Serum catecholamines and dysautonomia in diabetic gastroparesis and liver cirrhosis.

BACKGROUND: Plasma catecholamine influences autonomic function and control, but there are few reports correlating them. In this study, 47 individuals (mean age, 38 years) were studied: 19 diabetes mellitus (DM) patients with gastroparesis, 16 with liver disease and 12 control subjects. METHODS: Noninvasive autonomic function was assessed for sympathetic adrenergic functions as peripheral vasoconstriction in response to cold stress test and postural adjustment ratio (PAR) and cholinergic function as Valsalva ratio, represented by change in R-R intervals. Measurements were compared by analysis of variance and Spearman's correlation, and results were reported as mean ± standard error. RESULTS: Plasma norepinephrine (1902.7 ± 263.3; P = 0.001) and epinephrine (224.5 ± 66.5; P = 0.008) levels, as well as plasma dopamine levels (861.3 ± 381.7), and total plasma catecholamine levels were highest for patients with liver disease, who also had significant negative correlation between norepinephrine level and vasoconstriction (P = 0.01; r = -0.5), PAR1 (P = 0.01; r = -0.5), sympathetic adrenergic functions (P = 0.005; r = -0.6), total autonomic index (P = 0.01-0.5) and total autonomic function (P = 0.01; r = -0.2) and also negative correlation between epinephrine plasma level and total autonomic function (P = 0.04; r = 0.4). DM patients were next highest in norepinephrine level (133.26 ± 7.43), but lowest for plasma catecholamine; a positive correlation between dopamine level and PAR1 (P = 0.008; r = 0.6) was also seen in this group. Plasma dopamine levels and spider score correlated negatively (P = 0.04; r = -0.5) and total plasma catecholamine positively with encephalopathy (P = 0.04; r = 0.5) in patients with liver disease. CONCLUSIONS: Plasma catecholamine levels correlated with adrenergic functions in control subjects and patients with DM and liver disease, with no significant correlation seen for cholinergic function.

Autonomic and Enteric Nervous System Dysfunction May Play a Role in Hyperemesis Gravidarum.

BACKGROUND: Nausea and vomiting, seen in 70-85% of all pregnancies, becomes intractable in hyperemesis gravidarum (HG). We aimed to investigate the relationship between HG and autonomic nervous system functioning and gastric electrical activity. METHODS: Twenty-seven pregnant patients, 21 with HG and six normal, were studied with sympathetic adrenergic; percent vasoconstriction (%VC) and postural adjustment ratio (PAR); parasympathetic vagal cholinergic functions by R-to-R intervals (RRIs), a total autonomic score; and enteric nervous system measured by electrogastrography (EGG). RESULTS: Significant differences were found in parasympathetic measures (RRI for HG 29.98 ± 2.95 vs. control 40.91 ± 2.38, P < 0.05); sympathetic PAR was significantly lower in patients (PAR for HG 24.5 ± 5.0 vs. 67.6 ± 11.4 for controls, P < 0.01); mean total autonomic score was significantly lower in HG (131.75 ± 9.61 vs. 196.87 ± 12.8, P < 0.05). EGG results were borderline different (normal < 3.3, HG 3.4 vs. controls 3.0, P = 0.07). CONCLUSION: Autonomic and enteric nervous system dysfunction may play a role in the pathophysiology of HG.

The induction of type I interferon production in hepatitis C-infected patients.

Chronic infection with hepatitis C virus (HCV) is a major global health problem. One way HCV may evade the host immune response is by inhibiting the production of type I interferon (IFN). In addition, the standard treatment for chronic HCV infection involves treatment with IFN-alpha (or its pegylated derivative), alone or in combination with ribavirin. Therefore, it is believed that an important reason that most HCV-infected individuals progress from acute to chronic infection is due to a defect in the host response. In this study, we examined the host response to HCV infection in a cohort of patients enrolled in the UTHSC Cooperative HCV Research Center by determining levels of biologically active IFN in the sera of patients. We found that 15 of 35 enrolled HCV-infected patients show serum levels of IFN (ranging from 2 to 40 IU/mL) before initiation of therapy. Uninfected individuals do not have circulating levels of IFN. Basal IFN levels do not correlate with the clinical response to therapy, nor do they reflect the age, sex, or race of patients. These results suggest that the differential response of patients most likely reflects a defect in the later stages of the host innate immune response, such as the cellular response to endogenous or exogenous IFN. In contrast, the early stage of the host immune response in vivo of many HCV-infected patients (approximately 40%) is intact as determined by IFN production.

Sarcoidosis mimicking primary sclerosing cholangitis requiring liver transplantation.

Sarcoidosis is a systemic granulomatous disease of unknown etiology. The association of the cholestatic pattern usually seen in sarcoidosis, with biliary duct changes resembling primary sclerosing cholangitis (PSC) is rare. Liver transplantation permits the histological evaluation of the complete explanted liver, making the diagnosis more reliable. In conclusion we present our experience with two patients with sarcoidosis requiring liver transplantation, who presented with clinical and radiological findings characteristics of primary sclerosing cholangitis.

Intraperitoneal rupture of ectopic varices: two case reports and a review of literature.

Intraperitoneal rupture of ectopic varices is a rare complication of portal hypertension. Few case reports have been published in the literature. We report 2 cases of ectopic varices with intraperitoneal hemorrhage. This review details their presentation, hospital course and treatment. The first patient was managed conservatively, and second had a successful TIPS (transjugular intrahepatic portosystemic shunt). Few guidelines for treatment are available. The management is individualized according to the condition of the patient and the resources available. Objectives of management include early diagnosis, aggressive fluid resuscitation, correction of coagulopathy, reduction of portal hypertension and if possible direct control of the bleeding vessel.

Hepatitis C hypervariable region 1: association of reduced selection pressure in african americans with treatment failure.

In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of alpha-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.

Nonalcoholic fatty liver disease of obesity.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are part of the same continuum. They are a major, under-recognized cause of chronic liver disease. Good medical treatment options do not exist to date. The mainstay of treatment is weight loss. Bariatric surgery offers weight loss and improvement of NAFLD and NASH.

Neuropsychiatric complications after liver transplantation: role of immunosuppression and hepatitis C.

Neuropsychiatric complications are an important source of morbidity following orthotopic liver transplantation. Etiology of liver disease and type of immunosuppression are possible related factors. The aim of this study was to describe the prevalence of neuropsychiatric complications after liver transplantation, the role of immunosuppression, and the association between these and specific liver diseases such as hepatitis C. One hundred twenty-eight patients with liver transplants were studied. Tacrolimus was the primary immunosuppressant in 101 patients and cyclosporine in 27 patients. Seventy-five complications in 49 patients (38.2%) were reported. In 43 patients, the etiology was associated with immunosuppression: 36 on tacrolimus and 7 on cyclosporine (P = 0.34). Seventeen and four-tenths percent of patients with hepatitis C and 4.6% of patients without hepatitis C developed depression (P = 0.02). There is no difference between types of primary immunosuppression and neuropsychiatric complications. There is a significantly greater incidence of depression in patients transplanted for hepatitis C.

Overcoming obstacles to immunization in patients with chronic liver disease.

The importance of vaccination to protect against hepatitis A virus (HAV) and hepatitis B virus (HBV) infections in patients with chronic liver disease has been established. However, in this population, a number of obstacles can interfere with appropriate and timely hepatitis immunization. The costs of hepatitis A and B vaccine series are out of reach for many uninsured patients. Many private and government-sponsored insurance programs do not routinely cover these vaccinations for patients with chronic liver disease. Varying recommendations by government and national organizations, such as the Centers for Disease Control and Prevention (CDC) and the American Association for the Study of Liver Diseases (AASLD), may lead to uncertainty and inconsistent vaccination practices. Because of the need for multiple office visits for prescreening assessment and vaccine administration, patient adherence can be an issue as well. Improved coverage of vaccines by government and third-party health plans is needed, as are uniform guidelines regarding the vaccination of patients with chronic liver disease. Providers should counsel such patients about the serious health risks incurred by infection with HAV or HBV and encourage vaccination in these patients. A combination of interventions can be used to facilitate timely and appropriate vaccination against hepatitis and to improve the affordability of vaccination for patients with chronic liver disease.

Reproduction and transplantation: report on the AST Consensus Conference on Reproductive Issues and Transplantation.

It has been almost 50 years since the first child was born to a female transplant recipient. Since that time pregnancy has become common after transplantation, but physicians have been left to rely on case reports, small series and data from voluntary registries to guide the care of their patients. Many uncertainties exist including the risks that pregnancy presents to the graft, the patient herself, and the long-term risks to the fetus. It is also unclear how to best modify immunosuppressive agents or treat rejection during pregnancy, especially in light of newer agents available where pregnancy safety has not been established. To begin to address uncertainties and define clinical practice guidelines for the transplant physician and obstetrical caregivers, a consensus conference was held in Bethesda, Md. The conferees summarized both what is known and important gaps in our knowledge. They also identified key areas of agreement, and posed a number of critical questions, the resolution of which is necessary in order to establish evidence-based guidelines. The manuscript summarizes the deliberations and conclusions of the conference as well as specific recommendations based on current knowledge in the field.

Peginterferon alfa-2a for hepatitis C after liver transplantation: two randomized, controlled trials.

There is currently no effective treatment for recurrent hepatitis C after orthotopic liver transplantation (OLT). We therefore performed two randomized, controlled trials--a prophylaxis trial and a treatment trial--to evaluate the safety and efficacy of peginterferon alfa-2a in patients who had undergone OLT. The prophylaxis trial enrolled 54 patients within 3 weeks after OLT, and the treatment trial enrolled 67 patients 6 to 60 months after OLT. In each trial, patients were randomized to treatment with once weekly injections of 180 microg peginterferon alfa-2a or no antiviral treatment for 48 weeks and were followed up for 24 weeks thereafter. Peginterferon alfa-2a treated patients had significantly lower hepatitis C virus RNA levels and more favorable changes in hepatic histological features compared with untreated controls. However, only 2 treated patients in the prophylaxis trial (8%) and 3 in the treatment trial (12%) achieved a sustained virological response. In the prophylaxis trial, 8 patients (31%) in the peginterferon alfa-2a group and 9 (32%) in the untreated group were withdrawn prematurely; whereas in the treatment trial, 10 patients (30%) in the peginterferon alfa-2a group and 6 (19%) in the untreated group were withdrawn prematurely. The incidence of acute rejection was similar in the treated and untreated groups in both the prophylaxis (12% vs. 21%; P = .5) and treatment (12% vs. 0%; P = .1) trials. In conclusion, peginterferon alfa-2a treatment for 48 weeks is safe and tolerable and offers some efficacy in the post-OLT setting. Randomized controlled studies are needed to establish the efficacy of pegylated interferon and ribavirin in patients who have undergone OLT.

Intrahepatic cholestasis of pregnancy.

Patients with ICP should be considered to have a high-risk pregnancy. Once the diagnosis of ICP is suspected, usually because of generalized pruritus, it should be confirmed by liver function tests, and other causes of cholestasis should be ruled out. Treatment with UDCA is effective in ameliorating the cholestasis and is especially useful in severe forms or when there is a history of sudden fetal death in a previous pregnancy. The understanding of the pathogenesis of ICP has recently progressed as the result of the discovery of several defects in the MDR3 gene in isolated affected patients. More studies of this and other genes that regulate bile flow, linked with careful clinical observations to rule out unsuspected chronic liver disease not related to pregnancy, should lead to the discovery of the pathogenesis of this enigmatic disorder.

The epidemiology of chronic hepatitis C infection in survivors of childhood cancer: an update of the St Jude Children's Research Hospital hepatitis C seropositive cohort.

Childhood cancer survivors transfused before 1992 are at risk for chronic hepatitis C (HCV) infection. In 1995, St Jude Children's Research Hospital initiated an epidemiologic study of childhood cancer survivors with transfusion-acquired HCV. Of the 148 survivors with HCV confirmed by second-generation enzyme immunoassay, 122 consented to participate in the study. Their current median age is 29 years (range, 9 to 47 years). At enrollment, polymerase chain reaction (PCR) testing indicated chronic infection in 81.1%; genotype 1 was the most common viral genotype. Liver biopsy in 60 patients at a median of 12.4 years from the diagnosis of malignancy showed mild (28.8%) or moderate (35.6%) fibrosis; 13.6% had cirrhosis. Elevated body mass index was associated with histologic findings of increased steatosis (P=.008). Antimetabolite chemotherapy exposure was associated with early progression of fibrosis. Significant quality-of-life deficits were observed in noncirrhotic adult survivors. Antiviral therapy resulted in clearance of infection in 17 (44%) of 38 patients to date. Six patients have died; 1 patient with decompensated cirrhosis died of variceal bleeding. Despite a young age at HCV infection, the progression of liver disease in childhood cancer survivors is comparable to that seen in adults.

Liver disease in cystic fibrosis

En las últimas dos décadas, la sobrevida de los pacientes con fibrosis quística ha mejorado notablemente, permitiendo la aparición de complicaciones entre las cuales destaca el compromiso hepático. Hasta ahora ha sido difícil detectar la hepatopatía de la fibrosis quística y reconocer sus características. En años recientes se han conseguido progresos en la comprensión de su patogenia, así como una mayor experiencia con ciertas modalidades terapéuticas, lo que se discute en esta revisión