Suzanne Davison

Perinatal hepatitis C virus infection: diagnosis and management

Hepatitis C virus (HCV) infection in children is becoming an increasing challenge to health professionals. As our understanding of the disease evolves, so must our diagnostic and management strategies. In the 1990s, when HCV testing became available, children identified with HCV infection in the UK were mostly those who had required blood products, particularly those with haematological disorders. Acquiring knowledge of the natural history of HCV infection was confounded by the co-morbidity of iron overload, viral co-infection, and chemotherapy.

Biliary complications after paediatric liver transplantation: Birmingham's experience

Abstract Between 1983 and 1992, 112 children underwent liver transplantation. Of 138 grafts, 60 (43.4%) were whole livers, 77 (55.6%) were reduced livers, and 1 (0.7%) was a split liver. Biliary complications (BC) were defined as any abnormality, even minor, related to the biliary tract. Results were analysed with a minimum follow‐up of 9 months. Some 36 grafts (26.1%) in 34 patients (30.4%) presented with BC: bile leaks (17 grafts), biliary obstructions or dilatations (16 grafts), and other complications (3 grafts). Management was mainly surgical with biliary reconstruction via a Roux‐en‐Y loop. Interventional radiology had an increasing role in recent years. BC were associated with a mortality of 1.8% (2/112), a graft loss rate of 4.3% (6/138), and significant morbidity. Among the various factors whose association with BC was studied, the date of transplantation, the use of reduced grafts and the use of gallbladder conduits appeared to be the main determining factors for BC. From multivariate analysis the use of reduced grafts emerged as the most important factor in reducing BC. We therefore conclude that BC are associated with significant morbidity, but general improvements in both surgical and medical management seem to account for better results in recent years.

Management strategies for hepatitis C virus infection in children.

Chronic hepatitis C virus (HCV) infection is a major cause of morbidity and mortality worldwide. Progression to cirrhosis and hepatocellular carcinoma occurs in 20% of infected adults. The natural history following childhood infection is less well defined, although cirrhosis in children is described. Since blood product screening for HCV infection was introduced in 1990, most children who acquire HCV do so by vertical transmission from an infected mother. Transmission to offspring occurs in approximately 5%.Most children with HCV infection are asymptomatic. Diagnosis is made by testing those at risk for HCV RNA by polymerase chain reaction (PCR) and HCV antibody (anti-HCV) by enzyme immunoassay (EIA). The clinical impact of HCV infection is assessed by monitoring symptoms and signs, blood testing of liver enzymes, ultrasound imaging, and by liver biopsy.Improved efficacy and tolerability of treatment strategies in adults have had a significant impact on the management of children with HCV infection. The emphasis is now on promoting awareness, early diagnosis, and treatment. Treatment strategies have evolved from monotherapy with interferon alfa (IFNα), to combination therapy with ribavirin. Pegylated IFNα is superior to conventional IFNα, and forms the basis of current recommendations. The genotype of HCV influences treatment efficacy. Treatment is generally well tolerated in children, although adverse effects are common. Preparation and support throughout treatment for the whole family is needed.A proportion of children with HCV infection have co-morbidity, including viral co-infection or hematologic disease. Although treatment may be contraindicated, risks and benefits must be considered before denying treatment. Anemia is more common in those with HIV co-infection, renal insufficiency, thalassemia, or cirrhosis, and may be aggravated by treatment. Children with thalassemia may have iron overload, and transfusion requirements may increase during treatment.Further refinements of combination therapy and development of new drugs are in progress. Vaccine candidates are undergoing phase I and II treatment trials.

Chronic hepatitis in children after liver transplantation: role of hepatitis C virus and hepatitis G virus infections.

BACKGROUND/AIMS Chronic graft hepatitis occurs in 20-30% adults after liver transplantation but the prevalence and causes in children are not known. In adults, hepatitis C virus infection is prevalent prior to transplantation and recurrent infection is a frequent cause of graft dysfunction. The significance of the recently described hepatitis G virus infection remains unproven. The aim of this study was to examine the role of hepatitis C virus and hepatitis G virus infection in chronic graft hepatitis after paediatric liver transplantation. METHODS The prevalence of graft hepatitis and the role of hepatitis C virus and hepatitis G virus infections in 80 children after liver transplantation have been studied, with a median follow up of 4.4 years (range 0.4 to 10.7), and the persistence of hepatitis G infection in the presence of immunosuppression has been determined. RESULTS Chronic graft hepatitis was diagnosed in 19/80 (24%) children and was most frequently seen in children transplanted for cryptogenic cirrhosis (71%). There was no significant difference in the prevalence of chronic hepatitis in those transplanted before or after donor anti-HCV screening. Hepatitis C infection occurred in three children transplanted prior to donor screening but in only one was associated with chronic hepatitis. Hepatitis G infection was found in 22/79 (28%) transplant recipients but was not associated with graft hepatitis. In 17/21 children hepatitis G infection persisted for a median of 5.2 years after transplantation. CONCLUSION Chronic hepatitis occurred in 24% of children after liver transplantation, a similar prevalence to that in adults. Cryptogenic liver disease predisposed to graft hepatitis, but neither hepatitis C nor hepatitis G infection was associated. Hepatitis G virus caused a frequent and usually persistent infection after transplantation.

A national sample of individuals who acquired hepatitis C virus infections in childhood or adolescence: risk factors for advanced disease.

Objectives: To describe hepatitis C virus (HCV)–related liver disease in a national cohort of patients who acquired their infections in childhood or adolescence and to assess risk factors for progressive disease and response to antiviral therapy. Patients and Methods: Demographic, laboratory, and clinical outcome data on 246 individuals who acquired HCV infection before the age of 16 years were extracted from the UK HCV National Register database. Logistic regression analysis was used to investigate the independent effects of sex, age, duration and route of infection, and comorbidity on histological stage of liver disease. Results: Median ages at enrollment and follow-up were 14.0 years (range, 2.2–29.6 years) and 19.2 years (range, 2.3–35.5 years), respectively. Mean duration of infection at enrollment was 8.5 years (standard deviation [SD], 3.3 years), and mean duration of follow-up was 4.5 years (SD, 4.5 years). Fifty-nine (24%) had persistently abnormal liver aminotransferase levels; 22% reported physical signs and symptoms of liver disease. Among 123 individuals with liver biopsies, 117 (95%) had abnormal histological findings. Ninety-eight individuals had biopsies referred for independent blind scoring; median Ishak grade and stage scores were 3 and 1, respectively. Presence of comorbidities (odds ratio [OR], 7.19; 95% CI, 2.00–26.17; P = 0.003) and female sex (OR, 0.31; 95% CI, 0.10–1.00; P = 0.05) were independently associated with histological stage scores greater than the median. A total of 110 individuals received antiviral therapy; 47% achieved a sustained response. Conclusions: HCV-related liver disease in those who acquired the infection in childhood or adolescence was mild for most, although comorbidity and female sex were associated with more advanced disease. Antiviral therapy in childhood or adolescence successfully eradicates the virus for many patients.

Liver Failure in Early Infancy: Aetiology, Presentation, and Outcome

Objective: Acute liver failure (ALF) in early infancy is rare and challenging to recognize and manage. We aim to describe the presentation and outcome of infants with ALF according to their final aetiology to elucidate features to facilitate early recognition leading to prompt diagnosis and management. Methods: All infants presenting within 120 days from birth with liver failure were included in a retrospective review over a 19-year period. The aetiology, clinical features, presenting investigations, and outcome were collected. Results: Seventy-eight young infants presented with ALF. The aetiology was established in 94% and included metabolic disease (36%), hypoxic-ischaemic (HI) insult (19%), infection (17%), neonatal haemochromatosis (9%), and infiltrative disease (9%). Infections, infiltrative disease, and acute HI insult usually resulted in higher transaminases and international normalized ratio, whereas neonatal haemochromatosis and tyrosinaemia were characterized by lower or near normal transaminases. Overall jaundice was not visible in 24% of infants at presentation. Forty-five (58%) infants were alive at discharge from hospital. Survival at 1 year was 53% and survival with native liver 50%. Later deaths occurred in infants with mitochondrial disease. Six infants received a liver transplant and 4 subsequently died from their underlying disease. Conclusion: ALF should be considered in any young infant with a coagulopathy as transaminases and/or bilirubin levels can be near normal at presentation. Better intensive care and the judicious use of liver transplantation may have contributed to the improved outcomes for this group compared with previous decades.

Epstein-Barr virus-associated lymphoproliferative disorder in Crohn disease treated with azathioprine.

JPGN Volume 51, N etween inflammatory nal malignancies has T he association b bowel disease (IBD) and gastrointesti been well described (1,2). The potential risk of malignancy is probably augmented by the use of immunosuppressive therapy such as azathioprine and 6-mercaptopurine (3–5). Dayharsh et al (6) reported an increased risk of Epstein-Barr virus (EBV)–positive lymphoma in adults with IBD treated with azathioprine or 6-mercaptopurine. An adult with Crohn disease (CD) taking azathioprine who later developed fatal EBV infection with B-cell lymphoproliferative disorder (LPD) has been reported (7). The majority of reported cases of malignancies in IBD are adults and its occurrence in children is rare. We report on a boy who developed EBV-associated LPD following azathioprine treatment for his CD.

G107(P) Portal vein obstruction: The challenge of timely diagnosis

Background Portal vein obstruction (PVO) due to thrombosis with cavernoma formation is a major cause of portal hypertension. Significant morbidity occurs due to oesophageal variceal bleeding. Early diagnosis provides an opportunity for prophylactic intervention. Aim evaluate the spectrum of clinical presentation of PVO, and identify opportunities for early diagnosis. Methods Children born after 1990 with final diagnosis of PVO referred to single centre 2000 – 2015 were studied. Data collected retrospectively: initial symptoms, signs and investigations, incidence of gastrointestinal (GI) bleeding and time to diagnosis. Results Fifty-six children identified, one excluded (insufficient data). Age at presentation 3y 10m (1 m 13y 8 m), 26 male. Risk factors identified in 28/55 (51%): umbilical vein instrumentation (12), congenital heart disease (10) other congenital anomalies (6). Four patterns of presentation identified: (a) incidental finding of PVO on US (n=9); (b) neonatal jaundice +/ascites with US diagnosis of PVO (n=4); (c) upper GI bleed (n=22) and (d) ‘haematological presentation’ with splenomegaly and/or symptoms/signs of hypersplenism (n=20). Of 22 presenting with GI bleeding (mean age 3y 6m, 6m–10y6m) 15 had diagnosis established during admission. Seven were discharged without PVO identified: all readmitted after median 1m (7d – 18m) with further bleeding, after which diagnosis established. Three with GI bleed at presentation were initially referred to haematology for investigation of thrombocytopenia, two undergoing bone marrow (BM) assessment. Of 20 children (mean age 5y 2m, 17 m-13 y) with ‘haematological presentation’, 13 (65%) were referred to haematology (11) or immunology (2). BM assessment performed in 9/20 (45%) was normal. Only 9/20 (45%) in this group had diagnosis of PVO established within 2w of presentation. In 11 median interval to diagnosis was 10 m (2m – 6y). Of these, 10 had a significant GI bleed during the interval to diagnosis. Conclusion PVO has wide spectrum of presentation. Associated risk factors in 51% may aid diagnosis. Diagnosis was delayed in 18/42 (43%), most frequently in those with ‘haematological’ presentation (55%) but also in those with GI bleed (32%). Carefully focussed imaging by US with Doppler and/or other radiological modalities should be undertaken in a child with history, symptoms or signs compatible with PVO.