciitis as a paraneoplastic phenomenon associated with metastatic colorectal carcinoma

A 72-year-old man presented with erythema and induration of his calves and forearms. He had a past history of stage 1 colorectal carcinoma, treated with resection and primary anastamosis 4 years earlier. A diagnosis of eosinophilic fasciitis was made based on the characteristic clinical appearance, peripheral blood eosinophilia and a skin biopsy. There was no improvement in the condition following treatment with prednisolone or methotrexate. One year later, abnormal liver function studies were noted, and an abdominal computed tomography scan and subsequent needle biopsy of the liver confirmed a neoplastic lesion in the liver consistent with a metastatic colorectal carcinoma. Systemic chemotherapy with oxaliplatin, 5-fluorouracil and capecitabine was commenced, and resulted in partial remission of the colorectal carcinoma. Simultaneously, the indurations of the forearms and calves also improved, suggesting that the eosinophilic fasciitis was a paraneoplastic phenomenon.

CANCER CHEMOTHERAPY AND THE LIVER

The clinical issues involved in potential hepatotoxicity from cancer chemotherapy may be complex because it is sometimes difficult to assess the cause and effect relationship between the administration of chemotherapeutic agents and hepatic abnormalities.53 Patients with cancer frequently have a variety of reasons for liver abnormalities. In patients with solid tumors, the liver is a common site of metastasis, and the liver metastases will produce abnormal liver function studies and eventually hepatic failure. Also, many patients with malignant disease require frequent blood and blood-product transfusions, particularly in patients with hematologic malignancies. Such patients may develop transfusion-associated viral hepatitis-produced liver abnormalities,11 which may be difficult to separate from the potential toxic effects of chemotherapeutic agents. Finally, most patients with cancer are being treated with a variety of noncytotoxic drugs. They may be receiving antiemetics, analgesics and antibiotics, all of which may produce hepatic abnormalities. Although the attribution of specific liver abnormalities to specific chemotherapeutic drugs may sometimes be complex and problematical, there is no question that a number of commonly used chemotherapy drugs are associated with hepatotoxicity.56 The clinician managing patients with cancer should have an understanding of the drugs that are commonly associated with hepatotoxicity, whether that hepatotoxicity is reversible, and whether it is predictable or idiosyncratic in nature. Clinicians must also be aware that the potential for hepatotoxicity with chemotherapeutic drugs in many instances may be dose related. Al though this latter statement seems self-evident, it is a progressively important consideration now considering the widespread use of high-dose chemotherapy, with stem-cell support in both hematologic and nonhematologic malignancies. This article discusses some of the more important commercially available drugs that may cause hepatotoxicity, the severity of such hepatotoxicity, and the prevention or management of drug-induced hepatotoxicity where that information is known. It also discusses the interaction of high (bone marrow transplant)-dose chemotherapy and liver function, and the need to modify dose and schedule of chemotherapeutic drugs in patients with pre-existing liver function abnormalities.

The treatment and management of neuroleptic malignant syndrome

Gratz, Silvia S., Douglas F. Levinson and George M. Simpson. The Treatment and Management of Neuroleptic Malignant Syndrome. Prog. Neuro. Psychopharmacol. & Biol. Psychiat. 1992, 16(4):425–443. 1. 1. The neuroleptic malignant syndrome was initially described as a disorder specifically related to neuroleptic usage with frequent fatal outcome. The observations of variant or mild cases of this syndrome as well as case reports on neuroleptlc-malignant-like syndromes in the absence of neuroloptics raises the issue of the usefulness of this terminology and highlights the potential for inappropriate management of this “malignant” syndrome. It has been suggested that hypothalamic thermoregulatory responses may involve an interplay among noradrenergic, cholinergic and serotonergic pathways. Out treatment strategy is based on the pharmacology of neuroleptics and empirical data, verified in our own clinical practice and considers that it is often difficult to determine whether certain physiologic states are a consequence to or specific triggering factors. 2. 2. If a patient's temperature is less than 101, we emphasize vigorous treatment with anticholinergic agents, while simultaneously assessing the psychiatric need for neuroleptics versus medical risks. Given that the severe rigidity of NMS represents severe extrapyramidal effects of dopamine blockade, there is no reason to withhold anticholinergics in the absence of higher temperatures. Neuroleptics can be stopped at the discretion of the clinician even during circumstances when there is fever below 101. 3. 3. In cases of severe EPS with fever greater than or equal to 101, we recommend stopping neuroleptlcs, treating with anticholinergics and starting with dopamine agonists. In the event of a poor response to dopamine agonists, a brief trial of dantrolene and/or benzodiazepines is recommended. Dantrolene should not be introduced for prolonged periods, since abnormal liver function studies have been observed in approximately 1.8% of patients. 4. 4. In cases of extreme hyperpyrexia (fever greater than 103), clinicians should consider transfer to an ICU or another medical support. Extreme temperatures have been associated with potentially irreversible cerebellar or other brain damage, if not aggressively treated. If neuroleptlcs are later indicated, a 2 week interval after resolution of symptoms should be maintained before reinstituting neuroleptics. 5. 5. In patients with severe EPS without fever, we emphasize aggressive use of anticholinergic therapy, while simultaneously considering the psychiatric need for neuroleptics versus medical risks. In an cases where a patient's swallowing, respirations or physical mobility is severely compromised, we suggest stopping neuroleptlcs. Anticholinergic agents should be continued for 7 days after neuroleptics are stopped. If anticholinergic agents are unsuccessful after 2–3 dosages, dopamine agonlsts may be added, while simultaneously monitoring vital signs. It should be emphasized that severe EPS sometimes takes days to improve even after neuroleptic cessation and the addition of anticholinergics. 6. 6. If EPSs are intense or of long enough duration and, particularly, in the presence of akathisia and agitation, then a combination of excess heat production and interference with the hypothalamic temperature control mechanisms can produce a syndrome of NMS. If EPSs are avoided, neuroleptlcs are used in low dosages and benzodiazepines are used concomitantly for agitation, then we should see very little of NMS.

Prognostic factors for survival after pancreaticoduodenectomy for malignant disease

Forty patients underwent pancreaticoduodenectomy for malignant disease in a 25-year review of 6 Portland-area hospitals. After resection, 10 patients survived for greater than 5 years. Characteristics of survivors included a short prodrome of symptoms, minimal weight loss, tumor in the periampullary region, and female sex. Factors that did not influence survival included degree of jaundice, primary tumor size, and initial abnormal liver function studies.

Red blood cell transfusions for anemia

N THE LAST FOUR decades many advances have increased the safety and effectiveness of blood transfusion, t'2 including the identification of numerous clinically significant red cell antigens and antibodies. The risk of contracting transfusiontransmitted diseases has been vastly reduced by donor testing and thorough history screening. Technological developments have all but eliminated the use of whole blood, with most units being separated into components soon after blood donation. Concentrated products, such as packed red cells, maximize therapeutic benefit while limiting the risk of circulatory overload. This advance has had a significant impact on the treatment of oncology patients. Highly toxic treatment regimens, combined with aggressive transfusion support, are decreasing the morbidity and mortality of malignant disease and treatment. In spite of refinements in transfusion medicine practice which have made red blood cell (RBC) transfusion seem simple and safe, there are still potentially serious consequences. Approximately l in 100 transfusions is accompanied by fever, chills, or urticaria. Although these reactions are usually mild, 1 in 6,000 RBC transfusions results in an acute or delayed hemolytic reaction. Thirty fatal transfusion reactions are reported each year, almost all related to errors involving ABO incompatibility. The chance of contracting the human immunodeficiency virus (HIV) through transfusion is estimated to be 1 in 150,000, while 1 in 500 multiple-transfused recipients develop abnormal liver function studies, indicating some type of viral hepatitis) At the 1988 National Institutes of Health (NIH) Consensus Conference on Perioperative Red Cell Transfusion, experts in the field presented data which indicate that patients with hemoglobin levels below 10 g/dL do not have an increased incidence of surgical complications. There is no increase in anesthesia-induced hypotension or cardiac arrythmias, and wound healing is not delayed if perfusion remains adequate. 4 The recommendation resulting from the conference--to abolish hemoglobin trigger values and determine transfusion needs by the patient's clinical statushas significantly changed transfusion medicine practice.

Acute doxorubicin toxicity. Relationship to pretreatment liver function, response, and pharmacokinetics in patients with acute nonlymphocytic leukemia.

To determine if there is a relationship between development of acute doxorubicin toxicity, pretreatment liver function studies, and response, 64 acute nonlymphocytic leukemia patients undergoing induction chemotherapy with doxorubicin and cytosine arabinoside were evaluated. No statistically significant correlation could be found between the development of acute toxicity (mucositis) and the number or type of abnormal pretreatment liver functions. Patients receiving full doses of doxorubicin with mild hepatic dysfunction as determined by bromsulphalein (BSP) retention and serum liver function studies had the same incidence of toxicity and complete response rate as those with normal hepatic function. There was no significant difference between duration of response (P = 0.41) or survival (P = 0.17) between the two groups. Ten patients receiving a decreased dose of doxorubicin due to hepatic dysfunction had the same complete response rate but a lower incidence of toxicity as patients receiving full doxorubicin dose. Pharmacokinetic data from fluorescence plasma assays suggest no difference among patients with normal or mildly abnormal liver function studies receiving full doxorubicin doses. The results suggest that leukemia patients with mild hepatic dysfunction receiving a combination of full-dose doxorubicin and cytosine arabinoside for acute leukemia will have the same plasma pharmacokinetics, incidence of toxicity, and complete response rate as those with normal hepatic function. Reduction of doxorubicin dose in patients with abnormal liver function tests results in lower plasma concentrations, less toxicity, and the same response rate, but may also yield a shorter duration of response and survival.

Utility of radionuclide liver/spleen scanning and serum enzyme level in detecting hepatic metastases from ovarian carcinoma.

One hundred-five patients with ovarian carcinoma had radionuclide liver/spleen scanning done at the time of staging. Of the 105 initial scans, eight were interpreted as having hepatocellular dysfunction. Seven of these eight had abnormal liver function studies. One patient had a hepatic cyst but had elevated liver function studies. Six patients demonstrated hepatic metastases (at the time of staging). All but one of these occurred in Stage IV tumors of epithelial origin (adenocarcinoma). No hepatic metastases were demonstrated in Stage I or II tumors, and only one Stage III epithelial carcinoma had hepatic metastases. Three patients developed hepatic metastases during the course of treatment. All nine patients with hepatic metastases had abnormal concurrent liver function studies. It is suggested that screening for liver metastases in patients with ovarian carcinoma is of limited value in patients with normal liver function studies.

Radionuclide liver and bone scanning in the evaluation of patients with endometrial carcinoma.

Staging bone scans or skeletal surveys were obtained of 97 patients with endometrial carcinoma. Of the 77 patients with Stage I or II disease, no metastases were identified at staging. Three patients in the entire series demonstrated bony metastases; all of these metastases were detectable by radionuclide bone scan and radiographic bone survey. Eighty-nine patients were examined with radionuclide liver/spleen scanning at the time of staging. Four of the 89 initial scans were interpreted as demonstrating hepatocellular disease, and all four patients had abnormal liver function studies. Only one patient demonstrated a possible hepatic metastasis at initial diagnosis. This patient also had abnormal liver function studies. Based on these results, bone surveys and radionuclide bone scans are not indicated as screening procedures in endometrial carcinoma. It is suggested that screening for liver metastases in patients with endometrial carcinoma is not warranted in patients with normal liver function studies.

Erythropoietic protoporphyria 10 years experience

The clinical and laboratory findings in 32 patients with erythropoietic protoporphyria as well as a review of the pertinent literature on this relatively recently described form of porphyria are presented. The disease is thought to be transmitted in an autosomal dominant fashion with variable penetrance and was characterized in these 32 patients by the onset in childhood of burning (97 per cent) and itching (88 per cent) of the skin on exposure to sunlight. This was accompanied by edema (94 per cent) and erythema (69 per cent) of the exposed areas. Vesicles, petechiae and residual scarring occurred less frequently. Associated abnormalities included cholelithiasis (12 per cent), anemia (27 per cent) and abnormal liver function studies (4 per cent). Reports of associated liver disease including nine cases of fatal hepatic failure, are reviewed. Current methods of diagnosis as well as theories Of pathophysiology of the disease are presented. Nineteen of 23 of these patients recently treated with betacarotene responded with significant increase in their tolerance to sun exposure.

Significance of Abnormal Liver Function Studies in Psychiatric Admissions to Military Hospitals

Significance of Abnormal Liver Function Studies in Psychiatric Admissions to Military Hospitals

Problems in the Staging of Hodgkin Disease

To the Editor.— I agree in principle with Smith et al (224:1026, 1973) that a staging laparotomy may not be needed in all patients with Hodgkin disease, especially in those patients with stage I and II-A disease with favorable histology. To classify a patient as having clinical stage IV disease, however, on the basis of abnormal liver function studies or hepatomegaly, as was done by the authors preoperatively in four patients, is possibly a serious error. This has been demonstrated quite decisively by several studies, including those by Ultman1and Givler et al.2Ultman reported. liver biopsy studies on 120 patients who clinically had no evidence of liver involvement, four of whom were found to have Hodgkin disease in the liver. Thirty-two patients were thought to have liver involvement clinically; only three had positive liver biopsies on laparotomy. To avoid confusion in such patients it would be more

A prospective clinical trial of the "HIM" test.

The usefulness of the Hepatitis-Infectious Mononucleosis (HIM) Antibody Test in the differential diagnosis of the hospitalized patient with jaundice and elevated enzymes was evaluated. Fifty patients were selected for study by daily scannings of the bilirubin and transaminase determinations performed in the clinical laboratory of this hospital. Without knowledge of HIM test results, these patients were grouped clinically by two or three of the authors and by each patient's attending clinician. This grouping formed the following clinical classifications: 22 patients with abnormal liver function studies without infectious hepatitis, 21 patients with infectious hepatitis, 3 patients with chronic active hepatitis, 2 patients with infectious mononucleosis, and 2 patients who were categorized separately as a result of disagreement among the clinical reviewers regarding their diagnoses. HIM antibody titers were performed using coded serum specimens from the patients, 99 blood bank serum specimens, and sera from 21 infants and children 9 to 18 months of age. No significant differences were demonstrable among the means and ranges of HIM antibody titers of the groups studied. The authors concluded, therefore, that HIM testing of serum specimens from hospitalized jaundiced patients has no diagnostic value. Serial determinations of HIM antibody titers at weekly intervals in hospitalized jaundiced patients added no diagnostic potency to the HIM test.

Low plasminogen levels and liver disease.

The relationship between serum plasminogen levels and liver disease in patients without clinical bleeding disorders was investigated. The clinical history was evaluated, standard liver function tests were performed, and a plasminogen level based on the degradation of NPH insulin was determined. In all cases, low plasminogen levels were associated with abnormal liver function tests. Conversely, 75% of all patients with abnormal liver function studies also had low plasminogen levels. The mechanism involved in the low plasminogen values was not defined. It was demonstrated that plasminogen determinations offer no advantage as a liver function test. The consistent finding of low plasminogen levels associated with a variety of hepatic disorders considerably reduces the diagnostic utility of plasminogen determinations in the evaluation of bleeding disorders.

Wilson's disease presenting with rickets.

Wilson's disease is an inherited disorder of copper metabolism. Resultant kidney damage can induce metabolic bone disease, and in children the radiographic manifestations are indistinguishable from those of classical rickets. The patient who is the subject of this review was originally diagnosed as having vitamin D-resistant rickets. He had been well until the age of eight years, when pain and weakness of both knees developed in association with fever. Radiographs of knees and wrists (Fig. 1) taken at another hospital disclosed rachitic changes. Anemia, hypophosphatemia, and hypocalciuria were found. A diagnosis of vitamin D-resistant rickets was made. Treatment with vitamin D at a dose of 100,000 units daily induced symptomatic and radiographic evidence of remission (Fig. 2), but vitamin D intoxication supervened and the drug was discontinued at age ten. Initial evaluation at The New York Hospital in 1966, when the patient was eleven years old, showed return of rachitic changes on radiographs of the wrists and knees, a normal intravenous pyelogram, a serum calcium of 10.1 mg per 100 cc, and serum phosphorus of 2.2 mg per 100 cc. Vitamin D therapy was resumed with a dose of 20,000 units daily. Repeat films showed osteochondritis dissecans at the knees, rachitic changes, and a healing fracture of the distal radius (Fig. 3). In January 1967 a slit-lamp examination of the cornea, requested to evaluate the possible presence of calcium deposition, instead disclosed Kayser-Fleischer rings. Serum copper and ceruloplasmin were found to be low. A detailed neurological examination revealed slight tremor of tongue, moderate hyperreflexia, and mild terminal tremor. The liver and spleen were both slightly enlarged. A liver biopsy showed no fibrosis, but hepatic cell nuclei were seen to be enlarged and filled with glycogen. This latter finding is characteristic of first stage Wilson's disease. Members of the patient's immediate family were found to have low serum ceruloplasmin and copper levels. A sister has hepatomegaly, Kayser-Fleischer rings, and abnormal liver function studies The patient, at the age of twelve years, is currently receiving penicillamine 125 mg four times daily with pyridoxine 25 mg daily. This review is intended to draw attention to the radiologic manifestations of copper-induced nephropathy suffered by patients with Wilson's disease during a period of growth, when rickets may develop. This syndrome should be considered in the differential diagnosis of rickets, especially in the older child. It is hoped that children with Wilson's disease, who might otherwise be considered to have Fanconi's syndrome or vitamin D-resistant rickets, may be recognized early in the course of their disease. Under present modes of medical management, using D-penicillamine and low-copper diet, these patients can be spared an inexorably fatal disease, hopefully before significant morbidity has occurred.

Serum bilirubin levels in the newborn infant and their relation to clinical icterus and liver function studies

Summary Hemoglobin, hematocrit, and blood liver function studies were performed on twenty-five normal newborn infants during the first two days of life and repeated forty-eight to seventy-two hours later. Attempts were made to correlate total serum bilirubin with liver function studies, changes in the hemoglobin and hematocrit level and the degree of clinical icterus. No correlation could be established between the total serum bilirubin levels and the blood liver function studies. Even after a period of forty-eight to seventy-two hours had elapsed in cases where the blood bilirubin level was elevated, there were no signs of hepatic dysfunction as evidenced by abnormal liver function studies. Not all cases showed a significant drop in hemoglobin and hematocrit associated with a rise in serum bilirubin. Conversely, some cases showed an appreciable rise in bilirubin with little or no change in hemoglobin or hematocrit. In not all instances could the total serum bilirubin be directly correlated with the extent of clinical jaundice. In some cases jaundice was noted where the bilirubin level was only moderately elevated, whereas in other cases there was no jaundice with appreciably elevated serum bilirubin. When total serum cholesterol studies were performed on infants during the first or second day of life, the results tended to be significantly lower than the level obtained on the same infant on the third to fifth day of life.