Determination of hepatitis B phenotype using biochemical and serological markers.

The aim of this study was to assess the validity of categorization of chronic hepatitis B viral infection into stages or phases based upon measures of disease activity and viral load, assuming these phenotypes will be useful for prognostication and determining the need for antiviral therapy. We assessed the phenotype of hepatitis B of 1,390 adult participants enrolled in the Hepatitis B Research Network Cohort Study, using a computer algorithm. Only 4% were immune tolerant, while 35% had chronic hepatitis B (18% e antigen positive and 17% e antigen negative) while 23% were inactive carriers. Strikingly, 38% of participants did not fit clearly into any one of these groups and were considered indeterminant. The largest subset of indeterminants had elevated serum aminotransferases with low levels of HBV DNA (less than 10,000 iu/mL). Subsequent determination of hepatitis B phenotype on the next available laboratory tests showed that 64% remained indeterminant. These findings call into question the validity of conventional staging of hepatitis B, in large part because of the substantial proportion of patients who do not fit readily into one of the usual stages or phases. Further studies are needed of the indeterminant category of chronic hepatitis B viral infection, including assessments of whether patients in this group are perhaps in transition to another phase or if they are a distinct phenotype with a need to assess liver disease severity and need for antiviral therapy. (ClinicalTrials.gov identifier NCT01263587).

Clinical and metabolic effects associated with weight changes and obeticholic acid in non-alcoholic steatohepatitis.

BACKGROUND: In a 72-week, randomised controlled trial of obeticholic acid (OCA) in non-alcoholic steatohepatitis (NASH), OCA was superior to placebo in improving serum ALT levels and liver histology. OCA therapy also reduced weight. AIMS: Because weight loss by itself can improve histology, to perform a post hoc analysis of the effects of weight loss and OCA treatment in improving clinical and metabolic features of NASH. METHODS: The analysis was limited to the 200 patients with baseline and end-of-treatment liver biopsies. Weight loss was defined as a relative decline from baseline of 2% or more at treatment end. RESULTS: Weight loss occurred in 44% (45/102) of OCA and 32% (31/98) of placebo-treated patients (P = 0.08). The NAFLD Activity score (NAS) improved more in those with than without weight loss in both the OCA- (-2.4 vs -1.2, P<0.001) and placebo-treated patients (-1.2 vs -0.5, P = 0.03). ALT levels also improved in those with vs without weight loss in OCA- (-43 vs -34 U/L, P = 0.12) and placebo-treated patients (-29 vs -10 U/L, P = 0.02). However, among those who lost weight, OCA was associated with opposite effects from placebo on changes in alkaline phosphatase (+21 vs -12 U/L, P<0.001), total (+13 vs -14 mg/dL, P = 0.02) and LDL cholesterol (+18 vs -12 mg/dL, P = 0.01), and HbA1c (+0.1 vs -0.4%, P = 0.01). CONCLUSIONS: OCA leads to weight loss in up to 44% of patients with NASH, and OCA therapy and weight loss have additive benefits on serum aminotransferases and histology. However, favourable effects of weight loss on alkaline phosphatase, lipids and blood glucose seen in placebo-treated patients were absent or reversed on OCA treatment. These findings stress the importance of assessing concomitant metabolic effects of new therapies of NASH. Clinical trial number: NCT01265498.

Epidemiology of hepatocellular carcinoma in areas of low hepatitis B and hepatitis C endemicity.

Hepatocellular carcinoma (HCC) ranks among the 10 most common cancers worldwide. It evolves from several chronic liver diseases, most of which culminate in cirrhosis. As the most common causes, other than alcoholic cirrhosis, are chronic hepatitis B and C infections, its prevalence worldwide is linked to the prevalence of these two viruses. Thus, the highest rates are in southeast Asia and sub-Saharan Africa, the world's most populous nations, where hepatitis B virus infection is endemic. In most western countries, hepatitis C virus infection is the predominant cause, and hepatitis B-related liver cancer occurs largely among immigrants from countries of high hepatitis B endemicity. In most western countries, the incidence and mortality from HCC is increasing as a consequence of the chronic sequelae of the 'epidemic' of hepatitis C of the 1960-1980s. In the US, modeling of this infection predicts a continued rise in liver cancer over the next decade. Surveillance by the National Cancer Institute and the Centers for Disease Control confirms the increasing incidence of and mortality from HCC to the year 2000, although subsequent analyses suggest a slowing or possibly decline in the rate of increase. Whether this trend will continue requires further evaluation.

Cytotoxic T lymphocyte responsiveness after resolution of chronic hepatitis B virus infection.

Clearance of the hepatitis B virus (HBV) during acute hepatitis is associated with a strong, polyclonal, multispecific cytotoxic T lymphocyte (CTL) response to the viral envelope, nucleocapsid and polymerase proteins that persists for decades after clinical recovery. In contrast, chronically infected patients usually fail to mount a strong CTL response to this virus. In this study we demonstrate that chronically infected patients who experience a spontaneous or interferon-induced remission develop a CTL response to HBV that is similar in strength and specificity to patients who have recovered from acute hepatitis. The results suggest that specific immunotherapeutic enhancement of the CTL response to HBV should be possible in chronically infected patients, and that it could lead to viral clearance in these individuals with resolution of chronic liver disease.

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.

Synthesis of antibodies to hepatitis B virus by cultured lymphocytes from chronic hepatitis B surface antigen carriers.

It has been postulated that host immune defects are responsible for the development and persistence of the hepatitis B surface antigen (HBsAg) carrier state. The nature of these defects is unknown, but the absence of a readily detectable antibody response to HBsAg (anti-HBs) may be important. The synthesis of both anti-HBs and antibody to hepatitis B core antigen (anti-HBc) in cultures containing peripheral blood mononuclear cells from chronic HBsAg carriers and from control (antibody-positive) patients was measured in the presence of pokeweed mitogen. Similar amounts of polyclonal IgG and IgM were synthesized by cultures containing lymphocytes from chronic carriers and controls. Anti-HBc was detectable in lymphocyte supernatants from 2 of 20 controls and from 21 of 29 carriers. The presence of anti-HBc synthesis in vitro correlated with high serum titers of anti-HBc. In contrast, anti-HBs was detected in lymphocyte supernatants from 6 of 20 controls (predominantly in those who had high serum titers of anti-HBs) but in none of the supernatants from 29 HBsAg carriers. In order to identify the mechanisms for the lack of detectable anti-HBs synthesis by chronic HBsAg carrier lymphocytes, co-culture experiments were performed using T and B lymphocyte fractions that had been purified by affinity chromatography. B lymphocytes from carriers co-cultured with allogeneic irradiated ("helper") T lymphocytes from controls synthesized normal amounts of IgG, IgM, and anti-HBc but still did not synthesize detectable amounts of anti-HBs. In the converse experiments, B lymphocytes from controls were co-cultured with irradiated T lymphocytes from carriers. The T lymphocytes from 16 of 24 carriers augmented anti-HBs production by control B cells normally, the remaining eight did not. Finally, mixtures of control B cells and control irradiated T lymphocytes were co-cultured with T lymphocytes from chronic HBsAg carriers. 5 of 12 carriers demonstrated active suppression of anti-HBs production, and in three this suppression was specific, as IgG and IgM production remained normal. We conclude that chronic HBsAg carriers have a specific B lymphocyte defect in anti-HBs production. In addition, defects in the function of regulatory T lymphocytes may contribute to the absence of anti-HBs synthesis in some HBsAg carriers.

Noninvasive markers for staging fibrosis in chronic delta hepatitis.

BACKGROUND: Serum fibrosis markers are useful in staging chronic hepatitis B (HBV) and C (HCV) virus but have not been evaluated in chronic hepatitis D virus (HDV). AIM: To evaluate the utility of serum fibrosis markers [fibrosis-4 score (FIB-4), aspartate aminotransferase (AST) to alanine aminotransferase (ALT) ratio, aspartate aminotransferase ratio (AAR), age-platelet index (API), AST-to-platelet-ratio-index (APRI) and Hui score] in HDV infection. METHODS: Clinical and histologic laboratory data from HBV, HCV and HDV patients were evaluated and serum fibrosis markers were calculated. The ability of fibrosis markers to detect advanced fibrosis (Ishak ≥4) and cirrhosis (Ishak = 6) were evaluated and compared between viral infections. RESULTS: A total of 1003 subjects (HCV = 701, HBV = 240 and HDV = 62) with mean age of 46 ± 11 and 66% male were evaluated. HDV subjects had higher ALT and AST than HCV and lower platelets than both HBV and HCV. Histologically, HDV had the greatest percentage of Ishak ≥4 and necroinflammation. FIB-4 performed best in detecting advanced fibrosis and cirrhosis in all viral cohorts. In HDV, area under the receiver operator curve (AUROC) 95% confidence intervals for detecting advanced fibrosis were: FIB-4 = 0.70 (0.55-0.84), API = 0.69 (0.55-0.82), APRI = 0.68 (0.54-0.82), Hui score = 0.63 (0.49-0.78), AAR = 0.63 (0.48-0.77). The AUROC for detecting cirrhosis in HDV were: FIB-4 = 0.83 (0.69-0.97), API = 0.80 (0.66-0.95), APRI = 0.75 (0.61-0.89), Hui score = 0.70 (0.49-0.91) and AAR = 0.70 (0.48-0.93). Adjustment of published cut-offs led to marginal improvements in FIB4 for advanced fibrosis and of APRI for cirrhosis in HDV. CONCLUSIONS: Serum fibrosis markers have lower performance accuracy in chronic HDV infected patients compared to HBV and HCV patients. Other noninvasive fibrosis markers should be explored to assist in the management of these patients.

Complications of percutaneous liver biopsy with Klatskin needles: a 36-year single-centre experience.

BACKGROUND: Liver biopsy is the gold standard in evaluating liver diseases but is susceptible to complications. Safety data on aspiration needle biopsies remain limited. AIM: To evaluate the safety of percutaneous liver biopsy performed with Klatskin needle. METHODS: Clinical and biochemical data were retrospectively retrieved from sequential subjects who underwent liver biopsy with Klatskin needle from 1978 to 2015. Subjects with complications underwent thorough chart reviews for hospital course. RESULTS: Of 3357 biopsies performed, complications occurred in 135 (4%) biopsies with 33 (1%) resulting in major complications. Severe pain occurred in 78 (2.3%) subjects and bleeding occurred in 21 (0.6%) subjects. Biliary injury occurred in 8 (0.2%) biopsies. Three subjects died as a result of massive intraperitoneal bleeding. Compared to viral hepatitis, biopsies performed with certain diagnosis had significantly higher odds of major complications: NRH (OR: 17), DILI (OR: 20), GVHD (OR: 32) and HCC (OR: 34). Subjects with major complications had higher pre-biopsy median AP (153 vs. 78 U/L, P < 0.001), ALT (105 vs. 64 U/L, P < 0.05), AST (62 vs. 47 U/L, P < 0.02), along with marginally lower total bilirubin (1.0 vs. 0.7 mg/dL, P < 0.01) and albumin (3.7 vs. 4.0 g/dL, P < 0.001). By multivariate backward logistic regression, platelets ≤100 K/µL and aPTT >35 were independent risk factors of post-biopsy bleeding. CONCLUSION: Klatskin needle liver biopsies are safe with rare procedural morbidity. Our data suggests certain acutely ill subjects and those with systemic illnesses may be at higher risk of major complications. Clinicians should weigh the risks and benefits of liver biopsy in these patients with other alternative approaches.

Long-term lamivudine therapy in chronic hepatitis B.

BACKGROUND: One to 5 years of therapy of chronic hepatitis B with oral nucleoside analogues result in significant clinical improvements, but effects of more prolonged therapy are not well defined. AIM: To describe outcomes of chronic hepatitis B with long-term lamivudine therapy. METHODS: Forty-two patients with chronic hepatitis B treated with lamivudine were followed for 3.2-19.5 (median = 16.1) years. Therapy was switched to other agents (n = 16) if patients developed lamivudine resistance and relapse of disease. RESULTS: Among 22 HBeAg-positive patients, 17 (77%) became HBeAg negative, of whom 5 (23%) subsequently cleared HBsAg. Among 20 HBeAg-negative patients, 10 (50%) cleared HBsAg. The time to HBsAg clearance ranged from 0.9 to 16.8 (median = 9.3) years. Lamivudine resistance arose in 24 patients (57%) of whom 6 (25%) lost HBsAg. HBsAg clearance was not always accompanied by seroconversion; anti-HBs appearing concurrently in only five patients (33%). Nevertheless, HBsAg loss allowed for stopping therapy in all patients, none re-developing HBsAg or suffering relapse; all having normal alanine aminotransferase levels and no (n = 13) or unquantifiable HBV DNA levels (n = 2) when last seen. In contrast, seven of 27 patients (26%) who remained HBsAg-positive died of liver disease or liver cancer or underwent liver transplantation, all of whom had cirrhosis. CONCLUSIONS: Long-term viral suppression with nucleoside analogues leads to HBsAg loss in a substantial proportion of patients, particularly if HBeAg-negative. Serious outcomes during the first 10-20 years of treatment occur largely among patients with pre-existing cirrhosis who do not clear HBsAg with therapy.

Interleukin-2 induces profound reversible cholestasis: a detailed analysis in treated cancer patients.

Interleukin-2 (IL-2)-based immunotherapy is associated with profound reversible cholestasis and hyperbilirubinemia. We performed a nonrandomized retrospective and prospective analysis to determine the incidence, characteristics, clinical course, and nature of the IL-2-induced liver dysfunction in patients with cancer. Patients received IL-2 at a dose of 20,000 to 100,000 units (U)/kg thrice daily for up to 5 days. Fifty-one patients on adjuvant treatment protocols received a mean of 10.18 +/- 2.38 IL-2 doses and 11.67 +/- 4.16 doses were delivered to 210 patients with advanced disease during this period. Retrospective analysis of all patients receiving this therapy revealed increases in the following liver function tests expressed as median, 25th percentile, and 75th percentile (range): bilirubin (mg/dL) 4.5, 2.6, 6.5 (.4 to 38.5); alkaline phosphatase (U/L) 256, 179, 378 (56-1680); SGOT (U/L) 80, 52, 117 (18 to 483); SGPT (U/L) 91, 64, 132 (20-540); prothrombin time 13.4, 12.8, 14.5 (10.8 to 35.4); and albumin (g/dL) values decreased (trough) slightly 3.0, 2.8, 3.2 (2.3 to 3.8). Multiple regression analysis revealed several factors that were significantly associated with the increase in bilirubin when jointly considered (model P2 less than or equal to .001) including total IL-2 dosage, increase in creatinine, alkaline phosphatase, weight, and SGOT. Similar increases were noted in a prospectively evaluated group of 10 patients. A return to normal levels of bilirubin was noted within 5.6 days of stopping IL-2. Fasting serum cholylglycine increased from a mean of 32.3 +/- 1.6 to a peak of 1556.0 +/- 625.0 mg/mL. Although conventional ultrasound examinations were unrevealing, tissue ultrasound examinations revealed a mean scatterer spacing (MSS) increase compared to baseline of .10 +/- .04 (P less than .02) suggesting hepatic edema or an infiltrative process. Further, computerized hepatobiliary nuclear medicine scans revealed a delay in uptake (2.2 +/- 0.5 fold greater) and excretion (8.0 +/- 5.9 fold greater) of technetium-99m labeled disofenin. These findings support the development of profound reversible cholestasis as the primary basis for the elevated bilirubin in patients undergoing IL-2 treatment and may have implications for understanding the jaundice observed in some patients postoperatively as well as that associated with sepsis and other inflammatory disorders. Specifically, the release of IL-2 or the induction of other factors similarly induced by IL-2 may be responsible for these findings. Tissue ultrasound and computerized hepatobiliary scans provide additional noninvasive assessments of liver function and physiology.

Phenytoin hepatotoxicity masked by corticosteroids.

The association of phenytoin and liver toxicity is well documented. This article describes a patient who underwent a transsphenoidal resection of a pituitary tumor who developed phenytoin-induced hepatotoxicity that was masked by the simultaneous administration of corticosteroids for treatment of cerebral edema. In a patient receiving both medications, the systemic manifestations of the hypersensitivity to phenytoin may go unrecognized, leading to delayed identification of a potentially lethal complication of this commonly prescribed anticonvulsant.

Psychiatric complications of long-term interferon alfa therapy.

Ten (17%) of 58 patients with chronic viral hepatitis treated with a four- to 12-month course of recombinant human interferon alfa developed psychiatric side effects. The psychiatric side effects fell into three categories: an organic personality syndrome characterized by irritability and short temper; an organic affective syndrome marked by extreme emotional lability, depression, and tearfulness; and a delirium marked by clouding of consciousness, agitation, paranoia, and suicidal potential. These psychiatric side effects appeared after one to three months of therapy, usually improved within three to four days of decreasing the dose of interferon alfa, and invariably resolved once therapy was stopped. The organic personality and affective syndromes tended to occur in patients who received the highest dose of interferon alfa, who had relatively mild hepatitis, and who lost weight during interferon treatment. Delirium tended to occur in patients with severe hepatitis who had previous evidence of organic brain injury or dysfunction or previous drug and alcohol abuse. Failure to recognize these side effects quickly and to treat them with supportive therapy and modification of the dose of interferon alfa could result in limitation of therapy and serious personal and interpersonal consequences.

Liver injury is associated with mortality in sickle cell disease.

BACKGROUND: Increased life expectancy in sickle cell disease (SCD) has resulted in greater recognition of the consequences of repeated intravascular vaso-occlusion and chronic haemolysis to multiple organ systems. AIM: To report the long-term consequences of liver dysfunction in SCD. METHODS: A cohort of SCD patients was prospectively evaluated at the National Institutes of Health (NIH) Clinical Center. The association of mortality with liver enzymes, parameters of liver synthetic function and iron overload was evaluated using Cox regression. RESULTS: Exactly, 247 SCD patients were followed up for 30 months of whom 22 (9%) died. After controlling for predictors, increased direct bilirubin (DB), ferritin, alkaline phosphatase and decreased albumin were independently associated with mortality. In a multivariable model, only high DB and ferritin remained significant. Ferritin correlated with hepatic iron content and total blood transfusions but not haemolysis markers. Forty patients underwent liver biopsies and 11 (28%) had fibrosis. Twelve of 26 patients (48%) had portal hypertension by hepatic venous pressure gradient (HVPG) measurements. All patients with advanced liver fibrosis had iron overload; however, most patients (69%) with iron overload were without significant hepatic fibrosis. Ferritin did not correlate with left ventricular dysfunction by echocardiography. DB correlated with bile acid levels suggesting liver pathology. Platelet count and soluble CD14 correlated with HVPG indicating portal hypertension. CONCLUSIONS: Ferritin and direct bilirubin are independently associated with mortality in sickle cell disease. Ferritin likely relates to transfusional iron overload, while direct bilirubin suggests impairment of hepatic function, possibly impairing patients' ability to tolerate systemic insults.

Mephenytoin disposition and serum bile acids as indices of hepatic function in chronic viral hepatitis.

BACKGROUND AND OBJECTIVES: The effect of chronic viral hepatitis on liver function may vary from none to hepatic failure. Changes in function are usually the result of impaired hepatocyte function or altered vascular flow and architecture. Conventional liver function tests usually cannot distinguish contributions from these mechanisms or indicate degree of hepatic metabolic dysfunction. An alternative approach is to measure the hepatic metabolism of a highly extracted compound whose oral clearance and systemic bioavailability are dependent on both hepatocyte function and degree of portosystemic shunt. METHODS: The stereoselective metabolism of racemic mephenytoin (100 mg oral dose) was investigated in 35 patients with chronic viral hepatitis and compared with 153 healthy subjects. The mephenytoin R/S enantiomeric ratio and cumulative excretion of the 4'-hydroxymephenytoin metabolite in a 0- to 8-hour urine sample were used in addition to serum bile acid levels and pathologic examination of biopsy specimens to assess the severity of hepatic dysfunction and portosystemic shunting. RESULTS: The patients as a group excreted less 4'-hydroxymephenytoin and had a smaller R/S enantiomeric ratio of mephenytoin. The two measures were discriminatory between the patient groups classified by either serum cholylglycine level or pathologic examination of biopsy specimens. Combination of the two measures of mephenytoin metabolism allowed the patients to be classified into three groups: normal hepatocyte function without portosystemic shunt, normal hepatocyte function with portosystemic shunt, and low hepatocyte function with or without portosystemic shunt. CONCLUSION: This study has shown the potential usefulness of mephenytoin metabolism as a sensitive indicator of hepatic pathologic condition with an ability to discriminate between contributory alternative mechanisms.

Vitamin E deficiency in adults with chronic liver disease.

In order to determine the frequency of vitamin E deficiency in adults with chronic liver disease, we measured serum vitamin E concentrations and calculated the ratio of serum vitamin E to total serum lipids (E/lipids) in forty-two patients with primary biliary cirrhosis (PBC) (Group A), fifteen patients with other forms of chronic liver disease (Group B), and twenty-five healthy adult control subjects (Group C). Although the mean serum vitamin E concentration did not differ significantly among the three groups, the ratio of serum vitamin E/lipids was significantly lower in Group A than Groups B and C. Vitamin E deficiency, as defined by the ratio of serum vitamin E/lipids below 0.8 mg/gm, was present in seven (17%) Group A and one (7%) Group B patients. Serum cholylglycine, sulfated lithocholate conjugates, and bilirubin were significantly higher and the mean duration of symptomatic primary biliary cirrhosis was significantly longer (6.6 vs 2.3 years) in the vitamin E-deficient compared to the vitamin E-sufficient Group A patients. Our study demonstrates that vitamin E deficiency may occur in adults with severe, prolonged cholestatic liver disease.

Hepatitis in patients with acute nonlymphocytic leukemia.

Three consecutive groups (University of Maryland Cancer Center protocols 7110, 7405, and 7802) of patients with acute nonlymphocytic leukemia who achieved a complete hematologic remission with similar antileukemic therapy were reviewed for the development of hepatitis. Ninety-four (73 percent) experienced viral hepatitis; eight had type B hepatitis and 86 had non-A/non-B hepatitis. The hepatitis was mild in all patients. Hepatitis secondary to cytomegalovirus, herpes simplex virus, Epstein-Barr virus, or Toxoplasma gondii was not observed. Antibody to type A hepatitis was common, but acute infection could not be substantiated. All cases of type B hepatitis in which the surface antigen could be serotyped were found to have the less frequently observed ayw marker, suggesting a common donor as the source of infection. The median duration of complete remission was longer (p = 0.03) for patients in Group II (protocol 7405) who contracted hepatitis (247 days) compared with patients without hepatitis (125 days). Median overall survival was also longer (p = 0.01) for these patients in whom hepatitis developed (672 days versus 372 days, respectively). No prolongation of complete remission duration or survival could be demonstrated for patients from Group I (protocol 7110) or Group III (protocol 7802) who contracted hepatitis. In patients with hepatitis, the height of transaminase serum bilirubin levels or duration of abnormal results of liver function tests did not correlate with the duration of complete remission or survival. Hepatitis, a common infection in those patients with acute nonlymphocytic leukemia who undergo induction therapy, had an inconsistent effect on the duration of complete remission interval and overall survival.

Increased waiting time for liver transplantation results in higher mortality.

BACKGROUND: Waiting time to liver transplantation (LTx) has dramatically lengthened, but the proportion of candidates who die awaiting transplantation has not increased. We evaluated whether longer waiting time for LTx candidates increases mortality. METHODS: A cohort of candidates listed for LTx between 1990 and 1993 by three large transplantation programs was followed for 2 years. The exposure measure was ABO blood type, which is not inherently related to outcome, but is a major determinant of waiting time. The main outcome measure was 2-year mortality, as evaluated by logistic regression analysis that controlled for differences in clinical status at the time of evaluation for LTx. RESULTS: The 308 candidates with type O blood waited longer for LTx (median 109 days) than the 399 candidates with other blood types (median 58 days) (P=0.001). Candidates listed for LTx with type O blood had better clinical status at evaluation, but then had higher pretransplantation mortality (13.3%) than other candidates (7.0%) (P=0.005). Blood group O candidates had higher 2-year mortality (26.6%) than other candidates (22.1%), which on multivariate analysis resulted in a mortality odds ratio at 2 years of 1.52 (95% confidence interval=1.04-2.23). With the difference in median waiting time between blood groups increasing from 44 days in the first year to 108 days in the third year, the 2-year mortality odds ratio also rose from 0.94 to 1.97. CONCLUSIONS: When compared with LTx candidates with other blood types, blood type O candidates have longer waiting times and higher pretransplantation mortality, which results in higher 2-year mortality.

Age and liver transplantation: a report of the Liver Transplantation Database.

BACKGROUND: The average age of liver transplant recipients has increased steadily during the last decade. The effects of recipient age on outcome of liver transplantation were evaluated in a large prospective database. METHODS: A total of 735 adult recipients of single-organ liver transplants for nonfulminant liver disease enrolled in a large prospective database between 1990 and 1994 were analyzed for associations of patient age with outcomes. Patients were categorized into two groups: younger being <60 and older being > or = 60 years of age. RESULTS: Older liver transplant recipients were more likely to be female, white, and have the diagnoses of primary biliary cirrhosis or cryptogenic cirrhosis than younger recipients, who were more likely to have the diagnosis of alcoholic liver disease. Disease severity was similar between the two groups. After transplantation, the durations of stay in the intensive care unit and hospital were longer for older than for younger transplant recipients, but episodes of acute rejection were less frequent. The quality of life at 1 year was similar among older and younger recipients. Patient survival was lower for older than for younger recipients (81% vs. 90% at 1 year; P=0.004), whereas graft survival was not different (80% vs. 85% at 1 year; P=0.163). The excess mortality among older recipients was largely due to nonhepatic causes, including infectious, cardiac, and neurological diseases occurring within 6 months after transplantation. CONCLUSIONS: Although patient survival was significantly lower among liver transplant recipients above the age of 60 years, the excess mortality was due to nonhepatic, largely age-related problems. The overall success of liver transplantation and improvement in quality of life for older recipients is excellent.

Transmission of hepatitis B virus infection by asymptomatic chronic HBsAg carrier mothers.

The courses of 18 children born to 13 chronic hepatitis B surface antigen (HBsAg) carrier mothers were followed prospectively for serological and biochemical evidence of type B hepatitis. Three children developed transient HBsAg positivity accompanied by the appearance of antibody to the hepatitis B core antigen. Two others had no detectable HBsAg but developed antibody to HBsAg. These serological manifestations of hepatitis B virus infection occurred late--6 to 24 months after birth. None of the children had clinical evidence of hepatitis and none became chronic HBsAg carriers. The infrequency of transmission of infection, the mild course of disease, and the lack of persistence of HBsAg in these children probably reflected the low level of infectivity of the chronic carrier mothers and perhaps the healthy immunologic status of the children.

Evaluation of hepatitis B antigen testing in federally licensed blood banks in the United States.

Between August 1972 and January 1974, the Burear of Biologics distributed four panels of 20 coded serum samples to all federally licensed blood banks for hepatitis B antigen testing. Initially, all but six blood banks reported results by counterelectrophoresis (CEP) only, but by January 1974, 152 of 247 banks reported results by radioimmunoassay (RIA). On the four panels distributed, correct results were reported for 63 to 83% of all potentially detectable samples by CEP and for 98 to 100% of all samples potentially detectable by RIA. Perfect scores were obtained by only 5 to 25% of blood banks using CEP but by 77 to 100% using RIA. Nonreproducible results on duplicate reactive samples, included to evaluate internal consistency, ranged from 0.5 to 25% by CEP and from zero to 5% by RIA. These results demonstrate greater reliability in addition to greater sensitivity of "third generation" RIA testing in comparison with "second generation" CEP testing.