This review delves into the interactions between hepatitis C virus (HCV) and the host immune system, shedding light on how by using the mechanism of molecular mimicry, the virus strategically evades ...the immune system, resulting in a cascade of diverse complications. HCV, notorious for its ability to persistently infect hepatocytes, employs molecular mimicry to resemble host proteins, thereby avoiding immune detection and mounting an effective defense. This mimicry also triggers systemic autoimmune responses that lead to various sequelae. The objective of this review is to comprehensively explore the role of HCV-induced molecular mimicry, which not only facilitates viral survival but is also instrumental in developing autoimmune and inflammatory disorders. By mimicking host proteins, HCV triggers an immune response that inadvertently attacks the host, fostering the development of autoimmune and other inflammatory disorders. Understanding the nuanced mechanisms of HCV-mediated molecular mimicry provides crucial insights into the multifaceted sequelae of viral infections on host immune responses. Unravelling these complexities is paramount for advancing therapeutic strategies that not only target the virus directly but also mitigate the secondary autoimmune and inflammatory complications induced by HCV.
Objective To compare the impact of a transition coordinator on outcomes for pediatric liver transplant recipients vs a historical comparison group. Study design To examine the utility of a transition ...coordinator, medication adherence, as measured by SDs of tacrolimus blood levels (Tacrolimus SD), was compared between the “transition coordinator group” (20 transplant recipients transferred between 2007 and 2012) and comparison group for 1 year before and after transfer. Measures of health care management, quality of life, and acceptability were administered to the transition coordinator group as well. Results A repeated measures ANOVA was used to compare adherence values between the transition coordinator group and the comparison group. During the year before transfer, for the transition coordinator group, Tacrolimus SD was 1.98 (SD = 1.05) vs 3.25 (SD = 1.19) for comparison patients, F (1,25) = 4.77, P = .04. After transfer, levels remained stable for the transition coordinator group, Tacrolimus SD = 1.88 (SD = 1.57), but increased for comparison patients, Tacrolimus SD = 4.36 (SD = 0.99), F (1,25) = 6.99, P = .01. Psychosocial outcomes remained stable during the transfer period and acceptability was high. Conclusions Our findings, although limited by a small sample size, suggest that a transition coordinator is a promising method to improve this process.
Progressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of rare genetic disorders associated with bile acid secretion or transport defects. This is the first systematic review ...of the epidemiology, natural history and burden of PFIC.
MEDLINE and Embase were searched for publications on PFIC prevalence, incidence or natural history, and the economic burden or health-related quality of life (HRQoL) of patients with PFIC. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed.
Of 1269 records screened, 20 were eligible (epidemiology, 17; humanistic burden, 5; both, 2). Incidence of intrahepatic cholestasis, including but not limited to PFIC, was 1/18 000 live births in one study that did not use genetic testing. In two studies of infants and children (2-18 years) with cholestasis, 12-13% had genetically diagnosed PFIC. Of the three main PFIC subtypes, PFIC2 was the most common (21-91% of patients). Common symptoms (e.g. pruritus, jaundice, hepatomegaly, splenomegaly) generally appeared at about 3 months of age and tended to emerge earliest in patients with PFIC2. Patients reported that pruritus was often severe and led to dermal damage and reduced HRQoL. Disease progression led to complications including liver failure and hepatocellular carcinoma, with 20-83% of patients requiring liver transplantation. Mortality was 0-87% across 10 studies (treatment varied among studies), with a median age at death of ~4 years in one study.
Patients with PFIC face debilitating symptoms and poor prognosis. Further research is needed to inform patient management and clinical trial design. Published data on the epidemiology and socioeconomic burden of PFIC is limited.
Autoimmune hepatitis (AIH) is characterized by elevated serum aminotransferases, immunoglobulin G, autoantibodies, and interface hepatitis, in the absence of a known diagnosis. Presentation is ...varied. Therapy is with immunosuppression. There is inflammation of the intrahepatic and/or extrahepatic bile ducts in Sclerosing cholangitis (SC) and when associated with inflammatory bowel disease, it is known as primary SC, with Ursodeoxycholic acid used for therapy. The overlap of clinical, biochemical and histological features of AIH and PSC is known as autoimmune sclerosing cholangitis (ASC) or overlap syndrome. Liver transplantation is performed when medical treatment fails and both AIH and PSC may recur post-transplantation.
The goal was to improve immunosuppressant adherence for pediatric patients with orthotopic liver transplants by using text messaging (TM).
A prospective study of sending TM reminders to the primary ...medication administrator (patient or caregiver) for pediatric transplant recipients was performed. Patient records were reviewed, comparing the year before and the year of the study. The SD of serum tacrolimus levels was used as an indicator of adherence.
Forty-one patients provided consent. The median age was 15 years (range: 1-27 years), and the median age at the time of transplantation was 2 years (range: 4 months to 23 years). Fourteen patients (34%) were male. In 29 of 41 cases, the medications were self-administered by the patient. The mean duration of study was 13 +/- 1.5 months. Twenty-two patients were receiving 1 immunosuppressant, 14 were receiving 2, and 5 were receiving 3. Thirteen patients (37%) stopped the study after 4 months. The mean tacrolimus level SD decreased from 3.46 microg/L before the study to 1.37 microg/L (P < .005). The number of immunosuppressants taken and patient self/caregiver medication administration did not significantly affect the results. The number of acute cellular rejection episodes decreased from 12 to 2 during the study. Risk factors for rejection were older age (17.67 vs 13.28 years) and administration of >1 immunosuppressant.
We observed significant improvement in medication adherence and a reduction in rejection episodes with TM reminders for pediatric recipients of liver transplants.
: Obesity has emerged as a significant new health problem in the pediatric population. Non‐alcoholic steatohepatitis (NASH) is an entity in the spectrum of non‐alcoholic fatty liver disease (NAFLD) ...ranges from fat in the liver – simple steatosis, NASH/ steatohepatitis – fat with inflammation and/or fibrosis to advanced fibrosis and cirrhosis when fat may no longer be present. NASH is associated with obesity, diabetes, insulin resistance (IR), and hypertriglyceridemia. While majority of individuals with risk factors like obesity and IR have steatosis only a minority develop steatohepatitis, possible mechanisms have been discussed. Clinical experience with pediatric NASH is limited. Children generally present in the prepubertal age group, have a male predominance with a higher incidence in children of Hispanic origin. Body mass index (BMI) of 25–29.9 is considered to be overweight and that ≥30 obese. Acanthosis nigricans as a marker of IR should be looked for. As NASH is a diagnosis of exclusion, other causes of chronic liver disease must be excluded. Increased echogenicity in the liver is noted on ultrasound. Liver biopsy is considered the gold standard in establishing the diagnosis. Histopathological lesions thought to be necessary for diagnosis of NASH include steatosis (macrovesicular > microvesicular), mixed mild lobular inflammation and hepatocyte ballooning. A system of grading depending on degree of steatosis and/or inflammation and staging depending on the extent of fibrosis has also been proposed. Although there is no consensus for the treatment for NASH, effort needs to be made to prevent development of fibrosis, which results in cirrhosis and portal hypertension. Slow, consistent weight loss has been shown to be effective in childhood NAFLD, based on improvement of serum aminotransferases or liver sonogram. A low glycemic index diet has been shown to be more effective than a low fat diet in lowering BMI. Family based behavioral intervention may also enhance success with diet. Several pharmacological agents have been used including ursodeoxycholic acid, vitamin E, betaine, n‐acetyl cysteine, and insulin sensitizing agents like metformin, rosiglitazone, and pioglitazone. Transplantation for overt NASH is rare, accounting for <1% of liver transplantations in the USA. The disease can recur after liver transplantation. A strong association exists between the presence of steatosis in a donor liver and poor graft function. As a result, cadaveric donor livers with macrovesicular steatosis >40% are not used routinely. Prognosis in NASH is dependent not only on severity and number of risk factors but also on the degree of histological damage. Clinical trials are needed to identify an effective treatment that halts the progression of NAFLD to NASH in both pretransplantation and post‐transplantation patients.
Biliary atresia is the most common cause of pediatric end-stage liver disease and the leading indication for pediatric liver transplantation. Affected infants exhibit evidence of biliary obstruction ...within the first few weeks after birth. Early diagnosis and successful surgical drainage of bile are associated with greater survival with the child's native liver. Unfortunately, because noncholestatic jaundice is extremely common in early infancy, it is difficult to identify the rare infant with cholestatic jaundice who has biliary atresia. Hence, the need for timely diagnosis of this disease warrants a discussion of the feasibility of screening for biliary atresia to improve outcomes. Herein, newborn screening for biliary atresia in the United States is assessed by using criteria established by the Discretionary Advisory Committee on Heritable Disorders in Newborns and Children. Published analyses indicate that newborn screening for biliary atresia by using serum bilirubin concentrations or stool color cards is potentially life-saving and cost-effective. Further studies are necessary to evaluate the feasibility, effectiveness, and costs of potential screening strategies for early identification of biliary atresia in the United States.
Objectives To examine the medical status of children with biliary atresia (BA) with their native livers after hepato- portoenterostomy (HPE) surgery. Study design The Childhood Liver Disease Research ...and Education Network database was utilized to examine subjects with BA living with their native livers 5 or more years after HPE and to describe the prevalence of subjects with BA with an “ideal” outcome, defined as no clinical evidence of chronic liver disease, normal liver biochemical indices (aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transpeptidase, platelet count, total bilirubin, international normalized ratio, and albumin), and normal health-related quality of life 5 or more years after HPE. Results Children with BA (n = 219; 43% male) with median age 9.7 years were studied. Median age at HPE was 56 (range 7-125) days. Median age- and sex-adjusted height and weight z-scores at 5-year follow-up were 0.487 (IQR −0.27 to 1.02) and 0.00 (IQR −0.74 to 0.70), respectively. During the 12 preceding months, cholangitis and bone fractures occurred in 17% and 5.5%, respectively. Health-related quality of life was reported normal by 53% of patients. However, only 1.8% met the study definition of “ideal” outcome. Individual tests of liver synthetic function (total bilirubin, albumin, and international normalized ratio) were normal in 75%, 85%, and 73% of the study cohort. Conclusion Cholangitis and fractures in long-term survivors underscore the importance of ongoing medical surveillance. Over 98% of this North American cohort of subjects with BA living with native livers 5 or more years after HPE have clinical or biochemical evidence of chronic liver disease.
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