The impact of hepatitis C and biliary complications on patient and graft survival following liver transplantation.

Recurrent hepatitis C (HCV) and biliary complications (BC) are major causes of post liver transplant morbidity and mortality. The impact of these complications may be additive or synergistic. We performed a retrospective cohort study to analyze the effects of HCV and BC on all patients transplanted at two institutions over 6 years. BC was defined by imaging findings in the setting of abnormal liver function tests that required intervention. The primary outcomes were graft and patient survival over a mean 3.4 years. 709 patients (619 deceased, 90 living donor) were included, 337 with HCV and 372 without. BC was diagnosed more frequently in patients with HCV, 26% versus 18% (p = 0.008). One-year and overall patient and graft survival were significantly lower in patients with HCV, but BC impacted only 1-year graft survival. The combination of BC and HCV had no additional impact on survival or fibrosis rates on 1-year protocol biopsies. Multivariate analysis revealed HCV (HR 2.1) and HCC (HR 1.9) to be independent predictors of mortality. Since BC are diagnosed more frequently in HCV patients and only affect early graft loss, it is likely that recurrent HCV rather than BC accounts for the majority of adverse graft outcomes.

Partial hepatectomy and laparoscopic-guided liver biopsy in rhesus macaques (Macaca mulatta): novel approach for study of liver regeneration.

BACKGROUND AND PURPOSE: Although valuable information has been gained using a rodent partial hepatectomy model to assess liver regeneration, the ability to apply this research to humans remains uncertain. Thus, liver regeneration was assessed in a non-human primate, the rhesus macaque (Macaca mulatta). METHODS: One animal underwent 60% hepatectomy, a second animal underwent 30% hepatectomy, and control surgery (cholecystectomy) was performed on two separate animals. Laparoscopic-guided liver biopsy was performed on days 1, 2, 7, 14, and 30 after surgery. Changes in hemoglobin concentration and alanine transaminase activity were assessed, and liver regeneration was evaluated by measuring the expression of Ki-67. RESULTS: All animals survived surgery and laparoscopy. Substantial liver regeneration was induced in the animal that underwent 60% hepatectomy. Excellent tissue specimens were obtained via laparoscopic-assisted liver biopsy. CONCLUSIONS: Sixty percent partial hepatectomy in rhesus macaques appears to be an excellent model for the study of hepatocellular regeneration. The procedure was safe, and effectively induced liver regeneration. In addition, laparoscopic-guided liver biopsy allows observation of changes in the liver remnant as regeneration develops, and provides excellent tissue specimens for analysis. Thus, this rhesus macaque partial hepatectomy model will allow further characterization of liver regeneration in a species closer to humans.

The effect of HIV coinfection on hepatitis C: A review.

Many Hepatitis C (HCV) infected patients are coinfected with HIV. As HIV-directed anti-viral therapy has delayed HIV progression and mortality, pathologic consequences of HCV infection are occurring at an increased rate. In this review, a case presentation delineating the clinical course of an HIV/HCV coinfected patient at our institution is presented. The pathobiology, interrelation of HCV and HIV infection in coinfected patients is discussed as well as the effect of treatment in this unique patient population. The interaction of HIV and HCV coinfection is complex. It is clear that HIV infection negatively affects the natural history of HCV, while HIV-directed therapy may enhance immunologic response and exacerbate hepatocellular injury induced by HCV. Further studies assessing the effect of anti-HIV and anti-HCV-directed therapy on the clinical course of HCV/HIV coinfected patients is warranted.

Effect of fibrosis on adverse events in patients with hepatitis C treated with telaprevir.

BACKGROUND: Data about adverse events are needed to optimise telaprevir-based therapy in a broad spectrum of patients. AIM: To investigate adverse events of telaprevir-based therapy in patients with and without advanced fibrosis or cirrhosis in a real-world setting. METHODS: Data on 174 hepatitis C-infected patients initiating telaprevir-based therapy at Mount Sinai and Montefiore medical centres were collected. Biopsy data and FIB-4 scores identified patients with advanced fibrosis. Multivariable fully adjusted models were built to assess the effect of advanced fibrosis on specific adverse events and discontinuation of treatment due to an adverse event. RESULTS: Patients with (n = 71) and without (n = 103) advanced fibrosis were similar in BMI, ribavirin exposure, gender, prior treatment history, haemoglobin and creatinine, but differed in race. Overall, 47% of patients completed treatment and 40% of patients achieved SVR. Treated patients with and without advanced fibrosis or cirrhosis had similar rates of adverse events; advanced fibrosis, however, was independently associated with ano-rectal discomfort (P = 0.03). Three patients decompensated and had advanced fibrosis. The discontinuation of all treatment medications due to an adverse event was significantly associated with older age (P = 0.01), female gender (P = 0.01) and lower platelets (P = 0.03). CONCLUSIONS: Adverse events were common, but were not significantly related to the presence of advanced fibrosis or cirrhosis. More critical monitoring in older and female patients with low platelets throughout treatment may reduce adverse event-related discontinuations.

Select utilization of obese donors in living donor liver transplantation: implications for the donor pool.

Living donor liver transplantation evolved in response to donor shortage. Current guidelines recommend potential living donors (LD) have a body mass index (BMI) <30. With the current obesity epidemic, locating nonobese LD is difficult. From September 1999 to August 2003, 68 LD with normal liver function test (LFTs) and without significant comorbidities underwent donor hepatectomy at our center. Post-operative complications were collected, including wound infection, pneumonia, hernia, fever, ileus, biliary leak, biliary stricture, thrombosis, bleeding, hepatic dysfunction, thrombocytopenia, deep venous thrombosis, pulmonary embolism, difficult to control pain, depression and anxiety. Complication rates for LD with BMI >30 (n = 16) and BMI <30 (n = 52) were compared. The incidence of wound infection increased with BMI, 4% for nonobese and 25% for obese LD (p = 0.024). There were no statistically significant differences for all other complications. No LD died. Recipient survival was 100% with obese LD and 80% with nonobese LD (p = 0.1). Select donors with a BMI >30 may undergo donor hepatectomy with acceptable morbidity and excellent recipient results. Updating current guidelines to include select LD with BMI >30 has the potential to safely increase the donor pool.

Peri-operative chylous ascites.

Chylous ascites occurs when lymphatics are disrupted due to primary lymphatic disease, infection, malignancy, or chronic liver disease. It may also occur following inadvertent interruption of abdominal lymphatics during surgery involving retroperitoneal dissection. It is suggested by some that during liver transplantation, severed hepatic lymphatics should be ligated or stented to avoid post-operative pleural and abdominal accumulation of chylous fluid. The occurrence of chylous ascites and the need to ligate lymphatics after orthotopic transplantation was assessed in 180 consecutive patients subjected to this procedure. Pre-operative chylous ascites present in one patient resolved following transplantation. Three patients who required retroperitoneal dissection to complete the biliary anastomosis via choledochojejunostomy or perform a hepatic artery graft developed post-operative chylous ascites which rapidly resolved without complications. These findings indicate special attention to transacted hepatic lymphatics is not required during orthotopic liver transplantation. Chylous ascites rarely occurs after liver transplantation and its transitory development is due to retroperitoneal dissection.

Alpha-1 antitrypsin deficiency and splenic artery aneurysm rupture: an association?

OBJECTIVE: Theoretically, patients with alpha 1-antitrypsin deficiency may be vulnerable to the development of splenic artery aneurysms. alpha-1 antitrypsin deficiency can induce cirrhosis with portal hypertension, and resulting protease-antiprotease imbalances may exaggerate arterial wall weakness due to proteolysis of arterial structural proteins. A splenic artery aneurysm rupture 7 days after liver transplantation provoked a reassessment of the incidence of this phenomenon in a liver transplant population. METHODS: Case records from three institutions and the results of a survey sent to 126 liver transplantation programs in the United Network for Organ Sharing database were reviewed. The incidence of splenic artery aneurysm rupture in the peritransplantation period, etiology of liver disease associated with this phenomenon, and recommendations regarding management of splenic artery aneurysms was assessed. RESULTS: Twenty-one cases of splenic artery aneurysm rupture were identified. alpha-1 antitrypsin deficiency was the most common cause of cirrhosis in the majority of identified patients who presented with splenic artery aneurysm rupture, which was associated with a mortality rate of 57%. Respondents to the survey indicated that a preoperative evaluation was warranted if a splenic artery aneurysm was suspected; however, no consensus regarding management exists. CONCLUSIONS: The presence and risk of rupture of splenic artery aneurysms may be greater in patients with alpha-1 antitrypsin deficiency. If identified before rupture, an aggressive approach to diagnosing and treating these aneurysms should be initiated. At present, no consensus exists regarding the management of splenic artery aneurysms.