Blood loss during liver transplantation (OLTx) is a common consequence of pre-existing abnormalities of the hemostatic system, portal hypertension with multiple collateral vessels, portal vein thrombosis, previous abdominal surgery, splenomegaly, and poor “functional” recovery of the new liver. The intrinsic coagulopathic features of end stage cirrhosis along with surgical technical difficulties make transfusion-free liver transplantation a major challenge, and, despite the improvements in understanding of intraoperative coagulation profiles and strategies to control blood loss, the requirements for blood or blood products remains high. The impact of blood transfusion has been shown to be significant and independent of other well-known predictors of posttransplant-outcome. Negative effects on immunomodulation and an increased risk of postoperative complications and mortality have been repeatedly demonstrated. Isovolemic hemodilution, the extensive utilization of thromboelastogram and the use of autotransfusion devices are among the commonly adopted procedures to limit the amount of blood transfusion. The use of intraoperative blood salvage and autologous blood transfusion should still be considered an important method to reduce the need for allogenic blood and the associated complications. In this article we report on the common preoperative and intraoperative factors contributing to blood loss, intraoperative transfusion practices, anesthesiologic and surgical strategies to prevent blood loss, and on intraoperative blood salvaging techniques and autologous blood transfusion. Even though the advances in surgical technique and anesthetic management, as well as a better understanding of the risk factors, have resulted in a steady decrease in intraoperative bleeding, most patients still bleed extensively. Blood transfusion therapy is still a critical feature during OLTx and various studies have shown a large variability in the use of blood products among different centers and even among individual anesthesiologists within the same center. Unfortunately, despite the large number of OLTx performed each year, there is still paucity of large randomized, multicentre, and controlled studies which indicate how to prevent bleeding, the transfusion needs and thresholds, and the “evidence based” perioperative strategies to reduce the amount of transfusion.
Transplantation surgery; Liver dysfunction; Liver transplant; Intraoperative bleeding; Intraoperative transfusion; Autotransfusion; Autologous transfusions; Transfusion requirements; Blood salvage; Cell salvage
Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates. Patients with cirrhosis have altered and impaired immunity, which favours bacterial translocation. Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease. The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections, pneumonia, endocarditis and skin and soft-tissue infections. Patients with decompensated cirrhosis have increased risk of developing sepsis, multiple organ failure and death. Risk factors associated with the development of infections are severe liver failure, variceal bleeding, low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP). The prognosis of these patients is closely related to a prompt and accurate diagnosis. An appropriate treatment decreases the mortality rates. Preventive strategies are the mainstay of the management of these patients. Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins. However, the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP, compared to community-acquired episodes. This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamase-producing Enterobacteriaceae, which are resistant to the first line antimicrobial agents used for treatment. The emergence of resistant bacteria, underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections. Nosocomial infections should be treated with wide spectrum antibiotics. Further studies of early diagnosis, prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.
Cirrhosis; Infections; Spontaneous bacterial peritonitis; Ascites; Antibiotics
AIM: To determine feasibility of liver transplantation in patients from the intensive care unit (ICU) by estimating graft and patient survival.
METHODS: This single center retrospective study included 39 patients who had their first liver transplant directly from the intensive care unit and 927 non-ICU patients who were transplanted from hospital ward or home between January 2005 and December 2010.
RESULTS: In comparison to non-ICU patients, ICU patients had a higher model for end-stage liver disease (MELD) at transplant (median: 37 vs 20, P < 0.001). Fourteen out of 39 patients (36%) required vasopressor support immediately prior to liver transplantation (LT) with 6 patients (15%) requiring both vasopressin and norepinephrine. Sixteen ICU patients (41%) were ventilator dependent immediately prior to LT with 9 patients undergoing percutaneous tracheostomy prior to transplantation. Twenty-five ICU patients (64%) required dialysis preoperatively. At 1, 3 and 5 years after LT, graft survival was 76%, 68% and 62% in ICU patients vs 90%, 81% and 75% in non-ICU patients. Patient survival at 1, 3 and 5 years after LT was 78%, 70% and 65% in ICU patients vs 94%, 85% and 79% in non-ICU patients. When formally comparing graft survival and patient survival between ICU and non-ICU patients using Cox proportional hazards regression models, both graft survival [relative risk (RR): 1.94, 95%CI: 1.09-3.48, P = 0.026] and patient survival (RR: 2.32, 95%CI: 1.26-4.27, P = 0.007) were lower in ICU patients vs non-ICU patients in single variable analysis. These findings were consistent in multivariable analysis. Although not statistically significant, graft survival was worse in both patients with cryptogenic cirrhosis (RR: 3.29, P = 0.056) and patients who received donor after cardiac death (DCD) grafts (RR: 3.38, P = 0.060). These findings reached statistical significance when considering patient survival, which was worse for patients with cryptogenic cirrhosis (RR: 3.97, P = 0.031) and patients who were transplanted with DCD livers (RR: 4.19, P = 0.033). Graft survival and patient survival were not significantly worse for patients on mechanical ventilation (RR: 0.91, P = 0.88 in graft loss; RR: 0.69, P = 0.56 in death) or patients on vasopressors (RR: 1.06, P = 0.93 in graft loss; RR: 1.24, P = 0.74 in death) immediately prior to LT. Trends toward lower graft survival and patient survival were observed for patients on dialysis immediately before LT, however these findings did not approach statistical significance (RR: 1.70, P = 0.43 in graft loss; RR: 1.46, P = 0.58 in death).
CONCLUSION: Although ICU patients when compared to non-ICU patients have lower survivals, outcomes are still acceptable. Pre-transplant ventilation, hemodialysis, and vasopressors were not associated with adverse outcomes.
Donor pool; Donor outcomes; Onor after cardiac death grafts; Liver graft survival; Patient survival
AIM: To propose a percutaneous treatment for otherwise intractable pancreatic fistula (PF).
METHODS: From 2005 to 2011, 12 patients (9 men and 3 women, mean age 59 years, median 63 years, range 33-78 years) underwent radiological treatment for high-output PF associated with peripancreatic fluid collection. The percutaneous procedures were performed after at least 4 wk of unsuccessful conservative treatments. We chose either a one or two step procedure, depending on the size and characteristics of the fistula and the fluid collection (with an arbitrary cut-off of 2 cm). Initially, 2 to 6 pigtail drainages of variable size from 8.3 (8.3-Pig Duan Cook, Bloomington, Indiana, United States) to 14 Fr (Flexima, Boston Scientific, Natick, United States) were positioned inside the collection using a transgastric approach. In a second procedure, after 7-10 d, two or more endoprostheses (cystogastrostomic 8 Fr double-pigtail, Cook, Bloomington, Indiana, United States in 10 patients; covered Niti-S stent, TaeWoong Medical Co, Seoul, South Korea in 2 patients) were placed between the collection and the gastric lumen. In all cases the metal or plastic prostheses were removed within one year after positioning.
RESULTS: Four out of 12 high-output fistulas fistulas were external while 8/12 were internal. The origin of the fistulous tract was visualised by computer tomography (CT) imaging studies: in 11 patients it was at the body, and in 1 patient at the tail of the pancreas. Single or multiple drainages were positioned under CT guidance. The catheters were left in place for a varying period (0 to 40 d - median 10 and 25th-75th percentile 0-14). In one case external transgastric drainages were left in place for a prolonged time (40 d) due to the presence of vancomycin-resistant bacteria (Staphylococcus) and fluconazole-resistant fungi (Candida) in the drained fluid. In this latter case systemic and local antibiotic therapy was administered. In both single and two-step techniques, when infection was present, we carried out additional washing with antibiotics to improve the likelihood of the procedure’s success. In all cases the endoprostheses were left in situ for a few weeks and endoscopically removed after remission of collections, as ascertained by CT scan. Procedural success rate was 100% as the resolution of external PF was achieved in all cases. There were no peri-procedural complications in any of the patients. The minimum follow-up was 18 mo. In two cases the procedure was repeated after 1 year, due to the onset of new fluid collections and the development of pseudocysts. Indeed, this type of endoprosthesis is routinely employed for the treatment of pseudocysts. Endoscopy was adopted both for control of the positioning of the endoprosthesis in the stomach, and for its removal after resolution of the fistula and fluid collection. The resolution of the external fistula was assessed clinically and CT scan was employed to demonstrate the resolution of peripancreatic collections for both the internal and external fistulae.
CONCLUSION: The percutaneous placement of cistogastrostomic endoprostheses can be used for the treatment of PF that cannot be treated with other procedures.
Pancreas; Pancreatic fistula; Interventional radiology; Pancreatic surgery; Complications
AIM: To evaluate long-term complications and survival in patients with Budd-Chiari syndrome (BCS) referred to a Danish transjugular intrahepatic portosystemic shunt (TIPS) centre.
METHODS: Twenty-one consecutive patients from 1997-2008 were retrospectively included [15 women and 6 men, median age 40 years (range 17-66 years)]. Eighteen Danish patients came from the 1.8 million catchment population of Aarhus University Hospital and three patients were referred from Scandinavian hospitals. Management consisted of tests for underlying haematological, endocrinological, or hypercoagulative disorders parallel to initiation of specific treatment of BCS.
RESULTS: BCS was mainly caused by thrombophilic (33%) or myeloproliferative (19%) disorders. Forty-three percents had symptoms for less than one week with ascites as the most prevalent finding. Fourteen (67%) were treated with TIPS and 7 (33%) were manageable with treatment of the underlying condition and diuretics. The median follow-up time for the TIPS-treated patients was 50 mo (range 15-117 mo), and none required subsequent liver transplantation. Ascites control was achieved in all TIPS patients with a marked reduction in the dose of diuretics. A total of 14 TIPS revisions were needed, mostly of uncovered stents. Two died during follow-up: One non-TIPS patient worsened after 6 mo and died in relation to transplantation, and one TIPS patient died 4 years after the TIPS-procedure, unrelated to BCS.
CONCLUSION: In our BCS cohort TIPS-treated patients have near-complete survival, reduced need for diuretics and compared to historical data a reduced need for liver transplantation.
Ascites; Budd-Chiari syndrome; Myeloproliferative disorder; Thrombophilia; Thrombosis; Transjugular intrahepatic portosystemic shunt
Reactivation of hepatitis B virus (HBV) during chemotherapy is a well known complication in patients with chronic hepatitis B and cancer. The clinical manifestations range from subclinical elevation of liver enzymes to severe, potentially fatal fulminant hepatitis. Reactivation can occur in a patient with previous inactive HBV infection; either an inactive carrier or a patient with resolved hepatitis. Everolimus is a mammalian target of rapamycin (mTOR) inhibitor approved in renal cell carcinoma, neuroendocrine tumours and breast cancer. mTOR inhibitors are a new generation of drugs for targeted treatment; therefore, little about their side effects is known. Here, we report a patient with renal cell carcinoma who experienced a flare of hepatitis B infection during treatment with everolimus. Clinicians should be aware of HBV reactivation in patients who are undergoing treatment with everolimus, and screening for hepatitis B infection and prophylactic antiviral treatment should be considered.
Hepatitis B; Virus reactivation; Everolimus; Mammalian target of rapamycin inhibitors; Immunosuppressive treatment; Renal cell carcinoma
Hepatitis C virus (HCV) infects more than 170 million people worldwide, and thereby becomes a series global health challenge. Chronic infection with HCV is considered one of the major causes of end-stage liver disease including cirrhosis and hepatocellular carcinoma. Although the multiple functions of the HCV proteins and their impacts on the modulation of the intracellular signaling transduction processes, the drive of carcinogenesis during the infection with HCV, is thought to result from the interactions of viral proteins with host cell proteins. Thus, the induction of mutator phenotype, in liver, by the expression of HCV proteins provides a key mechanism for the development of HCV-associated hepatocellular carcinoma (HCC). HCC is considered one of the most common malignancies worldwide with increasing incidence during the past decades. In many countries, the trend of HCC is attributed to several liver diseases including HCV infection. However, the development of HCC is very complicated and results mainly from the imbalance between tumor suppressor genes and oncogenes, as well as from the alteration of cellular factors leading to a genomic instability. Besides the poor prognosis of HCC patients, this type of tumor is quite resistance to the available therapies. Thus, understanding the molecular mechanisms, which are implicated in the development of HCC during the course of HCV infection, may help to design a general therapeutic protocol for the treatment and/or the prevention of this malignancy. This review summarizes the current knowledge of the molecular mechanisms, which are involved in the development of HCV-associated HCC and the possible therapeutic strategies.
Hepatitis C virus; Hepatocellular carcinoma; Cirrhosis; Fibrosis; Inflammation; Carcinogenesis
Nonalcoholic fatty liver disease (NAFLD) is the commonest liver disease in Western countries. Treatment of NAFLD is currently based on lifestyle measures and no effective pharmacologic treatment is available so far. Emerging evidence, mainly from animal studies, suggests that the renin-angiotensin-aldosterone system may be of major importance in the pathogenesis of NAFLD and indicates that angiotensin-converting enzyme inhibitors (ACE-I) and angiotensin receptor blockers (ARBs) as a potentially useful therapeutic approach. However, data from human studies are limited and contradictory. In addition, there are few randomized controlled trials (RCTs) on the effects of ACE-I or ARB in patients with NAFLD and most data are from retrospective studies, pilot prospective studies and post hoc analyses of clinical trials. Accordingly, more and larger RCTs are needed to directly assess the effectiveness of ACE-I and ARBs in NAFLD.
Nonalcoholic fatty liver disease; Non alcoholic steatohepatitis; Renin-angiotensin-aldosterone system; Angiotensin-converting enzyme inhibitors; Angiotensin receptor blockers; Fibrosis
Nonalcoholic fatty liver disease (NAFLD) is generally considered as the hepatic manifestation of the metabolic syndrome (MS). Although there is no doubt that NAFLD is tightly linked to the MS, the diagnosis of NAFLD encompasses a broad range of histological entities and as a composite phenotype may be hindering attempts to understand the mechanistic basis of these variants. The awareness that NAFLD is not solely and invariably associated with the MS is a useful means to help direct future studies. We should be aware that mechanisms other than insulin resistance may contribute to the chronic inflammatory processes that underpin the development of liver fat accumulation and the subsequent architectural distortion of the liver. Further studies with special focus on hemoglobin as a risk factor for the development of NAFLD in the absence of MS should be performed.
Nonalcoholic fatty liver disease; Metabolic syndrome; Insulin resistance; Fibrosis; Hemoglobin
Alcoholic hepatitis is a devastating form of acute liver injury seen in chronic alcohol abusers with significant morbidity and mortality. It is a multisystem disease that is precipitated by ingesting large quantities of alcohol with genetic and environmental factors playing a role. Prognostic criteria have been developed to predict disease severity and these criteria can serve as indicators to initiate medical therapy. Primary therapy remains abstinence and supportive care, as continued alcohol abuse is the most important risk factor for disease progression. The cornerstone of supportive care remains aggressive nutritional support, and although acute alcoholic hepatitis has been extensively studied, few specific medical therapies have been successful. Corticosteroids remain the most effective medical therapy available in improving short term survival in a select group of patients with alcoholic hepatitis; however, the long-term outcome of drug therapies is still not entirely clear and further clinical investigation is necessary. While liver transplantation for acute alcoholic hepatitis have demonstrated promising results, this practice remains controversial and has not been advocated universally, with most transplant centers requiring a prolonged period of abstinence before considering transplantation. Extracorporeal liver support devices, although still experimental, have been developed as a form of liver support to give additional time for liver regeneration. These have the potential for a significant therapeutic option in the future for this unfortunately dreadful disease.
Alcholic hepatitis; Acute liver injury; Abstinence; Nutrition; Corticosteroids; Transplantation; Extracorporeal liver support
AIM: To elucidate the role of cytokine receptor-like factor 1 (CRLF1) in hepatic stellate cells and liver fibrosis.
METHODS: Rat hepatic stellate cells (HSCs) were isolated by Nykodenz gradient centrifugation and activated by culturing in vitro. Differentially expressed genes in quiescent and culture activated HSCs were identified using microarrays. Injections of carbon tetrachloride (CCl4) for 4 wk were employed to induce liver fibrosis. The degree of fibrosis was assessed by Sirius red staining. Adenovirus expressing CRLF1 was injected through tail vein into mice to achieve overexpression of CRLF1 in the liver. The same adenovirus was used to overexpress CRLF1 in quiescent HSCs cultured in vitro. Expression of CRLF1, CLCF1 and ciliary neurotrophic factor receptor (CNTFR) in hepatic stellate cells and fibrotic livers was analyzed by semi-quantitative reverse transcription-polymerase chain reaction and Western blotting. Expression of profibrotic cytokines and collagens was analyzed by the same method.
RESULTS: CRLF1 is a secreted cytokine with unknown function. Human mutations suggested a role in development of autonomous nervous system and a role of CRLF1 in immune response was implied by its similarity to interleukin (IL)-6. Here we show that expression of CRLF1 was undetectable in quiescent HSCs and was highly upregulated in activated HSCs. Likewise, expression of CRLF1 was very low in normal livers, but was highly upregulated in fibrotic livers, where its expression correlated with the degree of fibrosis. A cofactor of CLRF1, cardiotrophin-like cytokine factor 1 (CLCF1), and the receptor which binds CRLF1/CLCF1 dimer, the CNTFR, were expressed to similar levels in quiescent and activated HSCs and in normal and fibrotic livers, indicating a constitutive expression. Overexpression of CLRF1 alone in the normal liver did not stimulate expression of profibrotic cytokines, suggesting that the factor itself is not pro-inflammatory. Ectopic expression in quiescent HSCs, however, retarded their activation into myofibroblasts and specifically decreased expression of type III collagen. Inhibition of type III collagen expression by CRLF1 was also seen in the whole liver. Our results suggest that CLRF1 is the only component of the CRLF1/CLCF1/CNTFR signaling system that is inducible by a profibrotic stimulus and that activation of this system by CLRF1 may regulate expression of type III collagen in fibrosis.
CONCLUSION: By regulating activation of HSCs and expression of type III collagen, CRLF1 may have an ability to change the composition of extracellular matrix in fibrosis.
Hepatic stellate cells; Liver fibrosis; Cytokine receptor-like factor 1; Cardiotrophin-like cytokine factor 1; Ciliary neurotrophic factor receptor; Type III collagen
AIM: To estimate the prevalence of human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections in women in Mali and to evaluate the performance of serological assays.
METHODS: Two prospective studies were conducted in 2009 and 2010 in Mali. They concerned first, 1000 pregnant women attending six reference health centers in Bamako (Malian capital) between May 26 and June 16, 2009; and secondly, 231 women over 50 years who consulted general practitioners of two hospitals in Bamako between October 25 and December 24, 2010. Blood samples were collected and kept frozen in good condition before analysis. All samples depicted as positive using HIV/HCV enzyme immuno-assay screening assays were submitted to confirmation analysis. Molecular markers of HCV were characterized.
RESULTS: The seroprevalence of HIV and HCV in the population of pregnant women was 4.1% and 0.2% respectively. Among older women the seroprevalence was higher and similar for HIV and HCV (6.1% vs 6.5%). The anti-HIV prevalence was not different in young and older women (4.1% vs 6.1%). In contrast, the anti-HCV prevalence was higher in older compared to younger women (6.5% vs 0.2%, P < 0.01). Of 2 pregnant women who were HCV seropositive, only one was polymerase chain reaction (PCR) reactive and infected by genotype 2, with a viral load of 1600 IU/mL. Regarding older women who were HCV seropositive, 13 out of 15 were PCR reactive, infected by genotype 1 or 2. Globally HCV genotype 2 was predominant. The positive predictive value (PPV) measured with VIKIA HIV test in young women was 100% therefore significantly higher than the 87.5% measured in older women (P < 0.05). Conversely, the PPV measured with Monolisa HCV assay in older women was 88.2% and higher than the 14.3% measured in younger women (P < 0.01).
CONCLUSION: Whereas HIV prevalence was similar in both subpopulations HCV was more frequent among older women (P < 0.01). The PPV of screening assays varied with the age of the subjects.
Human immunodeficiency virus; Hepatitis C virus; Serology; Molecular diagnostics; Women; West Africa; Bamako
AIM: To investigate the association between B-mode ultrasound classification of small hepatocellular carcinoma (HCC) and outcome after radiofrequency ablation (RFA).
METHODS: Ninety-seven cases of HCC treated using RFA between April 2001 and March 2006 were reviewed. Ultrasound images were classified as follows: type 1, with halo (n = 29); and type 2, without halo (n = 68). Type 2 was further categorized into three subgroups: type 2a, homogenous hyperechoic (n = 9); type 2b, hypoechoic with smooth margins (n = 43); and type 2c (n = 16), hypoechoic with irregular or unclear margins. Patients with type 2a HCC were excluded from analysis due to the small number of cases.
RESULTS: Two year recurrence rates for type 2b, type 1 and type 2c were 26%, 42% and 69%, respectively, with significant differences between type 2b and type 2c (P < 0.01), and between type 1 and type 2c (P < 0.05). Five year survival rates were 89%, 43% and 65%, respectively. Survival was significantly longer for type 2b than for other types (type 1 vs type 2b, P < 0.01; type 2b vs type 2c, P < 0.05). On univariate analysis, factors contributing to recurrence were number of tumors, tumor stage, serum level of lens culinaris agglutinin-reactive alpha-fetoprotein and ultrasound classification (P < 0.05). Factors contributing to survival were tumor stage and ultrasound classification (P < 0.05). Multivariate analysis identified ultrasound classification as the only factor independently associated with both recurrence and survival (P < 0.05).
CONCLUSION: B-mode ultrasound classification of small HCC is a predictive factor for outcome after RFA.
B-mode ultrasound; Hepatocellular carcinoma; Radiofrequency ablation; Recurrence; Prognosis
AIM: To evaluate the effects of surgical weight loss (Roux-en-Y gastric bypass with a modified Fobi-Capella technique) on non alcoholic fatty liver disease in obese patients.
METHODS: A group of 26 morbidly obese patients aged 45 ± 2 years and with a body mass index > 40 kg/m2 who underwent open surgical weight loss operations had paired liver biopsies, the first at surgery and the second after 16 ± 3 mo of weight loss. Biopsies were evaluated and compared in a blinded fashion. The presence of metabolic syndrome, anthropometric and biochemical variables were also assessed at baseline and at the time of the second biopsy.
RESULTS: Percentage of excess weight loss was 72.1% ± 6.6%. There was a reduction in prevalence of metabolic syndrome from 57.7% (15 patients) to 7.7% (2 patients) (P < 0.001). Any significance difference was observed in aspartate aminotransferase or alanine aminotransferase between pre and postsurgery. There were improvements in steatosis (P < 0.001), lobular (P < 0.001) and portal (P < 0.05) inflammation and fibrosis (P < 0.001) at the second biopsy. There were 25 (96.1%) patients with non alcoholic steatohepatitis (NASH) in their index biopsy and only four (15.3%) of the repeat biopsies fulfilled the criteria for NASH. The persistence of fibrosis (F > 1) was present in five patients at second biopsy. Steatosis and fibrosis at surgery were predictors of significant fibrosis postsurgery.
CONCLUSION: Restrictive mildly malabsorptive surgery provides significant weight loss, resolution of metabolic syndrome and associated abnormal liver histological features in most obese patients.
Non alcoholic fatty liver disease; Bariatric surgery; Obesity; Non alcoholic steatohepatitis
AIM: To study the effect of rescue monotherapy with adefovir (ADV) in patients with chronic hepatitis B (CHB) who developed drug resistance to lamivudine (LAM).
METHODS: A total of 76 treated CHB patients with resistance to LAM were enrolled in the present study. The patients’ baseline characteristics, such as age, gender, blood tests and hepatitis B virus (HBV) DNA were collected; therapy duration and the response of each patient were also recorded. ADV monotherapy was set as the observation group A. Twenty-four patients with LAM resistance, who were set as group B, accepted combined therapy with LAM + ADV. Patients were followed up at 0, 12, 24, 52, 104 and 156 wk. Hepatitis B surface antigen status, hepatitis B e antigen (HBeAg)/anti-HBe status, HBV DNA level and biochemical indexes were monitored. Sequencer of HBV polymerase gene was performed on the ABI 3730 automated sequencer. If no desired effects had been achieved during the course of treatment, patients’ choices were also taken into account. The control group was tested at the same time.
RESULTS: In the two groups, 27 cases developed viral breakthrough after LAM treatment response. The remaining 49 cases underwent biochemical rebound accompanied by rtM204I/V or rtL180M mutation. In group A, 52 cases finished 156 wk of ADV monotherapy; of whom, 36 cases were HBeAg positive and 16 HBeAg negative. In patients whose baseline HBV DNAs were 103-105 copies/mL, 88.8% of patients’ HBV DNAs were lower than the lower test limit (103 copies/mL) after 12 to 156 wk of ADV treatment. In patients whose baseline HBV DNAs were ≥ 106 copies/mL, 41.1%-47.0% of patients’ HBV DNAs were lower than the lower test limit after the same course of ADV therapy (χ2 were 4.35-5.4, 41.1%-47.0% vs 88.8% group 103-105 copies/mL, P < 0.01). In group A, seroconversion of HBeAg developed in 8 of 36 cases (22.2%). In group B, 24 cases finished 156 wk of LAM + ADV; of whom, 17 cases were HBeAg positive and 7 HBeAg negative. In patients whose baseline HBV DNAs were 103-105 copies /mL, 81.8% of patients’ HBV DNAs were lower than the lower test limit (103 copies/mL) after 12 to 156 wk of treatment. In the patients whose baseline HBV DNAs were ≥ 106 copies/mL, 46.1%-53.8% of patients’ HBV DNAs were lower than the lower test limit after the same course of LAM + ADV therapy (χ2 were 4.1-5.0, 46.1%-53.8% vs 81.8% group 103-105 copies/mL, P < 0.05-0.01). In group B, 4 of 17 cases (23.5%) developed seroconversion of HBeAg. Treatment outcomes in groups A and B were comparable.
CONCLUSION: In both group A and B, the ratios of virological response have similar efficacy in patients with lower baseline HBV DNAs.
Adefovir; Lamivudine; Drug resistance; Chronic hepatitis B; Antiviral therapy; Monotherapy
We describe a patient with sudden onset of abdominal pain and ascites, leading to the diagnosis of autosomal dominant polycystic kidney disease (ADPKD). Her presentation was consistent with acute liver cyst rupture as the cause of her acute illness. A review of literature on polycystic liver disease in patients with ADPKD and current management strategies are presented. This case alerts physicians that ADPKD could occasionally present as an acute abdomen; cyst rupture related to ADPKD may be considered in the differential diagnoses of acute abdomen.
Autosomal dominant polycystic kidney disease; Acute abdominal pain; Ascites; Polycystic liver disease
Estrium Whey is an alternative nutritional support therapy for women. It’s enhanced with specific nutrients including phytoestrogens, folate, antioxidants and fiber to support healthy estrogen detoxification and hormone balance. We describe the first case of hepatotoxicity due to Estrium Whey in a 51-year old female with metastatic breast cancer with clinical, laboratory and histopathological changes.
Estrium Whey; Hepatotoxicity; Metastatic disease
Hepatic sarcoidosis is usually asymptomatic but rarely leads to adverse liver-related outcome. Co-existence of viral hepatitis and hepatic sarcoidosis is a rare, but recognised phenomenon. Obtaining a balance between immune suppression and anti-viral therapy may be problematic. Immunosuppression in the presence of viral hepatitis can lead to rapid deterioration of liver disease. Similarly, anti-viral therapy may exacerbate granulomatous hepatitis. Here we present two cases of viral hepatitis co-existing with sarcoidosis that illustrate successful management strategies. In one, hepatitis B replication was suppressed with oral anti-viral therapy before commencing prednisolone. In the second, remission of hepatic sarcoidosis was achieved with prednisolone, before treating hepatitis C and obtaining a sustained virological response with pegylated interferon and ribavirin therapy.
Hepatic sarcoidosis; Chronic hepatitis C infection; Chronic hepatitis B infection; Immune suppression; Anti-viral therapy
Liver cysts are common, affecting 5%-10% of the population. Most are asymptomatic, however 5% of patients develop symptoms, sometimes due to complications and will require intervention. There is no consensus on their management because complications are so uncommon. The aim of this study was to perform a collected review of how a series of complications were managed at our institutions. Six different patients presenting with rare complications of liver cysts were obtained from Hepatobiliary Units in the United Kingdom and The Netherlands. History and radiological imaging were obtained from case notes and computerised radiology. As a result, 1 patient admitted with inferior vena cava obstruction was managed by cyst aspiration and lanreotide; 1 patient with common bile duct obstruction was first managed by endoscopic retrograde cholangiopancreatography and stenting, followed by open fenestration; 1 patient with ruptured cysts and significant medical co-morbidities was managed by percutaneous drainage; 1 patient with portal vein occlusion and varices was managed by open liver resection; 1 patient with infected cysts was treated with intravenous antibiotics and is awaiting liver transplantation. The final patient with a simple liver cyst mimicking a hydatid was managed by open liver resection. In conclusion, complications of cystic liver disease are rare, and we have demonstrated in this series that both operative and non-operative strategies have defined roles in management. The mainstays of treatment are either aspiration/sclerotherapy or, alternatively laparoscopic fenestration. Medical management with somatostatin analogues is a potentially new and exciting treatment option but requires further study.
Liver; Cysts; Complications; Polycystic
Hepatectomy remains the only curative treatment for many primary and secondary liver cancers. Portal vein embolization (PVE) has been used to increase the volume of the future liver remnant and thus lower the risk of small-for-size syndrome and postoperative liver failure. This technique has proven its safety, with a low post-procedure morbidity rate. Here, we describe a very rare case in which a young patient suffered a glue embolism to the right atrial cavity following PVE in preparation for a major hepatectomy for colorectal metastasis. The foreign body was withdrawn from the heart with a femoral, percutaneous device and trapped against the wall of the femoral vein with a self-expanding metal stent. Our report shows that this previously unknown complication of PVE can be resolved without recourse to sternotomy and open heart surgery.
Liver metastasis; Percutaneous endovascular intervention; Portal vein; Embolization; Glue; Complications; Stenting
Resection of liver metastases from gynaecological tumours is uncommon. Endometrial stromal sarcomas (ESS) are low incidence gynecological tumours which can originate in previous sites of endometriosis or following metaplasia of the pelvic peritoneal wall, and which are exceptionally associated with liver metastasis. We present a 68-year-old woman with a ESS and metachronic liver metastasis treated by liver resection. There is very little literature on clinical management about liver metastasis from ESS, but extrapolating the data obtained with liver metastasis from sarcomas and uterine tumours, we should recommend resection as this is considered a resectable extrauterine metastasis. In cases with more sites of extrauterine disease, liver resection should also be performed if the other sites are resectable.
Sarcoma; Stromal; Endometrial; Liver; Metastasis; Review
A 59-year-old man underwent liver radiofrequency ablation under laparotomy for recurrent hepatic carcinoma located in the caudate lobe, however, near-fatal bleeding occurred 1 wk after the operation. The intra-operative ultrasound study during laparotomy revealed left hepatic artery pseudoaneurysm. Suture and packing with ribbon gauze was used to obtain hemostasis. A secondary hemorrhage followed 11 h later and hepatic angiography was performed immediately. Bleeding from the pseudoaneurysm in a branch of the left hepatic artery was found and the artery branch was embolized with coils. Other than slight bile leakage, post-embolization continued satisfactorily. Bleeding did not reoccur. The follow up visit 1 mo later found the pseudoaneurysm disappearing and no tumor recurrence.
Hepatocellular carcinoma; Radiofrequency ablation; Complication; Hepatic angiography; Embolization
AIM: To incorporate estimated glomerular filtration rate (eGFR) into the model for end-stage liver disease (MELD) score to evaluate the predictive value.
METHODS: From January 2004 to October 2008, the records of 4127 admitted cirrhotic patients were reviewed. Patients who survived and were followed up as outpatients were defined as survivors and their most recent available laboratory data were collected. Patients whose records indicated death at any time during the hospital stay were defined as non-survivors (in-hospital mortality). Patients with incomplete data or with cirrhosis due to a congenital abnormality such as primary biliary cirrhosis were excluded; thus, a total of 3857 patients were enrolled in the present study. The eGFR, which was calculated by using either the modification of diet in renal disease (MDRD) equation or the chronic kidney disease epidemiology collaboration (CKD-EPI) equation, was incorporated into the MELD score after adjustment with the original MELD equation by logistic regression analysis [bilirubin and international normalized ratio (INR) were set at 1.0 for values less than 1.0].
RESULTS: Patients defined as survivors were significantly younger, had a lower incidence of hepatoma, lower Child-Pugh and MELD scores, and better renal function. The underlying causes of cirrhosis were very different from those in Western countries. In Taiwan, most cirrhotic patients were associated with the hepatitis virus, especially hepatitis B. There were 16 parameters included in univariate logistic regression analysis to predict in-hospital mortality and those with significant predicting values were included in further multivariate analysis. Both 4-variable MDRD eGFR and 6-variable MDRD eGFR, rather than creatinine, were significant predictors of in-hospital mortality. Three new equations were constructed (MELD-MDRD-4, MELD-MDRD-6, MELD-CKD-EPI). As expected, original MELD score was a significant predictor of in-hospital mortality (odds ratio = 1.25, P < 0.001). MELD-MDRD-4 excluded serum creatinine, with the coefficients refit among the remaining 3 variables, i.e., total bilirubin, INR and 4-variable MDRD eGFR. This model represented an exacerbated outcome over MELD score, as suggested by a decrease in chi-square (2161.45 vs 2198.32) and an increase in -2 log (likelihood) (2810.77 vs 2773.90). MELD-MDRD-6 included 6-variable MDRD eGFR as one of the variables and showed an improvement over MELD score, as suggested by an increase in chi-square (2293.82 vs 2198.32) and a decrease in -2 log (likelihood) (2810.77 vs 2664.79). Finally, when serum creatinine was replaced by CKD-EPI eGFR, it showed a slight improvement compared to the original MELD score (chi-square: 2199.16, -2 log (likelihood): 2773.07). In the receiver-operating characteristic curve, the MELD-MDRD-6 score showed a marginal improvement in area under the curve (0.909 vs 0.902), sensitivity (0.854 vs 0.819) and specificity (0.818 vs 0.839) compared to the original MELD equation. In patients with a different eGFR, the MELD-MDRD-6 equation showed a better predictive value in patients with eGFR ≥ 90, 60-89, 30-59 and 15-29.
CONCLUSION: Incorporating eGFR obtained by the 6-variable MDRD equation into the MELD score showed an equal predictive performance in in-hospital mortality compared to a creatinine-based MELD score.
Liver cirrhosis; Estimated glomerular filtration rate; End-stage liver disease; Modification of diet in renal disease; Renal function
AIM: To study diagnostic laparoscopy as a tool for excluding donors on the day of surgery in living donor liver transplantation (LDLT).
METHODS: This study analyzed prospectively collected data from all potential donors for LDLT. All of the donors were subjected to a three-step donor evaluation protocol at our institution. Step one consisted of a clinical and social evaluation, including a liver profile, hepatitis markers, a renal profile, a complete blood count, and an abdominal ultrasound with Doppler. Step two involved tests to exclude liver diseases and to evaluate the donor’s serological status. This step also included a radiological evaluation of the biliary anatomy and liver vascular anatomy using magnetic resonance cholangiopancreatography and a computed tomography (CT) angiogram, respectively. A CT volumetric study was used to calculate the volume of the liver parenchyma. Step three included an ultrasound-guided liver biopsy. Between November 2002 and May 2009, sixty-nine potential living donors were assessed by open exploration prior to harvesting the planned part of the liver. Between the end of May 2009 and October 2010, 30 potential living donors were assessed laparoscopically to determine whether to proceed with the abdominal incision to harvest part of the liver for donation.
RESULTS: Ninety-nine living donor liver transplants were attempted at our center between November 2002 and October 2010. Twelve of these procedures were aborted on the day of surgery (12.1%) due to donor findings, and eighty-seven were completed (87.9%). These 87 liver transplants were divided into the following groups: Group A, which included 65 transplants that were performed between November 2002 and May 2009, and Group B, which included 22 transplants that were performed between the end of May 2009 and October 2010. The demographic data for the two groups of donors were found to match; moreover, no significant difference was observed between the two groups of donors with respect to hospital stay, narcotic and non-narcotic analgesia requirements or the incidence of complications. Regarding the recipients, our study clearly revealed that there was no significant difference in either the incidence of different complications or the incidence of retransplantation between the two groups. Day-of-surgery donor assessment for LDLT procedures at our center has passed through two eras, open and laparoscopic. In the first era, sixty-nine LDLT procedures were attempted between November 2002 and May 2009. Upon open exploration of the donors on the day of surgery, sixty-five donors were found to have livers with a grossly normal appearance. Four donors out of 69 (5.7%) were rejected on the day of surgery because their livers were grossly fatty and pale. In the laparoscopic era, thirty LDLT procedures were attempted between the end of May 2009 and October 2010. After the laparoscopic assessment on the day of surgery, twenty-two transplantation procedures were completed (73.4%), and eight were aborted (26.6%). Our data showed that the levels of steatosis in the rejected donors were in the acceptable range. Moreover, the results of the liver biopsies of rejected donors were comparable between the group A and group B donors. The laparoscopic assessment of donors presents many advantages relative to the assessment of donors through open exploration; in particular, the laparoscopic assessment causes less pain, requires a shorter hospital stay and leads to far superior cosmetic results.
CONCLUSION: The laparoscopic assessment of donors in LDLT is a safe and acceptable procedure that avoids unnecessary large abdominal incisions and increases the chance of achieving donor safety.
Live donor; Laparoscopic assessment; Rejected donors; Day of surgery; Fatty liver
AIM: To analyze the correlation of treatment method with the outcome of all the hepatic metastatic melanoma (HMM) patients from our hospital.
METHODS: There were altogether nine cases of HMM that had been treated in the PUMCH hospital during the past 25 years, from December 1984 to February 2010. All of the cases developed hepatic metastasis from primary cutaneous melanoma. A retrospective review was performed on all the cases in order to draw informative conclusion on diagnosis and treatment in correlation with the prognosis. Clinical features including symptoms, signs, blood test results, B-ultrasound and computed tomography (CT) imaging characteristics, and pathological data were analyzed in each case individually. A simple comparison was made on case by case basis instead of performing statistical analysis since the case numbers are low and patients were much diversified in each item that has been analyzed. Literatures on this subject were reviewed in order to draw a safe conclusion and found to be supportive to our finding in a much broad scope.
RESULTS: There are six males and three females whose ages ranged 39-74 years old with an average of 58.8. Patients were either with or without symptoms at the time of diagnosis. The liver function and tumor marker exam were normal in all but one patient. The incidence of HMM does not affect liver function and was not related to virus infection status in the liver. Most of these HMM patients were also accompanied by the metastases of other locations, including lung, abdominal cavity, and cervical lymph nodes. Ultrasound examinations showed lesions ranging 2-12 cm in diameter, with no- or low-echo peripheral areola. Doppler showed blood flow appeared inside some tumors as well as in the surrounding area. CT image demonstrated low density without uniformed lesions, characterized with calcification in periphery, and enhanced in the arterial phase. Contrast phase showed heterogeneous enhancement, with a density higher than normal liver tissue, which was especially apparent at the edge. Patients were treated differently with following procedures: patients #1, #6 and #8 were operated with hepatectomy with or without removal of primary lesion, and followed by comprehensive biotherapy/chemotherapy; patient #9 received hepatectomy only; patient #2 received bacille calmette-guerin treatment only; patient #7 had Mile’s surgery but no hepatectomy; and patients #3, #4 and #5 had supportive treatment without specific measurement. The patients who had resections of metastatic lesions followed by post-operative comprehensive therapy have an average survival time of 30.7 mo, which is much longer than those did not receive surgery treatment (4.6 mo). Even for the patient receiving a resection of HMM only, the post-operative survival time was 18 mo at the time we reviewed the data. This patient and the patient #6 are still alive currently and subjected to continue following up.
CONCLUSION: Surgical operation should be first choice for HMM treatment, and together with biotherapy/chemotherapy, hepatectomy is likely to bring better prognosis.
Malignant melanoma; Hepatic metastatic tumor; Hepatectomy; Hepatic metastatic melanoma; Prognosis; Biotherapy; Chemotherapy