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Biomedical subjects

J P Ong

Publications and source records attributed to J P Ong.

10 recordsLinked to original sources

The metabolic syndrome and nonalcoholic fatty liver disease.

Accumulating evidence supports an association between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome, diabetes, and obesity. The epidemiology, pathogenesis, and approach to treatment of NAFLD follow the same trends as these other metabolic disorders, and insulin resistance is the key event linking NAFLD to these diseases. The impairment in fat and glucose metabolism that ensues once insulin resistance occurs leads to similar biochemical and clinical abnormalities in patients with NAFLD. Many recent studies investigating the cellular and genetic basis of these diseases have led to a better understanding of their pathogenesis and insight into treatment and management. The most effective treatment thus far is weight loss and the use of insulin-modulating pharmacologic agents. A few additional treatment strategies include the use of lipid-lowering, antioxidants or cytoprotective agents, but there is no single therapeutic approach that is effective for managing NAFLD. Future therapies may combine drugs that target specific pathways involved in NAFLD pathogenesis.

Diabetes Mellitus, Type 2↗

Survival and resource utilization in liver transplant recipients: the impact of admission to the intensive care unit.

The organ allocation system for liver transplantation was recently changed to address criticisms that it was too subjective and relied too heavily on total waiting time. The new system, Model for End-Stage Liver Disease and Pediatric Model for End-Stage Liver Disease (MELD/PELD), stratifies patients based on the risk of 3-month pretransplant mortality, allocating livers thereby. There is concern that such a scheme gives priority to the sickest patients, who may not enjoy good posttransplant outcomes. The aim of the present study was to compare the outcomes of liver transplant recipients who had been admitted to the intensive care unit (ICU) to those who had not. Admission to the ICU is considered here to be another indicator of the severity of illness. Patients who underwent liver transplantation at the Cleveland Clinic between January 1, 1993 and October 31, 1998 and were at least 18 years of age were coded for liver transplantation as status 2, 2A, and 2B (n = 112). These patients fell into three groups: those who had been admitted to an ICU before transplantation (group A, n = 16), those who had been admitted to the hospital but not to an ICU (group B, n = 63), and those who were living at home and had undergone an elective transplant (group C, n = 33). Clinical and demographic information (age, sex, race, disease severity, disease etiology, and cold ischemia time) were associated with patient survival, patient/graft survival, and posttransplant resource utilization (hospital length of stay and hospital charges). Age, sex, race, etiology of disease, and cold ischemia time were similar among the three groups. Patient survival, patient/graft survival, and hospital charges were not statistically different between the three groups. The median length of stay was statistically different only between groups B and C (P =.006). Our data support the idea that if severely ill patients with end-stage liver disease are selected appropriately, liver transplant outcomes are similar to those observed among subjects who are less ill and are transplanted electively from home.

Female↗

Interferon alpha 2B and ribavirin in severe recurrent cholestatic hepatitis C.

Severe recurrent cholestatic hepatitis C after liver transplantation has a poor prognosis and no standard therapy is currently available. Four cases of severe recurrent cholestatic hepatitis C treated with a combination of interferon alpha 2b and ribavirin are described. All four patients were transplanted for hepatitis C-related cirrhosis. The mean age at transplantation was 45 years (range 41-51 years). Three of the patients were male and one was female. All four patients had hepatitis C virus viremia before and after liver transplantation. At 2 to 23 months after liver transplantation, all four patients developed jaundice, cholestatic elevation of liver enzymes, and histopathology consistent with severe recurrent cholestatic hepatitis C. Combination of interferon and ribavirin was given with prompt virological suppression. Despite this rapid viral suppression, all four patients developed progressive graft failure with three deaths.

Adult↗

Chronic hepatitis C and superimposed nonalcoholic fatty liver disease.

BACKGROUND/AIMS: Hepatitis C and nonalcoholic fatty liver disease (NAFL) are the two most common forms of liver disease in the United States. Recently, obesity and its associated risk factors have been suggested to enhance HCV-related fibrosis. The aim of this study was to assess the impact of hepatic steatosis, steatohepatitis, and its associated risk factors on HCV-related fibrosis. METHODS: Patients with untreated, biopsy-proven, chronic hepatitis C (6/97-3/99) were included. Clinical and demographic data at the time of liver biopsy were obtained from chart review and verified by telephone survey. One hepatopathologist reviewed all pathologic specimens, using the modified histological activity index score and the Ishak staging for fibrosis and a NAFL pathologic protocol. RESULTS: One hundred and seventy patients with hepatitis C were included [age: 48.7+/-9.33 (years), body mass index (BMI): 28.1+/-5.7 (kg/m2) and type 2 diabetes mellitus (DM): 14%]. Of these, 77 (45.3%) had no or mild fibrosis and 93 (54.7%) had advanced fibrosis. Hepatic steatosis was seen in 90 (52.9%) patients. The grade of steatosis was associated with markers of obesity only. Age (p=0.002), type 2 DM (p=0.04), and superimposed steatohepatitis (p=0.047) were independently associated with advanced fibrosis. Superimposed nonalcoholic steatohepatitis (NASH) was seen in 17 (10%) patients. Patients with superimposed NASH were mostly obese (76.5%), males (62%) with 16% having type 2 diabetes and a BMI 33.8+/-7.12. CONCLUSION: In patients with chronic hepatitis C, type 2 DM and superimposed steatohepatitis are independently associated with advanced fibrosis.

Adult↗

Hepatic encephalopathy.

In the last decade, a significant amount of research has been devoted to the pathogenesis and treatment of hepatic encephalopathy (HE). Non-invasive neuroimaging techniques such as magnetic resonance imaging and spectroscopy have become important research tools. The search for a suitable animal model of HE associated with cirrhosis is still ongoing. Moreover, consensus terminology and diagnostic criteria for HE in humans are badly needed.

Ammonia↗

Predictors of mortality and resource utilization in cirrhotic patients admitted to the medical ICU.

BACKGROUND AND OBJECTIVE: Cirrhotic patients admitted to the medical ICU (MICU) are associated with high mortality rates and high resource utilization. This study identifies specific predictors of increased mortality and resource utilization and uses them to develop and validate prognostic models in cirrhotic patients admitted to the MICU. METHODS: Cirrhotic patients admitted to the MICU were identified from the Critical Care Section database (January 1993 to October 1998). Clinical data were extracted from chart review including hospital course variables, mortality, and length of stay (LOS). Total cost per case (TCPC) was obtained from the Transition System INC: Multivariate logistic and linear regression analyses identified the independent predictors of increased mortality and resource utilization used for model building (MB) and model validation (MV). RESULTS: A total of 582 cases were randomized to the MB and MV groups. Each group contained 240 cases after exclusion criteria were applied. The MICU mortality rate was 36.6%, and the in-hospital mortality rate was 49.0%. Acute physiology, age, and chronic health evaluation (APACHE) III score (odds ratio [OR], 4.7; 95% confidence interval [CI], 2.70 to 8.16; p < 0.001), mechanical ventilation (OR, 4.57; 95% CI, 2.35 to 8.34); p < 0.001), and the use of pressors (OR, 7.57; 95% CI, 4.35 to 13.18; p < 0.001) were independent predictors of MICU mortality. APACHE III score (OR, 4.96; 95% CI, 2.97 to 8.29; p < 0.001), the use of pressors (OR, 6.55; 95% CI, 3.66 to 11.72; p < 0.001), and acute renal failure (ARF) (OR, 4.31; 95% CI, 2.41 to 7.71; p < 0.001) were independent predictors of in-hospital mortality. Increased LOS in the MICU was associated with mechanical ventilation, ARF, bronchoscopy, bacteremia, use of pressors, transjugular intrahepatic portosystemic shunt (TIPS), and never received cardiopulmonary resuscitation (CPR) (p < 0.005). Source of admission, platelet transfusion, bacteremia, pneumonia, and never received CPR were independently associated with increased total LOS (p < 0.001). Mechanical ventilation, platelet transfusion, bronchoscopy, TIPS, sepsis, and never received CPR were independent predictors of increased TCPC (p < 0.001). CONCLUSION: Simple prognostic models for mortality and resource utilization have been developed for cirrhotic patients admitted to the MICU.

APACHE↗

Transjugular intrahepatic portosystemic shunts (TIPS): a decade later.

Since the introduction of transjugular intrahepatic portosystemic shunt (TIPS) 10 years ago, it has been used increasingly in the management of portal hypertension and its complications. TIPS is now considered the procedure of choice for management of refractory variceal bleeding. Its role in the management of refractory ascites, hepatic hydrothorax, hepatorenal syndrome, and hepatopulmonary syndrome still awaits further prospective studies. The two main complications of TIPS are hepatic encephalopathy and shunt malfunction. Generally, TIPS stenosis or occlusion is a major drawback requiring routine surveillance of TIPS with doppler ultrasound. Venography with balloon dilation of the stent or placement of serial or parallel stents may be required in some cases. Promising modalities of preventing TIPS malfunction (e.g., brachy-therapy, covered stents, or anti-platelet derived growth factor) are currently being investigated.

Acute Disease↗

Outcome of de novo hepatitis C virus infection in heart transplant recipients.

The outcome of de novo hepatitis C virus (HCV) infection in heart transplant recipients of HCV-antibody positive organs is not known. The aim of the study was to determine the short-term outcome of de novo HCV infection in recipients of HCV-positive donor organs. HCV-antibody negative recipients of HCV-antibody positive hearts were identified from January 1, 1991 to February 28, 1998. Control patients matched for year of transplantation were also identified. Twenty-eight patients (22 males, mean age of 56 +/- 11 SD) received hearts from HCV-antibody-positive donors. The control group was similar to the patients in all clinical and demographic aspects. Twenty-three patients had detectable viremia by reverse-transcription polymerase chain reaction (RT-PCR). Of these 23 patients with de novo HCV infection, 7 (30%) developed HCV-related liver disease. Three patients (13%) had chronic hepatitis and 4 patients (17%) developed severe acute cholestatic hepatitis (ACH). Mycophenolate mofetil (MMF) use (P =.04) and high viral load at onset of acute liver disease (P =.02) were associated with ACH. Overall survival was similar between patients with de novo HCV infection and controls (P =.20). Development of ACH (P =.02) and MMF use (P =.0009) were associated with decreased survival in patients with de novo HCV infection. The present study showed that survival of patients with de novo HCV infection was similar to a matched control group. HCV-related severe ACH is associated with a poor short-term outcome in patients with de novo HCV infection. MMF use may be associated with a higher incidence of HCV-related severe ACH and a poor short-term outcome.

Actuarial Analysis↗