Clinical value and safety of liver biopsies in patients transplanted for hepatitis C virus-related end-stage liver disease.

BACKGROUND: Hepatitis C is the leading indication for liver transplantation. Differentiation between recurrent graft hepatitis C (RGH-C) and graft rejection (GR) is challenging. Liver biopsy is standard to diagnose both conditions; however, little information is available regarding this procedure in hepatitis C virus (HCV)-infected liver transplant recipients. METHODS: Liver biopsies (n = 211) from all consecutive patients (n = 138) transplanted for hepatitis C at Hannover Medical School between January 2000 and October 2011 were screened, and a final cohort of 96 patients with 196 biopsies was included. Indications, histopathological findings, and biopsy-related complications were documented. Modifications in the treatment based on the biopsy result and the biochemical outcome were analyzed. RESULTS: Most biopsies (196/211, 93%) were representative. Five patients (2.5%) developed non-fatal biopsy-related complications. Biopsy results were GR (35%), RGH-C (31%), and other diagnoses (34%). GR was independently associated with lower albumin (P = 0.025) and higher bilirubin levels (P = 0.011). Treatment was modified based on the biopsy result in 25% of cases. Alanine aminotransferase (ALT), gamma-glutamyl transferase (GGT), and bilirubin levels improved in 41%, 25%, and 31% of cases 4 weeks post biopsy respectively. ALT improvements were more significant in patients with GR than in those with RGH-C. CONCLUSION: Liver biopsy in HCV-infected liver transplant recipients is safe and representative in >90% of cases. GR is independently associated with lower albumin and higher bilirubin levels.

Hepatitis C virus core antigen testing in liver and kidney transplant recipients.

HCV RNA levels correlate with the long-term outcome of hepatitis C in liver transplant recipients. Nucleic acid testing (NAT) is usually used to confirm HCV reinfection and to examine viral loads after liver transplantation. HCV core antigen (HCVcoreAg) testing could be an alternative to NAT with some potential advantages including very low intra- and interassay variabilities and lower costs. The performance of HCVcoreAg testing in organ transplant recipients is unknown. We prospectively studied 1011 sera for HCV RNA and HCVcoreAg in a routine real-world setting including 222 samples obtained from patients after liver or kidney transplantation. HCV RNA and HCVcoreAg test results showed a consistency of 98% with a very good correlation in transplanted patients (r > 0.85). The correlation between HCV RNA and HCVcoreAg was higher in sera with high viral loads and in samples from patients with low biochemical disease. Patients treated with tacrolimus showed a better correlation between both parameters than individuals receiving cyclosporine A. HCV RNA/HCVcoreAg ratios did not differ between transplanted and nontransplanted patients, and HCV RNA and HCVcoreAg kinetics were almost identical during the first days after liver transplantation. HCVcoreAg testing can be used to monitor HCV viral loads in patients after organ transplantation. However, the assay is not recommended to monitor antiviral therapies.

Enrichment of regulatory T cells in acutely rejected human liver allografts.

Acute cellular rejection (ACR) occurs frequently after liver transplantation and can usually be controlled. Triggering of allospecific immune responses and lack of immunoregulation are currently suggested as a cause of ACR, but there are no investigations of intrahepatic immune responses during ACR. Therefore we prospectively analyzed the intrahepatic T cell infiltration pattern in correlation to the severity of ACR in a cohort of patients with graft hepatitis (n = 151). While CD4(+) cells dominated the portal infiltrates in mild-moderate ACR, CD8(+) cells prevailed in severe ACR. Furthermore portal CD8(+) and not CD4(+) infiltration correlated with serum transaminases and with the likelihood of subsequent ACRs. Surprisingly, the rise of portal effector T cells density during ACR was surpassed by the increase in portal infiltration of regulatory T cells by a factor of two. Thus ACRs rather showed an increase and not a lack of regulation, as was suggested by analysis of peripheral blood mononuclear cells. Despite the pattern of enhanced immunoregulation, patients with severe ACR had a higher risk for subsequent rejections and showed a trend to a reduced survival. Thus, patients with severe rejections might need a modification of their immunosuppression to improve prognosis.

[CMV-enterocolitis as a cause for repeated intestinal intussusceptions in an adult patient after liver transplantation?]. / CMV-Enterokolitis bei einer erwachsenen lebertransplantierten Patientin als Ursache rezidivierender Invaginationen?

Intestinal intussusception in the adult is often idiopathic but also known to be associated with chronic inflammatory bowel disease, coeliac disease, tumours or previous abdominal operations. A 22-year-old women after liver transplantation due to Crigler Najar Syndrome suffered from repeated episodes of abdominal pain. The diagnosis of repeated self-limited intestinal intussusceptions was made by computed tomography and ultrasonography. A laparoscopy revealed no cause for the intussusceptions. During a new episode of abdominal pain caused again by an intussusception a colonoscopy was performed that showed aspects of a discreet colitis. In the biopsies CMV was detected by qualitative PCR, while blood tests for CMV pp65 antigen were negative. A therapy with gancyclovir was initiated which lead to remission of the patient's symptoms. A colonoscopy six weeks later showed a completely normal colon, while in the biopsies CMV was not detectable. After a follow-up of one year the patient has not suffered from any further episodes. This case demonstrates the role of chronic intestinal CMV infection as a possible causative factor for repeated intussusceptions in immunosuppressed patients. Whenever possible a PCR for CMV in colon biopsies should be carried out to detect an intestinal CMV infection because as shown in our case results for immunohistopathology and CMV pp65 can be negative despite a chronic infection.

Fulminant hepatic failure due to chemotherapy-induced hepatitis B reactivation: role of rituximab.

Hepatitis B virus reactivation during immunosuppressive therapies can lead to liver failure with very limited treatment options available. We report here on two cases of severe hepatitis B reactivation during chemotherapy including rituximab for B cell lymphoma which were treated with liver or liver-cell transplantation. Liver function was normal and HBV infection was unknown in both patients before chemotherapy was started. Impaired liver function became apparent after 4 and 6 courses of chemotherapy, respectively, and both patients experienced fulminant hepatic failure despite antiviral treatment with lamivudine or entecavir. Patient A underwent liver transplantation after documentation of complete remission of the lymphoma and survived without any evidence for hepatitis B recurrence. Patient B received 4 courses of hepatocyte transplantation but did not survive. These cases underline the importance of anti-HBc screening in patients receiving immunosuppressive treatments in particular when rituximab is given. Pre-emptive antiviral treatments should be administered since delayed antiviral treatment is frequently unable to prevent liver failure.

[Quality assurance and teamwork in social medicine expert assessment exemplified by the expert assessment aid "corrective breast surgery" of the North Rhine Health Insurance Medical Service]. / Qualitätssicherung und Mitarbeiterpartizipation in der Sozialmedizinischen Begutachtung am Beispiel der Begutachtungshilfe "korrektive Mamma-Chirurgie" des MDK Nordrhein.

To standardise sociomedical expertising procedures in surgery of the breast a project team of medical advisors of the Medical Advisory and Expertising Service North Rhine worked out a manual. A form was created for sociomedical pre-advice occasions. Detail parameters for examination (time needed and advisor selection) were fixed in consent. Checklists were worked out, which may be admitted to quality assurance procedures. The manual "Medical opinion for surgery of the breast" has been implemented and is applied in the Medical Advisory and Expertising Service North Rhine since January 1999. In the sense of teamwork participation those who were involved as team-workers became participants in decision-making. The manual "Medical opinion for surgery of the breast" may be seen as an example of quality assurance and participation in socio-medical opinion procedures. The influence of this manual on the formal quality of medical opinion will be checked.

[Symptomatic compression of the vena cava caused by a small liver hemangioma]. / Symptomatische Kompression der Vena cava durch ein kleines Leberhämangiom.

Occasioned by a recurrent urinary infection, ultrasonography was performed on a 41-year-old otherwise healthy woman. There were no abnormal renal findings, but a 4.5 x 4.5 cm space-occupying lesion with the echo-typical pattern of an haemangioma was found in the right lobe of the liver. Magnetic resonance imaging and dynamic computed tomography demonstrated compression of the vena cava by the tumour which was localized to the caudate lobe. The T2-weighed pictures suggested a cavernous haemangioma which extended from the vena cava at the diaphragm to the portal vein bifurcation. Obstruction to flow became evident 10 months later as oedema of the lower legs, giving the indication for surgical removal of the haemangioma. The benign tumour was enucleated under total vascular occlusion without significant blood loss pre- and post-operatively. The patient was discharged symptom-free on the 13th postoperative day.

[Percutaneous drainage of abscesses, biliomas, seromas and hematomas following liver surgery. Experiences with 46 patients]. / Die perkutane Ableitung von Abszessen, Biliomen, Seromen und Hämatomen nach leberchirurgischen Eingriffen. Erfahrungen bei 46 Patienten.

Fifty-two fluid collections following hepatic surgery were diagnosed in 46 patients, mostly by sonography. These were treated percutaneously. In 7 patients ultrasound-guided puncture was used, in 36 patients catheter drainage was employed and in three drainage was instituted by a catheter in a pre-existing fistula. One patient with a bile leak in the hilar region had to undergo surgery. One patient died of multi organ failure following liver transplantation and another patient with advanced tumour died 78 days after the drainage procedure. The other patients recovered following conservative treatment (93.5%).

Unusually rapid development of a HBsAG-positive liver cirrhosis after liver transplantation.

We report the case of a 44-year-old man who was transplanted in 1986 for hepatocellular carcinoma in a HBsAG-positive liver cirrhosis. The patient had no severe complications postoperatively. He received passive immunization for the prevention of hepatitis B reinfection during the first 6 months after liver grafting. Twelve months after the transplantation the new liver was reinfected with hepatitis B virus. Without any clinical or laboratory signs of severe hepatitis, the patient developed a histologically proven complete liver cirrhosis within 8 months after reinfection of the graft. The reasons for this might have been, first, a deleterious course of the infection under immunosuppressive therapy, and, second, the additional influence of a postoperatively acquired CMV infection or the combined toxic influence of cyclosporin A and its metabolites on the acute inflammation in the liver.

[Surgery of benign liver tumors]. / Chirurgie bei benignen Lebertumoren.

The most frequent benign liver tumors are hemangioma, focal nodular hyperplasia (FNH) and adenoma. It is essential for the diagnosis to differentiate these lesions from malignant tumors. While sonography, bolus-CT scan, chole-/bloodpool scintigraphy usually yield a safe diagnosis of hemangioma or FNH, adenomas do not show characteristic features. Operation is indicated for hemangioma of FNH only in case of tumor growth and/or symptoms. Operation for adenoma is as a rule indicated because of possible malignant transformation or uncertain differentiation from malignoma. Operative procedures include anatomical/atypical liver resection, ex situ resection or liver transplantation.