Chronic hepatitis B virus (HBV) infection is an important cause of chronic liver disease worldwid... more Chronic hepatitis B virus (HBV) infection is an important cause of chronic liver disease worldwide. It affects a disproportionate number of individuals from areas of high endemicity, where perinatal transmission is the predominant mode of infection. Introduction of a safe, effective hepatitis B vaccine has led to universal infant vaccination, resulting in a reduced rate of perinatal HBV infection from infected mothers. Because of appropriate hepatitis B vaccination and passive immunoprophylaxis with hepatitis B immune globulin (HBIG) in infants of mothers with HBV infection, perinatal transmission has been reduced to less than 5% to 10%. Management of pregnant women with chronic HBV infection should be aimed at counseling on maternal risk of infection, rates of vertical transmission, and preparation for neonatal vaccination. Limited data suggest that intrauterine infection may occur at higher rates in mothers with high serum HBV DNA levels, leading to failure of standard passive-active immunoprophylaxis with HBIG and vaccine. Thus, treatment of these individuals with an oral HBV antiviral agent in the third trimester may be considered after discussion with the mother regarding the risks and benefits of therapy.
There are an estimated 350 million people who are chronically infected with the hepatitis B virus... more There are an estimated 350 million people who are chronically infected with the hepatitis B virus (HBV) worldwide. 1,2 HBV is a partially double-stranded DNA virus that is part of the Hepadnaviridae family. 3 The virus is transmitted vertically (mother-to-child transmission [MTCT]) and horizontally (sexual and blood products). In endemic areas, such as Asia, sub-Saharan Africa, the Pacific and Amazon basins, and regions of the Middle East, most infections occur during the perinatal period or in early childhood. 2 Infection of infants and children with HBV is also a problem in the United States; however, it varies by race and ethnicity, with the highest rate in Asian women (6%). The rates in African American, white, and Hispanic women are 1%, 0.6%, and 0.14%, respectively. In infants who are born to hepatitis B e antigen (HBeAg)-positive mothers, the risk of transmission can be as high as 70% to 90% at 6 months, and approximately 90% of these children who are exposed remain chronically infected. 2 In infants whose mothers are HBeAg positive, however, the administration of standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIg) and hepatitis B vaccination decreases the risk of transmission to 5% to 10%. 3 HBeAg-negative mothers carry a 10% to 40% transmission risk, and of those infants who are infected, 40% to 70% remain chronically infected. 2 As with HBeAg-positive mothers, there is also a significant decrease in transmission rates with passive-active immunoprophylaxis in those mothers who are HBeAg negative.
Chronic hepatitis B virus (HBV) infection remains an important cause of chronic liver disease wor... more Chronic hepatitis B virus (HBV) infection remains an important cause of chronic liver disease worldwide and affects a disproportionate number of individuals from areas of high endemicity, where perinatal transmission is the predominant mode of infection. Introduction of a safe and effective hepatitis B vaccine has led to universal infant vaccination and resulted in a reduced rate of perinatal HBV transmission from infected mothers. With appropriate hepatitis B vaccination and passive immunoprophylaxis using hepatitis B immune globulin (HBIG), infants born to mothers with HBV infection have perinatal transmission rates between 5% and 10%. Management of pregnant women with chronic HBV infection is aimed primarily at counseling regarding maternal risk of infection, rates of vertical transmission, and preparation for neonatal vaccination. Limited data suggest that intrauterine infection may occur at higher rates in mothers with high serum HBV DNA levels, leading to failure of standard passive-active immunoprophylaxis with HBIG and vaccine. Thus, treatment with an oral HBV antiviral agent in the third trimester may be considered after discussing the risks and benefits of therapy with the mother.
Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are of... more Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive therapies, potentially increasing their risk of developing an infection. Empiric data suggest that vaccines are underutilized in immunocompromised patients, despite published guidelines recommending their use. We aimed to assess exposure risk and immunization status among patients receiving care in an IBD specialty clinic. Patients completed a self-administered, pretested, structured questionnaire during a routine visit for the management of IBD. Survey questions related to medical and immunization histories, and exposures to known risk factors for influenza, pneumococcus, viral hepatitis, and varicella. Additionally, in a subgroup of patients who agreed to donate a sample of blood, immune status to hepatitis A (HAV), hepatitis B (HBV), and varicella was determined. Two hundred four patients were asked to participate in the study; 169 completed surveys and comprised the study population. Mean age was 35 yr (range 13-75 yr). One hundred forty-six respondents (86%) reported current or prior use of immunosuppressive medications. Only 45% of respondents recalled tetanus immunization within the past 10 yr, 41 (28%) reported regularly receiving flu shots, and 13 (9%) reported having received pneumococcal vaccine. The most common reasons for nonimmunization with influenza included lack of awareness (49%) and concern for side effects (18%). Responses indicated that 75 (44%) patients were at risk for HBV but only 47 (28%) had been vaccinated against the infection; of patients with previous HBV vaccination, only three of nine (33%) had measurable antibodies against hepatitis B surface antigen. Immunization against selected vaccine-preventable illnesses was uncommon in patients with IBD, despite the presence of significant risk factors. Efforts to improve immunization status among patients with IBD and other chronic, immune-mediated conditions are needed.
6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective in the treatment of IBD; however, dr... more 6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective in the treatment of IBD; however, drug-induced hepatotoxicity has been reported in 10-15% of pediatric patients and has been associated with the 6-MP metabolite 6-methylmercaptopurine ribonucleotide (6-MMPR) at levels >5,700 pmol/8 x 10(8) RBC. The aim of this study was to assess the prevalence of 6-MP/AZA hepatotoxicity and its correlation with serum 6-MMPR levels in adult IBD patients. Aminotransferases, bilirubin, and 6-MP metabolite levels were measured in 173 adult IBD patients treated with 6-MP or AZA from November 2002 to December 2003. Hepatotoxicity was defined as AST and/or ALT >2x upper limit of normal or cholestasis. Eight patients (4.6%) met criteria for a diagnosis of 6-MP/AZA-induced hepatotoxicity. The mean 6-MMPR level in these 8 patients was 10,537 pmol/8 x 10(8) RBC versus 3,452 pmol/8 x 10(8) RBC in the nonhepatotoxic group (P < 0.001). Risk of hepatotoxicity above the third quartile (6-MMPR…
Hepatitis C virus (HCV) is a human hepatotropic virus with an estimated worldwide prevalence of 1... more Hepatitis C virus (HCV) is a human hepatotropic virus with an estimated worldwide prevalence of 170 million cases, including approximately 4 million cases in the US. It is a major cause of liver disease and is the most common indication for liver transplantation in the US. The majority of infected individuals are eligible for therapy. Since it is difficult to predict who will have progressive disease, those with significant inflammation or fibrosis on histologic examination of liver biopsy are generally offered treatment. The following chapter is an overview of the patent literature during 2000-mid-2002, and discusses the potential of various treatment modalities for HCV.
Objective: With the continued shortage of deceased donor grafts, living donor liver transplantat... more Objective: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome.Methods: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed.Results: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation.Conclusions: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.
Current Treatment Options in Gastroenterology, 2001
Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the ... more Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.
Background & Aims: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammato... more Background & Aims: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammatory bowel disease (IBD). Short-term safety and efficacy data were favorable. Experience with 6-TG in patients with acute lymphoblastic leukemia raised long-term safety concerns when implicated in nodular regenerative hyperplasia (NRH) of the liver and portal hypertension. The aim of this study was to describe the association between 6-TG and NRH in IBD. Methods: Liver chemistries and complete blood counts were monitored, and patients were encouraged to undergo liver biopsy. Clinical data were collected by chart review, and associations were tested by univariate and multivariable analyses. Patients were classified based on the presence (group 1) or absence (group 2) of laboratory abnormalities. Results: Laboratory abnormalities occurred in 29 of 111 patients (26%). Elevations of liver enzymes and a decrease in platelet counts (<200,000) were most commonly observed. Male gender (odds ratio, 2.9; 95% CI, 1.1-7.3; P < 0.03) and preferential 6-methylmercaptopurine production on 6-mercaptopurine/azathioprine (odds ratio, 3.0; 95% CI, 1.2-7.4; P < 0.04) were independently associated with laboratory abnormalities. No association was seen with duration of 6-TG treatment, cumulative dose, or 6-TG nucleotide levels. The median increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels was 39, 30, and 75 U/L, respectively, in group 1, and the median decrease in platelet count was 115,000 in group 1 versus 7000 in group 2 (P < 0.001). NRH occurred in 76% of patients undergoing biopsy in group 1 and 33% in group 2. Conclusions: NRH is a common finding in 6-TG-treated patients with IBD. The progression or reversibility of NRH remains unknown. Our findings suggest that 6-TG should not be considered as therapy for patients with IBD.
Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for d... more Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for decades. Hepatocellular cancer (HCC) remains the most common malignant condition treated with LT, with almost 400 such transplants performed annually in the US. Refinement in the selection criteria for LT in patients with HCC has led to survival rates similar to those for LT in nonmalignant conditions. Excellent results have also been reported following LT for select patients with epithelioid hemangioendothelioma and hepatoblastoma. Patients with cholangiocarcinoma treated with LT have generally faired poorly, with survival rates far below that of LT for nonmalignant conditions. Improved survival has recently been reported following LT for cholangiocarcinoma in highly select patients treated with aggressive neoadjuvant therapy. The future utility of LT in the treatment of malignancy will be influenced by several factors, including a profound organ donor shortage faced worldwide; increasing prevalence of hepatitis C, HCC and cirrhosis; and the evolution of live donor liver transplantation.
6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (I... more 6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (IBD) patients not responsive to or intolerant of azathioprine (AZA) and 6-mercaptopurine (6-MP). 6-TG-related hepatotoxicity, including liver biochemistry value elevations, sinusoidal collagen deposition on electron microscopy, and veno-occlusive disease, have been described related to its use as therapy for neoplastic disease. We studied 38 liver biopsies from patients treated with 6-TG, almost all of whom (n = 125) received 6-TG for 1 to 3 years at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. All biopsies were fixed in 4% buffered formalin and prepared in the usual manner. Hematoxylin and eosin, Masson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s trichrome (trichrome), and reticulin silver impregnation (reticulin) stained slides were studied. In 23 cases, tissue was also prospectively fixed in glutaraldehyde and processed for electron microscopy. In 20 of the 37 patients studied (53%), nodular regeneration of varying degree was seen with reticulin. In only 4 of these 20 instances (11% of the total) were the changes seen with hematoxylin and eosin and in 3 of the 4, only in retrospect after studying the reticulin preparation. Minimal fibrosis was seen with trichrome in only 13 biopsies (34%), but sinusoidal collagen deposition was observed in 14 of the 23 cases studied with electron microscopy (60%). The biopsy from the 1 patient with nodular hyperplasia obvious with hematoxylin and eosin also demonstrated changes of venous outflow obstruction. 6-TG-treated IBD patients are at significant risk for nodular hyperplasia, early fibrosis and, less often, venous outflow disease (Budd-Chiari). The natural history of these changes is unknown and follow-up biopsies are needed to determine histologic and clinical sequela. Patients not demonstrating nodular hyperplasia or fibrosis who continue with 6-TG because there are no better therapeutic choices should be periodically rebiopsied.
To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as comp... more To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters. There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule. Normal serum CO-Hb levels in nonsmokers is 0% to 1.5% and 4% to 9% in smokers. Activity of the heme-oxygenase pathway may be increased in the cirrhotic patient, as measured indirectly by exhaled CO and serum CO-Hb. This may be due to alterations in vascular tone in the splanchnic circulation in cirrhotics that may lead to elevated CO production. One published study also showed that those with spontaneous bacterial peritonitis had higher levels of both CO and CO-Hb. The MELD score uses prothrombin time (INR), creatinine, and bilirubin in the prediction of short-term mortality in decompensated cirrhotics while awaiting liver transplant. Measurement of endogenous CO-Hb may correlate to severity of liver disease. Retrospective analysis was done of 113 adult patients who were evaluated for liver transplantation between September 1996 and July 2003 and had pulmonary function testing with CO-Hb as part of their evaluation. We excluded any patients with a history of smoking. Clinical parameters used for comparison included grade of esophageal varices (n=75), spleen size (n=51) measured on abdominal ultrasound or computed tomography scan, aminotransferases, and disease duration. Serum CO-Hb levels were measured from whole blood, sent refrigerated to ARUP laboratories (Salt Lake City, UT) and analyzed via spectrophotometry. Bivariate analysis was performed by means of the Pearson product moment correlation. The mean CO-Hb level was 2.1%, which is higher than the expected normal population controls. No correlation was found, however, with MELD score, Child Turcotte Pugh score, or other biochemical or clinical measurements of disease severity. Although CO and CO-Hb production may be increased in the cirrhotic patient, in this study no correlation was found to disease severity as measured by the MELD score. Further studies are needed to assess the role of CO in other complications of cirrhosis including infection and circulatory dysfunction.
Purpose: Liver biopsy (LB) is standard for assessment of disease severity in patients (pts) with ... more Purpose: Liver biopsy (LB) is standard for assessment of disease severity in patients (pts) with chronic HCV. However, associated risks have led to the development of non-invasive models, including FIB-4 and APRI. Because a significant proportion of pts with HIV-HCV coinfection have normal ALT, it is important to validate these models in both normal(NL)and elevated (EL) ALT pts. Methods: In a prospective study, FIB-4 and APRI were calculated in pts with HIV-HCV coinfection undergoing LB 1994-2008. Histology was assessed for Ishak fibrosis (0-6). Using published cut offs for FIB-4 and APRI, the performance of each model for predicting significant fibrosis (Ishak 4-6) were determined in the entire cohort and those with EL (≥ 60 in men, ≥40 U/L in women) and NL ALT. Results: 295 LBs in 237 pts without hepatic decompensation, renal insufficiency, or other liver diseases were included: 74% male, 20% white, 92% genotype 1, 84% on HAART, 53% with HIV <400 copies/ml, mean(SD) age 46(8.0), CD4 525(318), ALT 83 , AST 85 , Platelet 208 , and biopsy length 20.5mm(8.23). EL ALT was seen in 55% and only 6% had ALT < 30 for men and <19 for women. 15% had Ishak fibrosis score of 4-6. Below shows the performances of the models in predicting fibrosis of 4-6. Discordant results were lower for FIB-4 (1% for <1.45 and 45-50% for >3.25) than for APRI (2-7% for <0.5 and 40-67% for >1.5) in NL and EL ALT, respectively. Using these models, LB could be avoided in 70% of pts with NL and 58% of pts with EL ALT with accuracy of 97% for APRI in NL ALT and 71% for FIB-4 in those with EL ALT. Conclusion: Both models were validated in NL ALT HIV-HCV pts and may be used in combination. The performance of FIB-4 and APRI were higher in those with NL ALT compared to those with EL ALT. In those with EL ALT, FIB-4 was better than APRI. The high NPV for excluding significant fibrosis was higher for FIB-4 than APRI and both were excellent in excluding advanced fibrosis regardless of ALT. However, because of their moderate PPV in both analyses, LB may still be required in pts who have FIB-4 >1.45 or APRI >.5. The tradeoff of increasing the upper cutoff values for either test is improved PPV and accuracy versus increased proportion of patients with indeterminate values. Thus, the overall need for LB may not change.
Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despit... more Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despite recommendations and implementation of vaccination programs, the health and economic burdens are still significant. People in endemic areas and immigrants from these areas need to be adequately screened and treated. HBeAg-negative chronic hepatitis is increasingly recognized with additional challenges in management. Programs implementing primary prophylaxis strategies such as vaccination of high-risk adult and adolescent groups should continue.
Despite the increasing realization that health-related quality of life (HRQOL) is an important ou... more Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test–retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test–retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health. Conclusion: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials. (HEPATOLOGY 2007;46:113–121.)
Liver transplantation revolutionized the management of liver disease. Although the number of pati... more Liver transplantation revolutionized the management of liver disease. Although the number of patients who could benefit from a transplant far exceeds the number of available cadaveric donors, new strategies, such as splitting cadaveric organs and using living donors, have expanded access to transplantation. Here, a team of transplant physicians highlights these new strategies, as well as the long-term management issues of special relevance to primary care physicians caring for transplant recipients.
Chronic hepatitis B virus (HBV) infection is an important cause of chronic liver disease worldwid... more Chronic hepatitis B virus (HBV) infection is an important cause of chronic liver disease worldwide. It affects a disproportionate number of individuals from areas of high endemicity, where perinatal transmission is the predominant mode of infection. Introduction of a safe, effective hepatitis B vaccine has led to universal infant vaccination, resulting in a reduced rate of perinatal HBV infection from infected mothers. Because of appropriate hepatitis B vaccination and passive immunoprophylaxis with hepatitis B immune globulin (HBIG) in infants of mothers with HBV infection, perinatal transmission has been reduced to less than 5% to 10%. Management of pregnant women with chronic HBV infection should be aimed at counseling on maternal risk of infection, rates of vertical transmission, and preparation for neonatal vaccination. Limited data suggest that intrauterine infection may occur at higher rates in mothers with high serum HBV DNA levels, leading to failure of standard passive-active immunoprophylaxis with HBIG and vaccine. Thus, treatment of these individuals with an oral HBV antiviral agent in the third trimester may be considered after discussion with the mother regarding the risks and benefits of therapy.
There are an estimated 350 million people who are chronically infected with the hepatitis B virus... more There are an estimated 350 million people who are chronically infected with the hepatitis B virus (HBV) worldwide. 1,2 HBV is a partially double-stranded DNA virus that is part of the Hepadnaviridae family. 3 The virus is transmitted vertically (mother-to-child transmission [MTCT]) and horizontally (sexual and blood products). In endemic areas, such as Asia, sub-Saharan Africa, the Pacific and Amazon basins, and regions of the Middle East, most infections occur during the perinatal period or in early childhood. 2 Infection of infants and children with HBV is also a problem in the United States; however, it varies by race and ethnicity, with the highest rate in Asian women (6%). The rates in African American, white, and Hispanic women are 1%, 0.6%, and 0.14%, respectively. In infants who are born to hepatitis B e antigen (HBeAg)-positive mothers, the risk of transmission can be as high as 70% to 90% at 6 months, and approximately 90% of these children who are exposed remain chronically infected. 2 In infants whose mothers are HBeAg positive, however, the administration of standard passive-active immunoprophylaxis with hepatitis B immunoglobulin (HBIg) and hepatitis B vaccination decreases the risk of transmission to 5% to 10%. 3 HBeAg-negative mothers carry a 10% to 40% transmission risk, and of those infants who are infected, 40% to 70% remain chronically infected. 2 As with HBeAg-positive mothers, there is also a significant decrease in transmission rates with passive-active immunoprophylaxis in those mothers who are HBeAg negative.
Chronic hepatitis B virus (HBV) infection remains an important cause of chronic liver disease wor... more Chronic hepatitis B virus (HBV) infection remains an important cause of chronic liver disease worldwide and affects a disproportionate number of individuals from areas of high endemicity, where perinatal transmission is the predominant mode of infection. Introduction of a safe and effective hepatitis B vaccine has led to universal infant vaccination and resulted in a reduced rate of perinatal HBV transmission from infected mothers. With appropriate hepatitis B vaccination and passive immunoprophylaxis using hepatitis B immune globulin (HBIG), infants born to mothers with HBV infection have perinatal transmission rates between 5% and 10%. Management of pregnant women with chronic HBV infection is aimed primarily at counseling regarding maternal risk of infection, rates of vertical transmission, and preparation for neonatal vaccination. Limited data suggest that intrauterine infection may occur at higher rates in mothers with high serum HBV DNA levels, leading to failure of standard passive-active immunoprophylaxis with HBIG and vaccine. Thus, treatment with an oral HBV antiviral agent in the third trimester may be considered after discussing the risks and benefits of therapy with the mother.
Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are of... more Patients with chronic, immune-mediated conditions such as inflammatory bowel disease (IBD) are often treated with long-term immunosuppressive therapies, potentially increasing their risk of developing an infection. Empiric data suggest that vaccines are underutilized in immunocompromised patients, despite published guidelines recommending their use. We aimed to assess exposure risk and immunization status among patients receiving care in an IBD specialty clinic. Patients completed a self-administered, pretested, structured questionnaire during a routine visit for the management of IBD. Survey questions related to medical and immunization histories, and exposures to known risk factors for influenza, pneumococcus, viral hepatitis, and varicella. Additionally, in a subgroup of patients who agreed to donate a sample of blood, immune status to hepatitis A (HAV), hepatitis B (HBV), and varicella was determined. Two hundred four patients were asked to participate in the study; 169 completed surveys and comprised the study population. Mean age was 35 yr (range 13-75 yr). One hundred forty-six respondents (86%) reported current or prior use of immunosuppressive medications. Only 45% of respondents recalled tetanus immunization within the past 10 yr, 41 (28%) reported regularly receiving flu shots, and 13 (9%) reported having received pneumococcal vaccine. The most common reasons for nonimmunization with influenza included lack of awareness (49%) and concern for side effects (18%). Responses indicated that 75 (44%) patients were at risk for HBV but only 47 (28%) had been vaccinated against the infection; of patients with previous HBV vaccination, only three of nine (33%) had measurable antibodies against hepatitis B surface antigen. Immunization against selected vaccine-preventable illnesses was uncommon in patients with IBD, despite the presence of significant risk factors. Efforts to improve immunization status among patients with IBD and other chronic, immune-mediated conditions are needed.
6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective in the treatment of IBD; however, dr... more 6-Mercaptopurine (6-MP) and azathioprine (AZA) are effective in the treatment of IBD; however, drug-induced hepatotoxicity has been reported in 10-15% of pediatric patients and has been associated with the 6-MP metabolite 6-methylmercaptopurine ribonucleotide (6-MMPR) at levels &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;5,700 pmol/8 x 10(8) RBC. The aim of this study was to assess the prevalence of 6-MP/AZA hepatotoxicity and its correlation with serum 6-MMPR levels in adult IBD patients. Aminotransferases, bilirubin, and 6-MP metabolite levels were measured in 173 adult IBD patients treated with 6-MP or AZA from November 2002 to December 2003. Hepatotoxicity was defined as AST and/or ALT &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;2x upper limit of normal or cholestasis. Eight patients (4.6%) met criteria for a diagnosis of 6-MP/AZA-induced hepatotoxicity. The mean 6-MMPR level in these 8 patients was 10,537 pmol/8 x 10(8) RBC versus 3,452 pmol/8 x 10(8) RBC in the nonhepatotoxic group (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001). Risk of hepatotoxicity above the third quartile (6-MMPR…
Hepatitis C virus (HCV) is a human hepatotropic virus with an estimated worldwide prevalence of 1... more Hepatitis C virus (HCV) is a human hepatotropic virus with an estimated worldwide prevalence of 170 million cases, including approximately 4 million cases in the US. It is a major cause of liver disease and is the most common indication for liver transplantation in the US. The majority of infected individuals are eligible for therapy. Since it is difficult to predict who will have progressive disease, those with significant inflammation or fibrosis on histologic examination of liver biopsy are generally offered treatment. The following chapter is an overview of the patent literature during 2000-mid-2002, and discusses the potential of various treatment modalities for HCV.
Objective: With the continued shortage of deceased donor grafts, living donor liver transplantat... more Objective: With the continued shortage of deceased donor grafts, living donor liver transplantation has become an option for adult liver transplant candidates. In the non-transplant setting, liver biopsy is typically carried out to evaluate clinical or biochemical hepatic dysfunction. In living donor liver transplantation, assessment of histological abnormalities that are undetectable by serological, biochemical and radiological methods might play an important role in donor and recipient outcome.Methods: Seventy consecutive liver biopsies carried out as part of our evaluation of potential donor candidates for adult-to-adult or adult-to-child living donor liver transplants were analyzed.Results: Of the 70 potential donor candidates who underwent liver biopsy for evaluation for living donor liver transplantation, 67% had an unexpected abnormality, of which steatosis was the most common abnormality (38.5%). A variety of other histopathological abnormalities were found including granulomas of unknown etiology (7%), chronic hepatitis (6%) and a microabscess. None of the histological abnormalities had been suspected despite extensive clinical, serological or radiological investigation.Conclusions: Among the 70 potential donor candidates for living donor liver transplantation, 34% had unremarkable liver biopsies. The most common abnormality was steatosis (38.5%). These findings suggest that all potential candidates for living donor liver transplants should undergo screening liver biopsies. The precise significance of these changes remains to be determined, including which of these changes are contraindications to liver transplantation. These findings may also have implications in the non-transplant setting as changes ascribed to specific etiologies for liver disease might include changes occurring in apparently healthy individuals.
Current Treatment Options in Gastroenterology, 2001
Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the ... more Infection with hepatitis C virus (HCV) accounts for 40% of cases of chronic liver disease in the United States and is now the most common indication for liver transplantation. Estimates suggest that 4 million people (1.8%) of the American population are or have been infected with HCV. Currently, the treatment of choice for patients with chronic HCV infection is recombinant interferon alfa with ribavirin. Pegylated interferons are a promising new development, and in combination with ribavirin, they will rapidly become the standard of care. The goals of therapy are to slow disease progression, improve hepatic histology, reduce infectivity, and reduce the risk of hepatocellular carcinoma. Sustained virologic response, which generally implies the absence of viremia for 6 months or more following completion of therapy, is increasingly being regarded as a cure, with evidence of slowing or even regression of fibrosis on follow-up liver biopsy. A number of factors have been shown to be predictive of a sustained response, including viral genotype other than 1, low serum HCV RNA levels, absence of cirrhosis, younger age, female gender, and shorter duration of infection. Disease severity as assessed by liver biopsy, comorbidities, and possible contraindications to therapy should be weighed in the decision to begin treatment. Counseling patients regarding transmission, natural history, and drug and alcohol abstinence also should be included in management. Close monitoring should be done during treatment for side effects of interferon, including depression and bone marrow suppression. Hemolytic anemia is the major side effect of ribavirin.
Background & Aims: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammato... more Background & Aims: Thioguanine (6-TG) has been studied as an alternative thiopurine in inflammatory bowel disease (IBD). Short-term safety and efficacy data were favorable. Experience with 6-TG in patients with acute lymphoblastic leukemia raised long-term safety concerns when implicated in nodular regenerative hyperplasia (NRH) of the liver and portal hypertension. The aim of this study was to describe the association between 6-TG and NRH in IBD. Methods: Liver chemistries and complete blood counts were monitored, and patients were encouraged to undergo liver biopsy. Clinical data were collected by chart review, and associations were tested by univariate and multivariable analyses. Patients were classified based on the presence (group 1) or absence (group 2) of laboratory abnormalities. Results: Laboratory abnormalities occurred in 29 of 111 patients (26%). Elevations of liver enzymes and a decrease in platelet counts (<200,000) were most commonly observed. Male gender (odds ratio, 2.9; 95% CI, 1.1-7.3; P < 0.03) and preferential 6-methylmercaptopurine production on 6-mercaptopurine/azathioprine (odds ratio, 3.0; 95% CI, 1.2-7.4; P < 0.04) were independently associated with laboratory abnormalities. No association was seen with duration of 6-TG treatment, cumulative dose, or 6-TG nucleotide levels. The median increase in alanine aminotransferase, aspartate aminotransferase, and alkaline phosphatase levels was 39, 30, and 75 U/L, respectively, in group 1, and the median decrease in platelet count was 115,000 in group 1 versus 7000 in group 2 (P < 0.001). NRH occurred in 76% of patients undergoing biopsy in group 1 and 33% in group 2. Conclusions: NRH is a common finding in 6-TG-treated patients with IBD. The progression or reversibility of NRH remains unknown. Our findings suggest that 6-TG should not be considered as therapy for patients with IBD.
Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for d... more Liver transplantation (LT) has been utilized in the treatment of primary hepatic malignancy for decades. Hepatocellular cancer (HCC) remains the most common malignant condition treated with LT, with almost 400 such transplants performed annually in the US. Refinement in the selection criteria for LT in patients with HCC has led to survival rates similar to those for LT in nonmalignant conditions. Excellent results have also been reported following LT for select patients with epithelioid hemangioendothelioma and hepatoblastoma. Patients with cholangiocarcinoma treated with LT have generally faired poorly, with survival rates far below that of LT for nonmalignant conditions. Improved survival has recently been reported following LT for cholangiocarcinoma in highly select patients treated with aggressive neoadjuvant therapy. The future utility of LT in the treatment of malignancy will be influenced by several factors, including a profound organ donor shortage faced worldwide; increasing prevalence of hepatitis C, HCC and cirrhosis; and the evolution of live donor liver transplantation.
6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (I... more 6-Thioguanine (6-TG) has been used as an alternative thiopurine for inflammatory bowel disease (IBD) patients not responsive to or intolerant of azathioprine (AZA) and 6-mercaptopurine (6-MP). 6-TG-related hepatotoxicity, including liver biochemistry value elevations, sinusoidal collagen deposition on electron microscopy, and veno-occlusive disease, have been described related to its use as therapy for neoplastic disease. We studied 38 liver biopsies from patients treated with 6-TG, almost all of whom (n = 125) received 6-TG for 1 to 3 years at the Inflammatory Bowel Disease Center at Cedars-Sinai Medical Center. All biopsies were fixed in 4% buffered formalin and prepared in the usual manner. Hematoxylin and eosin, Masson&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;#39;s trichrome (trichrome), and reticulin silver impregnation (reticulin) stained slides were studied. In 23 cases, tissue was also prospectively fixed in glutaraldehyde and processed for electron microscopy. In 20 of the 37 patients studied (53%), nodular regeneration of varying degree was seen with reticulin. In only 4 of these 20 instances (11% of the total) were the changes seen with hematoxylin and eosin and in 3 of the 4, only in retrospect after studying the reticulin preparation. Minimal fibrosis was seen with trichrome in only 13 biopsies (34%), but sinusoidal collagen deposition was observed in 14 of the 23 cases studied with electron microscopy (60%). The biopsy from the 1 patient with nodular hyperplasia obvious with hematoxylin and eosin also demonstrated changes of venous outflow obstruction. 6-TG-treated IBD patients are at significant risk for nodular hyperplasia, early fibrosis and, less often, venous outflow disease (Budd-Chiari). The natural history of these changes is unknown and follow-up biopsies are needed to determine histologic and clinical sequela. Patients not demonstrating nodular hyperplasia or fibrosis who continue with 6-TG because there are no better therapeutic choices should be periodically rebiopsied.
To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as comp... more To assess the correlation of serum carboxyhemoglobin (CO-Hb) to severity of liver disease as compared with Model for End Stage Liver Disease (MELD) score, Child Pugh score, and clinical parameters. There are 2 sources of carbon monoxide (CO) in humans, exogenous sources include those such as tobacco smoke and inhaled motor vehicle exhaust. The endogenous source is via the heme-oxygenase pathway, in which a heme molecule is broken down into biliverdin with release of an iron (Fe) and CO molecule. Normal serum CO-Hb levels in nonsmokers is 0% to 1.5% and 4% to 9% in smokers. Activity of the heme-oxygenase pathway may be increased in the cirrhotic patient, as measured indirectly by exhaled CO and serum CO-Hb. This may be due to alterations in vascular tone in the splanchnic circulation in cirrhotics that may lead to elevated CO production. One published study also showed that those with spontaneous bacterial peritonitis had higher levels of both CO and CO-Hb. The MELD score uses prothrombin time (INR), creatinine, and bilirubin in the prediction of short-term mortality in decompensated cirrhotics while awaiting liver transplant. Measurement of endogenous CO-Hb may correlate to severity of liver disease. Retrospective analysis was done of 113 adult patients who were evaluated for liver transplantation between September 1996 and July 2003 and had pulmonary function testing with CO-Hb as part of their evaluation. We excluded any patients with a history of smoking. Clinical parameters used for comparison included grade of esophageal varices (n=75), spleen size (n=51) measured on abdominal ultrasound or computed tomography scan, aminotransferases, and disease duration. Serum CO-Hb levels were measured from whole blood, sent refrigerated to ARUP laboratories (Salt Lake City, UT) and analyzed via spectrophotometry. Bivariate analysis was performed by means of the Pearson product moment correlation. The mean CO-Hb level was 2.1%, which is higher than the expected normal population controls. No correlation was found, however, with MELD score, Child Turcotte Pugh score, or other biochemical or clinical measurements of disease severity. Although CO and CO-Hb production may be increased in the cirrhotic patient, in this study no correlation was found to disease severity as measured by the MELD score. Further studies are needed to assess the role of CO in other complications of cirrhosis including infection and circulatory dysfunction.
Purpose: Liver biopsy (LB) is standard for assessment of disease severity in patients (pts) with ... more Purpose: Liver biopsy (LB) is standard for assessment of disease severity in patients (pts) with chronic HCV. However, associated risks have led to the development of non-invasive models, including FIB-4 and APRI. Because a significant proportion of pts with HIV-HCV coinfection have normal ALT, it is important to validate these models in both normal(NL)and elevated (EL) ALT pts. Methods: In a prospective study, FIB-4 and APRI were calculated in pts with HIV-HCV coinfection undergoing LB 1994-2008. Histology was assessed for Ishak fibrosis (0-6). Using published cut offs for FIB-4 and APRI, the performance of each model for predicting significant fibrosis (Ishak 4-6) were determined in the entire cohort and those with EL (≥ 60 in men, ≥40 U/L in women) and NL ALT. Results: 295 LBs in 237 pts without hepatic decompensation, renal insufficiency, or other liver diseases were included: 74% male, 20% white, 92% genotype 1, 84% on HAART, 53% with HIV <400 copies/ml, mean(SD) age 46(8.0), CD4 525(318), ALT 83 , AST 85 , Platelet 208 , and biopsy length 20.5mm(8.23). EL ALT was seen in 55% and only 6% had ALT < 30 for men and <19 for women. 15% had Ishak fibrosis score of 4-6. Below shows the performances of the models in predicting fibrosis of 4-6. Discordant results were lower for FIB-4 (1% for <1.45 and 45-50% for >3.25) than for APRI (2-7% for <0.5 and 40-67% for >1.5) in NL and EL ALT, respectively. Using these models, LB could be avoided in 70% of pts with NL and 58% of pts with EL ALT with accuracy of 97% for APRI in NL ALT and 71% for FIB-4 in those with EL ALT. Conclusion: Both models were validated in NL ALT HIV-HCV pts and may be used in combination. The performance of FIB-4 and APRI were higher in those with NL ALT compared to those with EL ALT. In those with EL ALT, FIB-4 was better than APRI. The high NPV for excluding significant fibrosis was higher for FIB-4 than APRI and both were excellent in excluding advanced fibrosis regardless of ALT. However, because of their moderate PPV in both analyses, LB may still be required in pts who have FIB-4 >1.45 or APRI >.5. The tradeoff of increasing the upper cutoff values for either test is improved PPV and accuracy versus increased proportion of patients with indeterminate values. Thus, the overall need for LB may not change.
Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despit... more Chronic infection with hepatitis B and its sequelae remains a major global health concern. Despite recommendations and implementation of vaccination programs, the health and economic burdens are still significant. People in endemic areas and immigrants from these areas need to be adequately screened and treated. HBeAg-negative chronic hepatitis is increasingly recognized with additional challenges in management. Programs implementing primary prophylaxis strategies such as vaccination of high-risk adult and adolescent groups should continue.
Despite the increasing realization that health-related quality of life (HRQOL) is an important ou... more Despite the increasing realization that health-related quality of life (HRQOL) is an important outcome in chronic HBV infection, there are no validated, disease-targeted instruments currently available. We sought to develop and validate the first disease-targeted HRQOL instrument in noncirrhotic HBV: the Hepatitis B Quality of Life instrument, version 1.0 (HBQOL v1.0). We established content validity for the HBQOL v1.0 by conducting a systematic literature review, an expert focus group, and cognitive interviews with HBV patients. We administered the resultant questionnaire to 138 HBV patients. We used factor analysis to test hypotheses regarding HRQOL domains and measured construct validity by comparing HBQOL v1.0 scores across several anchors, including viral response to treatment, SF-36 scores, and global health. Finally, we measured test–retest and internal consistency reliability. Content validation revealed that HBV affects multiple aspects of psychological, social, and physical health. The resultant questionnaire summarized this HRQOL impact with 31 items across six subscales: psychological well-being, anticipation anxiety, vitality, disease stigma, vulnerability, and transmissibility. Internal consistency and test–retest reliability were excellent. The HBQOL v1.0 discriminated between viral responders versus nonresponders and correlated highly with SF-36 scores and global health. Conclusion: Patients with chronic HBV infection attribute a wide range of negative psychological, social, and physical symptoms to their condition, even in the absence of cirrhosis or cancer. The HBQOL v1.0 is a valid and reliable measure that captures this HRQOL decrement. This instrument may be useful in everyday clinical practice and in future clinical trials. (HEPATOLOGY 2007;46:113–121.)
Liver transplantation revolutionized the management of liver disease. Although the number of pati... more Liver transplantation revolutionized the management of liver disease. Although the number of patients who could benefit from a transplant far exceeds the number of available cadaveric donors, new strategies, such as splitting cadaveric organs and using living donors, have expanded access to transplantation. Here, a team of transplant physicians highlights these new strategies, as well as the long-term management issues of special relevance to primary care physicians caring for transplant recipients.
Uploads
Papers by Tram Tran