Demographic and serological characteristics of Asian Americans with hepatitis B infection diagnosed at community screenings.

There is limited information regarding follow-up and hepatitis B serological status of Asian Americans diagnosed with chronic hepatitis B (CHB) through community screening. The aims of this study were to evaluate the prevalence and characterize CHB among Asians living in Los Angeles, assess follow-up of individuals with CHB diagnosed at screening and compare with patients with CHB followed by community gastroenterologists. Between October 2007 and May 2010, 7387 Asians were tested for HBV. HBsAg positive individuals (CHB) underwent additional testing for ALT, HBeAg/anti-HBe and HBV DNA. Patients with CHB were contacted 6 months later to determine whether they received follow-up care. We compared serological patterns of these individuals with CHB to patients with CHB who were seen for the first time (treatment naïve) by community gastroenterologists during the study period. Prevalence of CHB was 5.2%. About 99% patients with CHB were foreign-born, and only 27% could read/write English. 297 (77%) patients with CHB could be reached 6 months after diagnosis; 43% did not receive follow-up care, mostly because of lack of medical insurance. Patients with CHB followed by gastroenterologists were more likely to have insurance (69% vs 26%, P < 0.0001). 90% patients with CHB at screening were HBeAg negative/anti-HBe positive with 62% having inactive disease compared to only 30% of patients seen by gastroenterologists (P < 0.0001). Among CHB participants, 13% met criteria for treatment compared to 51% of patients with CHB (P < 0.0001). Only a small number of CHB screening participants require antiviral therapy. Lack of medical insurance is the main reason for most patients with CHB not seeking follow-up care after screening.

Detection of replicative intermediates of hepatitis C viral RNA in liver and serum of patients with chronic hepatitis C.

The hepatitis C virus is a positive stranded hepatotropic RNA virus. We describe a method of detecting positive and negative strands of hepatitis C viral RNA using the polymerase chain reaction. We tested serum and liver tissue from nine patients with chronic hepatitis C. The positive RNA strand of HCV was detected in the sera and livers of all nine, the negative strand was detected in the livers of eight (89%), and in the sera of five (55%). Titers of both strands of HCV RNA were determined by serial endpoint dilutions. The amount of the negative strand in the serum and liver was usually 10-100 times less than the positive strand. Predigestion of serum with ribonucleases did not alter the detection of the negative strand. This suggests that the negative strand found in the serum may be protected from digestion by being associated with virions.

A comparison of sirolimus vs. calcineurin inhibitor-based immunosuppressive therapies in liver transplantation.

BACKGROUND: Sirolimus is a potent immunosuppressive agent whose role in liver transplantation has not been well-described. AIM: To evaluate the efficacy and side-effects of sirolimus-based immunosuppression in liver transplant patients. METHODS: Retrospective analysis of 185 patients who underwent orthotopic liver transplantation. Patients were divided into three groups: group SA, sirolimus alone (n = 28); group SC, sirolimus with calcineurin inhibitors (n =56) and group CNI, calcineurin inhibitors without sirolimus (n = 101). RESULTS: One-year patient and graft survival rates were 86.5% and 82.1% in group SA, 94.6% and 92.9% in group SC, and 83.2% and 75.2% in group CNI (P = N.S.). The rates of acute cellular rejection at 12 months were comparable among the three groups. At the time of transplantation, serum creatinine levels were significantly higher in group SA, but mean creatinine among the three groups at 1 month was similar. More patients in group SA required dialysis before orthotopic liver transplantation (group SA, 25%; group SC, 9%; group CNI, 5%; P = 0.008), but at 1 year, post-orthotopic liver transplantation dialysis rates were similar. CONCLUSIONS: Sirolimus given alone or in conjunction with calcineurin inhibitors appears to be an effective primary immunosuppressant regimen for orthotopic liver transplantation patients. Further studies to evaluate the efficacy and side-effect profile of sirolimus in liver transplant patients are warranted.

Pancreatic nesidioblastosis in adults.

Nesidioblastosis, a condition characterized by diffuse islet cell hyperplasia arising from the ductal epithelium, is often associated with hyperinsulinemic hypoglycemia. This is a childhood disease and is rarely found in adults. Only 10 histologically proven cases have been recorded, including 3 new cases described in this article. Most clinical and biochemical features are identical to those of an insulinoma, except the proinsulin-like component of circulating immunoreactive insulin, which is usually within the normal range in nesidioblastosis. Limited observations show that some patients may be managed medically with diazoxide. Patients who remain hypoglycemic despite medical therapy require pancreatectomy, although greater than 90% resection frequently results in insulin dependency and permanent diabetes.

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.

Concanavalin A affinity of alpha-fetoprotein. Its use in differentiating tumors.

Using affinity chromatography on concanavalin A Sepharose, the authors studied the molecular heterogeneity of the serum alpha-fetoprotein of 53 patients with hepatocellular carcinoma, 16 patients with metastatic tumors to the liver, and 16 patients with germ cell tumors. Mean concanavalin binding of alpha-fetoprotein in the sera of patients with hepatocellular carcinoma was 79%, whereas the mean binding in metastatic tumors was 52% and that of germ cell tumors was 45%. This striking molecular variation of the alpha-fetoprotein produced by these different tumors is helpful in the clinical distinction of these tumors.

Markers of viral replication in patients with chronic hepatitis B virus infection.

Serum samples from 56 patients with biopsy-proven chronic B viral hepatitis without superimposed delta hepatitis were analyzed for the various markers of viral replication, including serum hepatitis B e Ag (HBeAg), hepatitis B virus deoxyribonucleic acid (HBV-DNA), and hepatitis B core antigen (HBcAg) in the liver tissues. Twenty-seven patients had persistent viral hepatitis (PH) and 29 patients had chronic active hepatitis (CAH) with or without cirrhosis. HBV-DNA was identified in the sera of 81% of patients with PH and 60% of patients with CAH. Significantly higher levels of HBV-DNA were found in patients with PH than in those with CAH. Both HBeAg in serum and HBcAg in liver correlated positively with serum HBV-DNA. Nine patients had serum HBV-DNA in the absence of HBeAg (four had anti-HBe), and seven of these nine patients had stainable HBcAg in the liver (two did not have staining). None of these patients had hepatic HBcAg in the absence of serum HBV-DNA. When these patients were stratified according to their epidemiologic background, serum HBV-DNA was present in a significantly higher number of male homosexuals than in any other groups. This was unrelated to their status of human immunodeficiency viral serology.

The stability of serum hepatitis C viral RNA in various handling and storage conditions.

To investigate whether certain handling and storage conditions of serum samples could alter the sensitivity and specificity of the hepatitis C virus (HCV) RNA assay, we studied serum samples obtained from five patients known to be positive for HCV RNA and two patients with autoimmune chronic active hepatitis. Samples were subjected to one of the following conditions: (1) immediate storage at -20 degrees C, (2) five freeze-thaw cycles, (3) storage at 4 degrees C for 5 days, and (4) storage at room temperature for 5 days. Detection of HCV RNA was performed by polymerase chain reaction. Titers of HCV RNA were determined by serial end point dilutions. We found that the titer of HCV RNA was reduced by only one logfold in samples subjected to conditions 2 through 4 in two of the five patients. False-positive results were not seen with the serum samples that were subjected to similar conditions from the two negative control patients. We conclude that serum HCV RNA is resistant to degradation under routine laboratory handling and storage conditions.

Fluorescence technique for the characterization of natural organic matter in river water.

The complex nature of natural organic matter (NOM), and the impact of this matter on drinking water quality have necessitated the characterization studies of NOM. A fluorescence technique for the characterization of NOM in Malaysian river water is reported. Water samples from several river sampling sites were collected and concentrated using a low-pressure reverse osmosis (LPROM). Solid phase extraction (SPE) using C18 extraction cartridges were used to fractionate the water samples into humic and non-humic fractions. To differentiate and classify various types of humic substances, fluorescence was applied in emission, excitation and in synchronous-scan modes. A synchronous spectral profile was found to be able to differentiate humic and fulvic acids better than the emission or excitation spectra. Synchronous excitation spectra showed different spectral patterns for the water samples due to different origin. All water samples showed the presence of both fulvic and humic acids.

Oral anomalies in the neonate, by race and gender, in an urban setting.

A broad range of developmental anomalies and morphologic variants may occur in the oral cavity of the newborn. Because many of these are transient (e.g.: palatal and alveolar cysts, lymphangioma), self-correcting with age, conventional assessments of older children can yield significantly altered trait incidences. A total of 500 normal full-term newborns (blacks and whites) were assessed by standardized criteria for 11 oral conditions, in addition to collating data on maternal conditions (age, gravidity, tobacco and alcohol use). Leukoedema and median alveolar notches were significantly more common in blacks, whereas palatal cysts were 2.5 times as likely to occur in whites. Ankyloglossia, three times as common in males, was the one trait to exhibit a significant predilection by gender. Low maternal age (less than 20 years) significantly enhanced the risk of alveolar lymphangioma in these data.

Risk factors for graft survival after liver transplantation from donation after cardiac death donors: an analysis of OPTN/UNOS data.

Due to increasing use of allografts from donation after cardiac death (DCD) donors, we evaluated DCD liver transplants and impact of recipient and donor factors on graft survival. Liver transplants from DCD donors reported to UNOS were analyzed against donation after brain death (DBD) donor liver transplants performed between 1996 and 2003. We defined a recipient cumulative relative risk (RCRR) using significant risk factors identified from a Cox regression analysis: age; medical condition at transplantation; regraft status; dialysis received and serum creatinine. Graft survival from DCD donors (71% at 1 year and 60% at 3 years) were significantly inferior to DBD donors (80% at 1 year and 72% at 3 years, p < 0.001). Low-risk recipients (RCRR < or = 1.5) with low-risk DCD livers (DWIT < 30 min and CIT < 10 h, n = 226) achieved graft survival rates (81% and 67% at 1 and 3 years, respectively) not significantly different from recipients with DBD allografts (80% and 72% at 1 and 3 years, respectively, log-rank p = 0.23). Liver allografts from DCD donors may be used to increase the cadaveric donor pool, with favorable graft survival rates achieved when low-risk grafts are transplanted in a low-risk setting. Whether transplantation of these organs in low-risk recipients provides a survival benefit compared to the waiting list is unknown.

Hyperthyroidism and hepatic dysfunction. A case series analysis.

Liver dysfunction in hyperthyroid patients has not been well characterized. We analyzed the clinical records of 43 patients with hyperthyroidism to define the spectrum of clinical and liver test abnormalities. The patients were divided into three categories: (a) 18 patients with uncomplicated hyperthyroidism (HT) (b) 19 with hyperthyroidism and congestive heart failure (HT/CHF), and (c) 6 with hyperthyroidism and concomitant unrelated liver disease (HT/ULD). Hepatomegaly and/or spenomegaly were noted in 15 of 19 (79%) patients with HT/CHF as compared to 6 of 18 (33%) patients with HT and 3 of 6 (50%) patients with HT/ULD. Four patients with HT/CHF had ascites. Serum aminotransferase levels greater than 250 IU/L were noted in only 1 of 37 (3%) patients without unrelated liver disease. Patients with HT/ULD or HT/CHF had markedly low prothrombin time. Serum bilirubin levels as high as 323 microM were noted in patients with HT. No characteristic liver histology due to hyperthyroidism was noted. Severe liver test abnormalities, including deep jaundice and prolonged prothrombin time, can occur in patients with hyperthyroidism alone or with HT/CHF. This makes the diagnosis of concomitant, unrelated liver disease difficult until the hyperthyroidism has been controlled.

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.

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.

Polymorphonuclear cell count response and duration of antibiotic therapy in spontaneous bacterial peritonitis.

The purposes of this study were (a) to measure serially ascitic fluid polymorphonuclear cell response in treated spontaneous bacterial peritonitis and (b) to determine whether an ascitic fluid polymorphonuclear cell count of less than 250 per mm3 on serial paracenteses was a satisfactory endpoint for antibiotic therapy. Thirty of 33 patients showed an exponential fall in ascitic fluid polymorphonuclear cell count after 48 hr of antibiotic therapy; the magnitude of decrease correlated with survival (p less than 0.01). Among the patients whose antibiotic therapy was discontinued when the ascitic fluid polymorphonuclear cell count reached 250 per mm3 or less, the duration of therapy was considerably shorter than for the patients who received "conventional" therapy (p less than 0.01). Recurrence of spontaneous bacterial peritonitis was similar in the two groups. Mortality correlated with the severity of underlying liver disease but not with duration of antibiotic therapy.

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.

Spontaneous reactivation in chronic hepatitis B: patterns and natural history.

We identified spontaneous reactivation of hepatitis B virus (HBV) retrospectively by utilizing serum alanine aminotransferase and HBV DNA in 19 men (79% homosexual), with an estimated annual incidence of 7.3%. In 11 patients, spontaneous reactivation occurred as a single episode and in eight patients, reactivation was recurrent, with two to five episodes each. The mean serum alanine aminotransferase level was elevated over 10-fold at the peak of reactivation. Serum anti-HBc IgM was detected during 73% of the reactivation episodes. Actuarial analysis revealed that reactivation was long lasting with 45% and nearly 20% of episodes continued after 6 and 24 months, respectively. The course of 24 chronic HBV carriers with a negative serum HBV DNA test and normal alanine aminotransferase levels at initial appearance was unremarkable. We could not identify clinical features predictive of reactivation or its resolution. Severe reactivation hepatitis occurred in three patients (10%), with two deaths (6%). None of the patients lost HBsAg. Spontaneous reactivation in chronic hepatitis B can appear variably, persist long term, recur, and be fatal. Therefore, accurate classification of chronic HBV infection requires prolonged observation, and spontaneous reactivation should be considered a variable in therapeutic trials for chronic hepatitis B.

Status of hepatitis B virus DNA in alcoholic liver disease: a study of a large urban population in the United States.

Two reports have shown hepatitis B virus DNA in serum and liver tissue in alcoholic liver disease with negative serum HBsAg, suggesting a pathogenetic role for hepatitis B virus. We studied hepatitis B virus DNA in serum and liver from three groups of alcoholic patients; (Group 1) 50 patients without liver disease, (Group 2) 108 patients with alcoholic liver disease and (Group 3) five patients with alcoholic liver disease and hepatocellular carcinoma. Serum was tested for HBsAg, anti-hepatitis B core and anti-hepatitis B surface by radioimmunoassay and hepatitis B virus DNA by direct spot hybridization. Liver tissue from Groups 2 and 3 (113 patients) was examined by Southern blot analysis using 32P-labeled hepatitis B virus DNA clone from pBR322. Controls were 21 patients with chronic hepatitis B virus (14 patients with chronic active hepatitis, seven patients with cirrhosis and hepatocellular carcinoma). Serum and tissue were analyzed for hepatitis B virus DNA. Hepatitis B virus DNA was not detected in either serum or liver tissue in any of the 163 patients (Groups 1 to 3). In contrast, among the controls, hepatitis B virus DNA was present in the serum of 15 of the 21. Tissue DNA in those with chronic active hepatitis revealed 10/14 with free hepatitis B virus DNA, two with integrated sequences and two with no viral sequences. All seven patients with hepatocellular carcinoma had integrated viral DNA sequences in the tumor tissues. From these results, it appears that hepatitis B virus does not play a role in the pathogenesis of alcoholic liver disease.