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K V Kowdley

Publications and source records attributed to K V Kowdley.

At least 19 recordsLinked to original sources
PubMed1999

Etiology and outcome for 295 patients with acute liver failure in the United States.

Little information is available on acute liver failure (ALF) in the United States. We gathered demographic data retrospectively for a 2-year period from July 1994 to June 1996 on all cases of ALF from 13 hospitals (12 liver transplant centers). Data on the patients included age, hepatic coma grade on admission, presumed cause, transplantation, and outcome. Among 295 patients, 74 (25%) survived spontaneously, 121 (41%) underwent transplantation, and 99 (34%) died without undergoing transplantation. Ninety-two of 121 patients (76%) survived 1 year after transplantation. Acetaminophen overdose was the most frequent cause (60 patients; 20%), followed by cryptogenic/non A non B non C (NANBNC; 15%), idiosyncratic drug reactions (12%), hepatitis B (10%), and hepatitis A (7%). Spontaneous survival rates were highest for patients with acetaminophen overdose (57%) and hepatitis A (40%) and lowest for those with Wilson's disease (no survivors of 18 patients). The transplantation rate was highest for Wilson's disease (17 of 18 patients; 94%) and lowest for autoimmune hepatitis (29%) and acetaminophen overdose (12%). Age did not differ between survivors and nonsurvivors, perhaps reflecting a selection bias for patients transferred to liver transplant centers. Coma grade on admission was not a significant determinant of outcome, but showed a trend toward affecting both survival and transplantation rate. These findings on retrospectively studied patients from the United States differ from those previously gathered in the United Kingdom and France, highlighting the need for further study of trends in each country.

Acetaminophen↗
PubMed1998

Diagnosis of hemochromatosis.

If untreated, hemochromatosis can cause serious illness and early death, but the disease is still substantially under-diagnosed. The cornerstone of screening and case detection is the measurement of serum transferrin saturation and the serum ferritin level. Once the diagnosis is suspected, physicians must use serum ferritin levels and hepatic iron stores on liver biopsy specimens to assess patients for the presence of iron overload. Liver biopsy is also used to establish the presence or absence of cirrhosis, which can affect prognosis and management. A DNA-based test for the HFE gene is commercially available, but its place in the diagnosis of hemochromatosis is still being evaluated. Currently, the most useful role for this test is in the detection of hemochromatosis in the family members of patients with a proven case of the disease. It is crucial to diagnose hemochromatosis before hepatic cirrhosis develops because phlebotomy therapy can avert serious chronic disease and can even lead to normal life expectancy.

Biopsy↗
PubMed1998

Management of hemochromatosis. Hemochromatosis Management Working Group.

The complications of iron overload in hemochromatosis can be avoided by early diagnosis and appropriate management. Therapeutic phlebotomy is used to remove excess iron and maintain low normal body iron stores, and it should be initiated in men with serum ferritin levels of 300 microg/L or more and in women with serum ferritin levels of 200 microg/L or more, regardless of the presence or absence of symptoms. Typically, therapeutic phlebotomy consists of 1) removal of 1 unit (450 to 500 mL) of blood weekly until the serum ferritin level is 10 to 20 microg/L and 2) maintenance of the serum ferritin level at 50 microg/L or less thereafter by periodic removal of blood. Hyperferritinemia attributable to iron overload is resolved by therapeutic phlebotomy. When applied before iron overload becomes severe, this treatment also prevents complications of iron overload, including hepatic cirrhosis, primary liver cancer, diabetes mellitus, hypogonadotrophic hypogonadism, joint disease, and cardiomyopathy. In patients with established iron overload disease, weakness, fatigue, increased hepatic enzyme concentrations, right upper quadrant pain, and hyperpigmentation are often substantially alleviated by therapeutic phlebotomy. Patients with liver disease, joint disease, diabetes mellitus and other endocrinopathic abnormalities, and cardiac abnormalities often require additional, specific management. Dietary management of hemochromatosis includes avoidance of medicinal iron, mineral supplements, excess vitamin C, and uncooked seafoods. This can reduce the rate of iron reaccumulation; reduce retention of nonferrous metals; and help reduce complications of liver disease, diabetes mellitus, and Vibrio infection. This comprehensive approach to the management of hemochromatosis can decrease the frequency and severity of iron overload, improve quality of life, and increase longevity.

Diet↗
PubMed1998

Public health surveillance for hereditary hemochromatosis.

The recent realization that hemochromatosis is a common condition has created opportunities to develop unified public health surveillance for this disorder and its complications and to design programs to prevent unnecessary illness and death resulting from this disorder. Public health surveillance for hemochromatosis can be used to measure the magnitude of the problem (for example, to establish the number of persons with evidence of early iron overload); identify research needs; reveal the natural history of the disease; detect changes in health care practices, such as use of screening tests; and evaluate interventions, such as phlebotomy. Existing surveillance has been limited to periodic measurement of morbidity and mortality done by using hospital discharge records, health examination surveys, vital statistics, and data from small research registries. The improvement of surveillance will entail the ongoing collection of information from population-based surveys, such as the Behavioral Risk Factor Surveillance System; the collection of data on provider practices (for example, through the National Ambulatory Medical Care Survey); and the establishment of population-based registries. Creating population-based registries requires consensus on case definitions; strategies to encourage case ascertainment and reporting; policies and procedures for protecting privacy and ensuring confidentiality; and partnerships among providers, researchers, and public health officials. Longitudinal data from population-based registries will provide insight into determinants of disease expression, such as pattern or degree of iron overload. This information is critical for developing evidence-based recommendations for population screening, monitoring changes in medical practices, and assessing the effect of preventive measures.

Confidentiality↗
PubMed1998

Successful treatment of severe hepatitis C-associated pulmonary vasculitis in a liver transplant recipient.

BACKGROUND: We report the clinical course of a patient who developed fever, hypoxia, and bilateral pulmonary infiltrates two and a half years after orthotopic liver transplantation (OLT) for cirrhosis due to hepatitis C. The patient had a history of hepatitis C-associated vasculitis manifested by purpuric skin rashes, renal abnormalities, and elevated cryoglobulins, and was receiving interferon-alpha at the time of presentation. RESULTS: The results of bronchoscopy with bronchoalveolar lavage were unrevealing, and open lung biopsy revealed active small vessel vasculitis. The patient responded dramatically to plasmapheresis and the addition of high-dose corticosteroids with resolution of hypoxia, pulmonary infiltrates, and glomerulonephritis. This is, to our knowledge, the first report of the successful treatment of hepatitis C-associated pulmonary vasculitis after OLT. CONCLUSIONS: We conclude that hepatitis C-associated pulmonary vasculitis should be included in the differential diagnosis of a patient presenting with fever, hypoxia, and pulmonary infiltrates after OLT for hepatitis C. Treatment with plasmapheresis and high-dose corticosteroids may be effective in patients with this disorder.

Adrenal Cortex Hormones↗
PubMed1998

Predictors of bile leaks after T-tube removal in orthotopic liver transplant recipients.

Bile leaks after T-tube removal are a frequent cause of morbidity in orthotopic liver transplant recipients. The aim of this study was to determine factors that predict the development of these leaks in liver transplant recipients. Records of all patients who had undergone liver transplantation at the University of Washington Medical Center between January 1990 and September 1993 were reviewed. The following were excluded: patients with a Roux-en-Y anastomosis or inadvertent early T-tube removal and patients who died or underwent retransplantation before T-tube removal. All T-tube cholangiograms were reviewed blindly by two authors. Using logistic regression, several variables were assessed for possible association with bile leaks after T-tube removal; these included patient demographics, intraoperative variables, and clinical and cholangiographic variables related to T-tube removal. Of the 166 liver transplants performed in 150 patients, 99 transplants in 97 patients were evaluable for bile leak after T-tube removal. Thirty-three patients developed symptomatic bile leaks, and 21 underwent endoscopic or operative intervention for persistent symptoms. Only duct mural irregularities on the final cholangiogram were strongly associated with the development of a bile leak after T-tube removal (P = 0.001). In conclusion, bile leaks after T-tube removal occurred in one-third of patients undergoing orthotopic liver transplantation; the majority of these patients required some intervention. Duct mural irregularities were associated with bile leaks.

Adolescent↗
PubMed1998

Biliary lipid composition after liver transplantation: effect of allograft function and cyclosporine.

Biliary lipid composition and bile flow are altered after orthotopic liver transplantation. Cyclosporine may have additional effects on biliary lipid composition and secretion. We studied the effects of liver transplantation, allograft function, and cyclosporine on biliary lipids in humans. Changes in lipid composition and secretion were correlated with serum cyclosporine levels, clinical events, and allograft function. Bile samples were withdrawn via a T-tube at interval time points in 17 patients during the first 3 months posttransplantation. Total and individual bile acid, cholesterol, and phospholipid were determined using high-performance liquid chromatography. Biliary lipid profiles were then correlated with clinical events, serum cyclosporine levels, and other clinical laboratory values. Biliary lipid concentrations decreased in 3 patients during periods of graft dysfunction (acute cellular rejection, drug-induced hepatitis, and inferior vena caval thrombosis) and increased with resolution of the graft injury. Serum cyclosporine levels were positively correlated with total bile acid, cholesterol, and phospholipid concentrations in bile. There was no relationship between the composition of secreted bile acids and serum cyclosporine levels. Bile acid, cholesterol, and phospholipid secretion were not uncoupled in the presence of cyclosporine. We concluded that (1) a decrease in biliary lipid concentrations may be an indicator of worsened graft function in some allografts; (2) biliary lipid concentrations are correlated with increasing cyclosporine levels; and (3) bile acid composition is unchanged, and uncoupling of secretion of other biliary lipids is not observed in the presence of cyclosporine.

Adolescent↗
PubMed1998

Endoscopic management of biliary strictures in liver transplant recipients: effect on patient and graft survival.

BACKGROUND: Biliary strictures in liver transplant recipients cause significant morbidity and can lead to reduced patient and graft survival. METHODS: Of 251 liver transplant recipients, 22 patients with biliary strictures were categorized into two groups: donor hepatic duct (n = 12) or anastomotic (n = 10). Strictures were dilated and stented. Endoscopic therapy was considered successful if a patient did not require repeat stenting or dilation for 1 year. RESULTS: Patient and graft survival did not differ significantly in the 22 patients compared with patients without strictures (relative risk of death and graft survival 1.8 and 1.3). Donor hepatic duct strictures required significantly longer therapy than anastomotic strictures (median days 185 versus 67, p = 0.02). Twenty-two months after the first endoscopic treatment, 73% of the donor hepatic duct stricture group were stent free compared with 90% of the anastomotic group (p = 0.02). The former group had significantly more (p < 0.05) hepatic artery thrombosis (58.3% versus 10%), cholangitis (58.3% versus 30%), choledocholithiasis (91% versus 10%), and endoscopic interventions. No patient undergoing endoscopic treatment required retransplantation or biliary reconstruction during a median follow-up of 35.7 months. CONCLUSION: Endoscopic therapy of biliary strictures after liver transplantation is effective and is not accompanied by reduced patient or graft survival.

Adult↗
PubMed1998

End-stage liver disease without hemochromatosis associated with elevated hepatic iron index.

BACKGROUND/AIMS: The utility of standard diagnostic tests for hereditary hemochromatosis in end-stage liver disease is unknown. A homozygous mutation (Cys 282 Tyr) has been identified in most patients with hereditary hemochromatosis. We examined whether serum iron studies and hepatic iron measurement distinguish end-stage liver disease patients with Cys 282 Tyr-associated hereditary hemochromatosis. METHODS: Serum iron, total iron binding capacity, and ferritin were measured in 106 cirrhotic patients prior to liver transplantation. Hepatic iron concentration and hepatic iron index were measured from explant liver tissue. Genotyping was performed on explant liver tissue in patients with an elevated hepatic iron index (>1.9). RESULTS: Thirty-three of 106 (31%) patients had elevated serum iron studies suggestive of hereditary hemochromatosis. Only four of 33 (12%) had a mean hepatic iron index >1.9, and none of the four patients was homozygous for Cys 282 Tyr. All four had liver disease due to hepatitis C and/or alcohol. CONCLUSIONS: (i) Serum transferrin saturation and hepatic iron index lack specificity for hereditary hemochromatosis in end-stage liver disease. (ii) Genotyping for Cys 282 Tyr may provide the best method to identify hereditary hemochromatosis in the setting of end-stage liver disease.

Female↗
PubMed1998

Clinical management of iron overload.

HHC is a common inherited disorder, characterized by iron accumulation in the liver, heart, pancreas, and other organs. The clinical consequences of systemic iron loading are diverse and not always improved with iron reduction therapy. The most important prognostic factor at the time of diagnosis is the presence or absence of hepatic fibrosis or cirrhosis. Those without significant hepatic fibrosis may be expected to have a normal life expectancy with phlebotomy therapy. The availability of genetic testing for HHC has significantly changed the diagnostic approach to this disorder. Although liver biopsy remains vital to determining prognosis, genetic testing is increasingly used in the diagnosis and family screening of patients with HHC.

Hemochromatosis↗
PubMed1998

Iron overload in bone marrow transplant recipients.

We examined the degree of hepatic iron overload in patients receiving marrow transplant for hematologic malignancy and evaluated a new method of morphometric analysis of marrow iron content as a means of estimating hepatic iron stores in these patients. The iron content of marrow and liver specimens from 10 consecutive patients who died between 50 and 100 days after transplant was determined by spectrophotometry. Their mean age was 34.9 years (range 10-59). The mean time to death from disease onset was 2.2 years (0.5-8.7). Patients had received 30.2 +/- 17.4 units of red cells during the transplant period and 47.6 +/- 25.9 red cell units from diagnosis to death. The median hepatic iron concentration (HIC) was 4307 microg/g dry weight (range 1832-13120; normal 530-900) and the median hepatic iron index (HIC (micromol/g dry weight/age (years)) was 3.85 (0.76-8.14). The median biochemical marrow iron content was 1999 microg/g dry weight (range 932-3942). Morphometric analysis of the marrow iron content was performed on digital photomicrographs of a single Prussian blue-stained section of marrow. Strong correlations were demonstrated between morphometric marrow iron content and (1) biochemical marrow iron content (r = 0.8, P= 0.006) and (2) biochemical hepatic iron index (r = 0.82, P = 0.004). We conclude that marrow transplant recipients have a high liver iron content at 50-100 days post transplant with the hepatic iron index in the hereditary hemochromatosis range. Computerized morphometric marrow iron determination is a readily available means of estimating hepatic iron stores in these patients.

Adolescent↗
PubMed1998

Listeria infection after liver transplantation: report of a case and review of the literature.

Listeria monocytogenes is a well-recognized cause of bacteremia and meningitis in immunocompromised individuals, including recipients of solid organ transplants, but has only rarely been reported following orthotopic liver transplantation (OLT). Most previously reported cases of listeriosis occurred months to years following liver transplantation; we describe a case of listeriosis that occurred within 1 wk of liver transplantation, shortly after discontinuation of trimethoprim-sulfamethoxazole prophylaxis, and review the English literature on Listeria infection after OLT. The patient developed abdominal pain and fever that suggested a bile leak, but was definitively diagnosed with Listeria infection by blood culture. The infection was successfully treated with 3 wk of intravenous ampicillin. We conclude that serious systemic infection with Listeria monocytogenes is uncommon following OLT, may occur early in the postoperative period, and responds well to treatment with high dose ampicillin.

Adult↗
PubMed1997

Renal disease in hepatitis C-positive liver transplant recipients.

Glomerular abnormalities are frequent in patients undergoing liver transplantation; however, renal dysfunction following transplantation is mainly attributed to cyclosporine toxicity. Membranoproliferative glomerulonephritis (MPGN) is seen in patients infected with hepatitis C virus (HCV), the virus responsible for 30% of the end-stage liver disease leading to liver transplantation. To determine the incidence of renal abnormalities in liver transplant recipients and the association with HCV, we undertook a longitudinal study in HCV-positive (n=91) and HCV-negative (n=106) liver transplant recipients. Mean creatinine clearance before transplantation was 94 ml/min/1.73 m2 in HCV+ patients and 88 ml/min/1.73 m2 in HCV- patients. By 3 months after transplantation, the mean creatinine clearance decreased by approximately one third in both groups. A greater proportion of HCV+ patients excreted >2 g protein/day after transplantation (P=0.05) and had renal biopsies showing MPGN than did HCV- recipients (4/10 HCV+ patients vs. 0/7 HCV- patients; P=0.1). In the HCV+ group, proteinuria was not associated with recurrent HCV hepatitis, DQ matching, posttransplant diabetes, or hypertension. Treatment of HCV-related MPGN with interferon-alpha2b appeared to stabilize proteinuria and renal function but did not reverse renal dysfunction nor cause liver allograft rejection. After transplantation, HCV+ patients had similar renal function over 3 years after transplantation, compared with HCV- patients, but they had an increased risk of proteinuria and occurrence of MPGN that was only partially responsive to interferon.

Adult↗
PubMed1997

Infection complicating percutaneous liver biopsy in liver transplant recipients.

There is controversy about the frequency of and risk factors for infectious complications of percutaneous liver biopsy in liver transplant recipients. The aim of this study was to identify the incidence and nature of complications associated with liver biopsy after orthotopic liver transplantation (OLT), with particular emphasis on infection. The medical records of all patients undergoing OLT between January 1990 and August 1994 were reviewed retrospectively to identify complications requiring hospitalization within one week of percutaneous liver biopsy. The nature and severity of complications were recorded and possible risk factors for infectious complications were examined. One hundred ninety-eight patients underwent 1,136 percutaneous liver biopsies. There were eleven complications (0.96%), including as follows: 7 infections, 3 bleeding episodes, and 1 vasovagal reaction. Infections after percutaneous liver biopsy included fever and bacteremia (n = 6), and fever without bacteremia (n = 1). All infections developed only in patients with underlying biliary tract abnormalities; the frequency of infection was higher (9.8%) in patients with choledochojejunostomy when compared with those with choledochocholedochostomy (1.4%). Bacteremia was more likely caused by skin flora in patients with choledochocholedochostomy (CDC) and by enteric bacteria in patients with choledochojejunostomy (CDJ). All infections were treated successfully with parenteral antibiotics. We conclude that biliary tract abnormalities are the primary risk factors for infection after percutaneous liver biopsy, although the risk is higher in patients with CDJ than with CDC. These data support the use of antibiotic prophylaxis before percutaneous liver biopsy in OLT recipients with biliary tract abnormalities.

Anastomosis, Roux-en-Y↗
PubMed1997

Utility of hepatic iron index in American patients with hereditary hemochromatosis: a multicenter study.

BACKGROUND & AIMS: A hepatic iron index (hepatic iron concentration divided by age) of more than 1.9 has been proposed as useful to identify patients with homozygous hereditary hemochromatosis (HHC). There are limited data on the diagnostic use of the hepatic iron index in patients with HHC in the United States. This study evaluated the hepatic iron index in the diagnosis of HHC in a multicenter U.S. study. METHODS: Hepatic iron concentration was measured in 509 patients undergoing liver biopsy. The diagnosis of HHC was made using clinical, biochemical, and histopathologic criteria. RESULTS: Fifty-five patients met criteria for HHC; hepatic iron index was > 1.9 in 51 of 55 (93%) patients with HHC but in none of 454 patients with other liver diseases; hepatic iron concentration was > 71 mumol/g dry weight in 54 of 55 patients with HHC but only 1 of the other 454 patients. CONCLUSIONS: A hepatic iron index of > or = 1.9 can identify most U.S. patients with HHC but is < or = 1.9 in 7%. A "threshold" hepatic iron concentration of 71 mumol/g can almost always distinguish patients with HHC from patients with other liver diseases and may be a useful adjunct to the hepatic iron index in the diagnosis of HHC in the diverse U.S. population.

Adult↗