Comparative analysis of perioperative and long-term outcomes of patients with hepatocellular carcinoma: Nonalcoholic fatty liver disease versus viral hepatitis.

BACKGROUND: Despite the accumulating evidence regarding the oncological differences between nonalcoholic fatty liver disease (NAFLD)-related hepatocellular carcinoma (HCC) and viral infection-related HCC, the short- and long-term outcomes of surgical resection of NAFLD-related HCC remain unclear. While some reports indicate improved postoperative survival in NAFLD-related HCC, other studies suggest higher postoperative complications in these patients. METHODS: Patients with NAFLD and those with hepatitis viral infection who underwent hepatectomy for HCC at our department were retrospectively analyzed. The clinical, surgical, pathological, and survival outcomes were compared between the two groups. RESULTS: Among the 1047 consecutive patients who underwent hepatectomy for HCC, 57 had NAFLD-related HCC (NAFLD group), and 727 had virus-related HCC (VH group). The body mass index and serum glycated hemoglobin levels were significantly higher in the NAFLD group than in the VH group. There were no significant differences in operative time and bleeding amount. Moreover, the morbidity and the length of postoperative hospital stays were similar across both groups. The pathological results showed that the tumor size was significantly larger in the NAFLD group than in the VH group. No significant differences between the groups in overall or recurrence-free survival were found. In a subgroup analysis with matched tumor diameters, patients in the NAFLD group had a better prognosis after hepatectomy than those in the VH group. CONCLUSION: Surgical outcomes after hepatectomy were comparable between the groups. Subgroup analysis reveals early detection and surgical intervention in NAFLD-HCC may improve prognosis.

Minimally Invasive Donor Hepatectomy for Adult Living Donor Liver Transplantation: An International, Multi-institutional Evaluation of Safety, Efficacy and Early Outcomes.

OBJECTIVE: Evaluating the perioperative outcomes of minimally invasive (MIV) donor hepatectomy for adult live donor liver transplants in a large multi-institutional series from both Eastern and Western centers. BACKGROUND: Laparoscopic liver resection has become standard practice for minor resections in selected patients in whom it provides reduced postoperative morbidity and faster rehabilitation. Laparoscopic approaches in living donor hepatectomy for transplantation, however, remain controversial because of safety concerns. Following the recommendation of the Jury of the Morioka consensus conference to address this, a retrospective study was designed to assess the early postoperative outcomes after laparoscopic donor hepatectomy. The collective experience of 10 mature transplant teams from Eastern and Western countries was reviewed. METHODS: All centers provided data from prospectively maintained databases. Only left and right hepatectomies performed using a MIV technique were included in this study. Primary outcome was the occurrence of complications using the Clavien-Dindo graded classification and the Comprehensive Complication Index during the first 3 months. Logistic regression analysis was used to identify risk factors for complications. RESULTS: In all, 412 MIV donor hepatectomies were recorded including 164 left and 248 right hepatectomies. Surgical technique was either pure laparoscopy in 175 cases or hybrid approach in 237. Conversion into standard laparotomy was necessary in 17 donors (4.1%). None of the donors died. Also, 108 experienced 121 complications including 9.4% of severe (Clavien-Dindo 3-4) complications. Median Comprehensive Complication Index was 5.2. CONCLUSIONS: This study shows favorable early postoperative outcomes in more than 400 MIV donor hepatectomy from 10 experienced centers. These results are comparable to those of benchmarking series of open standard donor hepatectomy.

An Overview of Liver Transplant Pathology: Data from a Tertiary Referral Centre in Western India.

INTRODUCTION AND AIM: 1. Study of liver explants - Etiologic types of end-stage chronic liver disease (ESCLD) and acute liver failure (ALF) in adults and children. 2. Assessment of donor steatosis and incidental granulomas. 3. Post-transplant liver biopsies. MATERIAL AND METHODS: Specimens of 180 explant hepatectomies, 173 donor wedge and 30 core liver biopsies, and 58 post transplant liver biopsies received in our department from April 2013 to March 2017. RESULTS: 1. Most common causes of ESCLD in adults were: alcohol related (30.32%), hepatitis virus related (18.71%) and non-alcoholic steatohepatitis related (18.06%); and in children ≤ 12 years were: biliary atresia (27.27%), autoimmune disease (18.18%) and Wilson's disease (18.18%). Most common causes of ALF in adults and children were anti-tubercular therapy induced and idiopathic respectively. 2. Prevalence rate of moderate steatosis (between 30-60%) was 4.28%. Incidental granulomas were seen in 5 cases. 3. Most common diagnoses of post-transplant biopsies in adults included acute cellular rejection (ACR) (36.17%), recurrence of viral disease (8.51%) and moderate non-specific portal triaditis (8.51%). Among children ≤ 12 years, most common diagnoses included unremarkable liver parenchyma, ACR and ischemia/reperfusion injury. CONCLUSION: 1. Alcohol- and hepatitis- virus related ESCLD, and biliary atresia are leading indications for liver transplantation in adults and children respectively. 2. Prevalence of 4.28% of moderate steatosis, is much lower than that documented in western literature. Only 5 cases of incidental granulomas is unexpectedly low in a country endemic for tuberculosis. 3. Most common diagnoses of post-transplant liver biopsies in adults has been acute rejection, which is similar to the findings from much larger published series.

Liver transplantation in the Kingdom of Saudi Arabia.

The first liver transplantation (LT) in Saudi Arabia was performed in 1991; however, it was not until 1994 that the first structured LT program was launched. Until 1997, all LTs in the Kingdom of Saudi Arabia (KSA) were deceased donor liver transplantations. Programs performing LTs needed the authorization of the Saudi Center for Organ Transplantation (SCOT), which provides the essential support for organ procurement and allocation as well as regulatory support for organ transplantation in the country. Currently, there are 4 LT centers in the KSA. Three centers are in Riyadh, the capital city of KSA, and 1 is in the city of Dammam in the Eastern province. Pediatric living donor liver transplantation (LDLT) began in 1997, while the adult LDLT program started 4 years later in 2001. Currently, more than 2000 LTs have been performed by the 4 centers in the KSA. Over 50% of those were performed at King Faisal Specialist Hospital and Research Center in Riyadh. The outcomes of these transplants have been comparable with the international standards. The aim of this review is to provide an overview of LT in KSA. Liver Transplantation 23 1312-1317 2017 AASLD.

Living donor liver transplantation for neonatal fulminant hepatitis due to herpes simplex virus infection.

Although rare, ALF caused by disseminated HSV infection is associated with high mortality in the neonatal population. This condition is often diagnosed relatively late due to the absence of specific signs. We present a case involving a neonate with ALF submitted to living donor liver transplantation without a prior diagnosis. The patient had no skin or mucosal lesions, and IgM serology was negative for HSV-1 and HSV-2. Immunohistochemical staining of the liver explant was positive for herpes virus infection, and the patient subsequently received antiviral drug treatment, with a good outcome. Due to organ shortages and the rarity of the aforementioned condition, LT has seldom been reported for the treatment of ALF caused by herpes virus infection; however, LT may be the only option for neonates with fulminant hepatitis. The use of living donors in an urgent scenario is well established in Eastern countries and safely applicable for pediatric patients with ALF.

Prediction of portal pressure from intraoperative ultrasonography.

BACKGROUND: Portal hypertension is a major risk factor for hepatic failure or bleeding in patients who have undergone hepatectomy, but it cannot be measured indirectly. We attempted to evaluate the intraoperative ultrasonography parameters that correlate with portal pressure (PP) in patients undergoing hepatectomy. METHODS: We examined 30 patients in whom PP was directly measured during surgery. The background liver conditions included chronic viral liver disease in seven patients, chemotherapy-associated steatohepatitis in four patients, fatty liver in one patient, hepatolithiasis in one patient, obstructive jaundice in one patient, and a normal liver in 16 patients. A multivariate logistic analysis and linear regression analysis were conducted to develop a predictive formula for PP. RESULTS: The mean PP was 10.4 ± 4.1 mm Hg. The PP tended to be increased in patients with chronic viral hepatitis. A univariate analysis identified the association of the six following parameters with PP: the platelet count and the maximum (max), minimum (min), endo-diastolic, peak-systolic, and mean velocity in the portal vein (PV) flow. Using multiple linear regression analysis, the predictive formula using the PV max and min was as follows: Y (estimated PP) = 18.235-0.120 × (PV max.[m/s])-0.364 × (PV min). The calculated PP (10.44 ± 2.61 mm Hg) was nearly the same as the actual PP (10.43 ± 4.07 mm Hg). However, there was no significant relationship between the calculated PP and the intraoperative blood loss and post hepatectomy morbidity. CONCLUSIONS: This formula, which uses ultrasonographic Doppler flow parameters, appears to be useful for predicting PP.

[Executive summary of the recommendations on the evaluation and management of renal disease in human immunodeficiency virus-infected patients]. / Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por el virus de la inmunodeficiencia humana.

The aim of this article is to update the 2010 recommendations on the evaluation and management of renal disease in human immunodeficiency virus (HIV)-infected patients. Renal function should be monitored in all HIV-infected patients. The basic renal work-up should include measurements of serum creatinine, estimated glomerular filtration rate by CKD-EPI, urine protein-to-creatinine ratio, and urinary sediment. Tubular function tests should include determination of serum phosphate levels and urine dipstick for glycosuria. In the absence of abnormal values, renal screening should be performed annually. In patients treated with tenofovir, or with risk factors for chronic kidney disease (CKD), more frequent renal screening is recommended. In order to prevent disease progression, potentially nephrotoxic antiretroviral drugs are not recommended in patients with CKD or risk factors for CKD. The document provides indications for renal biopsy and advises on the optimal time for referral of a patient to the nephrologist. The indications for and evaluation and management of dialysis and renal transplantation are also addressed.

Liver stiffness measurement by transient elastography as a predictor on posthepatectomy outcomes.

BACKGROUND: Liver fibrosis and cirrhosis are well-known risk factors for morbidity after hepatectomy. Liver stiffness measurement (LSM) using transient elastography is a new method for detection of hepatic fibrosis and cirrhosis with high accuracy. Whether LSM can predict posthepatectomy outcomes has not been studied. METHODS: This was a prospective cohort study in which consecutive patients underwent hepatectomy for various indications from February 2010 to July 2011. All patients received detailed preoperative assessments including LSM and indocyanine green (ICG) clearance test. The primary outcome was major postoperative complication. RESULTS: One hundred five patients with a mean age of 59 years were included; 75 (71.4%) had chronic viral hepatitis and 76 (72.4%) had hepatocellular carcinoma. Thirty-four patients (32.4%) received major hepatectomy. The median ICG retention rate at 15 minutes was 4.2 (0.1%-32%) and the median LSM was 9.4 (3.3-75 kPa). For posthepatectomy outcomes, only LSM but not ICG showed significant correlation with major postoperative complications on receiver operating characteristic curves, with area under the curve of 0.79 (P < 0.001). Using the calculated cutoff at 12.0 kPa, LSM had sensitivity of 85.7% and specificity of 71.8% in the prediction of major postoperative complications. It was also an independent prognostic factor for major postoperative complications by multivariate analysis. The operative blood loss and transfusion rate were also significantly higher in patients with LSM >12.0 kPa. CONCLUSIONS: High LSM (>12.0 kPa) predicted worse posthepatectomy outcomes. Preoperative LSM was better than ICG test in the prediction of major postoperative complications. It was a useful preoperative investigation for risk stratification before hepatectomy.

Functional liver reserve parameters predictive for posthepatectomy complications.

BACKGROUND: Posthepatectomy complications have markedly decreased with advances in techniques and management; however, surgical risk to patients with injured livers is still not negligible. We evaluated several preoperative parameters of functional liver reserve tests in patients with various liver diseases as predictors of posthepatectomy complications. A comprehensive evaluation of preoperative liver functions is necessary for the prediction of the risk of posthepatectomy complications. METHODS: Over a 10-y period, we examined 442 patients who underwent hepatectomy for liver and biliary diseases. The patients' background liver diseases included chronic viral liver diseases in 211 patients, obstructive jaundice in 29 patients, and normal liver in 202 patients. Hepatectomy-related postoperative complications (i.e., long-term ascites, intra-abdominal infection, and hepatic failure) occurred in 115 (26%) patients. A multivariate logistic analysis was performed to detect the predictive parameters, and a multivariate linear regression analysis was performed to derive a predictive formula for complications. RESULTS: A univariate analysis identified 15 significant parameters associated with hepatectomy-related complications, and eight parameters (i.e., presence of chronic hepatic injury, clearance index by technetium-99 m galactosyl human serum albumin liver scintigraphy of ≥ 0.60, total bilirubin level of >1 mg/dL, serum hyaluronic acid level of ≥ 75 ng/mL, major hepatectomy, blood loss of ≥ 950 mL, operating time of ≥ 500 min, and combined resection of another organ or major vessel) were independent predictive factors identified in the multivariate analysis. Clearance index by technetium-99 m galactosyl human serum albumin liver, bilirubin level, hyaluronic acid level, and major hepatectomy were the parameters included in the predictive formula. CONCLUSIONS: In the present study, we present a comprehensive formula based on the predictive parameters for hepatic complications for prospective assessment to avoid posthepatectomy morbidity.

Cytomegalovirus infection-associated fulminant hepatitis in an immunocompetent adult requiring emergency living-donor liver transplantation: report of a case.

Human cytomegalovirus (CMV) infection is usually self-limiting in healthy adults, but it can lead to significant complications. This report presents the case of an immunocompetent adult with fulminant hepatitis caused by a CMV infection requiring emergency living-donor liver transplantation. A 39-year-old female with persistent fever for 6 weeks was referred for fulminant hepatitis, but the underlying etiology was not identified. Rapid deterioration of consciousness led to an emergency living-donor liver transplant using a modified right lobe graft. She showed increasing CMV antigenemia after surgery and the explant liver pathology showed massive hepatic necrosis with positive staining for CMV protein. Treatment with ganciclovir improved the graft liver function and her general condition recovered. This report presents a rare case of CMV-associated fulminant hepatitis which led to emergency liver transplantation. Although CMV is rare, it should be included in the differential diagnosis of patients with severe hepatitis, even immunocompetent patients, after other more common etiologies have been excluded.

Liver transplantation in HIV patients.

In the last three decades, the management of human immunodeficiency virus (HIV) has improved dramatically. The use of combination antiretroviral therapy (ART) has been successful at preventing death and the myriad infectious, malignant, and immune-mediated complications of HIV. Once considered to be a fatal disease, HIV is now considered by many to be a chronic disease; those affected may now live to experience complications of other coexistent diseases. Liver disease has been increasingly recognized as a leading cause of non-HIV/acquired immunodeficiency syndrome- (AIDS-) related morbidity and mortality in this population.Although liver transplantation offers the opportunity to prolong life, the transplant community has been slow to recognize the chronicity of HIV and potential for transplantation within this population. The experience with liver transplantation in HIV-positive patients is evolving and successful outcomes have been observed when specific criteria are used to select candidates.

Meeting report of the 2011 Joint International Congress of the International Liver Transplantation Society, the European Liver and Intestine Transplant Association, and the Liver Intensive Care Group of Europe.

The International Liver Transplantation Society held its yearly meeting as a joint conference with the European Liver and Intestine Transplant Association and the Liver Intensive Care Group of Europe at the Valencia Congress Center (Valencia, Spain) from June 22 to 25, 2011. Nearly 1500 registrants attended the meeting, which opened with a premeeting conference entitled "Global Challenges and Controversies in Liver Transplantation." This was followed by numerous oral and poster abstract sessions and topic sessions focused on medical, surgical, and intensive care aspects of liver transplantation (LT). This report summarizes key symposia and oral abstracts delivered at the meeting and is conveniently divided into subsections relevant to LT. It is not meant to be a critical or comprehensive evaluation of all the meeting presentations and is merely intended to highlight presentations and associated published literature dealing with key topics.

Persistent increase in alpha-fetoprotein level in a patient without underlying liver disease who underwent curative resection of hepatocellular carcinoma. A case report and review of the literature.

INTRODUCTION: Alpha-fetoprotein (AFP) is an oncofetal protein produced by hepatocellular carcinoma (HCC). AFP level can also be elevated in other neoplastic or non-neoplastic conditions. An elevated AFP level has high diagnostic significance for HCC; at a level of >200 ng/mL, the probability of HCC is >90%. The aim of the present paper is to report a patient who underwent curative resection of HCC, who had a persistently elevated AFP level postoperatively but did not develop recurrence during a 2-year follow-up period. A review of the literature is also presented. CASE REPORT: An 82-year-old male was referred following a computed tomography scan showing a 160 mm diameter mass in the left lobe of the liver. This huge mass was diagnosed as HCC, arising in the absence of cirrhosis or viral hepatitis. After tumor removal, the patient's high AFP level persisted for 2 years. CONCLUSION: As steatosis was the only pathological change in the remnant liver, this may have caused the persistently elevated AFP level in this patient.

Gender differences in patient receiving liver transplantation for viral hepatitis.

INTRODUCTION: The course of viral hepatitis shows wide interindividual differences, ranging from asymptomatic disease to liver failure. Only limited data on gender differences in patients undergoing liver transplantation (OLT) exist. We studied the gender distribution in patients who underwent liver transplantation for viral hepatitis. METHODS: A retrospective analysis was performed on a cohort of 368 patients who underwent OLT for viral hepatitis-associated acute or chronic liver failure. In 96 of them, additional hepatocellular carcinoma (HCC) was present at transplantation. Gender ratios of the different hepatitis virus infections and in relation to HCC were evaluated. RESULTS: Significantly more males than females underwent OLT for chronic HBV. In contrast, patients after OLT for fulminant HBV were more frequently females. In patients transplanted for chronic HCV or HDV, no significant gender differences were found. However, men presented more frequently with HCC in both groups of chronic liver disease. CONCLUSIONS: There was a gender difference in HBV infection with more women developing fulminant hepatic failure in acute HBV while more men progressed to end-stage liver disease in chronic HBV. The role of gender in chronic HCV and HDV infection was less pronounced, except for a male predominance among patients with HCC.

Demographics and outcomes of severe herpes simplex virus hepatitis: a registry-based study.

BACKGROUND & AIMS: Herpes simplex virus hepatitis is a rare, but severe disease, thus far only documented by case reports and short series. The present study was based on the SRTR registry, and included all listed patients for liver transplantation from 1985 to 2009 with a diagnosis of HSV hepatitis. METHODS: We assessed demographics and outcome of all listed patients, and further conducted a case-control study, matching each transplanted patient with 10 controls. Matching criteria included: transplant status, MELD score ±5, transplant date ±6 months, and age at transplant ±5 years. During the study period, 30 patients were listed for HSV hepatitis. Of the 30 listed patients, seven recovered spontaneously and five died, prior to transplantation. The remaining 10 children and eight adults were transplanted. RESULTS: The chance of recovery was significantly higher in children than in adults (7/19 vs. 0/11, p=0.02). In children, survival was similar between HSV patients and the matched controls (5-year survival: 69% vs. 64%, p=0.89). Conversely, survival was poor in adult HSV (5-year survival: 38% vs. 65%, p=0.006), with 62% of them dying within the first 12 months. All three reported post-transplant deaths in children were independent from HSV. Among the seven adult post-transplant deaths, four were related to infection (bacterial, fungal, or viral). CONCLUSIONS: Children listed for HSV hepatitis have a significantly better survival than adults both prior and after liver transplantation. While HSV fulminant hepatitis is an appropriate indication for liver transplantation in children, it should only be performed in selected adult patients in otherwise good condition.

Long-term follow-up after right hepatectomy for adult living donation and attitudes toward the procedure.

OBJECTIVES: To determine the long-term health status of donors after right hepatectomy for adult live donor liver transplantation (ALDLT). BACKGROUND: The long-term outcomes for ALDLT donors are unknown. METHODS: ALDLT donors undergoing right hepatectomy from April 1998 to June 2007 were invited to complete a questionnaire regarding health status, satisfaction (1-10/worst-best scale), self-esteem, willingness to donate again, and suggestions for improvement. In addition, donor files and cholecystectomy specimens were reviewed. Fisher's exact test, Kaplan-Meier and logistic regression analyses were performed. RESULTS: Eighty-three donors were contacted (median age: 36 years; median follow-up: 69 months). 39 (47%) were free of symptoms. The remaining 44 (53%) reported: intolerance to fatty meals and diarrhea (31%), gastroesophageal reflux associated with left liver hypertrophy (9%), incisional discomfort requiring pain medications (6%), severe depression requiring hospitalization (4%), rib pain affecting lifestyle (2%), and exacerbation of psoriasis (1%). Median satisfaction score was 8. Self-esteem diminished in 5%. Thirty-nine (47%) recommended improvements particularly more detailed informed donor consent and a centralized living donor liver registry. Seventy-eight (94%) were willing to donate again. There were no differences between donors with and without complaints with respect to: donor age, gender, early complications and follow-up time, young-to-old donation, recipient diagnosis of malignancy and death of the recipient. Noninflamed donor cholecystectomy specimens correlated with intolerance to fatty meals and diarrhea (P = 0.001). CONCLUSIONS: ALDLT donors are at risk for long-term complaints that are neither reflected nor related to early complications. This information should be included in both the donor evaluation and the ALDLT decision-making process.

Herpes simplex virus hepatitis in infants: clinical outcomes and correlates of disease severity.

OBJECTIVE: To better characterize the clinical outcomes of infants with herpes simplex virus (HSV) infection and identify useful correlates of disease severity. STUDY DESIGN: Infants aged ≤6 months with HSV infection treated between 1999 and 2009 were identified. In patients with concurrent hepatitis, laboratory and clinical variables were examined to identify predictors of specific outcomes, including death or the need for liver transplantation and the need for intensive care. RESULTS: Of the 15 patients enrolled, 4 (27%) had fatal disease and 2 (13%) required liver transplantation. Infants who lacked skin lesions (P = .04), had a positive HSV polymerase chain reaction result (P = .01), had more severe thrombocytopenia (P = .001), or had other organ system dysfunction (P = .002) were more likely to require intensive care. A higher International Normalized Ratio value (P = .001) and peak total bilirubin level (P = .0002) were predictive of death or the need for liver transplantation. Peak direct bilirubin level was predictive of the need for intensive care and of death or the need for liver transplantation (P = .04 and .009, respectively). CONCLUSIONS: HSV hepatitis represents a broad spectrum of disease from mild aminotransferase elevation to fulminant liver failure and death. HSV DNA detected by polymerase chain reaction, a lack of skin lesions, and the degree of coagulopathy, thrombocytopenia, and cholestasis portend unfavorable outcomes.

[Recommendations of Gesida/PNS/AEEH for the management and treatment of the adult patient co-infected with HIV and hepatitis A, B and C virus]. / Recomendaciones de Gesida/PNS/AEEH sobre tratamiento y manejo del paciente adulto coinfectado por VIH y virus de las hepatitis A, B y C.

OBJECTIVE: This review updates clinical guidelines on HIV+ and hepatitis A, B and C in coinfected adult patients. METHODS: This consensus has been adopted by an expert panel from several scientific societies (GESIDA/SPNS/AEEH). Published data on epidemiology, natural history, prevention and treatment of viral hepatitis in HIV+ patients have been reviewed. These statements are classified according to the rating scheme of the DHHS for the strength and quality of evidence of the data. The evidence has been sub-typed as "a" and "b", depending on whether the available data were from coinfected or non-coinfected patients. RESULTS: These guidelines focus on conditions associated with the care of the hepatic diseases, such as prevention of these hepatitis, alcohol intake, drug use, antiretroviral therapy with or without treatment of chronic hepatitis. Follow-up is individualised, based on virological data and non-invasive assessment of liver fibrosis. Several nucleoside/nucleotide analogues have activity against HBV and HIV, so the majority of the patients will receive combined therapy. A significant proportion of patients can resolve HCV infection. It is important to select the patient appropriately and a good knowledge of these therapies is required. With advanced liver disease, it may be necessary to adapt HAART and consider liver transplantation. CONCLUSIONS: We have effective drugs and diagnostic procedures in order to evaluate all coinfected patients and consider a high proportion suitable for therapy against hepatitis viruses. These patients should have the same therapeutic options as the general population.

Fulminant herpes simplex virus hepatic failure in pregnancy requiring liver transplantation.

Herpes simplex virus hepatitis is a rare but potentially fatal condition that usually affects the immunocompromised, including pregnant women. This case report details the course of fulminant hepatic failure in a woman at 31 weeks gestation resulting in emergent delivery of the fetus and liver transplant in the mother.