Hepatocellular carcinoma following chronic delta virus hepatitis in a patient cured of leukemia

A 20-year-old patient with chronic delta virus hepatitis (CDVH), cured of acute lymphoblastic leukemia (ALL), developed hepatocellular carcinoma (HCC) 14 years after hepatitis B virus (HBV) infection. The association between chronic HBV infection and HCC is well known, but CDVH patients affected by HCC are rarely reported in literature. To our knowledge, the case we describe is the first HCC case reported in literature occuring in a young boy with CDVH. We could expect further similar cases, considering 1) the high prevalence of HDV infection in children affected by ALL in our series, 2) the previous ALL treatment, and 3) a possible natural predisposition to cancer.     

Hepatitis B virus infection

Hepatitis B virus (HBV) infection is a worldwide health problem and may cause acute, fulminant, chronic hepatitis, liver cirrhosis, or hepatocelullar carcinoma (HCC). Infection with HBV in infancy or early childhood may lead to a high rate of persistent infection (25-90%), while the rates are lower if infection occurs during adulthood (5-10%). In most endemic areas, infection occurs mainly during early childhood and mother-to-infant transmission accounts for approximately 50% of the chronic infection cases. Hepatitis B during pregnancy does not increase maternal mortality or morbidity or the risk of fetal complications. Approximately 90% of the infants of HBsAg carrier mothers with positive hepatitis B e-antigen (HBeAg) will become carriers if no immunoprophylaxis is given. Transplacental HBeAg may induce a specific non-responsiveness of helper T cells and HBcAg. Spontaneous HBeAg seroconversion to anti-HBe may develop with time but liver damage may occur during the process of the immune clearance of HBV and HBeAg. Mother-to-infant transmission of HBV from HBeAg negative but HBsAg positive mothers is the most important cause of acute or fulminant hepatitis B in infancy. Although antiviral agents are available to treat and avoid the complications of chronic hepatitis B, prevention of HBV infection is the best way for control. Screening for maternal HBsAg with/without HBeAg, followed by three to four doses of HBV vaccine in infancy and hepatitis B immunoglobulin (HBIG) within 24h of birth is the most effective way to prevent HBV infection. In areas with a low prevalence of HBV infection or with limited resources, omitting maternal screening but giving three doses of HBV vaccine universally in infancy can also produce good protective efficacy. The first universal HBV immunisation programme in the world was launched in Taiwan 22 years ago. HBV infection rates, chronicity rates, incidence of HCC and incidence of fulminant hepatitis in children have been effectively reduced.     

Chronic hepatitis B in adopted Romanian children.

Four of five Romanian orphans adopted by U.S. families were found to have chronic hepatitis B virus (HBV) infection after negative test results were reported in Romania before adoption. Another child with known HBV infection was found to be coinfected with hepatitis D virus. There is a high incidence of HBV infection in Romanian orphans, and results of tests for HBV are unreliable in Romania.     

Hepatitis B in children: complexities in management

Chronic hepatitis B virus (HBV) infection by definition is persistence of hepatitis B surface antigen (HBsAg) in the serum for > or =6 months. The risk of developing chronic HBV infection ranges from 90% in neonates to <5% in immunocompetent adults. HBV acquired by perinatal infection has a prolonged immune-tolerant phase, characterized by the presence of hepatitis Be antigen (HBeAg), high HBV-DNA and normal alanine aminotransferase (ALT) levels. Efficient and multi-specific helper and cytotoxic T-cell response is essential for controlling HBV infection. Chronic HBV infection is characterized by a state of HBV-specific T-cell hyporesponsiveness. The goal of therapy in chronic HBV infection is to eliminate or significantly suppress HBV replication and prevent the progression of liver disease to cirrhosis with the potential development of liver failure or hepatocellular carcinoma (HCC). In adults, drugs currently licensed for treatment of HBV infection: are interferon-alpha (IFN-alpha), lamivudine (LMV) and adefovir dipivoxil (ADV), the first two are also licensed to use in children. IFN-alpha has the advantage of having a more durable response, fixed duration of treatment and lack of resistant mutants. The disadvantages of IFN-alpha include need for thrice-weekly injections, higher cost and more side-effects compared with the nucleoside analogues. Nucleoside analogues can be given orally and used in decompensated cirrhosis and transplant recipients. ADV and newer drugs like tenefovir can successfully treat mutants produced after prolonged LMV therapy. Current protocols exclude children with immunotolerant HBV. Periodic screening with liver ultrasound scan and alpha-fetoprotein (AFP) in all children with chronic HBV infection is recommended. The severe shortage of cadaveric donor organs has led to the use of marginal (including anti-HBc-positive) cadaveric donor livers in selected transplant candidates with high medical urgency; 5-10% of all liver transplants are because of HBV. Using hepatitis B immunoglobulin and nucleoside analogues has made the outcome following liver transplantation for hepatitis B, comparable with, if not slightly better, than that in patients with other diagnoses. Future treatments should be based on the restoration of HBV-specific T-cell responses to levels similar to that seen in subjects controlling HBV.     

Hepatitis B precore mutant in children with chronic hepatitis B virus infection

BACKGROUND: In adults, hepatitis B virus (HBV) with a G to A point mutation at nucleotide 83 in the precore region (mutant HBV 83), is commonly found in HB e antibody positive HBV carriers. It has been reported that this mutant is not able to produce HB e antigen. The exact prevalence of mutant HBV 83 in patients with chronic HBV infection is not fully understood, especially in children. METHODS: To investigate the role of mutant HBV 83 in children with chronic HBV infection, sera were tested for the presence of mutant HBV 83 using a mutation site-specific assay. RESULTS: Mutant HBV 83 was detected in 15 of 22 children (68%). Seven children were followed longitudinally, of which three were asymptomatic carriers and the other four had chronic hepatitis B on entry. There was no clear relationship between the disease activity and the presence of mutant HBV 83. CONCLUSIONS: It was concluded that mutant HBV 83 is commonly present in children with chronic HBV infection and this mutant is not necessarily associated with activation of hepatitis.     

Efficacy of primary hepatitis B immunization in children with acute lymphoblastic leukemia

BACKGROUND: Children with acute lymphoblastic leukemia (ALL) carry a high risk of hepatitis B virus (HIV) infection. The present study was conducted to see if prior routine hepatitis B vaccine received as a part of national immunization program could prevent HBV infection in these children. METHODOLOGY: Ninety-six children with ALL were screened for HBV. Children were divided into three groups according to their initial HBV serology; previously vaccinated children (Group I) (n=34) previously unvaccinated and seronegative children (Group II) (n=56),and unvaccinated but HBsAg negative and anti-HBs positive children (group III) (n=6). Sixty-seven of 96 (69.7%) children received vaccination. The schedule was initiated during the third month of maintenance therapy and each course consisted of three doses given at one month interval. RESULTS: Anti-HBs seroconversion following the first course of three doses of hepatitis B vaccination in group I, II and III was 57%, 33% and 100%, respectively. It increased to 97% in Group I, 62.5% in Group II, 100% in Group III. HBsAg positivity was found in 11 children (11.5%) and all of them developed chronic hepatitis B. Ten of them were in Group II whereas only one child was in Group I (P<0.04). CONCLUSION: This data reveals that routine HBV vaccination within the national immunization program plays an important role in decreasing subsequent hepatitis B infection in children with ALL.     

Hepatitis A and B virus infections in children in Kuwait

In a 1-year prospective study of 1788 cases of acute viral hepatitis, 26 (1.5%) presented with evidence of simultaneous hepatitis A (HAV) and hepatitis B (HBV) virus infection. Twenty-three of 26 (88.5%) of these cases had serological evidence of a recent HAV infection in a chronic HBV carrier. The remaining 3 (11.5%) showed serological evidence of a recent concomitant HAV/HBV infection. Twenty-four of the 26 (92.3%) patients with simultaneous infection were children with a mean age of 4.6 years. Clinical and laboratory data indicated that the disease in patients with a recent concomitant HAV/HBV infection was not different from that in patients who had HAV infection superimposed on a chronic HBV carrier or that in age and sex matched patients presenting with an acute viral hepatitis A infection alone. Furthermore, the outcome of the disease was not affected by the HBeAg/anti-HBe status of the hepatitis B positive patient. All patients recovered completely and on follow-up none showed any signs of chronic liver disease. Simultaneous HAV/HBV infection, therefore, does not result in a more severe disease.     

Hepatic dysfunction in children with acute lymphoblastic leukemia in remission: relation to hepatitis infection

BACKGROUND: Viral hepatitis is a cause of hepatic dysfunction in children with ALL in remission during maintenance therapy is debated. The aims of the current study were (1) to explore the incidence of hepatic dysfunction in a group of children (Egyptian and Saudi) with ALL under maintenance therapy, (2) to study the prevalence of hepatitis B (HBV) and/or C (HCV) infection and their contributions to chronic liver disease that might be induced by maintenance therapy. PROCEDURE: The current study included 105 children with ALL (54 Egyptian and 51 Saudi). All eligible patients had been on maintenance therapy for at least 12 months and all had serial assessments of liver function. These included determination of total bilirubin, AST, ALT, and alkaline phosphatase. Markers for HBV and HCV including HBsAg, anti-HBC, and anti-HCV and for some patients HCV RNA by PCR were studied. Percutaneous liver biopsy was performed for a group of children. RESULTS: The prevalence of hepatitis infection (HBV and/or HCV) among Egyptian children was found to be high (43/54-80%). Only five Saudi children had evidence of exposure to HBV (5/51-9.8%), P<0.0001. During the period of study, 22 Egyptian patients vs. four Saudi patients (41 vs. 7.8%, P<0.0001) experienced at least one episode of elevation of liver enzymes, three times the upper limit of normal or more. Twenty-six of the 48 patients (54%) with HBV and/or HCV infection had episodes of elevated liver enzymes, while there was no occurrence among the patients negative for HBV and HCV. In patients with HBV infection, the presence of HBsAg was strongly associated (100%) with elevated liver enzymes. Histopathologic examination of liver biopsies obtained from 35 patients revealed that all five patients negative for HBV and HCV had normal liver biopsies in spite of being under maintenance therapy. CONCLUSION: In children undergoing treatment for ALL, elevations in liver enzymes may be primarily due to hepatitis viruses. However, maintenance therapy using known hepatotoxic drugs, may have additive deleterious effects. Liver enzymes are normalized in affected patients when maintenance therapy is temporarily suspended.     

Delta Virus and Childhood Leukemia

We studied 145 children with acute lymphocytic leukemia (ALL) in remission who had been off chemotherapy for at least 2 years, to assess the prevalence of hepatitis delta virus (HDV) infection, and to determine whether HD V infection was associated with more severe chronic liver disease. The prevalence of chronic HBV infection was 41.5% (60/145). The prevalence of HDV infection among these patients with chronic HBV infection was 50% (30/60). Eighty-five patients were HBsAg-negative. There was evidence that HDV-infected children had more severe chronic liver disease than did HBsAg-positive, anti-HDV-negative patients: (1) their serum ALT levels were significantly more likely to be elevated at long-term follow-up (27/30 vs. 10/26, p = 0.0001); (2) their mean ALT levels were significantly higher 3 years after the cessation of chemotherapy (128 vs. 84 IU/L, p = 0.001); and (3) they were more likely to have either chronic acute hepatitis or cirrhosis when liver biopsy was done (18/23 vs. 6/18, p = 0.0038). Children who were HBsAg-negative had the lowest alanine aminotransferase (ALT) levels and were least likely to have chronic active hepatitis or cirrhosis (3/31).

We conclude that infection with HDV in children with ALL is associated with serious chronic liver disease. In long-term survivors, HDV infection is a major cause of morbidity and an adverse prognostic factor in terms of leukemia-free survival.     

Chronicity rate of hepatitis B virus infection in the families of 60 hepatitis B surface antigen positive chronic carrier children: Role of horizontal transmission

It is known that the 5%–10% of adults infected with hepatitis B virus (HBV) develop a chronic infection and that HBV infection acquired at birth by an hepatitis B surface antigen (HBsAg)/hepatitis B e antigen (HBeAg)-positive mother almost invariably leads to chronic infection. Little information is, however, available about the risk of HBV infection acquired in childhood becoming chronic. We have, therefore, studied the chronicity rate of HBV infection in the families of 60 consecutive HBsAg-positive chronic carrier children. Of parents 81.5% and 78.6% of children showed serological evidence of past or ongoing HBV infection. The chronicity rate was significantly higher among children (73.4%) than parents (35.6%). Such a high chronicity rate in these children was not correlated with vertical transmission, since this was reported in only 1.7% of them. It is noteworthy that the chronicity rate of HBV infection was not significantly different between children of HBsAg-positive mothers and those in whom infection must have been horizontally transmitted because their mothers were HBsAg-negative. Although the families studied represent a selected sample and the role of genetic factors could not be excluded, our results seem to show that the most important factor in determining the outcome of infection is the acquisition of hepatitis B during childhood.     

Regenerative nodule mimicking hepatocellular carcinoma in a cirrhotic child due to hepatitis B: an imaging dilemma

Viral hepatitis B, post-hepatitic cirrhosis and hepatocellular carcinoma (HCC) is the classical sequence of events in hepatitis B virus (HBV) infected children and serum Alpha-fetoprotein (AFP) and ultrasound (USG) screening is recommended during follow up. We present a 13-yr-old girl with cirrhosis related to chronic HBV infection with normal AFP level and a 4 cm mass appearance by USG. Contrast spiral evaluation computed tomography (CT) study demonstrated a single mass located at 8th segment of the liver. Pre-contrast CT and portal venous phase studies showed heterogeneous liver parenchyma without mass appearance. HCC was suspected based on strong arterial enhancement. Two mediastinal lymphadenopathies, 1 cm under the xyphoid and 2 cm above the pericardium, were detected by thorax CT. Mediastinal exploration was undertaken with living related liver transplant donor in a second operating room. She was transplanted with the right lobe of her ABO compatible mother after evaluation of the lymph nodes revealed reactive histology by frozen section. Histologic evaluation of the explant liver documented cirrhosis with a cirrhotic nodule without histologic malignant evidence. False negative results from screening methods are familiar in the literature; however false positivity of a contrast CT study is rare. The significance of screening methods is discussed.     

Chronic viral hepatitis

Among hepatitis A to E viruses, hepatitis B, C, and D viruses can cause chronic hepatitis, in both children and adults. Hepatitis B virus (HBV) infection is the most prevalent and important one. Perinatal transmission accounts for about 40–45% of chronic HBV infection in hyperendemic areas. Horizontal transmission through intramuscular injection using non-sterile needles and intrafamilial spread accounts for the other half of carriers. During the natural course of HBV infection, the host gradually clears HBV and hepatitis B e antigen (HBeAg), liver damage and elevation of aminotransferases occur during the process of HBV clearance. The most effective way to eliminate HBV infection is immunoprophylaxis starting since birth. It can prevent both HBV and hepatitis D virus (HDV) infections. Hepatitis C virus (HCV) infection in children occurs mainly in high risk children, such as those who received blood product or injection using non-sterile needles, or infants of HCV viremic mothers, etc. Screening of blood product reduced markedly the prevalence of post-transfusion HCV infection, but the prevention of sporadic cases requires HCV vaccination which is still under investigation.     

Pediatric HBsAg chronic liver disease and adult asymptomatic carrier status: two stages of the same entity

Unlike adults (greater than 60% of cases), it is rare to find the chronic hepatitis B virus (HBV) carrier status with normal transaminases among children. The aim of this study was to investigate whether this status would depend on the duration of HBV infection, that is, whether chronic hepatitis in childhood would lead to the asymptomatic carrier status in later life. We reexamined all of our patients with chronic HBV infection of greater than 10 years' duration and with histologically documented chronic hepatitis during childhood. This was a group of 36 adolescents and young adults. All subjects were screened for tumor using alpha-fetoprotein assay and hepatic ultrasound. Eight patients with cirrhosis underwent esophageal fiberoptic endoscopy. All patients were in good general condition, with no clinical signs of liver failure. Only two patients had abnormal transaminase levels, both of whom had evidence of delta infection. All but one patient became anti-HBe positive. Five cases had HBsAg clearance. (Seventy-one percent of patients were HBeAg positive and 14% anti-HBe positive at the onset of the disease.) Hepatic ultrasound revealed no tumors in any of the subjects, and fiberoptic endoscopy demonstrated no esophageal varices. This study suggests that (a) chronic hepatitis and asymptomatic carrier status may be subsequent stages of the B virus infection; and (b) chronic hepatitis in childhood is generally benign and may evolve into an asymptomatic carrier status. The main problem with the chronic carrier status is probably the increased risk of hepatocellular carcinoma.     

乙型肝炎病毒母婴传播影响因素探讨

目的：探讨乙型肝炎病毒(HBV)母婴传播的影响因素,寻求降低婴儿HBV感染率的方法。方法：HBV携带及慢性乙型肝炎孕妇共635例,分别比较不同血HBV DNA滴度,不同分娩方式（剖宫产或自然分娩）,以及不同肝功能状态孕妇所生婴儿出生时及3月龄时HBV的感染率。新生儿生后12 h内肌注乙肝免疫球蛋白200 U 及重组酵母乙肝疫苗10 μg;生后即刻显示血清HBV感染存在者,14 d时再肌注乙肝免疫球蛋白200 U。结果：孕妇高滴度组（HBV DNA>105拷贝/mL）所生新生儿出生时（14.4% vs 4.1%,P<0.01）与3月龄时（4.7% vs 0,P<0.01）HBV感染率均高于低滴度组（HBV DNA ≤105拷贝/mL）。两组新生儿3月龄时HBV感染率均低于出生时（P<0.05）。自然分娩的孕妇其婴儿出生时HBV感染率明显高于剖宫产组（P<0.01）,但3月龄时,两组感染率接近。HBV携带孕妇所生婴儿出生时HBV感染率明显高于慢性乙型肝炎孕妇所生婴儿（P<0.01）,但3月龄时两组婴儿HBV感染率亦接近。结论：孕妇血清HBV DNA水平与新生儿HBV宫内感染密切相关,故降低孕妇血清HBV DNA水平可能成为减少新生儿HBV感染的一种有效途径。在乙肝免疫球蛋白及重组酵母乙肝疫苗的双重保护下,孕妇的分娩方式与肝功能状态对HBV母婴传播无影响。     

Nutritional status and growth in children with chronic hepatitis B.

As reported for other chronic liver diseases, hepatitis B virus (HBV) chronic infection might result in malnutrition. In order to establish whether this disease could be responsible of malnutrition and hence influence growth, 75 children, chronically infected with HBV, have been followed up for 4 years. Thirty-one of them had chronic active hepatitis (CAH), 25 chronic persistent hepatitis (CPH), 14 chronic lobular hepatitis (CLH), and five cirrhosis (three active, two inactive). The nutritional status was evaluated every 12 months, with careful physical and laboratory examinations. General nutritional status was estimated according to Waterlow criteria (13, 14). At our first observation, 50 children were following a balanced diet with a caloric intake adequate for age and weight, whereas 25 were on a low-fat diet, begun in the belief of its therapeutic value. For seven patients of this second group, the caloric intake was below the daily requirement. The latter group showed a growth failure in weight when they were first seen at our center and gained weight when the dietary intake was normalized. However, no biochemical feature of malnutrition was observed in all the 75 children. At the end of the follow-up period, the nutritional status was satisfactory for all of them.     

Hepatitis B in childhood: An update for the paediatrician

Hepatitis B virus (HBV) infection may lead to acute or chronic hepatitis, cirrhosis and hepatocellular carcinoma. The incidence rate of paediatric hepatitis B is 0.2/100,000 to 1.8/100,000 in Canada. Hepatitis B virus infection is acquired largely through mother-to-infant (vertical) or community-based (horizontal) transmission in early childhood, whereas older children are susceptible to HBV infection through exposure to contaminated blood during intravenous drug use or through sexual transmission. Immigrants from endemic areas and some Native Canadian populations are also at a higher risk for HBV infection. Infection with HBV may manifest in three forms: acute self-limited hepatitis, chronic hepatitis or massive hepatic necrosis causing acute liver failure. The identification of HBV infection and the characterization of the disease relies on serological and virological tests. The course of chronic hepatitis B may be classified into three phases: an immunotolerant phase, an active phase and an inactive phase. Current treatment options include interferon-alpha and lamivudine for individuals with elevated serum alanine aminotransferase levels and markers of persistent viral replication. Children with chronic hepatitis B require regular monitoring and age-appropriate lifestyle counselling. Paediatricians are well-positioned to promote vaccination and encourage testing of those who are at risk for hepatitis B. With effective universal vaccination against hepatitis B, this infection could be essentially eliminated in Canada.     

Increased risk of chronic hepatitis in children with cancer

BACKGROUND: There is a risk of viral hepatitis for children with cancer. Both hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in countries with high prevalence cause major problems in the management of cancer patients. In this study, we evaluated the incidence and chronicity of HBV and HCV infections in children with malignant diseases receiving chemotherapy. PROCEDURE: One hundred ninety-eight children with cancer (mean age = 7.5 +/- 2.5 years) and 100 healthy children as a control group were screened for HBV and HCV. Liver function tests, the number of transfusions, HBV and HCV serology were regularly monitored. In seropositive children, HBV-DNA and HCV-RNA were measured. Chronic hepatitis was defined as having an alanine aminotransferase (ALT) level three times of upper normal limit, positive HBV and HCV antigenemia for longer than 6 months. Liver biopsies were performed in all children with chronic hepatitis. The relationship between the chronic hepatitis and study parameters was statistically analyzed. RESULTS: HBsAg positivity, anti-HCV, and mixed (HBV and HCV) infection were found in 11.6, 5.5, 2% of children, respectively. Most HBV infected children developed chronic hepatitis (48%) while 26 and 21.7% became carriers and immune, respectively. One died of acute fulminant HBV hepatitis. Of HCV infected children, 63.6% also had positive HCV-RNA. Four children with mixed infection (100%) all progressed to chronic hepatitis. In this setting, chronic hepatitis was observed in 22 of 38 infected children (57.8%). The majority had leukemia and lymphoma. Children with HBsAg antigenemia developed chronic hepatitis in shorter time than HCV positive children (median 13 months vs. 51 months, P < 0.001). CONCLUSION: We observed an increased incidence of chronic hepatitis and even mortality due to HBV infection. This suggests that HBV and HCV infections are serious causes of morbidity and mortality in children with cancer.     

Correlation of hepatitis B virus,hepatitis D virus and human immunodeficiency virus type I infection markers in hepatitis B surface antigen positive haemophiliacs and patients without haemophilia with clinical and histopathological outcome of hepatitis

The hepatitis D virus (HDV) infection plays a major role in severe liver damage caused by hepatitis. To establish the prevalence of HDV infection in haemophilic patients and patients without haemophilia, 87 patients with chronic hepatitis B virus (HBV) infection were examined for serological evidence of delta hepatitis. In addition HBV, HDV and human immunodeficiency virus type 1 (HIV) infection markers were compared to clinical and histopathological outcome of hepatitis. Out of 46 haemophiliacs 30 (65%) were anti-HD-seropositive; 10 out of 30 anti-HD-positive patients (33%) had pathological liver function tests compared to 2 out of 16 anti-HD-negative haemophiliacs (13%). The rate of HIV infection did not differ between the HDV infected and the non-HDV infected individuals with haemophilia (17/27 anti-HD-positive patients versus 12/16 anti-HD-negative patients). Two haemophilic anti-HD-positive patients underwent liver biopsy, in both cases hepatitis D antigen (HDAg) was detected in the biopsies. Only 2 out of 41 patients without haemophilia were anti-HD-positive. Both had pathological liver function tests; chronic active hepatitis and cirrhosis, respectively, were diagnosed and HDAg was found in the liver biopsies. Out of 39 anti-HD-seronegative patients without haemophilia, 26 (67%) were hepatitis B e antigen positive; in the sera of 20 patients )51%) HBV-DNA was demonstrated, but only 6 patients (15%) had pathological liver function tests. In conclusion a high seroprevalence of HDV infection was found in haemophilic patients treated with non-pasteurized commercial clotting factor concentrates. An endemic spreading of HDV infection in patients without haemophilia with chronic HBV infection could not be detected. In haemophilic patients pathological liver function tests were more frequently associated with HDV superinfection than with chronic HBV infection alone. HIV infection was diagnosed at a similar rate in anti-HD-positive and anti-HD-negative patients.     

小儿庚型肝炎的探讨

为了探讨一种新型肝炎病毒，即庚型肝炎病毒（ｈｅｐａｔｉｔｉｓＧｖｉｒｕｓ，ＨＧＶ）在小儿中的感染特点，检测了３６例肝炎患儿及１６例健康体检儿童血清中ＨＧＶ－ＲＮＡ（套式逆转录ＰＣＲ法）。结果表明，３６例肝炎中有１１例ＨＧＶ感染者，其中６例合并慢性ＨＣＶ感染（３例接受过干扰素治疗），２例合并慢性ＨＢＶ感染，２例为慢性非Ａ－Ｅ肝炎，１例合并ＨＢＶ＋ＨＡＶ感染。１６例健康儿童均阴性。ＨＧＶ感染率在血制品输入者１０例中７例阳性，在未输入者２２例中３例阳性（两者比较，Ｐ＜０．０１），在血制品使用情况不明者２０例中１例阳性。提示输入血制品是小儿ＨＧＶ感染的主要途径，但不排除还有其他途径，感染者主要为慢性肝炎患儿，干扰素的疗效有待进一步研究     

De novo hepatocellular carcinoma post‐multivisceral transplantation in a child

De novo hepatocellular carcinoma (HCC) post‐transplantation in patients without viral hepatitis is extremely rare, with only three reported adult cases in the English literature. Here, we present a case of de novo HCC that developed in a 7‐year‐old female, who at 8 months of age received a liver, small bowel, spleen, and pancreas transplantation 6.5 years ago for gastroschisis and total parenteral nutrition (TPN)‐related cirrhosis. The post‐transplant course was complicated by Epstein‐Barr virus (EBV) infection, post‐transplant lymphoproliferative disease, and subsequent development of multifocal EBV‐associated post‐transplant smooth muscle tumors (EBV‐PTSMT) in the small bowel 1 year and 10 months after transplantation, respectively. This was managed by reducing immunosuppression with rituximab and EBV‐specific cytotoxic T‐cell therapy. She was noted to have a new lesion in her transplanted liver graft 6.5 years post‐transplantation that was diagnosed as HCC. The HCC was resected, and the patient remained clinically stable for 7 months. At that time, recurrence of the HCC was discovered on MRI. She passed away 6 months after. To the best of our knowledge, this is the first reported occurrence of de novo HCC post‐transplantation in the pediatric population that is unrelated to viral hepatitis in either recipient or donor.