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T L Fong

Publications and source records attributed to T L Fong.

At least 19 recordsLinked to original sources
PubMed2001

Transmission of hepatitis B infection from hepatitis B core antibody--positive liver allografts is prevented by lamivudine therapy.

Donor shortage has led to the use of hepatitis B core antibody (anti-HBc)--positive (anti-HBc(+)) liver allografts for patients in need of relatively urgent orthotopic liver transplantation (OLT). Because anti-HBc(+) allografts transmit hepatitis B virus (HBV) infection at a high rate, effective prophylaxis is required. We assessed the effectiveness of lamivudine in preventing HBV transmission by anti-HBc(+) allografts. Between March 1996 and March 2000 at Cedars-Sinai Medical Center (Los Angeles, CA), 15 of 169 patients (8.9%) received liver allografts from anti-HBc(+) donors. Six patients were hepatitis B surface antigen (HBsAg)(+) (group 1), and 9 patients were HBsAg negative (HBsAg(-); group 2) before OLT. All patients were administered lamivudine, 100 or 150 mg/d, orally after OLT. Patients who were HBsAg(+) before OLT also were administered hepatitis B immunoglobulin (HBIG) prophylaxis. Hepatitis B serological tests were performed on all patients, and HBV DNA was determined in liver tissues in 10 patients. All 15 patients remained HBsAg(-) at their last follow-up 2 to 40 months (mean, 17 months) post-OLT. All patients in group 1 had antibody to HBsAg (anti-HBs) titers greater than 250 mIU/mL post-OLT (mean follow-up, 20 months; range, 7 to 40 months). Of the 2 patients in group 1 who underwent liver biopsy after OLT, 1 patient had detectable hepatic HBV DNA despite being anti-HBs(+) and HBsAg(-). Among the patients in group 2, none acquired anti-HBc or HBsAg. Hepatic HBV DNA was undetectable in the 7 patients in group 2 who underwent liver biopsy after OLT. Anti-HBc(+) allografts can be safely used in patients who undergo OLT for chronic hepatitis B and susceptible transplant recipients if prophylaxis with combination HBIG and lamivudine or lamividine alone is administered after OLT, respectively. However, more data are needed to determine the efficacy of lamivudine monotherapy in preventing transmission of HBV infection from anti-HBc(+) liver allografts to susceptible recipients.

Adult↗
PubMed2001

Analysis of causes of death in liver transplant recipients who survived more than 3 years.

Few studies have examined causes of death in long-term survivors of orthotopic liver transplantation (OLT). We reviewed causes of death among 299 adult liver transplant recipients who survived more than 3 years after OLT at 2 centers. Thirty-eight of the 299 patients subsequently died. Nonhepatic causes accounted for 22 of 38 late deaths (58%). Death caused by malignancies occurred in 9 patients between 3.3 and 8.0 years after OLT. Eight patients died of cardiovascular complications. The 6 patients who died of myocardial infarction had risk factors for coronary artery disease. Hepatic failure caused by recurrent liver disease or chronic rejection accounted for 16 of 38 late deaths (42%). These 16 patients were younger than patients who died of nonhepatic complications (mean ages, 50.7 v 62.1 years; P =.001). However, the mean interval between OLT and death was similar among patients who died of nonhepatic versus hepatic causes. Nine patients had recurrent liver disease leading to death, and 8 of 9 patients had recurrent chronic hepatitis C virus (HCV) infection. Chronic rejection resulting in graft failure and death occurred in 7 patients. In summary, de novo malignancies and cardiovascular complications accounted for more than half the late deaths. Patients who died of nonhepatic causes were significantly older than patients who died of hepatic causes. Chronic rejection and recurrent HCV infection accounted for the majority of hepatic causes of death. With longer follow-up, graft failure resulting from recurrent HCV infection will become the major cause of death in late survivors.

Adult↗
PubMed1999

Cyclosporine therapy in patients with steroid resistant autoimmune hepatitis.

Autoimmune hepatitis is a form of chronic liver disease characterized by progressive hepatocellular inflammation, which usually responds to treatment with corticosteroids. However, 10% of patients with autoimmune hepatitis are refractory to corticosteroids and develop progressive liver disease and cirrhosis. We describe five patients with autoimmune hepatitis who did not respond to conventional corticosteroids and azathioprine therapy who were then treated with cyclosporine A. Cyclosporine A was started at 2-3 mg/kg/day and induced biochemical remission in four of five patients within 3 months. One of the four responders relapsed within 1 month of discontinuing cyclosporine on two occasions. Each time, liver tests promptly normalized after reinitiation of cyclosporine. Two responders were managed with cyclosporine alone. The single patient who did not respond to cyclosporine developed progressive liver failure, underwent orthotopic liver transplantation, and subsequently died of disseminated cytomegalovirus infection. Cyclosporine was generally well tolerated and none of the patients developed renal insufficiency. These data and review of 11 cases in the literature show that cyclosporine can induce remission of liver disease in patients with autoimmune hepatitis who are refractory to corticosteroids.

Adult↗
PubMed1999

A pilot study of rimantadine for patients with chronic hepatitis C unresponsive to interferon therapy.

OBJECTIVE: Therapeutic options are limited for chronic hepatitis C patients who have not responded to a course of interferon therapy. Recently, a 6-month course of amantadine was shown to result in a sustained virological response in chronic hepatitis C patients who were unresponsive to interferon therapy. The aim of this study was to evaluate the effect of rimantadine on chronic hepatitis C patients who had not responded to interferon therapy. METHODS: This was an open label trial involving 17 patients who were treated with rimantadine 100 mg b.i.d. for 6 months. Changes in serum aminotransferase activities and HCV-RNA levels were determined. RESULTS: Mean alanine aminotransferase activities and HCV RNA levels did not change significantly during therapy. HCV RNA remained detectable in all patients throughout therapy. Neurologic symptoms (headaches, nervousness, and dizziness) developed in 29% of patients. A total of 12% of patients required dose reduction after 12 wk of therapy because of dizziness. CONCLUSION: Rimantadine has no significant antiviral activity against HCV.

Adult↗
PubMed1998

A pilot randomized, controlled trial of the effect of iron depletion on long-term response to alpha-interferon in patients with chronic hepatitis C.

BACKGROUND/AIMS: Some studies have suggested that hepatic iron may influence the response to interferon therapy in chronic hepatitis C patients. We conducted this randomized, controlled trial to evaluate the effect of iron depletion on: (1) aminotransferase activity and hepatitis C RNA levels; and (2) response to interferon therapy in 38 patients with elevated alanine aminotransferase levels and who were HCV RNA positive. METHODS: Seventeen patients underwent a 500-ml phlebotomy every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of alpha-interferon 2b (3 mu tiw). Controls were 21 patients who were monitored for a 6- to 8-week period without phlebotomy prior to interferon therapy. Response to interferon was defined as loss of serum HCV RNA by reverse transcriptase-polymerase chain reaction. Serum HCV RNA was quantitated by bDNA technique. RESULTS: Alanine aminotransferase levels decreased in 15/17 patients after phlebotomy. Mean alanine aminotransferase fell from 156.8 to 89.7 U/l (p=0.008). Changes in iron indices and alanine aminotransferase after phlebotomy were not accompanied by changes in HCV RNA levels. In control patients, neither alanine aminotransferase nor HCV RNA levels changed during the observation period. At the end of 24 weeks of interferon therapy, 7/17 phlebotomized patients had a response, compared to 6/21 control patients (p=ns). After 6 months of follow-up, 5/17 phlebotomized patients remained HCV RNA negative, in contrast to only 1/21 controls (p=0.07). CONCLUSIONS: Iron depletion led to a reduction in aminotransferase levels; this was not accompanied by changes in levels of hepatitis C RNA. There may be an improvement in the sustained response to interferon therapy, but this requires confirmation.

Adult↗
PubMed1998

Nephrogenic ascites. Analysis of 16 cases and review of the literature.

Nephrogenic ascites is an entity that manifests as refractory ascites in patients with end-stage renal disease, where portal hypertensive, infectious, and malignant processes have been excluded. Most of these patients are undergoing hemodialysis. Hypoalbuminemia may predispose these uremic patients to ascites formation. The characteristics of the ascitic fluid suggest that the pathogenesis of the ascites is an alteration in peritoneal membrane permeability or impaired resorption due to peritoneal lymphatic channel obstruction. The ascitic fluid has a high protein content, low serum-ascites albumin gradient (SAAG), and low leukocyte count. Daily hemodialysis should be the initial therapy and is successful in one-third to three-fourths of patients within 3 weeks. Continuous ambulatory peritoneal dialysis or insertion of a peritoneovenous shunt are alternative treatments. Other therapies include instillation of intraperitoneal corticosteroids and binephrectomy, which have less predictable outcomes. Renal transplantation is the definitive treatment for nephrogenic ascites. Control of ascites reverses the progressive cachexia associated with uncontrolled disease, resulting in improved quality of life and survival approaching that of end-stage renal disease patients without ascites.

Adult↗
PubMed1998

Terbinafine hepatotoxicity: case report and review of the literature.

We report a patient who developed significant liver dysfunction following therapy with terbinafine. At the end of a 3 1/2-wk course of terbinafine, he developed progressive jaundice and pruritus. His serum bilirubin peaked at 30.9 mg/dl 3 wk after discontinuing terbinafine. A liver biopsy revealed mild to moderate mixed cellular infiltrate in the portal tracts, and hepatocellular and canicular cholestasis. His liver tests normalized 100 days after stopping terbinafine.

Adult↗
PubMed1997

Hepatitis C virus infection in patients with B-cell non-Hodgkin lymphoma.

BACKGROUND: Several studies from Europe have reported a high prevalence (9% to 32%) of chronic hepatitis C virus (HCV) infection in patients with B-cell non-Hodgkin lymphoma. It has been suggested that HCV plays a role in the pathogenesis of B-cell non-Hodgkin lymphoma. OBJECTIVE: To determine the prevalence of HCV infection in patients with B-cell lymphoma in the United States. DESIGN: Controlled, cross-sectional analysis. SETTING: University medical center. PATIENTS: 120 patients with B-cell lymphoma (78% were Hispanic, 9% were black, 7% were Asian, and 6% were white), 154 patients with other malignant hematologic conditions (control group 1), and 114 patients with nonmalignant conditions (control group 2). MEASUREMENTS: Samples were tested for antibodies to HCV by enzyme-linked immunosorbent assay. Hepatitis C virus RNA was detected by reverse-transcription polymerase chain reaction. Genotyping for HCV was done with genotype-specific primers from the HCV core region. RESULTS: Infection with HCV was detected in 26 patients (22% [95% CI, 15% to 30%]) with B-cell lymphoma compared with 7 of 154 patients (4.5%) in control group 1 and 6 of 114 patients (5%) in control group 2 (P < 0.001). Risk factors for HCV infection were present in 15 patients (60%) with B-cell lymphoma and occurred a median of 15 years before diagnosis of lymphoma. Monocytoid B-cell lymphoma was the most common type of lymphoma found in HCV-positive patients (23% compared with 7% in HCV-negative patients) (P = 0.034). CONCLUSIONS: The prevalence of HCV infection was higher in patients with B-cell non-Hodgkin lymphoma than in controls. The possible role of HCV in the pathogenesis of B-cell lymphoma warrants further investigation.

Adult↗
PubMed1997

Effect of iron depletion on long-term response to interferon-alpha in patients with chronic hepatitis C who previously did not respond to interferon therapy.

About half of patients with chronic hepatitis C treated with interferon will not have a biochemical or virological response. Several studies suggested that increased hepatic iron content may negatively influence the response to interferon. We conducted this prospective trial to evaluate the effect of iron depletion on the response to a repeat course of interferon in 20 chronic hepatitis C patients who previously had not responded to interferon. The patients underwent 500-ml phlebotomies every 2 weeks until iron deficiency was achieved. Patients were then started on a 6-month course of interferon alfa-2b (3 million units, t.i.w.). These patients required a mean of 6.0 (range, 1-14) phlebotomies to become iron deficient. ALT levels decreased in 18 of 20 patients and became normal in 4 patients. Mean ALT levels decreased from 154.2 to 87.9 U/L (p = 0.0006). At the end of 24 wk of interferon therapy, ALT levels were normal in 11 patients, 3 of whom had undetectable HCV RNA in the serum. One additional patient with abnormal ALT had undetectable HCV RNA. After 6 months of follow-up, one of the HCV RNA negative patients relapsed with reappearance of HCV RNA and elevation of ALT. In summary, 15% of chronic hepatitis C patients who previously failed interferon now had a sustained response to interferon therapy that was preceded by iron depletion.

Adult↗
PubMed1996

Clinical significance of hepatitis C viral RNA status and its correlation to antibodies to structural HCV antigens in anti-HCV reactive patients with normal liver tests.

Extensive serological testing and HCV RNA determination by RT-PCR was performed in serum, PBMCs, and liver tissue in thirteen anti-HCV reactive patients with persistently normal liver tests. Absolute concordance in the status of HCV RNA between serum, PBMCs, and liver was noted. Five patients were HCV RNA positive but only three had mild histological changes. Eight patients were HCV RNA negative in all three sites and had virtually normal liver histology. Patterns of reactivity in RIBA 2.0 strip immunoblot assay did not differentiate viremic from nonviremic patients. ELISA testing using multiple individual HCV recombinant antigens from the structural and non-structural regions of HCV demonstrated mean antibody titers to the structural antigens, in particular HCV E2 antibodies, to be significantly lower in HCV RNA negative patients. The status of HCV RNA in the serum appears to infer the status of HCV RNA in the liver and PBMCs in patients with persistently normal liver tests. Patients with persistently normal liver tests and undetectable HCV RNA have probably spontaneously cleared HCV infection.

Adult↗
PubMed1995

Hepatic involvement in mastocytosis: clinicopathologic correlations in 41 cases.

Mastocytosis is a disease of mast cell hyperplasia that may involve several organ systems, including liver. Between 1988 and 1991, we conducted a retrospective-prospective study of 41 patients with mastocytosis and found 61% had evidence of liver disease. Hepatomegaly was detected in 24%, splenomegaly in 41%, and elevated serum alkaline phosphatase, serum aminotransaminases, 5'nucleotidase, or gamma-glutamyltranspeptidase (GGTP) in 54% of the patients. Alkaline phosphatase levels directly correlated with GGTP levels, hepatomegaly, splenomegaly, and liver mast cell infiltration and fibrosis. Elevated alkaline phosphatase levels and splenomegaly were observed more frequently in patients with categories II and III mastocytosis. Five patients in combined disease categories II or III developed ascites or portal hypertension and died of complications of mastocytosis; three had hypoprothrombinemia at the time of death. Thirty-five liver biopsy specimens from 25 patients were examined. Mast cell infiltration was commonly observed in the biopsy specimens, more severe in those patients with either category II or III disease, and correlated with hepatomegaly, splenomegaly, alkaline phosphatase levels, and GGTP levels. Mast cells were often only detected by using special stains (toluidine blue and chloracetate esterase). Increased portal fibrosis was seen in 68% of the biopsy specimens and correlated with mast cell infiltration and portal inflammation. Cirrhosis was not observed. Nodular regenerative hyperplasia, portal venopathy, and venoocclusive disease was observed in eight biopsy specimens and may have been the cause of the portal hypertension or ascites in four patients. These findings demonstrate that liver disease with mast cell infiltration is a common finding in patients with mastocytosis.(ABSTRACT TRUNCATED AT 250 WORDS)

5'-Nucleotidase↗
PubMed1995

Raising the dose of interferon does not improve the response in chronic hepatitis C.

We report results of dose escalation to 5 or 6 million units (MU) three times weekly (t.i.w.) of interferon-alpha in 17 consecutive patients with chronic active hepatitis C who were not responding to 3 MU t.i.w. after > or = 12 weeks of therapy. The mean pretreatment alanine aminotransferase (ALT) level was 206 +/- 62 U/L and, at the time of dose escalation, 113 +/- 71 U/L. Two patients could not tolerate the dose escalation. The remaining 15 patients were treated for an additional 10 +/- 3.5 weeks. Three patients had a complete response 3-8 weeks after dose escalation. At the end of high-dose therapy, the mean ALT level was 105 +/- 76 U/L (n = 15). During the 6-month posttreatment follow-up time, the mean ALT level was 147 +/- 85 U/L. All three responders had a relapse. Increasing the dose of interferon-alpha to 5-6 MU t.i.w. in chronic hepatitis C patients who are not responding to interferon-alpha, 3 MU t.i.w., at the 12th week of therapy is unlikely to result in sustained normalization of ALT levels.

Adult↗
PubMed1994

The physical state of the negative strand of hepatitis C virus RNA in serum of patients with chronic hepatitis C.

Negative strands of the hepatitis C virus (HCV) genome (a positive-stranded RNA virus) have been found in a nuclease-resistant form in the serum of patients with HCV infections. We determined whether a complete negative-strand copy is present in the serum, whether the negative strand is particle-associated, and finally, whether it is virion-associated and encapsidated like the positive (genomic) strand. Isopyknic sucrose and cesium chloride density ultracentrifugation followed by a strand-specific reverse transcription-polymerase chain reaction on the collected fractions was performed to determine whether both positive and negative strands were associated with similar particles. Both strands comigrated to approximately the same density (1.11-1.16 g/cm3) in sucrose. After treatment of the plasma with detergent (0.1% Nonidet P-40) to remove the viral envelope and centrifugation on cesium chloride gradients, the positive strands shifted to a density of 1.35 g/cm3, and the negative strands were not detected. By using antibodies specific for the HCV core or envelope glycoproteins E1 or E2 coated onto the wells of a microtiter plate, it was possible to specifically bind HCV or viral cores to the solid phase. Pelleted virus particles were resuspended in either PBS or PBS with 0.1% Nonidet P-40 to expose the core. These pellets were then incubated in antibody-coated microtiter wells. RNA extracted from the bound and unbound fractions was tested for HCV RNA. The anti-core antibody was able to bind positive strands but not negative strands only in detergent-treated samples. In the nondetergent-treated pellets, the anti-E1 and -E2 bound the positive strand, but only anti-E1 bound the negative strands. These findings indicate that while both strands of HCV RNA can be detected in serum, the positive strand is encapsidated within the enveloped core, and the negative strand appears to be in a membrane particle associated with the viral envelope protein E1 but does not appear to be within the HCV core of circulating virions.

Base Sequence↗
PubMed1994

Clinical significance of concomitant hepatitis C infection in patients with alcoholic liver disease.

The significance of antibodies to hepatitis C virus in patients with chronic alcoholic liver disease is unclear. Prior studies have utilized the first-generation enzyme-linked immunosorbent assay, which is limited by problems with sensitivity and specificity. Hepatitis C virus infection in 137 patients with biopsy-proven alcoholic liver disease was assessed with second-generation hepatitis C virus antibody assays and reverse transcription-polymerase chain reaction for detection of hepatitis C virus RNA in the serum. The patients were categorized into three groups according to results of serological testing. Discriminant-function analysis was used to determine which factors (risk, biochemical and histological) could best differentiate the three groups. Thirty-three patients were reactive on second-generation enzyme-linked immunosorbent assay/second-generation recombinant immunoblot assay and RNA positive (group 1). Twelve were reactive on second-generation enzyme-linked immunosorbent assay/second-generation recombinant immunoblot assay but RNA negative (group 2). Eighty-six were nonreactive on second-generation enzyme-linked immunosorbent assay, and six were reactive on second-generation enzyme-linked immunosorbent assay but negative on second-generation recombinant immunoblot assay and negative for hepatitis C virus RNA (group 3). Seventy-six percent of patients in group 1 and 58% in group 2 had parenteral risk factors, compared with only 1% in group 3 (p < 0.00001). The mean ALT level was higher in group 1 patients (p < 0.05). The mean histologic activity index was significantly higher in group 1 (p = 0.0007).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1994

High levels of viral replication during acute hepatitis B infection predict progression to chronicity.

To assess the pattern of development of serologic markers during acute hepatitis B, levels of HBsAg, HBeAg, and hepatitis B virus (HBV) DNA were assayed in stored serum samples obtained sequentially from 12 subjects infected with HBV during experimental studies conducted in the 1950s. Six patients developed acute self-limited hepatitis, three developed chronic hepatitis, and three had an asymptomatic infection without HBsAg. HBsAg was the first serologic marker detected (mean = 52 days after exposure), followed by HBeAg (62 days) and HBV DNA (72 days). Peak HBsAg levels occurred before onset of symptoms and correlated with peak titers of HBeAg and HBV DNA. Patients who developed chronic hepatitis had higher peak levels of viral markers than those with self-limited disease: HBsAg (30 versus 5.4 micrograms/ml), HBeAg (1:2,000 versus 1:60 titer) and HBV DNA (3,192 versus 444 pg/ml). Thus, chronic HBV infection is characterized by high levels of viral replication appearing early during the acute phase of infection.

Acute Disease↗
PubMed1994

Short-term prednisone therapy affects aminotransferase activity and hepatitis C virus RNA levels in chronic hepatitis C.

BACKGROUND/AIMS: The effects of corticosteroids on chronic hepatitis B have provided insight into the mechanism of liver cell injury caused by hepatitis B. In this study, this model was applied to investigate the effects of prednisone on alanine aminotransferase (ALT) and hepatitis C virus (HCV) RNA levels in chronic hepatitis C. METHODS: Ten patients with chronic hepatitis C who had increased levels of ALT and HCV RNA detectable in serum were given a 7-week course of a tapering dose of prednisone. Quantitation of serum HCV RNA was determined by polymerase chain reaction (PCR) and by branched-chain DNA amplification. RESULTS: ALT levels decreased in 8 of 10 patients during therapy. Mean ALT levels of all 10 patients decreased from 184 to 84 U/L (P = 0.002) and then rebounded in 7 of the 8 patients after discontinuation of prednisone. HCV RNA was detectable by the branched DNA technique in 9 of 10 patients. These values increased in all 9 patients during prednisone therapy. The mean serum HCV RNA levels increased from 40.9 before treatment to 414.3 Eq/mL x 10(5) during treatment (P = 0.043). Using PCR, HCV RNA titers increased one log-fold in 8 of 10 patients (geometric mean of 1:4420 to 1:23410). HCV RNA levels decreased to pretreatment values within a mean of 2.8 weeks (range, 1-5) after discontinuation of prednisone. CONCLUSIONS: These responses in ALT and HCV RNA suggest the participation of an immune-mediated mechanism in the liver cell injury in chronic hepatitis C.

Adult↗
PubMed1994

Therapy of chronic hepatitis B with a 6-month course of ribavirin.

Ribavirin is a nucleoside analogue with broad spectrum antiviral activity that has been shown to inhibit viral replication in the woodchuck model of hepatitis B virus infection. We studied the effect of ribavirin on viral replication in 18 patients with chronic hepatitis B who were positive for hepatitis B e antigen. Patients were randomized to receive a 24-week course of oral ribavirin at a dose of either 800, 1000, or 1200 mg/kg per day. All patients completed 24 weeks of treatment and an additional 24 weeks of follow up without significant side effects except for mild, reversible hemolytic anemia. Response to ribavirin was similar among all three dosage groups (p > 0.5); hence the data were pooled and analyzed together. Mean hepatitis B virus DNA levels decreased from 162.7 (95% confidence interval, 106 to 219) pg/ml before treatment to its lowest level of 114.3 (95% confidence interval, 53 to 175) pg/ml at week 20 (p < 0.05). Two patients became negative for HBV DNA and lost hepatitis B e antigen. Mean serum alanine aminotransferase activity decreased markedly from 131.1 (95% confidence interval, 84 to 178) U/l before treatment to 62.4 (95% confidence interval, 48 to 77) U/l at the end of 24 weeks of ribavirin (p < 0.05) and became normal in four patients (22%). Aminotransferase levels returned to baseline within 4 weeks once ribavirin was discontinued, while HBV DNA concentrations remained below baseline even at the end of 24 weeks of follow up.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗