Liver transplantation for hepatitis B-induced liver disease: long-term outcome and effectiveness of antiviral therapy for prevention of recurrent hepatitis B infection.

OBJECTIVE: The aim of this study was to examine the efficacy of preoperative, perioperative, and long-term treatment in liver transplant (OLT) patients suffering hepatitis B (HBV)-induced liver disease, in terms of graft and survivals as well as disease recurrence. MATERIALS AND METHODS: We reviewed the medical records of 19 HBV-infected patients who underwent OLT between 2000 and 2010 using antiviral treatment with either lamivudine (LAM, n = 14) and/or adefovir/entecavir/tenofovir (n = 8) before OLT. Fifteen subjects showed a HBV DNA-negative status prior to OLT. All patients were administered HBIG (antiHBs immunoglobulin) perioperatively: 10,000 international units (IU) in the anhepatic phase and 2.000 IU/d until day 7 after OLT. The preoperative antiviral regimen was continued as maintenance prophylaxis from day 1 after OLT. In cases of the YMMD mutation the antiviral treatment was switched to combination therapy with entecavir and tenofovir. RESULTS: Patient follow-up as of December 2011 or till time of death ranged from 6 to 129 months (median = 47). All patients were prescribed tacrolimus. None of them experienced HBV-related graft dysfunction or graft loss. All subjects were HBV DNA negative at 6 months after OLT. HBV recurrence in the post-OLT phase was discovered in 3 patients, 2 of whom had undergone OLT because of acute liver failure due to hepatitis B. They showed LAM-resistant mutations at the time of recurrence and underwent entecavir/tenofovir therapy to achieve HBV DNA negative status. CONCLUSIONS: Our study demonstrated excellent long-term outcomes among patients after successful preoperative antiviral treatment for HBV. Patients should be given a high dosage of HBIG during the first week after OLT in combination with the preoperatively established antiviral treatment. In presence of a LAM-resistance mutation, antiviral treatment should be adapted individually to achieve HBV recurrence freedom and graft survival.

Long-term outcome of liver transplantation as treatment modality in patients with hepatocellular carcinoma in cirrhosis: a single-center experience.

BACKGROUND: Hepatocellular carcinoma (HCC) is among the most frequent malignant diseases worldwide. In the vast majority of cases, it is associated with liver cirrhosis. Liver transplantation (OLT) is potentially the gold standard treatment for patients suffering HCC in cirrhosis, because of synchronous eradication of HCC and of the underlying hepatic disease. The aim of this study was to evaluate long-term outcomes of OLT in HCC patients. MATERIAL AND METHODS: Between January 2000 and December 2011, 43 patients who were diagnosed with HCC in liver cirrhosis and underwent OLT in our department, were identified from a prospective database. All patients received their grafts from deceased donors. We analyzed demographic data, laboratory values, number and size of lesions, primary liver disease, diagnostic methods, bridging therapy modalities, and postoperative outcomes, including complications, recurrences, and their treatment. RESULTS: Patient follow-up as of January 2012 or to death ranged from 0 to 138 months (median, 59; mean, 63). None of the patients were lost to follow-up. The gender bias was 85%:15% (male:female) and the median age, 57.8 years (range, 44-69). The most common underlying diseases for cirrhosis and HCC were alcoholic (n = 12) and hepatitis C (n = 16). Thirty-one subjects underwent bridging therapy through transarterial chemoembolization (TACE), and/or radiofrequency ablation. All patients underwent OLT within the Milan criteria according to the preoperative evaluation and histopathologic examination of the explanted liver. Twenty-one of them suffered postoperative complications (48.8%). HCC recurrence, which occurred in 5 (10.4%), was treated by surgery (n = 3), systemic chemotherapy with sorafenib (n = 1), or TACE (n = 1). CONCLUSIONS: OLT for HCC in cirrhosis, displays a relatively high complication rate. It shows good survivals with and low recurrence.

The diagnostic value of systolic acceleration time and resistive index as noninvasive modality for detection of graft rejection after orthotopic liver transplantation.

BACKGROUND: Acute cellular and chronic graft rejection are major disorders in the postoperative setting after orthotopic liver transplantation (OLT). An immediate diagnosis and successful therapy are essential for graft survival. We sought to determine whether quantitative and qualitative analysis of Doppler sonography data was predictive and sensitive as noninvasive diagnostic tools for rejection episodes. MATERIALS AND METHODS: We prospectively recorded and retrospectively analyzed the medical records of patients who underwent OLT between January 2000 and November 2011, identifying patients with acute cellular (ACR) and chronic rejection (CR) and the grade classified the activity index according to BANFF criteria. Analyzed parameters included resistive index (R/I), systolic acceleration time (SAT) in the hepatic artery, laboratory values, histopathologic grade and therapy as well as graft and patient survival. RESULTS: Patient follow-up as of December 2011 or to the time of death ranged from 2 to 132 months (median follow- up: 79 months, mean = 83 months). We registered 29 rejection episodes (ACR n = 20 and CR n = 9) in 20 subjects. The majority of patients received a tacrolimus-based immunsuppressive regimen (n = 14, trough level: 7-12 ng/mL) in addition to high-dose corticosteroids, and sometimes a third drug. One patient displayed a corticosteroid-resistant ACR and 4 CR cases, graft loss followed by retransplantation. R/I was calculated for all patients and SA for those who underwent OLT since 2009. As a control group we used subjects with delayed SAT and high R/I without graft rejection. In all patients with a high R/I (>0.7, range: 0.71-0.91) and in all patients who suffered graft rejection since 2009 (n = 14), we observed a delayed SAT (>0.08, range: 0.08-0.18). The sensitivity and specificity for R/I were 82%, and 54.9%; for SAT 100% and 78%, respectively. CONCLUSION: Delayed SAT (>0.08) and high R/I (>0.7) were sensitive indices of graft rejection episode. The limitation of these diagnostic parameters is their specificity, especially in the immediate postoperative period, where early vascular disorders trigger similar sonographic results. Nevertheless SAT and R/I may be considered to be important diagnostic tools, in combination with elevated laboratory liver values they can provide an early diagnosis of graft rejection.

The value of pre-emptive therapy for cytomegalovirus after liver transplantation.

BACKGROUND: Cytomegalovirus (CMV) infections are among the most common infections following liver transplantation. The main preventive methods for CMV infections are universal prophylaxis and pre-emptive therapy. In our study, we adopted a pre-emptive strategy in a higth-risk group of donor CMV-positive (D+)/recipient CMV-negative (R-) casses. We investigated whether this strategy was safe and effective to prevent CMV disease. METHODS: One hundred fifty-nine liver transplantation recipients who underwent over a 15-year period were retrospectively analyzed after follow-up for at least 6 months (mean, 63 months). Weekly quantitative polymerase chain reaction (PCR) measurements were performed to detect viral DNA. No CMV drug prophylaxis was given: antiviral CMV therapy was initiated when the PCR for CMV-DNA was >400 copies/mL. RESULTS: Fifty-one of 159 liver transplant recipients enrolled in the study received antiviral therapy. High-risk patients (D+/R-) developed CMV infections significantly more often than D-/R- serostatus (P = .005). CMV disease was diagnosed in 12% of CMV-positive patients. Independent of serostatus in 14 cases (27.5%) virological recurrence of CMV infection occurred after primary treatment. Survival analysis showed no significant difference between patients with versus without CMV infection (P = .950). No relationship could be found between transplant rejection and CMV infection (P = .349). CONCLUSION: Our results showed that a pre-emptive strategy to prevent CMV disease was possible, even among the serological high-risk group. Only 12% of cases with CMV infection went on to manifest CMV disease with organ involvement. Survival curves were similar among patients with versus without CMV infections.

Outcome of operative therapy of hepatic metastatic stomach carcinoma: a retrospective analysis.

BACKGROUND: In general, hepatic metastasis from stomach carcinoma has an unfavorable prognosis. In addition, there are often further metastases in other organs, such as peritoneal carcinomatosis. The major aim of the present study was to investigate a potential curative surgical approach in these patients. MATERIAL AND METHODS: Thirty-one patients with hepatic metastases from stomach cancer were treated in the University Clinic Erlangen-Nürnberg. The data were collected retrospectively from 1972 to 1977 and prospectively since 1978 at the Erlangen Cancer Registry. The time frame of this retrospective analysis from patients who had surgical resection of hepatic metatases from gastric cancer was from 1972 to 2008. The median age of the patients was 65 years, and the ratio of men to women was 2:1. RESULTS: Atypical or anatomical resections of segments were possible in 21 cases. Larger operations, such as hemihepatectomy (right/left), were performed in 10 patients. The postoperative complication rate was 29%, and the hospital mortality was 6%. The five-year survival rate was 13%; R0 resection was achieved in 23 patients. We also found a significant difference in the 5-year survival rate between synchronous and metachronous metastases (0 vs. 29%; p < 0.001) and R0 resected patients (p = 0.002). Patients with solitary metastases had a significantly better median survival than patients with multiple metastases (21 vs. 4 months; p < 0.005.) CONCLUSIONS: The overall survival in our study was 13%; therefore gastric cancer with liver metastases is not in every case a palliative situation. It seems that patients with liver metastases benefit from resection, especially if the metastases are metachronous (p < 0.001) and solitary, provided that a curative R0 resection has been achieved. An interdisciplinary approach with neoadjuvant chemotherapy appears useful. Additional controlled studies should be conducted.

Impact of the conversion of the immunosuppressive regimen from prograf to advagraf or to sirolimus in long-term stable liver transplant recipients: indications, safety, and outcome.

BACKGROUND: Compliance problems have arisen due to the twice a day administration of calcineurin inhibitors (CNI). We examined the safety, indications, and efficacy in terms of graft and patient survivals after conversion from tacrolimus to sirolimus or advagraf. PATIENTS AND METHODS: Between January 2006 and December 2009, 36 orthotopic liver transplantation patients underwent conversion of the immunosuppressive regimen from prograf to either sirolimus (group 1; n=10) or advagraf (group 2; n=26). A group of patients taking prograf was used as a control group (group 3; n=15). We identified 51 patients of mean age 57 years and male:female percentages of 57%:43% from a prospective database. Renal and liver graft functions, patient survival, as well as laboratory and clinical data over at least 12 months (mean, 38) were the investigated parameters. RESULTS: Patients converted to sirolimus did not show significantly improved renal function at 12 months as evidenced by creatinine levels (1.31 mg/dL+/-0.47 vs 1.34 mg/dL+/-0.78) and glomerular filtration rate (GFR, 57+/-16 vs 56+/-16 mL/min). However, there were significant antiproliferative effects. Patients with a hepatocellular carcinoma in the pretransplantation phase remained without a recurrence. The side effects including ankle edema, aphthae, and tachyarrhythmia absoluta, required reconversion to the CNI. Patients prescribed advagraf reported a better life quality because of the single administration and a slight, insignificant improvement in renal function. An acute rejection episode was evidenced under either immunosuppresant. CONCLUSION: Sirolimus is a safe immunosuppressive option in liver transplant recipients suffering from hepatocellular carcinoma. Advagraf showed a lower incidence of side effects than prograf and probably is not as harmful for renal function, offering better compliance and better life quality.

The effect and safety of the treatment of recurrent hepatitis C infection after orthotopic liver transplantation with pegylated interferon α2b and ribavirin.

INTRODUCTION: Recurrent hepatitis C infection in the posttransplant setting is a serious problem. The aim of this study was to evaluate the efficacy, safety, indications, optimal time of administration and adequate duration of antiviral therapy with pegylated interferon alpha 2 b (PEG-IFN) and ribavirin (RIB). PATIENTS AND METHODS: Between 2003 and 2009, 16 patients received antiviral therapy (PEG-IFN: 0.8-1.6 µg/kg/wk, RIB 800-1200 mg/d) for at least 6 months. Patients with a biochemical without a virologicalresponse after 12 months of therapy received antiviral treatment for a further 6 months. Hepatitis C virus load was determined at 1, 3, 6, and 12 months after start of therapy. Liver biopsy was performed in all patients before the beginning and after the end of treatment. RESULTS: The mean period of antiviral therapy was 14 months. The four patients who received the full-length treatment (12 months, 33%) showed sustained virological responses (SVR) and 8 showed virological and biochemical responses (VR, BR). Patients with SVR showed significant improvement in the grading and staging of HAI (histological activity index; P=.03). Nine patients had several side effects under antiviral treatment. Acute rejection episodes were not observed. CONCLUSION: The antiviral treatment combination using PEG-IFN and RIB for recurrent hepatitis C is effective procedure. The SVR of 33% after 12 months of treatment with significant improvement in HAI grading and staging and stable HAI in all treated patients favor early initiation and 12-month administration of antiviral treatment. Furthermore, all patients with BR without VR, who underwent antiviral treatment for a further 6 months, achieved a VR. However, the optimal duration of treatment needs to be investigated in large prospective studies.

Procalcitonin in the setting of complicated postoperative course after liver transplantation.

BACKGROUND: Orthotopic liver transplantation (OLT) is a treatment for end-stage liver disease. The shortage of available organs leads to the acceptance of marginal grafts, thereby increasing the risk of perioperative complications such as acute rejection, infection, and graft dysfunction Procalcitonin (PCT) has been shown to be a reliable marker for a complicated course after traumatic injury as well as in the courses of systemic inflammatory response syndrome and sepsis. The aim of our study was to evaluate PCT as an early prognostic marker for the occurrence of complication during the postoperative course after OLT. METHOD: We analyzed PCT levels and clinical and paraclinical data of 32 patients who underwent 33 OLTs. The highest PCT was termed as peak-PCT. Patients were stratified into noncomplication and complication groups. Renal replacement therapy, respiratory insufficiency, postoperative bleeding, refractory ascites, pleural effusion, rejection, sepsis, and fatal outcome were defined as complications. A secondary stratification, using a peak-PCT of 5 ng/mL, was used to analyzed the risk of a complication. We also analyzed the course of PCT after OLT in each group. RESULTS: The peak-PCT, which occurred between the first and third postoperative day in 30 patients, was followed by halving of the value every second day. Three subjects died because of sepsis. A constantly rising PCT or a secondary rise observed in 2 patients was associated with a fatal outcome. The noncomplication group included 18 patients, 8 of them showing a peakPCT <5 ng/mL and 10 above. The complication group included 14 patients who underwent 15 transplantations; Only 1 displayed a peakPCT <5 ng/mL. When the peak-PCT was >5 ng/mL, the odds ratio of a complication was 11.2 (95% Confidence interval, 10.81-11.59; P < .025). However, not before the 7th postoperative day was the course of mean PCT levels significantly different between the complication and noncomplication groups. In transplant patients, an elevation of PCT was observed only in the presence of bacterial infection and not rejection or wound infection. PCT rose during respiratory failure and sepsis, but not renal replacement therapy, ascites, pleural effusion, rejection, or bleeding. CONCLUSION: PCT was a reliable marker. A decline was observed in 31 cases with subject, who both had fatal outcomes showing a constantly rising level. An initial high PCT indicated a poor prognosis; some members of the noncomplication group also had levels >15 ng/mL. The patients in the complication group showed a higher mean PCT, which was significant at 7 days, most probably because of the high variation among levels. Still, a peak-PCT >5 ng/mL showed an odds ratio of 11.2 for patients to experience a complication.

Neoadjuvant chemotherapy does not increase postoperative complication rate after resection of colorectal liver metastases.

BACKGROUND: This paper discusses, whether neoadjuvant chemotherapy has an impact on the rate of postoperative complications after primary resection of liver metastases from colorectal carcinoma. METHODS: Of 183 patients 64 were studied. The patients were subdivided into two matched groups of 32 patients each-prior neoadjuvant chemotherapy (CT-group) vs. (control-group, primary resection). RESULTS: There were no postoperative complications in 24 patients of the control group (75%) and 26 patients of the CT-group (81%). Following prior chemotherapy, no major complications such as liver failure were observed, even after extended resections. CONCLUSION: Neoadjuvant chemotherapy prior to surgical resection of colorectal liver metastases does not result in an increase of postoperative morbidity and mortality.

Does conversion of immunosuppressive monotherapy from cyclosporine A to tacrolimus improve bone mineral density in long-term stable liver transplant recipients?

The effects of converting cyclosporine A to tacrolimus on bone mineral density (BMD) have not yet been evaluated thoroughly in liver transplant patients. Interfering factors in this patient population often are concomitant glucocorticoid treatment or exposure to estrogens. Here, we investigated in a homogeneous population of 10 male liver transplant recipients the impact of converting low-dose cyclosporine A monotherapy to low-dose tacrolimus monotherapy on BMD by using dual-energy x-ray absorptiometry. During the 12-month study period, an increase in BMD at the lumbar spine was observed in 9 out of 10 men (P <.01), whereas BMD at the femoral neck remained stable. Converting cyclosporine A to tacrolimus appears to be safe and efficaceous with regard to maintaining or even increasing BMD in male liver transplant recipients.

Clinical value of MRC in the follow-up of liver transplant patients with a choledochojejunostomy.

BACKGROUND: We investigated the clinical value of magnetic resonance cholangiography (MRC) in liver transplant patients receiving choledochojejunostomy (CDJ). METHODS: Twenty-five MRCs were performed in 23 initially asymptomatic patients 19 months (mean) after liver transplantation with biliary reconstruction via CDJ. The images were evaluated by consensus (two investigators) for bile duct strictures and dilatations. As a standard of reference, clinical follow-up (including laboratory analysis) was used in 20 cases and direct cholangiography or surgery in three cases. RESULTS: Fourteen pathologic findings were observed in 11 patients (anastomotic strictures in four, left or right bile duct strictures in three, and peripheral segmental dilatations with or without strictures in seven). Patients with pathologic MRC findings had significantly higher levels of alkaline phosphatase (p < 0.05) and more frequently had histories of cholangitis than did patients with normal MRC. Four of six patients with stenoses of the central bile ducts subsequently developed biliary complications requiring treatment (three confirmed by direct cholangiography). In patients with unremarkable bile ducts or only peripherally located changes on MRC, no bile duct complications or relevant changes in the cholestasis parameters occurred during follow-up (mean = 30 months). CONCLUSION: MRC can noninvasively detect pathologic biliary tract changes in liver transplant patients in the asymptomatic stage and provide information for planning invasive therapeutic procedures.

[Dislocated supracondylar humerus fracture in the child. Surgical technique and outcome with dorsal approach]. / Die dislozierte suprakondyläre Humerusfraktur des Kindes. Operationstechnik und Ergebnisse mit dem dorsolateralen Zugang.

Anatomical reduction and stabilization of displaced supracondylar humeral fractures in children is necessary to obtain good results. For most cases percutaneous crossed pinning is recommended. Sometimes open reduction is necessary but even in these cases neurological complications and varus deformities have been reported. So the technique of open pinning was modified. From 1995 to 1998 22 children were treated by a dorsolateral approach. The fracture was stabilized by crossed pinning: The proximal K-wire is drilled 10 degrees ascending to the dorsal humerus through the medial pillar into the ventral part of the medial epicondyle, after shortening it is not bent. The distal K-wire stabilizes the lateral pillar, after shortening its end is bent down. Immobilization for 3-4 weeks, mobilization is done by the patient. The implants are removed 2 weeks later. The follow up in 21 out of 22 patients (8-57 months, mean 35 months) according to Flynn's criteria showed 16 excellent, 4 good and 1 fair result. The fair result was due to valgus deformity. One patient has been reoperated due to displacement of K-wire. Neither iatrogenic nerve lesions nor varus deformities nor infections did occur. The dorsolateral approach combined with the above mentioned technique of pinning shows excellent and good results.

[Resection of liver metastases--goal, timing and results]. / Resektion von Lebermetastasen--Ziel, Zeitpunkt und Ergebnisse.

If left to run their natural course, numerous malignant diseases will eventually produce liver metastases. Without treatment, afflicted patients have a life expectancy of only eight months. At the present time, the only therapeutic option that offers the patient with liver metastases from colorectal carcinoma the chance of a cure is resection of the metastases. Depending on the primary tumour, this also applies to some patients with carcinomas at sites other than the colorectum. A point of continuing controversy is the timing of such resection. While some authors recommend a test 'of time' ranging from several weeks to months, others call for resection of the metastases immediately after their detection. Solitary synchronous liver metastases involving only a single segment can be resected at the same time as surgical treatment of the primary when, in particular, the surgical access is readily possible and the risk of complications calculable. Most authors advocate surgery in two sessions. The location, number and size of the metastases, together with the presence of concomitant diseases, provide the basis for the decision to perform a resection. At the same time, however, the risk to the patient must be within justifiable limits. This applies in particular to non-colorectal, non-endocrine metastases. Following curative resection of colorectal hepatic metastases, 25-51% of the patients are still alive after 5 years. During the same period, some 51-76% of the patients develop a recurrence. From these data, the calculated resulting median survival for all patients undergoing resection is roughly 30 months. A tumour-free 5-year survival rate of up to 34% is achieved. In view of their different clinical course and prognosis, non-colorectal liver metastases should be classified into non-colorectal neuroendocrine (NCNE) and non-colorectal non-endocrine (NCNN) metastases. While the former group has a 5-year survival rate following curative resection of up to 62%, the figure for the latter group is only 15-35%.

[Undifferentiated, embryonal sarcoma as a rare cause of spontaneous liver rupture in adults]. / Undifferenziertes, embryonales Sarkom als seltene Ursache einer Leberruptur beim Erwachsenen.

INTRODUCTION: Undifferentiated, embryonal sarcoma is a rare malignant tumour of the liver, the incidence of which is highest in children between 6 and 10 years of age (14.1 %). Among the primary tumours of the liver in childhood it ranks in third place after hepatocellular carcinoma and focal nodular hyperplasia. Embryonal sarcoma is much rarer in adults. To our knowledge, only 18 cases have been published in the last 50 years. METHODS AND RESULTS: We now present the case of a 29-year-old woman with spontaneous rupture of the liver caused by an undifferentiated sarcoma. CONCLUSION: This case report illustrates the possibility of an embryonal sarcoma being the reason for spontaneous rupture of the liver. The management of this case comprised primary tamponade, interventional embolisation of the feeding artery, and secondary resection under stable conditions.