Idiopathic Chronic Hepatitis Research Articles

Copper hepatopathies in Australian dogs.

To evaluate hepatopathies in Australian dogs according to the World Small Animal Veterinary Association (WSAVA) guidelines. Specifically, to describe the prevalence and survival of dogs with copper-associated hepatopathy. Medical records from the Small Animal Specialist Hospital were reviewed to identify dogs with liver disease and liver biopsy between November 2008 and November 2021. Liver histopathology reports were reviewed with a board-certified veterinary pathologist and classified according to the WSAVA guidelines. Histopathology reports and clinical records were reviewed to ascertain the most important histological process for statistical analysis. Copper-associated hepatopathy was defined as (i) histological evidence of copper accumulation in centrilobular areas (Zone 3) associated with hepatocyte necrosis, inflammation with copper-laden macrophages and chronic hepatitis (ii) histochemical copper staining showing hepatocyte copper accumulation in the centrilobular areas and iii) hepatic copper measurement with concentrations greater than 600 μg/g dry weight of liver. Dogs with primary inflammatory parenchymal disease included dogs with copper-associated hepatopathy, idiopathic chronic hepatitis, non-specific reactive hepatitis, chronic bacterial hepatitis and immune-mediated chronic hepatitis. Descriptive statistics were performed for all dogs. Age, weight and clinicopathologic data were compared between dogs with copper-associated hepatopathy and dogs with other causes of chronic primary inflammatory parenchymal liver disease (Kruskal-Wallis test). Survival times were calculated and compared (Kaplan-Meier curves and log rank test) between dogs with copper-associated hepatopathy and dogs with other chronic primary inflammatory parenchymal liver diseases. Breed was evaluated to determine the breed most commonly affected with copper-associated hepatopathy and identify any breed in which this disease has not previously been described. Sixty-seven (43 female, 24 male) dogs with a median age of 7.8 years (quartile [Q] Q1-Q3 4.5-9.6 years) were included. Thirteen dogs had copper-associated hepatopathy, eight dogs had idiopathic chronic hepatitis, eight dogs had non-specific reactive hepatitis, seven dogs had disorders associated with portal hypertension, five dogs had chronic bacterial hepatitis and four dogs had immune-mediated chronic hepatitis. Compared with dogs with other causes of chronic primary inflammatory parenchymal liver disease, dogs with copper-associated hepatopathy tended to be younger (6.73 vs. 8.01 years, P = 0.057) and heavier (19.8 vs. 9.6 kg, P = 0.052) than dogs with other causes of primary chronic inflammatory parenchymal diseases. There was no statistically significant difference when ALT (P = 0.30), ALP (P = 0.18) and total bilirubin (P = 0.13) were compared between the two groups. The median survival time for all dogs after liver biopsy was 2010 days (CI 1321 days - not reached). There was no significant difference in survival between dogs with copper-associated hepatopathy and dogs with other causes of chronic primary inflammatory parenchymal liver disease (P = 0.5). Copper-associated hepatopathy was common among Australian dogs with chronic hepatopathies, occurring in younger and heavier dogs than other causes of primary inflammatory parenchymal liver disease. Clinical pathology is not useful for differentiating between copper-associated hepatopathy and other causes of chronic primary inflammatory parenchymal liver disease. When copper-associated hepatopathy is treated, the prognosis can be good. This is the first report of copper-associated hepatopathy in Australian Cavalier King Charles Spaniels.

Primary hypoaldosteronism in a dog with concurrent suspected chronic hepatitis

A 3-year-old female spayed English Cocker Spaniel presented with a 2-month history of lethargy. The owner reported a single tonic-clonic seizure 7 months before presentation and intermittent mild gastrointestinal signs for the past 18 months. Initial investigations revealed hyponatraemia, hyperkalaemia and increased levels of liver enzymes. An adrenocorticotropic hormone stimulation test excluded hypocortisolism. The gastrointestinal signs resolved following a dietary change, suggesting that chronic enteropathy and most primary and secondary causes of hepatic disease were excluded, leaving idiopathic chronic hepatitis as the most likely cause of increased levels of liver enzymes. Liver parameters reduced to levels just above reference range after immunosuppressive doses of prednisolone. Aldosterone levels pre- and post-adrenocorticotrophic hormone stimulation were <20 pmol/litre, consistent with mineralocorticoid deficiency. The mineralocorticoid deficiency was treated with desoxycorticosterone pivalate at 1–1.3 mg/kg subcutaneously every 48–87 days, which resulted in immediate and complete resolution of the clinical signs and electrolyte imbalance. Given the dog's signalment and results from clinical investigations, the isolated hypoaldosteronism is speculated to be caused by immune-mediated adrenal gland destruction. Isolated hypoaldosteronism should be considered a differential diagnosis for hyponatraemia in dogs, when an adrenocorticotrophic hormone stimulation test excludes hypocortisolism.

Mycophenolate mofetil as a treatment for presumed idiopathic chronic hepatitis in dogs: Six cases (2010-2022).

The objectives of this study were to describe the clinical findings, treatment and outcomes of six dogs with presumed idiopathic chronic hepatitis treated with mycophenolate mofetil (MMF). Medical records were retrospectively searched to identify dogs in which idiopathic chronic hepatitis was diagnosed on histopathology between January 2010 and June 2022 that were treated with MMF for at least two weeks with >2 follow-up examinations. Data recorded from each dog included signalment, clinical signs, diagnostic test results and treatment. Six dogs were treated with MMF at a median initial dosage of 9.6mg/kg PO q 12h. Reported adverse effects from MMF included decreased appetite, vomiting and diarrhoea. In all six dogs, MMF was used successfully long term for the treatment of idiopathic chronic hepatitis as determined by 46% or greater improvement of alanine aminotransferase (ALT) between 4 and 18 weeks of starting MMF. Three dogs were also temporarily treated for 4-6 months on a tapering dose of prednisone. In two dogs, ALT remained within the reference interval, and in one dog, it was very mildly elevated when on MMF alone. In all six dogs, owners reported that the medication was well tolerated. To the authors' knowledge, this is the first report describing the use of MMF with and without a tapering dose of prednisone for the treatment of idiopathic chronic hepatitis in six dogs. Based on the outcomes of the dogs in this report, MMF can be effective for the long-term treatment of idiopathic chronic hepatitis as measured by reduction in ALT and improvement of clinical signs.

Predictive Factors for Two-Year Survival in Dogs with Hepatobiliary Diseases: Importance of Clinical and Laboratory Monitoring.

Long-term outcomes and survival predictors for different clinicopathologies (idiopathic chronic hepatitis, liver fibrosis, vacuolar hepatopathy) in dogs with hepatobiliary diseases are poorly described. In this study, ninety dogs were followed up for up to five years to investigate clinical factors that predict two-year survival in canine patients after liver biopsy. Univariate and multivariate analyses were performed based on clinical and laboratory data to determine the association between clinical and laboratory data and mortality rates. Overall, the one-, two-, and five-year mortality rates were 28.9%, 45.6%, and 78.9%, respectively. Univariate analysis indicated that male gender, ascites, elevated serum gamma-glutamyl transpeptidase (GGT), hypercholesterolemia, hypoalbuminemia, prolonged activated partial thromboplastin clotting time (aPTT), and prolonged thrombin clotting time (TT) were associated with an increased two-year mortality rate. Results from multivariate analysis demonstrated a significant association between male gender (p = 0.022), elevated serum GGT (p < 0.001), hypoalbuminemia (p < 0.001), and prolonged aPTT (p < 0.001) and an increased two-year mortality rate, regardless of the specific type of liver pathology. Elevated GGT was associated with the highest risk for increased two-year mortality (95% CI: hazard ratio 6.02-41.21). In conclusion, various clinical factors in dogs with liver diseases are useful for prognosis prediction.

Hepadnavirus DNA Is Detected in Canine Blood Samples in Hong Kong but Not in Liver Biopsies of Chronic Hepatitis or Hepatocellular Carcinoma.

Chronic hepatitis and hepatocellular carcinoma (HCC) caused by the hepadnavirus hepatitis B virus (HBV) are significant causes of human mortality. A hepatitis-B-like virus infecting cats, domestic cat hepadnavirus (DCH), was reported in 2018. DCH DNA is hepatotropic and detectable in feline blood or serum (3.2 to 12.3%). Detection of HBV DNA has been reported in sera from 10% of free-roaming dogs in Brazil, whereas 6.3% of sera from dogs in Italy tested positive for DCH DNA by real-time quantitative PCR (qPCR). If DCH, HBV, or another hepadnavirus is hepatotropic in dogs, a role for such a virus in the etiology of canine idiopathic chronic hepatitis (CH) or HCC warrants investigation. This study investigated whether DCH DNA could be detected via qPCR in blood from dogs in Hong Kong and also whether liver biopsies from dogs with confirmed idiopathic CH or HCC contained hepadnaviral DNA using two panhepadnavirus conventional PCRs (cPCR) and a DCH-specific cPCR. DCH DNA was amplified from 2 of 501 (0.4%) canine whole-blood DNA samples. A second sample taken 6 or 7 months later from each dog tested negative in DCH qPCR. DNA extracted from 101 liver biopsies from dogs in Hong Kong or the USA, diagnosed by board-certified pathologists as idiopathic CH (n = 47) or HCC (n = 54), tested negative for DCH DNA and also tested negative using panhepadnavirus cPCRs. This study confirms that DCH DNA can be detected in canine blood by qPCR, although at a much lower prevalence than that reported previously. We identified no evidence to support a pathogenic role for a hepadnavirus in canine idiopathic CH or HCC.

Prednisolone therapy for chronic hepatitis in English springer spaniels: a prospective study of 12 cases

BackgroundEnglish springer spaniels (ESS) show an increased risk of chronic hepatitis (CH). In a previous study of 68 ESS with CH, in which only one dog received corticosteroids, a median...

Retrospective evaluation of cyclosporine in the treatment of presumed idiopathic chronic hepatitis in dogs.

BackgroundThe etiology of idiopathic chronic hepatitis (ICH) in dogs is poorly understood, but evidence supports an immune‐mediated pathogenesis in some dogs.ObjectivesTo describe a case series of dogs with presumed ICH treated with cyclosporine (CsA) with or without concurrent medications and to document the incidence of biochemical remission and factors associated with failure to attain remission.AnimalsForty‐eight client‐owned dogs diagnosed with presumed ICH, treatment of which included CsA.MethodsTwo‐institution, retrospective case series of dogs between 2010 and 2017. All dogs were treated with CsA with or without concurrent medications for ≥2 weeks. Data were collected from medical records.ResultsBiochemical remission (<1.1 times the upper limit of normal for alanine aminotransferase activity) was attained in 79% of dogs (38/48). Median dose of CsA at remission was 7.9 mg/kg/d (range, 2.5‐12.7 mg/kg/d) and median time to remission was 2.5 months (range, 0.75‐18 months). Concurrent hepatoprotectant treatment was not associated with likelihood of remission. Clinical score, ascites, hypoalbuminemia, hyperbilirubinemia, prolonged coagulation times, dose, and duration of treatment were not associated with the probability of remission or time to remission. Common adverse effects of CsA were gastrointestinal signs in 38% (18/48) and gingival hyperplasia in 25% (12/48) of treated dogs.Conclusion and Clinical ImportanceA treatment regimen including CsA and frequent hepatoprotectant use resulted in biochemical remission of ICH in most dogs. None of the evaluated factors, including hepatoprotectant use, were significantly associated with likelihood of remission. Future prospective studies are indicated to evaluate CsA monotherapy in ICH dogs.

Clinical Impact of Liver Biopsies in Liver Transplant Recipients

BACKGROUND Percutaneous liver biopsy is an established diagnostic procedure for the assessment of liver pathologies. Limited data are available on the clinical impact of liver biopsies in liver transplant recipients. MATERIAL AND METHODS Liver transplant recipients undergoing liver biopsy between 2000 and 2013 were analyzed. Demographic characteristics and transplantation data were extracted from the transplantation database. RESULTS A total of 496 liver biopsies were performed in 312 patients. The main biopsy indications were suspected rejection (66%, 327/496), protocol biopsy (22%, 108/496), and suspected recurrence of the primary disease (7%, 34/496). Histological findings showed acute cellular rejection in 36% (179/496), idiopathic chronic hepatitis in 28% (141/496), and normal histology in 11% (54/496). Liver biopsies in patients with clinically suspected rejection showed histological findings compatible with acute or chronic rejection in 46% (151/327). In 41% (205/496) of the patients, the immunosuppressive therapy was adjusted due to the biopsy result. For alanine-aminotransferase and bilirubin, significant differences were detected between baseline and week 4 and 12 after treatment modification (p<0.05). CONCLUSIONS Liver biopsies in liver transplant recipients have potential impact on the modification of the immunosuppressive therapy. The correlation between suspected rejection and histological findings is limited; therefore, a liver biopsy is indicated in unclear cases.

Total serum bilirubin as a negative prognostic factor in idiopathic canine chronic hepatitis

Total serum bilirubin (TBIL) is used as a prognostic factor in chronic hepatitis (CH) in human beings. To date, the authors are unaware of any studies looking at the value of TBIL as a prognostic factor in idiopathic canine CH. The objective of the current study was to assess if TBIL is a negative prognostic factor in idiopathic canine CH, and to identify other prognostic factors. Thirty-nine dogs with histologically confirmed idiopathic CH admitted to 2 referral centers between 1999 and 2010 were included in the study. Patients with concurrent diseases that could affect TBIL or the survival time were excluded. Total serum bilirubin was measured prior to liver biopsy, and CH was diagnosed according to standardized histological criteria. Survival time was calculated from time of diagnosis to time of death or euthanasia. Cox proportional hazard analysis was performed to identify prognostic factors. The mean survival time for the 39 dogs included in the analysis was 197 days (1-2,677), and the mean total serum bilirubin was 11 μmol/l (2-265). Total serum bilirubin was statistically significantly associated with survival (odds ratio = 1.082, P = 0.047) as were weight (odds ratio = 1.028, P = 0.028) and the presence of ascites (odds ratio = 6.758, P = 0.013). The current study demonstrates that TBIL could be used as an additional prognostic factor in canine CH.

A retrospective study of oral prednisolone treatment in canine chronic hepatitis

Background: Only one study reports prednisone to prolong survival in dogs with chronic hepatitis irrespective of the causative agent. The aim of this retrospective study was to investigate the effects of prednisolone treatment on survival, clinicopathological variables, and histological grade and stage of idiopathic chronic hepatitis in 36 dogs.Animals and methods: Medical records were reviewed of 36 prednisolone-treated dogs (median age: 8.6 years; range: 2.0–14.6 years) with chronic hepatitis not associated with primary copper accumulation. Clinicopathological results were analyzed pair-wise for 20 dogs, before and after oral prednisolone administration (1 mg/kg BW/day). Dogs were treated for at least 6 weeks, and for an additional 6 weeks if hepatitis was still present at rebiopsy. Follow-up data pertaining to clinical outcome and survival time (Kaplan–Meier estimate procedure) were analyzed.Results: At the follow-up, 11 dogs were in complete remission, 8 dogs had recurrent clinical signs, and 17 dogs had residual disease. Despite treatment, 20 dogs died of hepatitis-related causes. Dogs without cirrhosis survived significantly longer than dogs with cirrhosis. Prednisolone treatment normalized coagulopathies associated with chronic idiopathic hepatitis within one week in all 10 dogs that had coagulopathies at initial diagnosis.Conclusions: Our findings suggest that prednisolone has, in part, beneficial effects on hepatic inflammation and that it may, at least in some cases, limit the progression of fibrosis, which emphasizes the importance of early diagnosis and treatment. We did not see any benefit of prednisolone treatment for dogs with cirrhosis. We could document a highly favorable effect of prednisolone treatment on the coagulopathy associated with canine chronic idiopathic hepatitis.

The Impact of Donor Specific Antibodies on the Long-Term Liver Allograft after Pediatric Living Donor Liver Transplantation

Introduction: The protocol biopsies of liver allograft revealed that some pediatric liver transplant recipients on the way of weaning of immunosuppressants (IS) showed fibrosis in their liver allograft though their blood examination indicated normal liver function tests. The method of evaluation for immunological state against donor-derived alloantigens after liver transplantation has not been established yet. The absence of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) has been expected as a promising biomarker for safe withdrawal of IS. In this study, we analyzed DSA in sera and the pathological findings of liver biopsies more than 12 months after pediatric living donor liver transplantation (LDLT) to elucidate the relevance of DSA against HLA to the late post-transplant liver allograft. Methods: 75 pediatric LDLT recipients were undertaken liver biopsies more than 12 months after operation in 2011; including 73 protocol biopsies and 2 episode biopsies. DSA in sera from those recipients were determined and quantified by single antigen beads method, where mean fluorescence intensity (MFI) over 1,000 was considered as positive. In pathological findings, each evaluation was blindly conducted by pathologists, and fibrosis was graded following Metavir fibrosis socring system. Results: Thirty-two recipients showed DSA in sera; the numbers of recipients with DSA against HLA class I, HLA class II, and both HLA calss I and class II (DSA-positive) were 2, 28, and 2, respectively, while 43 recipients did not show DSA (DSA-negative). MFI of DSA against HLA class I was not high; median 3520, (range 1170-6310). On the other hand, MFI of DSA against HLA Class II showed high; HLA-DRB1 9356, (2216-23140) and HLA-DQB1 20844, (2862-24834). The pathological findings of DSA-negative recipients were no remarkable finding in 14 (32.6%), idiopathic chronic hepatitis in 2 (4.7%), fibrosis in 20 (46.5%), and rejection including acute cellular rejection, late acute rejection, and central perivenulitis in 7 (16.3%). On the other hand, those of DSA-positive recipients were no remarkable finding in 1 (3.1%), fibrosis in 17 (53.1%) and rejection in 13 (40.6%). Most of normal finding of liver biopsy were showed in DSA-negative recipients. (p=0.002) The frequency of rejection was significantly higher in DSA-positive recipients than DSA-negative. (p=0.009) The fibrosis graded more than F2 was observed in 7 of DSA-negative (16.3%) and 12 of DSA-positive recipients (37.5%). (p=0.037) Conclusion: The existence of DSA in sera from pediatric LDLT recipients more than 12 months after operation has been related to severe fibrosis and allo-immune responses, such as acute cellular rejection and central perivenulitis. The measurement of DSA suggests that immunosuppressive therapy should be maintained or strengthened for DSA-positive recipients.

The Impact of Donor Specific Antibodies on the Long-Term Liver Allograft after Pediatric Living Donor Liver Transplantation

Introduction: The protocol biopsies of liver allograft revealed that some pediatric liver transplant recipients on the way of weaning of immunosuppressants (IS) showed fibrosis in their liver allograft though their blood examination indicated normal liver function tests. The method of evaluation for immunological state against donor-derived alloantigens after liver transplantation has not been established yet. The absence of donor-specific antibodies (DSA) against human leukocyte antigens (HLA) has been expected as a promising biomarker for safe withdrawal of IS. In this study, we analyzed DSA in sera and the pathological findings of liver biopsies more than 12 months after pediatric living donor liver transplantation (LDLT) to elucidate the relevance of DSA against HLA to the late post-transplant liver allograft. Methods: 75 pediatric LDLT recipients were undertaken liver biopsies more than 12 months after operation in 2011; including 73 protocol biopsies and 2 episode biopsies. DSA in sera from those recipients were determined and quantified by single antigen beads method, where mean fluorescence intensity (MFI) over 1,000 was considered as positive. In pathological findings, each evaluation was blindly conducted by pathologists, and fibrosis was graded following Metavir fibrosis socring system. Results: Thirty-two recipients showed DSA in sera; the numbers of recipients with DSA against HLA class I, HLA class II, and both HLA calss I and class II (DSA-positive) were 2, 28, and 2, respectively, while 43 recipients did not show DSA (DSA-negative). MFI of DSA against HLA class I was not high; median 3520, (range 1170-6310). On the other hand, MFI of DSA against HLA Class II showed high; HLA-DRB1 9356, (2216-23140) and HLA-DQB1 20844, (2862-24834). The pathological findings of DSA-negative recipients were no remarkable finding in 14 (32.6%), idiopathic chronic hepatitis in 2 (4.7%), fibrosis in 20 (46.5%), and rejection including acute cellular rejection, late acute rejection, and central perivenulitis in 7 (16.3%). On the other hand, those of DSA-positive recipients were no remarkable finding in 1 (3.1%), fibrosis in 17 (53.1%) and rejection in 13 (40.6%). Most of normal finding of liver biopsy were showed in DSA-negative recipients. (p=0.002) The frequency of rejection was significantly higher in DSA-positive recipients than DSA-negative. (p=0.009) The fibrosis graded more than F2 was observed in 7 of DSA-negative (16.3%) and 12 of DSA-positive recipients (37.5%). (p=0.037) Conclusion: The existence of DSA in sera from pediatric LDLT recipients more than 12 months after operation has been related to severe fibrosis and allo-immune responses, such as acute cellular rejection and central perivenulitis. The measurement of DSA suggests that immunosuppressive therapy should be maintained or strengthened for DSA-positive recipients.

Transient elastography identifies liver recipients with nonviral graft disease after transplantation: A guide for liver biopsy

Transient elastography (TE) reliably predicts the severity of recurrent hepatitis C virus after orthotopic liver transplantation (OLT); however, its accuracy in evaluating nonviral liver graft damage is unknown. Between 2006 and 2009, 69 OLT recipients [37 for hepatitis B virus/hepatitis D virus (recurrence-free), 20 for autoimmune/cholestatic liver disease, 6 for alcoholic liver disease, and 6 for mixed etiologies] underwent protocol/on-demand liver biopsy (LB) and concomitant TE. A histological diagnosis of graft disease was made according to criteria defined by the Banff working group. Sixty-five patients (94%) had reliable TE examinations during a median post-OLT follow-up of 18 months (range = 7-251 months). LB samples (median length = 35 mm) showed graft damage in 28 patients (43%): idiopathic chronic hepatitis (11), steatohepatitis (3), rejection (3), cholangitis (2), and autoimmune/cholestatic recurrence (9). Patients with graft damage had significantly higher serum liver enzyme levels and TE results (median = 7.8 kPa, range = 5.4-27.4 kPa) than the 37 patients without graft damage (median = 5.3 kPa, range = 3.1-7.4 kPa, P < 0.001). By a receiver operating characteristic curve analysis, 2 TE cutoffs for the diagnosis of graft damage were identified: 5.3 kPa with 100% sensitivity and 7.4 kPa with 100% specificity. The pretest probability of graft damage was 43%; in patients with TE values ≤5.3 kPa, the posttest probability of graft damage fell to 0%, but in patients with TE results >7.4 kPa, the posttest probability increased to 100%. In conclusion, the dual TE cutoff allows accurate discrimination between the absence and presence of nonviral liver graft damage and improves the clinical management of OLT recipients in terms of the selection of patients most in need of LB.

The long-term liver graft and protocol biopsy

Histological abnormalities are commonly present in late posttransplant biopsies. Many of these changes are seen in recipients who are clinically well with good graft function. This review includes discussion of a small number of studies published within the past 18 months and details future directions in this area of research. An analysis of protocol liver biopsies in adult liver allograft recipients revealed normal or near normal histology in less than one third of recipients. Idiopathic chronic hepatitis (not related to disease recurrence) was present in 33%. Interpreted in light of the calculated creatinine clearance, the histological findings led to a documented change in immunosuppression in 32% of the recipients studied. Another study that assessed the natural history of graft fibrosis after pediatric liver transplantation revealed that fibrosis was strongly related to transplant-related factors, and that by 10 years following liver transplantation, the severity had progressed in 25% of the studied recipients. Current studies suggest protocol liver biopsies may provide important histological information about graft function that is not available from standard liver tests and may allow modification of immunosuppression to ensure long-term side-effects of drug therapy are minimized while graft function is maintained.

Liver allograft pathology: approach to interpretation of needle biopsies with clinicopathological correlation

The spectrum of diseases encountered in post-transplant liver pathology biopsies is broad. In this review, these have been divided as belonging to one of three categories: (1) new-onset/de novo post-transplant...

Transplantationspathologie der Leber

Histopathology plays an important role in the diagnosis of graft complications following liver transplantation (LTX) and includes the diagnosis of underlying liver disease, assessment of the donor liver before LTX and control biopsies after LTX. Within the early period after LTX (time zero and first month) preservation/reperfusion injury, as well as hyperacute and acute rejection may occur. Surgical vascular or biliary complications can cause parenchymal morphological changes. Within 12 months following LTX, histological signs of opportunistic infections and chronic rejection are frequent findings and disease recurrence is typical beyond the first year. Drug toxicity in liver allograft recipients can be induced by immunosuppressive therapy or other drugs. A high percentage of adult patients reveal histological features of idiopathic chronic hepatitis 6 months after LTX. Histopathological differential diagnosis of the combined underlying causes or complications is often difficult.

Pathology of liver transplantation

Summary Liver transplantation has been increasingly used over the past four decades as an effective treatment for end-stage liver disease. Although the demand exceeds the supply of cadaveric organs, the donor pool has expanded with the increasing use of split-liver grafts, non-heart-beating donor livers and living-related donors. Histopathologists play a role in the pre-transplant and post-transplant period; their input is crucial in both identifying and monitoring post-transplant complications. The degree of acute cellular rejection is best assessed histologically, and biopsy interpretation informs changes to the immunosuppressive regimen. Chronic rejection is characterised by progressive ductopenia; a number of lesions have been identified that predict the likelihood of progression to chronic rejection. Other post-transplant complications readily assessed on liver core biopsies include vascular and biliary complications, infectious, recurrent and de novo disease. De novo hepatitis with ‘autoimmune' features is described as is idiopathic chronic hepatitis, but the relationship of these lesions to alloimmune pathways remains uncertain. Although liver transplantation is generally performed in specialist centres, an increasing number of histopathologists working in non-specialist units are being exposed to post-transplant biopsies and need to be aware of the spectrum of changes that can occur.

Current concepts in the treatment of canine chronic hepatitis

Chronic hepatitis is a common disorder in dogs seen by general practitioners. Several new drugs have been marketed for treating this disease. Unfortunately, there are few controlled studies that examine the efficacy of these medications for the treatment of canine chronic hepatitis. A rational therapeutic approach can be implemented based on histopathologic findings of a liver biopsy. A liver biopsy is essential for establishing a definitive diagnosis and guiding the optimal therapy. The biopsy allows characterizing the inflammatory process, quantitating hepatic copper concentrations, and determining if fibrosis is present. Copper associated hepatopathy is treated with zinc and copper chelators. Idiopathic chronic hepatitis is thought to be immune mediated. The treatment of idiopathic chronic hepatitis consists of controlling inflammation (prednisone, azathioprine), reversing fibrosis (colchicine), and protecting against oxidant damage (vitamin E, ursodeoxycholic acid, S-adenosylmethionine). The prognosis for chronic hepatitis is quite variable. Dogs with end-stage disease have a poor prognosis, while dogs diagnosed earlier can have a mean survival of years. Early diagnosis and intervention are key to the successful treatment of dogs with chronic hepatitis.

TTV-DNA IN SERA OF PAEDIATRIC PATIENTS WITH CRYPTOGENIC HEPATITIS

11 Background Recently a new DNA virus has been reported in patients with posttransfusion hepatitis of unknown etiology, in blood donors and in patients with cryptogenic cirrhosis and fulminant hepatic failure. Neverthless the several reports, it is not yet clear the role of TTV in the pathogenisis of acute and chronic liver disease. Furthermore, there are no data on the role of TTV in paediatric patients with cryptogenic hepatitis. Patients and Methods Stored sera of eight children (age, range: 4-10 years) who referred to our Department for cryptogenic hepatitis were retrospectively studied. All patients had no serological markers for A-G hepatitis, HIV, TORCH, EBV. Metabolic and genetic causes of liver disease were also excluded. TTV DNA was extracted from serum samples using DNAzol reagent. Semi-nested PCR was used to amplify 279 bp of TTV DNA, as previously described by Naoumov NV et al. Results TTV-DNA has been found in all sera tested from one out eight children studied. The patient presented in 1996 at the age of four years old for cryptogenic hepatitis and associated extrahepatic symptoms, namely arthritis, myositis, skin rush, recurrent fever and weight loss. Liver biopsy showed the histological picture of mild chronic hepatitis and mild bile duct proliferation. Any therapeutic attempt with steroidal and non-steroidal anti-inflammatory agents was without benefit on the hepatic and systemic symptoms. The enteral nutrition with elemental formulas, established for the appearance of abdominal pain and gastrointestinal signs of inflammatory bowel disease, resulted effective in restoring nutritional status but did not significantly affect the hepatic function. Conclusions The TTV-DNA was detected in a child with a clinical history of idiopathic chronic hepatitis and associated autoimmune extrahepatic symptoms. Further follow-up and evaluation will be necessary to clarify the exact role of TTV in the pathogenesis of hepatic and extrahepatic manifestations in this patients, especially for a more appropriate therapeutic approach. Larger investigations of TTV in paediatric patients with posttransfusional and cryptogenic hepatitis are required.

Hepatitis C virus-related chronic liver disease with autoantibodies to liver-kidney microsomes (LKM): Clinical characterization from idiopathic LKM-positive disorders

This study was carried out on 33 patients who were sero-positive for liver-kidney microsomal antibodies (LKM) in order to examine clinical features and the presence of underlying hepatitis C virus infection. Twenty-four sera were positive for antibodies against HCV (anti-HCV) as detected by enzyme immunoassay and confirmed by recombinant immunoblot assay. These patients had chronic liver disease and the majority of those treated with interferon responded favourably. Three of the nine anti-HCV-negative patients had idiopathic chronic hepatitis and two responded favourably to steroids. Two patients were diagnosed as having toxic hepatitis and the other four had various extrahepatic disorders without evidence of liver involvement. The immunoblotting analysis showed reactivity with a 50 kDa microsomal protein which presumably corresponded to cytochrome P-450 db1 both in anti-HCV-positive and -negative sera. In addition a few anti-HCV-positive sera also reacted with a 35 kDa microsomal antigen. Autoimmune markers different from LKM were absent in both groups. The high prevalence of antibodies to the hepatitis C virus among LKM-positive sera confirms that this infection plays a role in forms of chronic hepatitis that had previously been labelled autoimmune. In patients with LKM the presence of anti-HCV may help to forecast a therapeutic response to interferon, while its absence may forecast response to steroid therapy.