Renal outcomes after liver transplantation in fulminant hepatitis A with acute kidney injury: comparison with hepatorenal syndrome.

BACKGROUND: Liver transplantation (LT) is the treatment of choice for hepatorenal syndrome (HRS). Recently, acute kidney injury (AKI) due to acute hepatitis A (HA) is increasing, but the outcome of LT is not well established. We investigated the outcomes of LT in patients with AKI due to acute HA compared with those of patients with HRS due to other causes. METHODS: We investigated the outcomes of LT in 20 patients with AKI associated with acute HA (HAV group) compared with 76 patients with hepatorenal syndrome (HRS) due to other causes (HRS group) at 3 Korea centers. RESULTS: Preoperative mean prothrombin time and serum creatinine level were higher in the HAV group than in the HRS group. But mean total bilirubin level was lower in the HAV group. There was no difference in Model for End-Stage Liver Disease scores. Post-transplantation patient and graft survival rates were similar between the 2 groups. More patients in the HAV group needed post-transplantation hemodialysis than in the HRS group (65.0% vs 38.2%; P = .043). However, post-transplantation estimated glomerular filtration rate was significantly higher in the HAV group after post-transplantation month 2 (P < .05). CONCLUSIONS: Peri-transplantation kidney function of the HAV group was poorer than that of HRS group. However, post-transplantation long-term renal outcome could be better in the HAV group.

Fulminant hepatitis A infection in second trimester of pregnancy requiring living-donor liver transplantation.

We present an 18-year-old pregnant woman who was referred to our emergency clinic as a case of acute hepatic failure and hepatic encephalopathy. Laboratory tests showed abnormal liver function tests and serological workup was consistent with acute hepatitis A infection. Ultrasonography revealed a single live fetus with fetal biometry compatible with 18 gestational weeks. The patient underwent a highly urgent liver transplantation using a right lobe graft from her husband. Histological examination of the explanted liver showed acute, lymphocyte-rich, diffuse necrotizing hepatitis, consistent with acute necrotizing hepatitis A. After the operation her allograft function gradually recovered. Her follow-up obstetrics ultrasound revealed a male fetus with severely decreased amniotic fluid. The patient was informed about the poor prognosis of her pregnancy and the pregnancy was terminated by vaginal misoprostol induction. She has maintained a good general condition and liver function for 4 months postoperatively, up to the present time.

What factors determine the severity of hepatitis A-related acute liver failure?

The reason(s) that hepatitis A virus (HAV) infection may progress infrequently to acute liver failure are poorly understood. We examined host and viral factors in 29 consecutive adult patients with HAV-associated acute liver failure enrolled at 10 sites participating in the US ALF Study Group. Eighteen of twenty-four acute liver failure sera were PCR positive while six had no detectable virus. HAV genotype was determined using phylogenetic analysis and the full-length genome sequences of the HAV from a cute liver failure sera were compared to those from self-limited acute HAV cases selected from the CDC database. We found that rates of nucleotide substitution did not vary significantly between the liver failure and non-liver failure cases and there was no significant variation in amino acid sequences between the two groups. Four of 18 HAV isolates were sub-genotype IB, acquired from the same study site over a 3.5-year period. Sub-genotype IB was found more frequently among acute liver failure cases compared to the non-liver failure cases (chi-square test, P < 0.01). At another centre, a mother and her son presented with HAV and liver failure within 1 month of each other. Predictors of spontaneous survival included detectable serum HAV RNA, while age, gender, HAV genotype and nucleotide substitutions were not associated with outcome. The more frequent appearance of rapid viral clearance and its association with poor outcomes in acute liver failure as well as the finding of familial cases imply a possible host genetic predisposition that contributes to a fulminant course. Recurrent cases of the rare sub-genotype IB over several years at a single centre imply a community reservoir of infection and possible increased pathogenicity of certain infrequent viral genotypes.

Intractable recurrent hepatitis A virus infection requiring repeated liver transplantation: a case report.

Although hepatitis A virus (HAV) infection is usually self-limited, it may induce fulminant hepatitis. We present an unusual case of a 40-year-old, otherwise healthy man with intractable recurrent HAV infection requiring retransplantation after primary liver transplantation for HAV-associated fulminant liver failure. After the first living-donor liver transplantation, allograft function recovered uneventfully; however, beginning at 35 days, his serum total bilirubin concentration increased, reaching 40 mg/dL, with a slight increase in liver enzymes. Detection of genomic HAV RNA in serum at the time of graft dysfunction led to a diagnosis of recurrent HAV infection. Fifty-one days after the first transplant, he underwent a deceased donor retransplantation. His allograft function recovered; the patient was discharged from the hospital. Sixty-five days later, however, he was readmitted for colitis-like symptoms and was again treated for acute rejection, but died owing to overwhelming sepsis and persistence of HAV infection. These findings indicate that patients who undergo liver transplantation for HAV-associated liver disease may be at risk of HAV reinfection, particularly if they require anti-rejection therapy. Routine measurements of anti-HAV immunoglobulin M and HAV RNA during the early posttransplant period in HAV-associated liver transplant recipients may differentiate reinfection from an acute cellular rejection episode.

Routine use of auxiliary partial orthotopic liver transplantation for children with fulminant hepatic failure: Preliminary report.

Auxiliary partial orthotopic liver transplantation (APOLT) has been performed for both metabolic disorders and fulminant liver failure (FHF). When the native liver regenerates, the patients with FHF who undergo APOLT have a chance to withdraw immunosuppression. It may be most beneficial for children. This preliminary report describes our start to routinely offer APOLT as an option to standard OLT for children with FHF in 2005. Six children (ages 8 months to 8 years) received APOLT: 1 in 1996 and the others in 2005 and 2006. The donor ages ranged from 4 to 40 years. We used either a left lateral segment or a left lobe graft. The recipient left lobe, which was removed, showed submassive to massive necrosis at the time of transplantation. All children are alive and well. The first patient who received APOLT in 1996 is currently off immunosuppression with a fully recovered native liver; the grafted liver underwent complete atrophy. The 5 remaining subjects are receiving reduced levels of immunosuppression with close monitoring. Their serial liver biopsy specimens show slight to significant recovery. One developed hepatic artery thrombosis, requiring retransplantation. The native liver was retained at the time of retransplantation (redo APOLT). Other postoperative complications included a bile leak (n = 1), invasive mucomycosis of the arm (preexisting condition; n = 1), biliary stricture (n = 1), and acute cellular rejection (n = 3). Posttransplantation length of stay was 6 to 60 days (median, 15 days). In conclusion, APOLT can be safely performed in children with FHF displaying short-term outcomes comparable to standard transplantations.

Acute fatty liver of pregnancy -- an underlying condition for herpes simplex type 2 fulminant hepatitis necessitating liver transplantation.

The infrequent occurrence of herpes simplex virus (HSV) hepatitis in healthy women in comparison with the high prevalence of HSV infections suggests that, in addition to deranged immunity, an underlying condition in the liver might be necessary to develop HSV hepatitis. We report the case of a 28-year-old pregnant woman in the 28 (th) week of gestation. Following HSV type 2 infection of the uterine cervix, acute liver failure developed, necessitating urgent liver transplantation. In addition to fulminant HSV type 2 hepatitis, the explanted liver also showed the histological features of acute fatty liver of pregnancy. The presented case suggests a possible pathogenetic role of acute fatty liver of pregnancy in the development of fulminant HSV hepatitis following recurrent infection with HSV in healthy pregnant women. We believe that early histopathological diagnosis, followed by specific antiviral treatment and liver transplantation in selected patients may improve the clinical outcome of otherwise almost uniformly fatal HSV hepatitis.

Epidemiology and results of liver transplantation for acute liver failure in Chile.

Acute liver failure (ALF) is a severe, life-threatening condition associated with a high mortality rate. The objective of this study is to present the experience of a Chilean liver transplant program with orthotopic liver transplantation (OLT) for ALF. All patients with the diagnosis of ALF evaluated in our program between January 1995 and May 2003 were included in the analyses of etiology and outcomes. Candidates for OLT activated on a national waiting list were transplanted with cadaveric or living-related donor (LRD) organs. Twenty-seven patients age 1 to 19 years (median, 7.4 years) were transplanted at a median weight of 30.7 kg including 17 cadaveric and 10 with LRD livers. Most frequent etiologies were hepatitis A in 10 cases (37%) and unknown in 12 (48.1%). One donor experienced superficial phlebitis. Four patients were retransplanted (14.8%). Twenty patients are alive with 1- and 5-year survival rates of 74.1% At a median follow up of 34 months (range = 2 to 120). Seven patients died due to sepsis, multiorganic failure, graft primary nonfunction, intracranial hemorrhage, and intraoperative cardiac arrest. This experience revealed results comparable to international reports, allowing survival of patients destined to die.

Viral and clinical factors associated with the fulminant course of hepatitis A infection.

Fulminant hepatitis is a severe complication of hepatitis A virus infection. Its mechanism is unknown. Liver transplantation can be necessary, but spontaneous recovery is frequent. There are no data on the level of viral replication according to the clinical form of hepatitis A. We reviewed the files of 50 patients with acute hepatitis A. Nineteen patients had fulminant hepatitis (defined by encephalopathy and factor V <50%), and, from them, 10 patients underwent transplantation. Hepatitis A virus (HAV) RNA was quantified by real-time PCR on sera obtained at admission. The genotype was determined by phylogenetic analysis of HAV RNA. HAV RNA was detected in serum by RT-PCR in 39 out of 50 patients. Encephalopathy and low factor V level were significantly related to female gender, HAV PCR negativity (9/19 vs. 5/31, respectively; P =.03), a low serum HAV RNA level (log, 3.6 +/- 0.6 vs. 4.4 +/- 0.9, respectively; P =.02), genotypes other than IA, and acetaminophen intake. In multivariate analysis, low or undetectable HAV viral load and a high bilirubin level were independently associated with both low factor V levels and fulminant hepatitis and also with death or transplantation. In conclusion, HAV-related liver failure is due to an excessive host response associated with a marked reduction in viral load. Serum HAV RNA assay could be of help in the management of severe hepatitis A.

Acute hepatitis A virus infection: a review of prognostic factors from 25 years experience in a tertiary referral center.

BACKGROUND/AIMS: Hepatitis A is usually a mild, self-limiting illness but can result in severe or fatal disease. We reviewed 25 years experience to determine what factors predispose to severe or fatal disease. METHODOLOGY: We identified 97 patients admitted between 1974-1999 with acute hepatitis A. Clinical, biochemical and histological data were correlated with outcome and patients were screened for evidence of hepatitis B or C virus coinfection and coexisting autoimmunity. RESULTS: Fifty-five patients had liver failure with hepatic encephalopathy of whom 29 died and 6 underwent liver transplantation. Patients with liver failure were significantly older than those without (mean age: 42.2 +/- 13.3 vs. 29.2 +/- 7.8, P = 0.0001), and liver failure patients who died were older than those surviving (47.5 +/- 12.7 vs. 36.3 +/- 11.6, P = 0.0001). Hyperacute liver failure predicted good outcome (P = 0.0001). Three patients with viral coinfection had established cirrhosis and died. Detectable autoantibodies did not correlate with outcome or severity. Patients acquiring infection abroad were more likely to have liver failure than those acquiring infection in the UK (P = 0.023). CONCLUSIONS: Age is the best predictor for outcome in patients with liver failure from hepatitis A. Underlying chronic liver disease, and the time of onset of encephalopathy are also factors affecting outcome. Infection acquired abroad has a worse prognosis.

Efficacy of lamivudine for the treatment of hepatitis B virus infection after liver transplantation in children.

BACKGROUND: There is at present very little information about hepatitis B virus (HBV) infection in children after liver transplantation. This is the first study to assess the safety and efficacy of lamivudine in this patient population. METHODS: We describe three children aged 5-14 years who underwent liver transplantation for fulminant hepatitis A, hyperoxaluria, and cystic fibrosis. Despite adequate immunoprophylaxis, two of the children who were serum hepatitis B surface antigen-positive before transplantation (HBV DNA-negative by hybridization) had a reactivation of the disease, and one had a de novo HBV infection, at 12-18 months after transplantation. Lamivudine 3 mg/kg was administered on a compassionate-use basis for 14-36 months. RESULTS: After 1 month of therapy, HBV DNA disappeared from the serum in all patients by hybridization and in two patients by polymerase chain reaction. In all three children, alanine transaminase levels normalized. One child developed lamivudine resistance after 22 months with no evidence of hepatic decompensation. Repeated liver histological studies revealed progression of hepatic fibrosis in one child. All children remained serum hepatitis B surface antigen- and hepatitis B e antigen-positive. No adverse effects of the drug were noted. CONCLUSION: Lamivudine is beneficial and well tolerated in children with HBV infection after liver transplantation.

Clinical course and consequences of hepatitis A infection.

Hepatitis A virus (HAV) is a small, non-enveloped RNA virus belonging to the Picornaviridae, for which only one serotype has been identified. Transmission is usually through the faecal-oral route by person-to-person contact. The most common risk factors are household or sexual contact with a sufferer, attendance or working at a day-care centre, international travel, and association with food or waterborne outbreaks; 55% of cases have no identifiable risk factors. HAV infection may be symptomatic or asymptomatic, and shows three phases. Virus is shed during the incubation phase, anti-HAV IgM appears during the symptomatic phase and can be used for diagnosis, and anti-HAV IgG appears at the same time but persists lifelong. Unusual clinical manifestations of hepatitis A include cholestatic, relapsing and fulminant hepatitis. Hepatitis A accounts for 93% of cases of acute hepatitis in Argentina, including 7% of atypical clinical cases. Hepatitis A is the major cause of fulminant hepatitis, and has been reported to account for 10% of liver transplants in children in France and 20% in Argentina. One-year survival after liver transplantation is 64%. Prevention must be considered as the main means of averting this severe illness.

Gallbladder and pancreatic involvement in hepatitis A.

Gallbladder (GB) abnormalities are rarely reported in children, but involvement of the GB has been demonstrated in various inflammatory disorders. Thirty-nine children hospitalized with hepatitis A virus infection were evaluated by ultrasound. Pseudosurgical gallbladder wall of 10 mm or more with striation was found in 10. Pathological echographic findings were found in the pancreas of three patients, one with frank pancreatitis. Ascitic fluid was noted in eight. Pediatricians and pediatric surgeons alike should be familiar with this gallbladder and pancreatic involvement, which might avoid unnecessary procedures or surgery.

[Living-related liver transplantation--first experiences at Rabin Medical Center].

Our experience with living-related liver transplantation is described. In 2 boys and 1 girl, aged 4-4.5 years with acute, fulminating hepatitis A, the presence of very severe jaundice (bilirubin levels > 18 mg%) associated with severe coagulopathy (INR > 10) and encephalopathy indicated the need for urgent liver transplantation. In all 3 cases the left lateral hepatic segment of a matched blood type parent was transplanted. None of the donors suffered a serious complication postoperatively and all returned to full activity in 6-16 weeks. The post-transplantation course was uneventful in 1 child, but in the other 2 there was hepatic arterial thrombosis in 1 at 1 day and in the other at 8 days post-transplantation. Early detection of arterial thrombosis by Doppler sonography permitted salvage of the 2 hepatic grafts after thrombectomy and re-anastomosis. In 1 of these 2 children an anastomotic biliary stricture was found 2 months after transplantation. It was corrected at surgery and a percutaneous stent was inserted. All 3 children are alive with normal graft function at 2, 7 and 8 months post-transplantation, respectively. This initial experience indicates that living-related liver transplantation is feasible in Israel. The technique might help to solve our severe organ shortage for children awaiting liver transplantation.

Role of liver transplantation in viral hepatitis.

Liver transplantation remains difficult in end-stage liver disease caused by chronic viral hepatitis because of recurrent viral infection in the liver graft. After transplantation for chronic hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis delta virus (HDV) disease, recurrence is nearly universal. Patients with actively replicating HBV infection before transplantation appear to be the most likely to experience clinically significant recurrent hepatitis, whereas recurrence in liver transplant patients with HCV and HDV infection before transplantation seems to be less serious in the transplanted liver. At present, hepatitis B Ig immunoprophylaxis can be given to reduce the rate of HBV recurrence in liver graft. However, further studies are needed on ways to prevent and treat viral recurrence in liver transplant patients with viral hepatitis.

Clinical recurrence of hepatitis A following liver transplantation for acute liver failure.

This paper documents clinically significant recurrence of hepatitis A virus (HAV) infection in a 63-year-old man transplanted for HAV-related acute liver failure. HAV RNA was documented in the explant and, following early clearance from the blood and graft, was again detected in post-operative biopsies at the time of an acute hepatic illness. Although the clinical and biochemical abnormalities resolved completely, the patient had a second episode of graft dysfunction 6 months later and investigations revealed hepatitis C virus (HCV)-related chronic active hepatitis consistent with acquired HCV infection at the time of transplantation. The possible interaction with hepatitis A may have delayed the appearance of hepatitis C. Administration of HAV immunoglobulin at the time of transplantation should be considered in all cases of HAV-related fulminant hepatic failure.

[Temporary auxiliary orthotopic transplantation of a reduced liver for fulminant hepatitis. A successful case in a child]. / Transplantation auxiliaire orthotopique transitoire d'un foie réduit pour hépatite fulminante. A propos d'un succès chez l'enfant.

A 4 years boy with fulminant hepatitis due to virus A, underwent a temporary auxiliary liver transplantation. The graft which consisted in an adult reduced-liver, was implanted orthotopically after a left hepatectomy was performed on the recipient own liver. A good liver function was immediately restituted and the remaining native liver, that was 90% necrotic at time of transplantation, regained normal histological structure within 3 months. The auxiliary graft was then removed and immunosuppressive therapy permanently stopped.

[Experience with unilateral portalization of the adrenal and renal blood in chronic hepatitis]. / Opyt odnostoronnei portalizatsii nadpochechnikovoi i pochechnoi krovi pri khronicheskom gepatite.

An experience with treatment of 46 patients with chronic hepatitis and liver cirrhosis with the help of left-sided renoportal venous anastomosis is described. Unsuccessful therapeutic treatment is an indication to operation. In remote period after operation from 50 to 100% of clinical symptoms disappeared in 80% of the patients. Positive dynamics of the results of biochemical analyses and scanning of the liver was noted. The operation is not indicated in patients with formed cirrhosis, portal hypertension over 240 mm water column, decompensation of the liver functions.

Liver transplantation for viral hepatitis.

Current one year survival rates of 73-83% for elective transplantation, and 55-70% for emergency transplantation, render liver transplantation an appropriate treatment for both end-stage chronic liver disease and acute liver failure. Candidates for transplantation for acute liver failure need to be identified as early as possible, and a model for selection using clinical criteria is described. Recurrent viral infection after transplantation is either a possible or proven problem in all patient subgroups, but the clearest manifestation is in patients with chronic hepatitis B infection. In our series of 29 patients surviving at least 60 days after transplantation, 41% died as a consequence of recurrent infection at 3-13 months. Delta virus infection appears to confer some protection in this regard, and the role of long-term immunoprophylaxis in preventing this serious complication remains to be established.

Persistence of hepatitis A virus in fulminant hepatitis and after liver transplantation.

A peroxidase-labelled, specific mouse monoclonal antibody to hepatitis A virus (HAV) and an in situ hybridization technique (streptavidin-biotin-horseradish peroxidase reaction) with an HAV-specific cDNA probe (recombinant plasmid pAWHA comprising 1.8 kb of the HAV-specific cDNA, located toward the 3' end of the genome) were used to detect HAV in liver tissues in two patients with fulminant viral hepatitis type A treated by liver transplantation after a protracted (day 40: case 1) and relapsing (day 60: case 2) clinical course. HAV antigens and HAV-specific genomic sequences were detected in the hepatectomy tissues and in serial biopsies of the liver grafts through to final follow-up at 2 months (case 2) or death at 7 months after re-grafting for chronic rejection (case 1). In the fulminant liver parenchyma, numerous degenerating and some surviving hepatocytes were positive and randomly scattered. The immunoperoxidase staining was predominantly cytoplasmic and often granular. The localization of the cDNA probe was predominantly nuclear/perinuclear but was occasionally cytoplasmic. High-titre IgM-anti-HAV antibodies persisted until death (case 1) or resolution (5 months) of an acute hepatitis (case 2), which occurred at 2 months, accompanied by HAV antigen (ELISA), in stool. Intact replicating virus particles must have been present in one or more sites in each case, including extrahepatic locations, with a viraemia as the most likely explanation for subsequent reinfection of the grafts.

[Subfulminant hepatitis A treated by hepatic transplant]. / Hépatite subfulminante à virus A traitée par transplantation hépatique.

A case of subfulminant hepatitis A in a 3 1/2 year-old boy is reported. This child is alive after a liver transplantation. Such a procedure should modify the prognosis of severe hepatic failure whatever its origin, viral or toxic. Some practical problems concerning this new management of fulminant hepatitis are considered.