Prospective evaluation of patients with non-cirrhotic portal hypertension: A single centre study.

BACKGROUND: Non-cirrhotic portal hypertension (NCPH) is a spectrum of liver diseases, including porto-sinusoidal vascular disorder, with portal hypertension (PH) in the absence of cirrhosis. The natural history and diagnostic approach to NCPH are not well understood. AIM: We aimed to evaluate disease progression and outcomes in NCPH. METHODS: Patients with or at risk for NCPH were enrolled in a single centre prospective study; two groups were formed based on the presence of specific features of PH, such as varices, collaterals, portal hypertensive gastropathy or portal hypertensive bleeding. All participants underwent a baseline liver biopsy. Liver stiffness measurement (LSM), and imaging were repeated every 6-12 months. RESULTS: Fifteen patients without specific features of PH (Group I), and 35 patients with specific features (Group II) were enrolled. The median follow-up time was 50 months. Group II had higher hepatic venous pressure gradients, non-invasive measures of PH and a lower platelet count (PLT) when compared to Group I. Rates of survival and decompensation were similar in both groups. Patients with PLT ≤100 K/mcL had lower survival compared to those with PLT >100 K/mcL. Patients with LSM ≥10 kPa had lower survival and survival without decompensation when compared to patients with LSM <10 kPa. CONCLUSIONS: Patients irrespective of specific features of PH had similar survival or survival without decompensation. Patients without specific features are at risk for disease progression and should be monitored closely. Thrombocytopenia and increased LSM are associated with severe forms of liver disease, which are strongly associated with outcomes.

Hepatitis B Virus/Hepatitis D Virus-Coinfected Liver Transplant Candidate Receiving Hepatitis B Virus-Deoxyribonucleic Acid-Positive Allograft and Treated With High-Dose Hepatitis B Immune Globulin.

Liver transplantation (LT) for patients with hepatitis D virus (HDV) and hepatitis B virus (HBV) coinfection is uncommon in the United States. Previous case reports described poor outcomes when hepatitis B surface antigen (HBsAg)-positive grafts are transplanted in HBV/HDV-coinfected recipients. However, LT from an HBsAg-negative/HBV-deoxyribonucleic acid-positive donor in an HBV/HDV-coinfected recipient has not been reported. We describe the clinical course and management of an HBV/HDV-coinfected recipient who had LT from an HBsAg-negative/HBV-deoxyribonucleic acid-positive deceased donor and was treated with high-dose hepatitis B immune globulin in combination with an oral tenofovir alafenamide.

Donor Factors Including Donor Risk Index Predict Fibrosis Progression, Allograft Loss, and Patient Survival following Liver Transplantation for Hepatitis C Virus.

BACKGROUND: The utilization of liver transplantation (LT) is limited by the availability of suitable organs. This study aimed to assess the impact of the donor risk index (DRI) and other donor characteristics on fibrosis progression, graft, and patient survival in hepatitis C virus (HCV)-infected LT recipients. METHODS: HCV-infected LT recipients who had at least 2 post-LT protocol liver biopsy specimens available were included. Hazard ratio for bivariate analysis was computed using Cox proportional hazard regression analysis. RESULTS: Of 312 recipients, 26.6% died over a median follow-up of 58.5 months (95% CI: 46.5-67.3). Fourteen patients underwent re-transplantation. Mean time to graft failure was 84.3 months, median follow-up: 59 months, 95% CI (48.2, 68.3). DRI >1.5 was significantly associated with patient and graft survival (P = 0.04). Of the subset of 104 individuals who underwent histological analysis, 67.3% progressed to ≥F2. On multivariate analysis, significant donor-specific predictors of fibrosis progression were: donor age >50 years and DRI >1.7. CONCLUSIONS: (1) Fibrosis progression in HCV-infected LT recipients is strongly associated with donor characteristics, specifically donor age and DRI. (2) DRI, an objective measure of donor quality, appears to correlate both with rate of histological progression and overall patient/graft survival.

Use of adjuvant sorafenib in liver transplant recipients with high-risk hepatocellular carcinoma.

The efficacy of liver transplantation (LT) for hepatocellular (HCC) is limited by tumor recurrence rates of 10-15%. We undertook this pilot study to examine the use of sorafenib as adjuvant therapy in high-risk LT recipients. Methods. We prospectively enrolled patients transplanted for HCC into a treatment protocol utilizing sorafenib if their explant examination showed evidence of viable tumor exceeding Milan criteria. We utilized as historical controls patients transplanted previously, whose explant tumor characteristics exceeded Milan criteria, but who were not "preemptively" treated with sorafenib. Wilcoxon two-sample test and Fisher's exact test were used to compare survival and recurrence rates between the two groups. Results. Seven patients were treated with sorafenib and compared to 12 historical "controls." Two of 7 treated patients suffered from HCC recurrence. Of the comparison group, 9 experienced HCC recurrence and all succumbed to disease. Dose reduction improved tolerance of drug. The overall rate of HCC recurrence was decreased in the adjuvant therapy group compared to historical controls (29% versus 75%, P = 0.07). Disease free 1-year survival for the treated versus untreated group was 100% versus 66%, respectively. Conclusion. Adjuvant use of sorafenib is safe and decreases risk of HCC recurrence in high-risk LT recipients.

Dobutamine stress echocardiography in patients undergoing orthotopic liver transplantation: a pooled analysis of accuracy, perioperative and long term cardiovascular prognosis.

Pre-transplant evaluation for orthotopic liver transplantation (OLT) commonly includes a cardiac evaluation using dobutamine stress echocardiography (DSE). We performed a quantitative systematic review assessing DSE's use in detecting coronary artery disease (CAD) and predicting perioperative and long term cardiac events in patients undergoing OLT. Published studies in pubmed were accessed using keyword searches and bibliographic review. Included studies evaluated the use of DSE in patients undergoing OLT, including its accuracy for detection of CAD, and in predicting perioperative and long term cardiac prognosis for both hard (myocardial infarction, cardiac death, cardiac arrest, and asystole) and soft cardiac events (all other events that were cardiovascular in nature). We calculated DSE's sensitivity, specificity, negative predictive value (NPV), and positive predictive value (PPV) in the above areas. We identified 7 studies, including a total of 580 patients, which included 4 accuracy studies (n = 110 patients), 4 perioperative studies, and 3 long term studies. Accuracy for CAD included a sensitivity of 0.32, specificity of 0.78, PPV of 0.37, and NPV of 0.75. Accuracy for prediction of perioperative hard and soft cardiac events was a sensitivity of 0.20 and 0, specificity of 0.99 and 0.99, PPV of 0.33 and 0, and NPV of 0.98 and 0.89, respectively. For long term hard and soft cardiac events, sensitivity was 0.5 and 0, specificity 0.99 and 0.98, PPV 0.33 and 0, and NPV 0.99 and 0.96, respectively. DSE has a limited accuracy for the detection of CAD in candidates for OLT. However, among those patients selected for OLT, the negative predictive value of DSE for both perioperative and long term cardiac events is high.

Liver allograft outcomes after laparoscopic-assisted and minimal access live donor hepatectomy for transplantation.

BACKGROUND: The critical shortage of deceased organ donors has led to live-donor hepatectomy as an alternative donor option for transplantation. Although laparoscopic hepatectomy has been well described for management of liver tumors and can be performed safely, few studies have examined early recipient allograft outcomes after laparoscopic live-donor hepatectomy. We describe our initial experience with laparoscopic-assisted and minimal-access donor hepatectomy and its potential as a safe alternative with graft function comparable with open resection in live-donor liver transplantation. METHODS: We performed a retrospective analysis of our past 30 successive live-donor transplants between 2005 and 2009. Fifteen allografts were procured by standard open live-donor (OLD) hepatectomy, and 15 by laparoscopic-assisted (LALD) or minimal-access (MA) live-donor hepatectomy. Left lateral segment grafts were subcategorized and analyzed further. RESULTS: Mean donor age, sex, and liver anatomy were comparable between donor groups. Early graft function as measured by peak total bilirubin level, aspartate aminotransferase level, alanine aminotransferase level, and international normalized ratio on postoperative days 2, 7, 30, and 90 were similar between groups, although the international normalized ratio was slightly more increased on postoperative day 7 in LALD grafts (1.75 ± .45 vs 1.28 ± .16; P = .02). Perioperative allograft biliary (2 of 15 vs 0 of 15; P = .48) and vascular (3 of 15 vs 1 of 15; P = .6) complication rates also were comparable between OLD and LALD/MA grafts. One-year graft and patient survival for LALD/MA was 100% compared with 93% for OLD. CONCLUSIONS: Our experience shows that LALD or MA live-donor hepatectomy is a safe procedure and produces early graft function comparable with standard OLD hepatectomy. Multicenter, larger-volume experience will determine the widespread application of this technique.

Racial differences in liver inflammation and fibrosis related to chronic hepatitis C.

BACKGROUND & AIMS: Hepatitis C virus (HCV) infection is more prevalent in black compared with white Americans. However, the natural course of HCV in black patients has not been defined. METHODS: We performed a retrospective comparison of initial liver tests, HCV genotype and viral load, and liver histology findings in 87 black and 136 white American chronic hepatitis C patients who were evaluated at the University of Maryland between 1995 and 1998. The liver biopsy examinations were interpreted by using the Knodell Histologic Activity Index (HAI) criteria. RESULTS: Black HCV patients were older (46.3 vs. 43.3 yr; P = 0.004) and were more likely to be infected with HCV genotype 1 (95% vs. 75%). The modes of HCV transmission, estimated duration of HCV infection, and prevalence of alcohol abuse were similar in the 2 groups. Yet, black patients had lower mean total HAI scores (7.6 vs. 8.7; P = 0.021), periportal hepatocyte necrosis scores (P = 0.021), and liver fibrosis scores (P = 0.049). In keeping with less hepatic necroinflammatory activity, black patients had a lower mean serum alanine transaminase (ALT) level (85.5 vs. 122.7; P = 0.002). Black patients also had lower serum iron levels (P = 0.009). There were no racial differences in the prevalence of increased iron studies and hepatic iron loading. CONCLUSIONS: Black chronic HCV patients have milder liver necroinflammation and fibrosis than white patients with similar HCV duration. These differences in liver histology were not explained by a variance in hepatic iron loading.

Motion - all patients with NASH need to have a liver biopsy: arguments against the motion.

Most cases of nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are suspected on the basis of the exclusion of viral, autoimmune, metabolic and genetic causes of chronic liver disease in patients with chronic elevation of aminotransferase enzymes. However, the definitive diagnosis of NASH requires liver biopsy. Valuable blood tests include hepatitis B and C serology, iron profile, alpha 1-antitrypsin phenotype, ceruloplasmin, antinuclear antibody and antismooth muscle antibody, and serum protein electrophoresis. If these tests are negative or normal, and if there are no symptoms or signs of chronic liver disease, it is unlikely that a specifically treatable liver disease would be discovered at biopsy. The prevalence of NAFLD in the general population appears to be approximately 20%, and 2% to 3% of people have NASH. There is no proven specific therapy for the spectrum of nonalcoholic liver disease; therefore, the management of the patient with NASH is not likely to be changed after histological assessment. Bleeding, sometimes fatal, and other complications requiring hospitalization can occur, and liver biopsies should not be undertaken without clear clinical indications. The high cost of undertaking histological assessment of all persons with asymptomatic elevations of liver enzymes cannot be justified in view of the risks and limited clinical benefits.