Is liver biopsy necessary in the evaluation of a living donor for liver transplantation?

BACKGROUND: The role of liver biopsy in the evaluation of a candidate for living liver donation is controversial. Some authors suggest doing it routinely, but others do it only in selected cases. The aim of this work was to evaluate the usefulness of protocol liver biopsy in the evaluation of candidates for living liver donation. METHODS: Ninety potential candidates for living liver donation were evaluated. In 46 cases donation was contraindicated without the need of liver biopsy. In the remaining 44 candidates, liver biopsy was done on a protocol basis. The usefulness of protocol biopsy was compared with the use of biopsy according to the recommendations of the Vancouver Forum. RESULTS: Fifteen of the 44 biopsies were indicated according to the recommendations of the Vancouver Forum. Twelve of them were normal, and 3 had liver steatosis or steatohepatitis. Of the 29 biopsies done per protocol, 28 were normal and 1 showed liver steatosis. Donation was contraindicated according to liver biopsy findings in 3 of the 15 patients with liver biopsy done according to the Vancouver Forum recommendations and in none of the 29 patients with biopsy done per protocol (P = .034). CONCLUSIONS: Protocol liver biopsy has a limited utility in the evaluation of the candidates for living liver donation.

Increased liver stiffness values in patients with heart failure.

BACKGROUND: Liver stiffness has been claimed to be increased in patients with heart failure. AIMS: To determine the magnitude of this increase in liver stiffness, and to clarify whether it is related to the degree of heart failure or not. METHODS: Twenty-six patients were prospectively collected, and divided in groups CHF (those with compensated chronic heart failure) and AHF (those with acute decompensated heart failure). Patients underwent routine blood chemistries, pro-BNP determination, echocardiography and transient elastography during outpatient care (group CHF) or at hospital admission (group AHF). Blood chemistries, pro-BNP and transient elastography were repeated in patients in group AHF before being discharged. RESULTS: Correlation between liver stiffness and pro-BNP levels was statistically significant (Rho = 0.747, p = 0.001). Patients in group CHF had lower values of liver stiffness and pro-BNP when compared with patients in group AHF at admission. Median liver stiffness and pro-BNP values were 6.5 vs 14.4 kPa (p = 0.009) and 1511 vs 3535 pg/ml (p = 0.025) respectively. After clinical compensation, liver stiffness decreased in all patients in group AHF. Liver stiffness was 14.4 kPa at admission and 8.2 kPa at discharge (p = 0.008). Pro-BNP values also decreased from a median of 3535 pg/ml to a median of 1098 pg/ml (p = 0.025). CONCLUSIONS: Patients with heart failure have increased liver stiffness, that appears to be related with the severity of heart failure.

Efficacy of transjugular intrahepatic portosystemic shunt to prevent total portal vein thrombosis in cirrhotic patients awaiting for liver transplantation.

INTRODUCTION: Complete portal vein thrombosis (PVT) may complicate orthotopic liver transplantation (OLT), increasing its technical difficulty and the transfusion requirements and as well as affecting survival in some cases. Transjugular intrahepatic portosystemic shunt (TIPS) prevents total portal vein occlusion in patients with partial PVT. OBJECTIVE: We aimed to assess the efficacy and safety of TIPS to prevent total portal vein occlusion among patients listed for OLT. PATIENTS AND METHODS: We analyzed the clinical records of 15 consecutive patients with partial PVT who underwent TIPS before OLT. The control group consisted of 8 transplanted patients without TIPS but partial PVT diagnosed before OLT. Portal vein patency at surgery, ischemia time, and transfusion requirements during OLT, and survival thereafter were compared between both groups. The main complications were also compared: mortality after TIPS (from TIPS placement to OLT), intraoperative technical complications, and technical complications during the 6 months after OLT. RESULTS: Clinical characteristics at the time of OLT were similar between the groups. No relevant complications were observed after TIPS; all patients underwent transplantation. One- and 5-year actuarial survival rates were similar in both groups (92% and 85% in TIPS-group versus 100 and 75% in the control group, respectively). No differences in transfusion requirement, duration of ischemia, and frequency of technical complications during and after OLT were observed between the groups. The portal vein was patent at surgery in all TIPS patients and 4 of 8 (50%) in the control group (P = .008). CONCLUSION: TIPS may prevent PVT in liver transplantation candidates with partial PVT.

Subsequent nonmelanoma skin cancer after liver transplantation.

BACKGROUND: Liver transplant recipients have a high risk of developing nonmelanoma skin cancer (NMSC). Some develop multiple NMSC. METHODS: Patients with a follow-up of >1 year have been prospectively followed to detect NMSC. We studied the risk of developing >1 NMSC. RESULTS: After a follow-up of 2658 patient-years (mean, 8.5 years per patient), 59/312 (19%) patients were diagnosed with NMSC. Twenty-five had >1 NMSC. The 5-year risk of developing 1 NMSC, >1 NMSC, and a subsequent NMSC (a new NMSC after a first one) were 15%, 5.5%, and 46.5%, respectively. Age >60 years and transplantation for hepatocellular carcinoma were independently associated with a higher risk of developing >1 NMSC. CONCLUSION: NMSC are frequent complications after liver transplantation and they may show a high rate of recurrence. Older age and hepatocellular carcinoma were related to the development of multiple NMSC.

Response to radioembolization with yttrium-90 resin microspheres may allow surgical treatment with curative intent and prolonged survival in previously unresectable hepatocellular carcinoma.

BACKGROUND: Occasionally, patients with hepatocellular carcinoma (HCC) who receive radioembolization with palliative intent are downstaged for radical treatments. The aim of this study was to describe and analyze the overall survival (OS) in these patients compared with patients of the same baseline stage (UNOS T3), who were not eligible for radical treatment after radioembolization. METHODS: Between September 2003 and August 2010, 118 patients with HCC received radioembolization with yttrium-90 ((90)Y) resin microspheres. Of these, 21 patients with UNOS T3 stage were retrospectively identified and included in this analysis. RESULTS: In total, 6 of 21 patients were downstaged and treated radically between 2 and 35 months post-radioembolization. Three patients were resected, 2 received liver transplantation and 1 was ablated and then resected. Patients treated radically were significantly younger (62 vs. 73 years, p = 0.006) and had higher tumor volume (583 mL vs. 137 mL, p = 0.001) than patients who did not achieve radical treatment. There were no differences between the groups in number of lesions, BCLC stage, previous cirrhosis, activity administered per tumor volume, or median levels of alpha-fetoprotein or total bilirubin. Across the whole series, the median OS was 27.0 months (95% CI 5.0-48.9), varying significantly between those treated radically (OS not reached after a median follow-up of 41.5 months since radical therapy) and those who received palliative treatment only (22.0 months; 95% CI 15.0-30.9). CONCLUSIONS: Radical therapy following tumor downstaging with radioembolization provides the possibility of long-term survival in a select subgroup (UNOS T3 stage) with otherwise limited options.

Applicability of living donor liver transplantation in a program of adult liver transplantation.

INTRODUCTION: The aim of this study was to investigate the applicability of living donor liver transplantation in a program of adult liver transplantation. PATIENTS AND METHODS: We studied the outcomes of the evaluation of 71 potential donor candidates for 53 adult candidates to liver transplantation. RESULTS: Ten of the potential donor candidates did not complete their evaluation. Among the remaining 61 potential donors, 29 (47.5%) were considered to be suitable donors. Only 17 (24% of the 71 initial candidates) underwent donation. The main causes for unsuitability for liver donation were a small remnant liver and vascular anatomic variants. CONCLUSION: Fewer than 25% of potential liver donors became effective donors leading us to conclude that adult living donor liver transplantation has a low applicability.

Prophylaxis and treatment of hepatitis B infection in the setting of liver transplantation.

Without any treatment, the prognosis of hepatitis B in liver transplant recipients is very poor. So, antiviral prophylaxis is very important in patients with hepatitis B who undergo liver transplantation. Before liver transplantation, a suppression of viral replication has to be achieved by nucleos(t)ide analogs. Drugs used in the prophylaxis of post-transplant hepatitis B include immunoglobulin against HBV and nucleos(t)ide analogs. Prophylaxis against graft infection must be based on the individual risk of recurrence. When prophylactic measures have failed and graft infection has occurred, treatment of recurrent hepatitis B may be based on the resistance profile of the virus and previous antiviral exposure. Finally, lamivudine seems to be very effective in the prevention of de novo hepatitis B in patients transplanted with a graft from an anti-HBc positive donor.

Subcellular shift of the hepatic growth hormone receptor with progression of hepatitis C virus-related chronic liver disease.

AIMS: To evaluate the cytoplasmic and nuclear expression of hepatic growth hormone receptor (GHR) in different stages (S0, S1, S3 and S4, according to Knodell's classification) of chronic liver disease (CLD) and in hepatocellular carcinoma (HCC). METHODS AND RESULTS: Liver specimens from 31 patients with hepatitis C virus-related CLD, five patients with HCC and nine controls were examined for expression of hepatic GHR by immunohistochemistry with MAb 263. Cytoplasmic and nuclear staining were evaluated as a percentage of positively stained cells. The cytoplasmic expression of GHR was comparable between normal liver and S0 hepatitis, while it progressively decreased in S1, S3 and S4 CLD (P < 0.01). Conversely, nuclear GHR showed increased expression in S3 and S4 CLD (P < 0.05). No differences were observed between HCC and normal liver in terms of GHR immunoreactivity. CONCLUSIONS: This is the first study to show that the subcellular expression of hepatic GHR changes with the progression of CLD. The increase in nuclear expression of GHR with advanced stages of CLD suggests that GH may act directly at the nuclear level to promote hepatocyte proliferation/regeneration.

Frequency of diabetes and thyroid autoantibodies in patients with autoimmune endocrine disease from Cameroon.

BACKGROUND: Diabetes is a major cause of morbidity and mortality in both industrialized and developing countries. In Africa, there are little data on the prevalence and immunological features of patients with autoimmune endocrine diseases. AIM OF THE STUDY: The present hospital-based study was carried out to evaluate disease-associated autoantibodies in both type 1 diabetes and thyrotoxicosis attending the Central Hospital of Yaoundee in Cameroon. PATIENTS AND METHODS: Samples were collected from a total of 101 subjects, 47 of whom clinically had established type 1 diabetes (mean age 30.1 years +/- 7.6, mean disease duration 3.3 years), 18 had thyrotoxicosis (mean age 32.7 years +/- 7.6, mean disease duration 6.3 years +/- 2.8) and 36 normal subjects (mean age 26 years +/- 4.5). All subjects were tested for diabetes-associated glutamic acid decarboxylase (GAD) and tyrosine phosphatase (IA2) autoantibodies using antigen-specific radioimmunoassay as well as thyroiditis-associated thyroglobulin (Tg) and thyroid peroxidase (TPO) autoantibodies using commercially available kits. RESULTS: Of 47 patients with type 1 diabetes, 16 (34%) had GAD autoantibodies (Abs), 3 (6.4%) had IA2 Abs, and 2 (4.3%) had TPO Abs. Of 18 patients with thyrotoxicosis 4 (22.2%) had GAD Abs, 5 (27.8%) showed IA2 Abs, while 8 patients (44.4%) were TPO Abs positive. No patients in either group had Tg Abs. Among normal subjects, 2 (5.6%) showed GAD Abs, and one of these was also IA2 Abs positive, but none had thyroid autoantibodies. CONCLUSION: Adult-onset type 1 diabetic patients some years post-diagnosis from central Africa show GAD, IA2 or TPO Abs; and surprisingly, patients with thyrotoxicosis had a similar frequency of diabetes-associated autoantibodies. We conclude that, despite a different genetic and environmental background to European populations, islet cell autoimmunity is common in autoimmune endocrine patients in central Africa.

The role of ribavirin in the combination therapy of hepatitis C virus infection.

Ribavirin is a very broad-spectrum anti-viral agent used clinically to treat infections by Lassa fever virus, respiratory syncytial virus (RSV) and, in combination with Interferon-alpha (IFN-alpha), hepatitis C virus (HCV). Although it was originally synthesized over 30 years ago, the precise mechanisms of its therapeutic activities are still not fully understood. Ribavirin was shown to possess both direct and indirect action mechanisms against several DNA and RNA viruses. These include direct inhibition of viral RNA-dependent RNA polymerases, inhibition of the host inosine monophosphate dehydrogenase, modulation of the host immune response and inhibition of viral capping enzymes. More recently, ribavirin was demonstrated to be able to act as an RNA virus mutagen, increasing mutations in the RNA virus genome and reducing their infectivity. Still the real challenge is to identify which of its biological properties is responsible for the observed clinical efficacy on specific infections. Under this aspect, renewed interest results from its synergistic enhancement of interferon-alpha (IFN-alpha) therapy, which could open the way to develop more powerful anti-HCV compounds. This work purpose is to provide a broad overview of all the recognized ribavirin action mechanisms against HCV, which can possibly also explain its synergistic behavior with IFN-alpha. An overview on the corresponding HCV treatment clinical observations is also provided in the second part of this work.

A hospital survey of the clinical features of diabetes in Congo.

The occurrence of diabetes mellitus is increasing throughout the world, both in industrialised nations and in developing countries. While this disease is not a leading cause of death in developing country populations, it must nevertheless be considered for its social and economic impact. This study examines the clinical and epidemiological situation of diabetes mellitus in the city of Kinshasa, Democratic Republic of Congo, as based on data from two city hospitals: Saint Joseph's Hospital (SJH) and the Centre Hospitalier Monkole (CHM), two urban health facilities typical of those developing countries. The results show that diabetes is a real public health problem in Congo. Average blood glucose levels were above 300 mg/dl in 44.4% of patients at SJH and 41.5% at CHM, and hypertension (> or = 140/90 mmHg) was reported in 35.8% of patients at SJH and 20% at CHM. The management of diabetes and, in particular, its complications is suffering because of some cultural influences but mainly economic ones. In fact, incidence of disease complications is closely linked to the financial status of patients and facilities. SJH, which serves mainly the low-income community, has a greater incidence of severe diabetes-associated complications than CHM, which treats patients with a higher mean income level. SJH hospitalised patients had a 24.7% incidence of diabetic foot with 3 amputations as compared to only a 10% incidence and no amputations for CHM hospitalised patients. At SJH, 17.3% of patients died during the study, while at CHM none died. Overall, differences in the prevalence of complications between SJH and CHM patients were found not to be significant. For the large majority of Congo population, education on diabetes is not available, and due to the failure of the national health system, access to treatment is impossible. Furthermore, because most diabetic people in Congo go untreated, the mortality rate for the disease is high. Congo would greatly benefit from a national diabetes program in order to give all diabetic patients in Congo access to good and consistent medical care.