Outcomes of liver transplantation in patients 70 years or older: a systematic review and meta-analysis.

INTRODUCTION AND OBJECTIVES: The rate of liver transplantation is increasing among the elderly population; however, data is limited on the post-liver transplantation outcomes in patients ≥70 years. Given the scarcity in liver allograft resources, a meta-analysis on the outcomes of liver transplantation in patients ≥70 years is warranted. MATERIALS AND METHODS: Multiple databases were searched through March 2022 for studies that reported on the outcomes of liver-transplantation in patients ≥70 years. Meta-analysis was conducted using the random-effects model and heterogeneity was assessed using the I2 statistics. RESULTS: Ten studies were included that analyzed 162,725 patients. The pooled rate of 1-year, 3-years and 5-years post liver transplant survival for patients ≥70 years was 78.7% (72.6-83.7; I2=74%), 61.2% (52.3-69.5; I2=87%), and 48.9% (39.3-58.6; I2=96%), respectively. The corresponding 1-year, 3-years and 5-years survival for patients <70 years were 86.6% (82.4-89.9; I2=99%), 73.2% (63-81.3; I2=99%), and 70.1% (66.8-73.2; I2=99%); respectively. Descriptive p-values of comparison were statistically significant at 1-year and 5-years (p = 0.02 and <0.001). The pooled rate of perioperative complications in patients ≥70 years was 40.7% (26.2-57; I2=93%). The pooled rate of graft failure in patients ≥70 years was 6.7% (3.3-13.1; I2=93%) and in patients <70 years was 3.7% (1-12.4; I2=99%). The pooled rate of perioperative mortality in patients ≥70 years was 16.6% (7.6-32.5; I2=99%) and in patients <70 years was 0.8% (0-33.1; I2=88%). CONCLUSION: Patients ≥70 years undergoing liver transplantation seem to demonstrate significantly lower 1-year and 5-year survival rates as compared to patients <70 years, albeit limited by heterogeneity.

Hepatitis viruses: Not always what it seems to be / Los virus de las hepatitis no siempre son habituales

The classic hepatotropic viruses, hepatitis A through E, are not the only viral agents able to infect the liver. Other systemic viruses may cause hepatic injury that can range from mild and transient elevation of aminotransferases to acute hepatitis and occasionally acute liver failure and fulminant hepatitis. The clinical presentation may be indistinguishable from that associated with classic hepatotropic viruses. These agents include cytomegalovirus; Epstein-Barr virus; herpes simplex virus; varicella-zoster virus; human herpesvirus 6, 7, and 8; human parvovirus B19; adenoviruses among others. Wide spectrums of clinical syndromes are associated with cytomegalovirus disease. Unique clinical syndromes may present in neonates, young adults and immunocompromised hosts infected with cytomegalovirus. Cases of fulminant hepatitis have been reported in both immunocompromised and immunocompetent hosts infected with Epstein Barr virus. Occasionally, these patients with acute hepatic failure may need liver transplantation. Herpes simplex viruses may involve the liver in neonatal infections, pregnancy, immunocompromised hosts and occasionally, immunocompetent adults. Varicella-Zoster virus has also been associated with severe acute hepatitis and fulminant hepatitis in adults. The drug of choice for these conditions is intravenous acyclovir. These may also need liver transplantation in the more severe forms of clinical presentation. Typical liver biopsy findings can be useful in determining the diagnosis of these viral infections. Human herpesviruses 6, 7, and 8, human parvovirus B19, and adenoviruses can also be present with features of acute liver injury and occasionally as fulminant hepatitis. The clinical syndromes are less well delineated than those associated with herpesviruses. It is important to consider these viruses as possible etiologic agents in patients who have acute liver injury and their serologic markers for the classic hepatotropic viruses are not indicative of an active infection.

Los agentes de la hepatitis viral A, B, C, D y E no son los únicos virus que pueden causar un síndrome de daño hepático agudo. Agentes virales como el citomegalovirus, Epstein-Barr, herpes simplex 1 y 2, Varicella-Zoster, virus herpes humano 6, 7, y 8, parvovirus B19 y adenovirus pueden causar daño hepático agudo e inclusive presentarse como hepatitis fulminante. Los cuadros clínicos de daño hepático agudo por citomegalovirus, Epstein Barr y herpes simplex 1 y 2 han sido caracterizado mejor. Se ha intentado el uso de drogas antivirales específicas como el uso intravenoso de aciclovir. Ocasionalmente, se ha requerido el trasplante hepático para rescatar pacientes con hepatitis fulminantes por estos agentes virales. La biopsia hepática puede ser de utilidad en estos casos puesto que los hallazgos son bastante característicos. La expresión clínica asociada a infecciones por virus herpes humano 6, 7 y 8, parvovirus B19 y adenovirus son menos características. Ha habido varios casos de hepatitis fulminante causada por estos agentes virales. Estos agentes virales deben ser considerados en el diagnóstico de casos de daño hepático agudo e inclusive hepatitis fulminante cuando los marcadores virales para los virus de hepatitis A-E son negativos.

Hepatitis viruses: not always what it seems to be.

The classic hepatotropic viruses, hepatitis A through E, are not the only viral agents able to infect the liver. Other systemic viruses may cause hepatic injury that can range from mild and transient elevation of aminotransferases to acute hepatitis and occasionally acute liver failure and fulminant hepatitis. The clinical presentation may be indistinguishable from that associated with classic hepatotropic viruses. These agents include cytomegalovirus; Epstein-Barr virus; herpes simplex virus; varicella-zoster virus; human herpesvirus 6, 7, and 8; human parvovirus B19; adenoviruses among others. Wide spectrums of clinical syndromes are associated with cytomegalovirus disease. Unique clinical syndromes may present in neonates, young adults and immunocompromised hosts infected with cytomegalovirus. Cases of fulminant hepatitis have been reported in both immunocompromised and immunocompetent hosts infected with Epstein Barr virus. Occasionally, these patients with acute hepatic failure may need liver transplantation. Herpes simplex viruses may involve the liver in neonatal infections, pregnancy, immunocompromised hosts and occasionally, immunocompetent adults. Varicella-Zoster virus has also been associated with severe acute hepatitis and fulminant hepatitis in adults. The drug of choice for these conditions is intravenous acyclovir. These may also need liver transplantation in the more severe forms of clinical presentation. Typical liver biopsy findings can be useful in determining the diagnosis of these viral infections. Human herpesviruses 6, 7, and 8, human parvovirus B19, and adenoviruses can also be present with features of acute liver injury and occasionally as fulminant hepatitis. The clinical syndromes are less well delineated than those associated with herpesviruses. It is important to consider these viruses as possible etiologic agents in patients who have acute liver injury and their serologic markers for the classic hepatotropic viruses are not indicative of an active infection.

[Autoimmune hepatitis and primary sclerosing cholangitis: dependent or independent association?]. / Hepatitis autoinmune y colangitis esclerosante primaria: asociación dependiente o independiente?

BACKGROUND AND OBJECTIVE: The diagnosis of an autoimmune liver disease is based on clinical, biochemical, immunological and histological criteria particular to each disease, such as autoimmune hepatitis (AIH), primary biliary cirrhosis (PBC) or primary sclerosing cholangitis (PSC). Hepatic overlap syndromes (OS) are defined by the presence of a well established autoimmune liver disease, primarily AIH plus two or more characteristics associated with another liver disease (PBC or PSC); however the association of HAI and PSC is considered rare in adult population, and only 43 cases have been reported in the literature. The aim of this study is to review and reappraise the characteristics of this rare association, and to discuss current concepts on OS. METHODS: We describe the clinical presentation, evolution, radiologic studies, histological characteristics and therapeutic options in a Mexican woman with OS (HAI-PSC). We also include an updated review of the literature. RESULTS: Overlap ofAIH and PSC has been described in a number of repqrts during the last decade, and is assumed to exist in a considerable part of mainly young patients with autoimmune liver diseases. Sequential appearance of AIH and PSC has been described in children, but also may be observed in adults. This association has been reported between 1.4%-8%, probably because differences in age of the study populations, range of autoantibodies taken into consideration, and degree of completeness of analyzed data. CONCLUSIONS: HAI-PSC is a rare disease, more common in children, and its outcome and evolution seem to be similar of AIH alone. Ursodesoxycholic acid in combination with an immunosuppressive regimen may be an adequate medical treatment for most patients with this association, and liver transplantation should be considered in late stage disease.

Early HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin.

INTRODUCTION: Currently, interferon alfa and ribavirin are the mainstay of therapy for patients with chronic hepatitis C. Recently the pegylation of interferon has allowed a once weekly application, resulting in an increased sustained viral response rate. The analysis of serum HCV dynamics has been shown to be useful in predicting clinical effects and optimizing the treatment regimen. AIM: The aim of the present study was to assess early serum HCV RNA changes in patients with chronic hepatitis C treated with peginterferon alfa 2b plus ribavirin. METHODS: Male and female patients aged 18 to 65 years with chronic hepatitis C were eligible for the study. All patients received peginterferon alfa 2b 1.5 micrograms/kg once-weekly for 4 weeks and then peginterferon alfa 2b 0.5 microgram/kg once-weekly until the completion of the 48 week trial period, plus ribavirin orally with meals, adjusted to body weight. HCV RNA was determined at base-line, 48 hours, 4 and 12 weeks of therapy. RESULTS: Data were obtained from 20 patients with chronic hepatitis C treated with peginterferon alfa 2b and ribavirin; 16 male, 4 female, with a mean age of 44.4 +/- 11.9 years, 16 patients (80%) were infected with HCV genotype 1, the remainder were infected with genotype 2. Mean baseline HCV RNA for the total group was 1,091,405 +/- 972,715 IU/mL. Mean reductions in viral load at 48 hours, 4 and 12 weeks for the 20 patients were 1.31 +/- 0.91 log, 1.99 +/- 1.27 log and 2.31 +/- 1.25 log, respectively. A > 2 log reduction in HCV RNA was noticed in 12/20 patients (60%) at 4 weeks (early viral responders), in 9 of them (45%) HCV RNA was undetectable. This response in HCV RNA persisted at 12 weeks of therapy. Early viral responders had a significant reduction in HCV RNA at 48 hours after the initial peginterferon alfa 2b injection (> 1 log reduction). Early viral response was observed in 8/16 patients with HCV genotype 1, and in all genotype 2 patients. CONCLUSION: Treatment with peginterferon alfa 2b and ribavirin produces significant changes in the early HCV viral dynamics supporting the concept that such changes may be pivotal in achieving a sustained viral response.

Health-related quality of life and depression in patients with chronic hepatitis C.

BACKGROUND: Hepatitis C is a major cause of liver disease worldwide. It has been associated with decreased health-related quality of life (HRQL) and psychiatric symptoms. Our aim was to assess HRQL, depression, and illness understanding in patients with chronic hepatitis C without previous interferon therapy. METHODS: Consecutive patients attending a referral center were enrolled. HRQL was measured using SF-36 questionnaire, depression with Zung self-rating depression scale, and illness understanding with self-applied knowledge test. RESULTS: Of 157 patients enrolled, 112 were female (71%) and 45 male (29%). Ninety-seven patients (61.8%) had cirrhosis. HRQL was significantly decreased in chronic hepatitis C patients compared to historical normal controls in all eight domains of the SF-36 (p < 0.001). In hepatitis C cirrhotic patients, HRQL was significantly lower among Child-Pugh class B and C subjects in domains reflecting physical health (p <0.05). Ninety-two patients (58.6%) had depression that resulted in lower HRQL when compared to nondepressed patients (p <0.05). One hundred fourteen patients (72.6%) had poor illness understanding of hepatitis C. These subjects had significantly lower HRQL scores in six of eight SF-36 domains when compared to patients with better understanding of the disease (p <0.05). CONCLUSIONS: Chronic hepatitis C patients attending a tertiary-referral center had significant decrease in HRQL associated with depression (58.6%) and poor illness understanding (72.6%). Educational programs and their impact on HRQL need to be addressed in detail, particularly for the pre-treatment scenario.

[Interferon-alpha and liver fibrosis in patients with chronic damage due to hepatitis C virus]. / Interferón alfa y fibrosis hepática en pacientes con daño crónico por el virus de hepatitis C.

The present review focuses on the published information published regarding the effects of interferon alpha therapy on liver fibrosis in patients with chronic liver damage secondary to hepatitis C infection. Data reviewed included results of the in vitro effects of interferon on hepatic cell line cultures with regards to indirect markers of fibrosis, activation of hepatic stellate cells and oxidative stress response. In the clinical arena, there is current clear evidence of a favorable histological outcome in patients with sustained viral response to interferon therapy. For this reason, the current review focuses more on the histological outcomes regarding liver fibrosis in patients who have not attained viral response to therapy (non-responders) or who already have biopsy defined cirrhosis. Data in these patients were analyzed according to the results of objective testing of fibrosis through the assessment of liver biopsy and its change during time, specially because the morbidity and mortality of this disease is directly related to the complications of liver cirrhosis and not necessarily to the persistence of the hepatitis C virus. Lastly, it is concluded that the process of liver fibrosis/cirrhosis is a dynamic one and that there is some evidence to support the usefulness of interferon alpha therapy as a means to halt or retard the progression of hepatic fibrosis. The result of current clinical trials in which interferon therapy is being used to modify the progression of fibrosis in non-responders or cirrhotic patients is eagerly awaited.