Management of hepatitis B in patients with HBeAg-negative disease

Chronic hepatitis B with negative hepatitis B e antigen (HBeAg) is becoming a more prevalent form of chronic hepatitis B. This change is the result of selection pressure on the virus leading to a precore or double core promoter mutation of hepatitis B virus that either abolishes or downregulates synthesis of HBeAg. De novo acute infection with HBeAg-negative mutant virus rarely leads to chronic infection but usually results in acute hepatitis with a course ranging from benign to fulminant. Chronic HBeAg-negative hepatitis B is thought to evolve from wildtype HBeAg-positive chronic hepatitis B and is associated with a worse natural history than HBeAg-positive disease. Long-term treatment is required to maintain suppression of viral replication when using the oral nucleoside or nucleotide analogues, which have improved management of this condition. However, the need for extended therapy makes strategies to reduce or avoid resistance to antiviral drugs an important consideration.     

Noninvasive assessment of coronary vasodilation using magnetic resonance angiography

OBJECTIVES: The purpose of this study was to investigate the use of coronary magnetic resonance angiography (MRA) for assessing human epicardial coronary artery vasodilation. BACKGROUND: Coronary vasodilation plays a vital role in the human coronary circulation. Previous studies of epicardial coronary vasodilation have used invasive coronary angiography. Coronary MRA may provide an alternative noninvasive method to directly assess changes in coronary size. METHODS: Thirty-two subjects were studied: 12 patients (age 55 +/- 18 years) and 20 healthy subjects (age 34 +/- 4 years). High-resolution multi-slice spiral coronary MRA (in-plane resolution of 0.52 to 0.75 mm) was performed before and after sublingual nitroglycerin (NTG). Quantitative analysis of coronary vasodilation was performed on cross-sectional images of the right coronary artery (RCA). A time-course analysis of coronary vasodilation was performed in a subset of eight subjects for 30 min after NTG. Signal-to-noise ratio was also measured on the in-plane RCA images. RESULTS: Coronary MRA demonstrated a 23% increase in cross-sectional area after NTG (16.9 +/- 7.8 mm2 to 20.8 +/- 8.9 mm2, p <0.0001), with significant vasodilation between 3 and 15 min after NTG on time-course analysis. The MRA measurements had low interobserver variability (< or =5%) and good correlation with X-ray angiography (r=0.98). The magnitude of vasodilation correlated with baseline cross-sectional area (r=0.52, p=0.03) and age (r=0.40, p=0.019). Post-NTG images also demonstrated a 31% improvement in coronary signal-to-noise ratio (p = 0.002). CONCLUSIONS: Nitroglycerin-enhanced coronary MRA can noninvasively measure coronary artery vasodilation and is a promising noninvasive technique to study coronary vasomotor function.     

Hepatitis C virus and liver transplantation.

Advances in immunosuppressive therapy, operative techniques, and perioperative management have resulted in long-term patient survival rates approaching 90% following liver transplantation for chronic viral hepatitis. The increasing number of referrals for liver transplantation reflects the impact of chronic HCV infection as a cause of end-stage liver disease. Unlike hepatitis B, there is still no effective treatment in preventing recurrent hepatitis C after liver transplantation. The spectrum of allograft injury related to universal HCV infection recurrence ranges from no evidence of histologic injury to mild inflammation to severe disease with allograft failure in small proportion of patients. Various factors may explain these differing outcomes, including degree of pretransplantation viremia, HLA compatibility, presence of more pathogenic HCV genotypes, integrity of cellular immune response, and type of immunosuppression. Fortunately, patient survival does not seem to be affected short-term; the long-term outcome of liver transplantation for chronic hepatitis C is unclear but is likely to be decreased. Combination therapy with interferon plus ribavirin seems to be a promising treatment strategy for posttransplantation recurrent hepatitis C, and the use of pegylated interferon plus ribavirin may improve these results. Patients with moderate to severe allograft hepatitis are appropriate candidates for combination antiviral therapy. Histopathologically documented recurrent hepatitis C in liver transplant recipients is associated with impaired quality of life, inferior physical condition, and a higher incidence of depression compared with patients who did not have HCV and in those without HCV recurrence. In conclusion, it is possible that the continued improvements in antiviral therapy against HCV infection may ultimately decrease the number of patients needing liver transplantation. Suitable candidates with chronic HCV infection thus warrant treatment with pegylated interferon plus ribavirin combination therapy in the hope of decreasing disease progression. Recent studies, which require confirmation, suggest that nonresponders to standard antiviral therapy may benefit from maintenance therapy. The donor pool for patients with chronic hepatitis C and decompensated cirrhosis can be improved by using HCV-positive donors and by increasing utilization of newer surgical techniques, including adult-to-adult living-donor liver transplantation and split-liver transplantation.     

Management of chronic liver failure until liver transplantation

Chronic liver failure is an important cause of morbidity and mortality and is the long-term consequence of many chronic liver diseases. In addition to determining the specific cause of the chronic liver disease, which may be amenable to targeted therapy, it is important to treat the sequelae of chronic liver failure effectively to improve quality of life, to prolong survival, and to provide a bridge to liver transplantation. Once a patient who has chronic liver failure develops hepatic decompensation, liver transplantation is the definitive treatment for those who qualify. Management of chronic liver failure is the focus of this article.     

Managing depression in patients with vision impairment: A descriptive study of practitioners' beliefs and confidence

Aim: Depression is common in older adults with vision impairment yet it often remains unidentified and untreated. Eye health professionals (EHPs) and rehabilitation workers (RWs) may be able to assist in detecting depression. This study identified EHPs' and RWs' beliefs about depression and confidence in working with patients with vision impairment and depression. Methods: A self‐administered cross‐sectional survey of 94 EHPs and RWs assessed beliefs about the symptoms and treatment for depression, and confidence in working with depressed people with vision impairment. Results: Participants showed awareness of both the symptoms and treatment options for depression. However, some important misconceptions were identified and many symptoms of depression were commonly attributed to vision loss. Participants lacked confidence in communicating about depression with patients and their families. Conclusions: Training programs are needed to enable EHPs and RWs to confidently identify depression and discuss appropriate treatment and referral options with their patients.     

Hepatitis B virus genotypes in the United States: results of a nationwide study

BACKGROUND & AIMS: Hepatitis B virus (HBV) genotypes may be related to severity of liver disease and treatment response. The aims of this nationwide study were to determine the prevalence of HBV genotypes in the United States and the association between HBV genotypes and patient demographics, mode of infection, and clinical status. METHODS: A total of 694 consecutive chronic HBV-infected patients seen in 17 U.S. liver centers during a 1-year period were enrolled. Demographic, clinical, and laboratory data were collected. Sera were tested for HBV genotyping, precore, and core promoter variants by line-probe assays. RESULTS: All 7 HBV genotypes (A-G) were found, with genotypes A and C the most common. The prevalence of HBV genotypes was different in different regions of the United States. A strong correlation was found between HBV genotypes and ethnicity. HBV genotype A was prevalent among white and black patients, whereas genotypes B and C were most common among Asian patients. The predominant genotype among patients born in the United States, Europe, the Far East, and Southeast Asia were A, D, C, and B, respectively. Genotypes A and C were associated with a higher prevalence of hepatitis B e antigen. Precore variant was detected in 27% of patients and core promoter variant in 44% of patients. CONCLUSIONS: Our study suggests that the epidemiology of HBV infection in the United States may have changed over time as a result of immigration from countries with a high prevalence of HBV infection. HBV genotypes may account for the heterogeneity in disease manifestations among patients with chronic HBV infection.     

Liver Biopsy for Histological Assessment �C The Case Against

Percutaneous liver biopsy (LB) remains an important tool in the diagnosis and management of parenchymal liver diseases. In current practice, it is most frequently performed to assess the inflammatory grade and fibrotic stage of commonly encountered liver diseases, with the diagnostic role relegated to secondary importance. The role of LB remains a vastly controversial and debated subject, with an ever-increasing burden of evidence that questions its routine application in all patients with liver dysfunction. It remains, essentially, an invasive procedure with certain unavoidable risks and complications. It also suffers shortcomings in diagnostic accuracy since a large liver sample is required for an ideal assessment, which in clinical practice is not feasible. LB is also open to observer interpretation and prone to sampling errors. In recent years, a number of noninvasive biomarkers have evolved, each with an impressive range of diagnostic certainty approaching that achieved with LB. These noninvasive tests represent a lower-cost option, are easily reproducible, and serve as suitable alternatives to assess hepatic inflammation and fibrosis. This article aims to debate the shortcomings of LB while simultaneously demonstrating the diagnostic accuracy, reliability and usefulness of noninvasive markers of liver disease thereby making the case for their utilization as suitable alternatives to LB in many, although not all, circumstances.     

Racial differences in effectiveness of alpha-fetoprotein for diagnosis of hepatocellular carcinoma in hepatitis C virus cirrhosis

alpha-Fetoprotein (AFP) is frequently used as a diagnostic marker for hepatocellular carcinoma (HCC). Most available data concerning AFP come from studies of patients with chronic hepatitis B or other chronic liver diseases of mixed etiologies. Limited data concerning the diagnostic value of AFP for hepatitis C virus (HCV)-related HCC have to date come only from Asian and European studies, and results are conflicting. There may be significant differences in AFP levels depending on racial backgrounds and etiologies of primary liver disease. We conducted a multicenter, retrospective, case-control study of 163 HCC patients with HCV infection and 149 control patients with HCV-related cirrhosis. The positive likelihood ratios for AFP at 0 to 20, 21 to 50, 51 to 100, and 101 to 200 ng/mL were 0.46, 1.31, 1.15, and 6.90, respectively. No controls had AFP greater than 200 ng/mL. The sensitivity of AFP for the diagnosis of HCC in African Americans with HCV infection was lower than that of patients of all other ethnic groups combined (57.1% vs. 81.6% for AFP > 10 ng/mL, P =.02, and 42.9% vs. 66.0% for AFP > 20 ng/mL, P =.05). The area under the receiver operating characteristics curve was 0.81 for non-African Americans but only 0.56 for African Americans. In conclusion, AFP greater than 200 ng/mL can be used to confirm HCC in patients with HCV-related cirrhosis and a hepatic mass. However, AFP is insensitive for the diagnosis of HCC in African Americans.     

Sarcoidosis and primary biliary cirrhosis. Literature review and illustrative case

An illustrative case of a middle-aged woman with primary biliary cirrhosis and the onset of liver disease coincident with acute, self-limited sarcoidosis is presented. The distinctive characteristics of sarcoidosis and primary biliary cirrhosis are described, and the literature regarding a number of potential relationships between these two disorders is summarized. First, the simultaneous occurrence of primary biliary cirrhosis and sarcoidosis has been documented in a few patients. Second, some of these patients had an overlap syndrome characterized by features of both disorders, inviting speculation regarding a common pathogenesis. Third, in patients with sarcoidosis, advanced cholestatic sarcoid liver disease may develop, which may cause diagnostic confusion with primary biliary cirrhosis. Finally, patients with primary biliary cirrhosis may have pulmonary fibrosis as an associated disease.     

A selective cyclooxygenase 2 inhibitor suppresses the growth of H-ras-transformed rat intestinal epithelial cells

BACKGROUND & AIMS: Constitutive expression of cyclooxygenase 2 (COX-2) has been found in 85% of colorectal cancers. Ras mutations are found in 50% of colorectal adenocarcinomas. The aim of this study was to determine the role of COX-2 in ras-induced transformation in rat intestinal epithelial (RIE) cells. METHODS: Cell growth was determined by cell counts. The expression of COX-2 was examined by Northern and Western analyses. For tumorigenicity assays, cells were inoculated into dorsal subcutaneous tissue of athymic nude mice. DNA-fragmentation assays were performed to detect apoptosis. RESULTS: The expression of COX-2 was increased in RIE-Ras cells at both messenger RNA (9-fold) and protein (12-fold) levels. Prostaglandin I2 levels were elevated 2.15-fold in RIE-Ras cells. Serum deprivation further increased COX-2 expression 3.8-fold in RIE-Ras cells. Treatment with a selective COX-2 antagonist (SC58125) inhibited the growth of RIE-Ras cells through inhibition of cell proliferation and by induction of apoptosis. SC-58125 treatment reduced the colony formation in Matrigel by 83.0%. Intraperitoneal administration of SC-58125 suppressed RIE-Ras tumor growth in nude mice by 60.3% in 4 weeks. SC-58125 treatment also induced apoptosis in RIE-Ras cells as indicated by increased DNA fragmentation. CONCLUSIONS: Overexpression of COX-2 may contribute to tumorigenicity of ras-transformed intestinal epithelial cells. Selective inhibition of COX-2 activity inhibits growth of ras-transformed intestinal epithelial cells and induces apoptosis. (Gastroenterology 1997 Dec;113(6):1883-91)