HERACLIS-HDV cohort for the factors of underdiagnosis and prevalence of hepatitis D virus infection in HBsAg-positive patients.

BACKGROUND AND AIMS: Hepatitis D virus (HDV) underdiagnosis remains common. We assessed the HDV screening and prevalence rates in HBsAg-positive patients seen at tertiary liver centres throughout Greece as well as factors affecting HDV diagnosis. METHODS: All adult HBsAg-positive patients seen within the last 5 years were included. Non-screened patients who visited or could be recalled to the clinics over a 6-month period were prospectively tested for anti-HDV. RESULTS: Of 5079 HBsAg-positive patients, 53% had anti-HDV screening (41% before and 12% after study initiation). Pre-study (8%-88%) and total screening rates (14%-100%) varied widely among centres. Screening rates were associated with older age, known risk group, elevated ALT, centre location and size and period of first visit. Anti-HDV prevalence was 5.8% without significant difference in patients screened before (6.1%) or after study initiation (4.7%, p = 0.240). Anti-HDV positivity was associated with younger age, parenteral drug use, born abroad, advanced liver disease and centre location. Overall, HDV RNA detectability rate was 71.6% being more frequent in anti-HDV-positive patients with elevated ALT, advanced liver disease and hepatitis B therapy. CONCLUSIONS: Anti-HDV screening rates and recall capabilities vary widely among Greek liver clinics being higher in HBsAg-positive patients of known risk group with active/advanced liver disease seen at smaller centres, while non-medical factors are also important. Anti-HDV prevalence varies throughout Greece being higher in patients born abroad with younger age, parenteral drug use and advanced liver disease. Viremia is more frequently but not exclusively detected in anti-HDV-positive patients with elevated ALT and advanced liver disease.

HERACLIS-TAF: a multi-centre prospective cohort study on 2-year safety and efficacy of tenofovir alafenamide in patients with chronic hepatitis B with renal and/or bone disorders or risks.

BACKGROUND: Tenofovir alafenamide (TAF) has exhibited a favourable safety profile on estimated glomerular filtration (eGFR) and bone mineral density (BMD), but has not been extensively studied in patients with renal impairment and/or BMD disorders. AIMS: To assess predictors of eGFR changes and other safety and efficacy outcomes during 24-month TAF therapy in patients with chronic hepatitis B with renal and/or BMD disorders/risks. METHODS: Adult patients who started TAF at 13 clinics throughout Greece were prospectively included. Main exclusion criteria were hepatitis D, active malignancy and bisphosphonates recent use. MDRD formula was used for eGFR estimation. RESULTS: TAF was initiated in 176 patients (91% switched from another agent). At 12 and 24 months, HBV DNA was undetectable in 97% and 100%, and ALT was normal in 96% and 95% of patients. Median ALT decreased from baseline to month 12/24 (p < 0.001). Mean eGFR decreased from previous treatment initiation to baseline (p < 0.001), increased at 12 months and remained stable at 24 months (p ≤ 0.001). An increase in eGFR of >3 ml/min at 12 month was observed in 50% of patients and was associated mainly with baseline eGFR 30-60 ml/min. In patients with baseline phosphate <2.5 mg/dl, mean serum phosphate increased at month-12/24 (p < 0.001). Median BMD did not change significantly from baseline to 12 months but improved at 24 months (p = 0.001). CONCLUSIONS: In mostly switched patients with renal and/or BMD disorders/risks, eGFR improved after 12-24 months of TAF treatment, especially in patients with baseline eGFR 30-60 ml/min. TAF may also improve low serum phosphate, BMD and ALT, whereas it maintains or induces virological suppression.

Free Cortisol Is a More Accurate Marker for Adrenal Function and Does Not Correlate with Renal Function in Cirrhosis.

BACKGROUND: The accuracy of diagnosis and clinical implications of the hepatoadrenal syndrome, as currently diagnosed using total cortisol, remain to be validated. AIM: The aim of this study was to assess adrenal function using free cortisol in stable cirrhosis and study the potential implications of any abnormalities for renal and/or cardiac function. METHODS: Sixty-one stable consecutively enrolled patients with cirrhosis underwent assessment of adrenal function using the low-dose short Synacthen test, renal function by 51Cr-EDTA glomerular filtration rate (GFR), and cardiac function by two-dimensional echocardiography. RESULTS: Eleven patients (18%) had total peak cortisol (PC) < 500 nmol/L, but no patient had free PC < 33 nmol/L indicating that diagnosis of AI using total cortisol is not confirmed using free cortisol. Free cortisol did not correlate with GFR or parameters of cardiac function. Patients with higher Child-Pugh class had progressively lower free cortisol. Patients with low GFR < 60 mL/min (N = 22) had more frequently grade II-III diastolic dysfunction (66.7% vs. 17.6%; p = 0.005) and had higher Child-Pugh and MELD score compared to those with normal GFR. CONCLUSIONS: Diagnosis of AI using total cortisol is not confirmed using free cortisol and is thus considered unreliable in cirrhosis. Free cortisol is not associated with renal or cardiac dysfunction. Lower free cortisol in more advanced stages of liver disease might be secondary to decreased synthesis due to lower cholesterol levels. Irrespective of free cortisol, parameters of cardiac dysfunction are associated with renal impairment supporting the cardio-renal hypothesis.

Laparoscopic vs open donor nephrectomy: Lessons learnt from single academic center experience.

AIM: To compare laparoscopic and open living donor nephrectomy, based on the results from a single center during a decade. METHODS: This is a retrospective review of all living donor nephrectomies performed at the Massachusetts General Hospital, Harvard Medical School, Boston, between 1/1998 - 12/2009. Overall there were 490 living donors, with 279 undergoing laparoscopic living donor nephrectomy (LLDN) and 211 undergoing open donor nephrectomy (OLDN). Demographic data, operating room time, the effect of the learning curve, the number of conversions from laparoscopic to open surgery, donor preoperative glomerular filtration rate and creatinine (Cr), donor and recipient postoperative Cr, delayed graft function and donor complications were analyzed. Statistical analysis was performed. RESULTS: Overall there was no statistically significant difference between the LLDN and the OLDN groups regarding operating time, donor preoperative renal function, donor and recipient postoperative kidney function, delayed graft function or the incidence of major complications. When the last 100 laparoscopic cases were analyzed, there was a statistically significant difference regarding operating time in favor of the LLDN, pointing out the importance of the learning curve. Furthermore, another significant difference between the two groups was the decreased length of stay for the LLDN (2.87 d for LLDN vs 3.6 d for OLDN). CONCLUSION: Recognizing the importance of the learning curve, this paper provides evidence that LLDN has a safety profile comparable to OLDN and decreased length of stay for the donor.

Current and future challenges in the surgical treatment of hepatocellular carcinoma: a review.

Challenges in the treatment of hepatocellular carcinoma Hepatocellular carcinoma (HCC) represents one of the most frequent types of cancer worldwide. Surgery, although only a part of the armamentarium against HCC, represents the cornerstone in the management of this aggressive disease. This article will review the current and future challenges in the surgical management of HCC, with a special emphasis on the following areas: (1) the evolution of staging of the disease and the importance of the biological nature and behavior of HCC, (2) the effort to increase resectability, (3) technical innovations and the role of image-guided surgery, and, finally, (4) the role of liver transplantation in the continuum of care for these patients. Although by no means an exhaustive list, the issues mentioned above represent some of the most promising prospects for significant progress in the management of HCC.

Surgical treatment for large hepatocellular carcinoma: does size matter?

Despite significant progress in the management of hepatocellular carcinoma (HCC), patients with large HCC (defined as >10 cm) continue to present a significant challenge. The goal of this paper is to review the existing literature regarding large HCC, with emphasis on identifying the issues and challenges involved in approaching these tumours surgically. A computerized search was made of the Medline database from January 1992 to December 2010. The MESH heading 'large' or 'huge' in combination with the keyword 'hepatocellular carcinoma' was used. After excluding further studies that identified 'large' HCC as less than 10 cm and/or sequential publications with overlapping patient populations, the search produced a study population of 22 non-duplicated papers, reporting on a total of 5223 patients with HCC tumours >10 cm. Regarding resection for large HCC, the overall 5-year survival in these studies ranged from 25% to 45%, with few outliers on both sides, whereas in most studies, the 5-year disease-free survival ranged between 15% and 35%, with the only exception being studies with patients with single lesions and no cirrhosis showing disease-free survival of 41% and 56%, respectively. Risk factors identified included vascular invasion, cirrhosis, high level of alpha-fetoprotein and the presence of multiple lesions. Finally, liver transplantation, although an attractive concept, did not appear to offer a survival benefit in any of the studies. In conclusion, identifying the risk factors that affect the outcome in patients undergoing surgery for large HCC is critical. The reason is that surgical resection can have excellent outcomes in carefully selected patients.

Liver transplantation results in complete neurologic recovery from malignant hypertension secondary to fulminant hepatic failure: a case report.

BACKGROUND: Uncontrolled intracranial hypertension can lead to cerebral herniation and death in patients with acute liver failure. CASE REPORT: A 26-year-old female was admitted for acute liver failure following inadvertent acetaminophen overdose. The pH on admission was 6.9. Her neurologic status precipitously deteriorated and she was listed for liver transplantation. An intracranial pressure (ICP) monitoring catheter was inserted, which revealed a pressure >60 mmHg. After neurointensive care treatment, ICP was lowered and an emergency left lobe living donor liver transplant was performed. Intraoperative management of the ICP, which rose to 80 mmHg during the explant phase, was achieved by therapy with barbiturates and hypothermia. After surgery, hepatic function improved initially, but 7 days post transplantation the graft showed signs of acute failure. The pathology report of a liver biopsy suggested acute rejection and liver retransplantation using a deceased donor liver was then carried out. The postoperative course was uneventful and the patient recovered completely without any residual neurologic deficits. CONCLUSIONS: This case states that favourable outcomes can result from sub-optimal starting points, and that the human brain has the ability to overcome extremely adverse conditions. Critical in this effort is the role of proper neuromonitoring which helps implement the appropriate treatment measures.

Role of living donor liver transplantation in the treatment of hepatitis C virus infection.

Hepatitis C virus (HCV) infection is one of the most common indications for liver transplantation worldwide. Because of the existing organ shortage, adult-to-adult living donor liver transplantation (LDLT) has become an important method of expanding the donor pool to meet the ever-increasing need. However, despite advantages such as the quality of the hepatic graft and the timing of the transplant, the exact role of LDLT in the treatment of HCV is still unclear. In this review, we aim to address some of these issues in an effort to highlight both the advantages and disadvantages, as well as to identify the main challenges, of using LDLT for treating patients with HCV infection.

Long-term experience with liver transplantation for hepatocellular carcinoma.

BACKGROUND: The effect of the model for end-stage liver disease (MELD) system on the post-transplant survival of patients with hepatocellular carcinoma (HCC) has not been fully elucidated. Our objective is to review the results of liver transplantation (LT) for HCC at the Massachusetts General Hospital over a period of 12 years, with special emphasis on the effect of the MELD system. METHODS: A retrospective review of 73 patients who underwent liver transplantation for HCC between 1995 and 2007. Outcome measures included demographics, tumor stage at explant, patient survival, and tumor recurrence. RESULTS: On pathologic review of the explanted liver, 12.3% of patients were classified as stage I; 42.5% as stage II, 21.9% as stage III, and 23.3% as stage IV. The overall actual survival rate was 85% at 1 year, 82% at 3 years, 73% at 5 years, and 66% at 10 years. Overall tumor recurrence was 11%. Survival rates were higher after the MELD system (5 year survival 60% before MELD vs. 85% after MELD). Recurrence decreased from 21% to 7.5%. CONCLUSION: We showed improved survival for HCC after LT over the last 12 years, and especially improved survival and decreased recurrence in the time since the implementation of the MELD system.