Serum ferritin level predicts advanced hepatic fibrosis among U.S. patients with phenotypic hemochromatosis.

BACKGROUND: DNA-based HFE gene testing can confirm hereditary hemochromatosis in most people of Northern European descent. However, liver biopsy is important to detect cirrhosis. OBJECTIVE: To develop noninvasive criteria to predict the presence or absence of advanced hepatic fibrosis or cirrhosis in Americans with hemochromatosis. DESIGN: Cross-sectional study. SETTING: Six tertiary care referral clinics. PATIENTS: 182 patients with phenotypically defined hemochromatosis. MEASUREMENTS: Liver histopathology and serum ferritin, aspartate aminotransferase, and alanine aminotransferase levels. Multivariate logistic regression analysis was used to examine factors associated with cirrhosis (defined as bridging fibrosis or unequivocal cirrhosis on biopsy). RESULTS: Cirrhosis was present in 40 of 182 (22%) patients in the overall group and in 35 of 147 (24%) of C282Y homozygotes. Only 1 of 93 patients with a serum ferritin level less than 1000 microg/L had cirrhosis compared with 39 of 89 patients with serum ferritin levels greater than 1000 microg/L (P < 0.001). No C282Y homozygotes or C282Y/H63D compound heterozygotes with serum ferritin levels less than 1000 microg/L had cirrhosis. Elevated serum aminotransferase levels (P = 0.001) and serum ferritin levels greater than 1000 microg/L (P = 0.001), but not age older than 40 years (P = 0.2), were independently associated with cirrhosis. In a multivariate model, the probability of cirrhosis was 7.4% among patients with serum ferritin levels less than 1000 microg/L compared with 72% among patients with serum ferritin levels greater than 1000 microg/L after adjustment for age and elevated serum liver enzyme levels. CONCLUSIONS: Patients with hemochromatosis and serum ferritin levels less than 1000 microg/L are unlikely to have cirrhosis. Liver biopsy to screen for cirrhosis may be unnecessary in such patients, regardless of age or serum liver enzyme levels.

Association of porphyria cutanea tarda with hereditary hemochromatosis.

BACKGROUND: An increased frequency of hereditary hemochromatosis gene mutations occurs in patients with porphyria cutanea tarda. Polymerase chain reaction analysis of peripheral blood for hemochromatosis gene (HFE) mutations is available for clinical use. Early detection and treatment of hereditary hemochromatosis limit disease progression and improve life expectancy. OBJECTIVE: We present 8 patients with porphyria cutanea tarda subsequently found to have hereditary hemochromatosis or mutations in the HFE gene. METHODS: Retrospective review of patients in whom both porphyria cutanea tarda and hereditary hemochromatosis or HFE gene mutations were diagnosed between 1976 and 2000. RESULTS: Eight patients with porphyria cutanea tarda (6 males, 2 females; age range, 4-60 years; mean age at diagnosis of porphyria cutanea tarda, 42 years) were subsequently found to have hepatic iron overload or HFE gene mutations. Two patients had liver biopsy findings compatible with homozygous hereditary hemochromatosis. In the other 6 patients, HFE gene analysis revealed 3 homozygous C282Y, 1 compound heterozygous C282Y/H63D, and 2 heterozygous C282Y mutations. Seven patients (88%) had no specific signs or symptoms of hereditary hemochromatosis at diagnosis. In 5 patients (63%), the diagnosis of hereditary hemochromatosis or HFE gene mutation was initially suspected by the dermatologist. CONCLUSION: Porphyria cutanea tarda can be an important cutaneous marker for patients with mutations of the HFE gene. HFE gene analysis should be done in patients who present with porphyria cutanea tarda. The dermatologist may play a key role in the early diagnosis of subclinical hereditary hemochromatosis in patients who present with porphyria cutanea tarda.

Hypophosphatemia after right hepatectomy for living donor liver transplantation.

Hypophosphatemia has been described in patients undergoing right hepatectomy for liver cancer and in living donors for liver transplantation who also received total parenteral nutrition. At the study centre, significant hypophosphatemia (0.36 mmol/L or less) requiring intravenous replacement was seen in two of the first nine living donors for adult-to-adult liver transplantation. To determine the frequency of hypophosphatemia in living donors, the authors obtained phosphate levels on stored serum samples from postoperative days 0, 1, 3 and 7 in all nine patients, none of whom were on total parenteral nutrition. Within the first week, hypophosphatemia developed in 55.6% of patients and phosphate levels returned to normal by day 7 in all nine patients. One patient had normal phosphate levels during the first week, but had profound hypophosphatemia (0.32 mmol/L) on day 14 when he presented with a Staphylococcus aureus infection of a bile collection and significant hypoxemia. The extent of hepatectomy and the rate of liver regeneration, estimated by baseline and postoperative day 7 volumetric computed tomography scans, did not correlate with the development of hypophosphatemia. In conclusion, hypophosphatemia is common in living donors undergoing right hepatectomy and may be associated with complications. All living donors should be monitored for the development of hypophosphatemia during the first two postoperative weeks.

Successful treatment of hepatocellular adenoma with percutaneous radiofrequency ablation.

OBJECTIVE: The purpose of our study was to report the safe and successful treatment of hepatocellular adenoma with percutaneous radiofrequency ablation. CONCLUSION: Our limited experience indicates that percutaneous radiofrequency ablation is both safe and effective in the treatment of the small hepatocellular adenoma in carefully selected patients.

Survival after liver transplantation in patients with hepatic iron overload: the national hemochromatosis transplant registry.

BACKGROUND & AIMS: Previous uncontrolled studies have suggested that patients with hepatic iron overload have a poor outcome after liver transplantation. We examined the effect of HFE mutations on posttransplantation survival in patients with hepatic iron overload. METHODS: Two hundred sixty patients with end-stage liver disease and hepatic iron overload were enrolled from 12 liver transplantation centers. Hepatic iron concentration (HIC), hepatic iron index (HII), HFE mutation status, and survival after liver transplantation were recorded. RESULTS: HFE-associated hemochromatosis (HH) defined as homozygosity for the C282Y (n = 14, 7.2%) mutation or compound heterozygosity for the C282Y/H63D (n = 11, 5.6%) mutation was identified in 12.8% of patients. Survival postliver transplantation was significantly lower among patients with HH (1-, 3-, and 5-year survival rates of 64%, 48%, 34%, respectively) compared with simple heterozygotes (C282Y/wt or H63D/wt) or wild-type patients. Patients with HH had a hazard ratio for death of 2.6 (P = .002) after adjustment for age, United Network for Organ Sharing status, year of transplantation, and either elevated HII or HIC. Non-HH patients with hepatic iron overload also had significantly decreased survival when compared with the overall population undergoing liver transplantation (OR = 1.4, 95% CI: 1.15-1.61, P < .001). CONCLUSIONS: One- and 5-year survivals after liver transplantation are significantly lower among patients with HFE-associated HH. Our data also suggest that hepatic iron overload may be associated with decreased survival after liver transplantation, even in patients without HH. Early diagnosis of hepatic iron overload using HFE gene testing and iron depletion prior to liver transplantation may improve posttransplantation survival, particularly among patients with HH.

Recognition and management of hereditary hemochromatosis.

Hereditary hemochromatosis is the most common inherited single-gene disorder in people of northern European descent. It is characterized by increased intestinal absorption of iron, with deposition of the iron in multiple organs. Previously, the classic description was combined diabetes mellitus, cutaneous hyperpigmentation and cirrhosis. Increasingly, however, hereditary hemochromatosis is being diagnosed at an earlier, less symptomatic stage. The diagnosis is based on a combination of clinical, laboratory and pathologic findings, including elevated serum transferrin saturation. Life expectancy is usually normal if phlebotomy is initiated before the development of cirrhosis or diabetes mellitus. Hereditary hemochromatosis is associated with mutations in the HFE gene. Between 60 and 93 percent of patients with the disorder are homozygous for a mutation designated C282Y. The HFE gene test is useful in confirming the diagnosis of hereditary hemochromatosis, screening adult family members of patients with HFE mutations and resolving ambiguities concerning iron overload.

Ultrasound-assisted percutaneous liver biopsy performed by a physician assistant.

OBJECTIVE: Percutaneous liver biopsy is an essential diagnostic tool utilized in the management of patients with liver disease. This procedure is generally performed by a physician and has a small but well-defined complication rate. We report on the complication rate and efficiency of ultrasound-assisted percutaneous liver biopsy performed by an experienced physician assistant. METHODS: One thousand eighty-six consecutive outpatient liver biopsies (847 hepatic allografts and 239 native livers) were performed at a single center by a physician assistant between June, 1996 and June, 2000. Patients with hepatic mass lesions, unusual hepatic anatomy, and uncorrectable coagulopathy (international normalized ratio > 1.7, platelet count < 50 x 10(9)/L) were excluded. Bedside ultrasonography was used to determine the optimal site for the liver biopsy. Liver biopsies were performed with a 15-gauge Jamshidi aspiration biopsy needle. Patients were observed for 3 h after biopsy, followed by dismissal with subsequent contact in 24 h to assess outcome and complications. RESULTS: Adequate tissue was obtained in 1084 cases (99.8%), with a mean tissue length of 3.2 cm. After the procedure, narcotic analgesia was necessary in 116 (10%) of the patients undergoing liver biopsies. The overall complication rate requiring hospitalization was 0.6%. Major complications requiring intervention occurred in four patients (0.4%). There were no deaths resulting from liver biopsies. CONCLUSION: We conclude that outpatient percutaneous liver biopsy can be safely and effectively performed by a trained physician assistant.

Liver allograft iron accumulation in patients with and without pretransplantation hepatic hemosiderosis.

There is a paucity of data regarding hepatic allograft iron accumulation in patients undergoing orthotopic liver transplantation (OLT) in whom severe iron overload was present in the native explanted liver. Our aim is to evaluate the frequency and cellular distribution of stainable iron in early and late post-OLT hepatic allograft biopsy specimens from patients undergoing their first OLT who had excess iron in their native explanted liver. We compared iron-staining patterns in hepatic allograft biopsy specimens at approximately 1 month (early) and 1 to 2 years (late) post OLT in 41 patients with hepatic iron indices greater than 1.9 in the explanted liver (cases) with a selected group of matched controls without explant hemosiderosis. Our cases included 6 patients with a pre-OLT diagnosis of hereditary hemochromatosis and 35 patients with cirrhosis and secondary iron overload. Early iron deposition was mild in most cases, commonly affected Kupffer's cells, and was seen with similar frequency in cases and controls (41% v 27%; P =.29). Stainable iron was observed in 20 donor livers (12 cases, 8 controls), and all 20 subjects showed stainable iron in 1-month hepatic allograft biopsy specimens. Liver samples from 35 matched pairs were studied for late iron deposition. Iron deposition was observed in 43% of cases versus 17% of controls (P =.06). In conclusion, the frequency of stainable iron in early hepatic allograft biopsy specimens was not different between patients with versus without pre-OLT hepatic hemosiderosis. There was a suggestion that patients with severe pre-OLT hemosiderosis had a greater frequency of iron accumulation in late hepatic biopsy specimens.

Outcome of liver transplantation for familial amyloidotic polyneuropathy.

Familial amyloidotic polyneuropathy (FAP) is an autosomal dominant disorder caused by mutation in the transthyretin gene. The most common mutation is substitution of valine for methionine at position 30 (MET30). Liver transplantation (LT) is the preferred treatment. After LT, although many patients show stabilization or improvement in the disease, adverse outcomes have been reported in those who have malnutrition, long-standing disease, and non-MET (NMET) mutations at position 30. Our aim is to compare survival and outcome of symptoms associated with FAP after LT in patients with MET30 and NMET30 mutations. Medical records of all patients who underwent LT for amyloidosis at our institution were reviewed to obtain demographic information and clinical features, such as severity of neuropathy, diarrhea, orthostatic hypotension, and posterior wall or ventricle septal thickness before and after LT. Fifteen patients underwent LT for amyloidosis at our institution between 1990 and 2000 (MET30, n = 5; NMET30, n = 7; hereditary amyloidosis, n = 2; primary amyloidosis, AL type, n = 1). Patients with hereditary and primary amyloidosis were excluded from analysis. One- and 3-year survival rates after LT in MET30 patients were 100%. Before LT, five of five patients had sensorimotor neuropathy; five of five patients had diarrhea, and four of five patients had orthostatic hypotension. After LT, improvement or stabilization of neuropathy was seen in two of five patients; of diarrheal symptoms, in three of five patients; and of orthostatic hypotension, in three of four patients. One- and 3-year survival rates after LT in NMET30 patients were 100% and 85.7%, respectively. Before LT, six of seven patients had sensorimotor neuropathy, six of seven patients had diarrhea, and five of seven patients had orthostatic hypotension. After LT in this group, improvement or stabilization of neuropathy was seen in two of six patients; of diarrhea, in six of six patients; and of orthostatic hypotension, in five of five patients. Before LT, posterior wall and/or ventricle septal thickness was increased in two of five MET patients and seven of seven NMET patients. Five of seven NMET30 patients (71.4%) who received a combined liver and heart transplant had stabilization, and two patients in the NMET group and one patient in the MET group had progression of heart disease. Outcomes for LT for patients with FAP with MET or NMET mutations were similar. Earlier LT for patients with FAP with MET30 or NMET30 mutation would improve outcomes after LT.