Navigating Complex Challenges: Preoperative Assessment and Surgical Strategies for Liver Resection in Patients with Fibrosis or Cirrhosis.

This review explores the intricacies of evaluating cirrhotic patients for liver resection while exploring how to extend surgical intervention to those typically excluded by the Barcelona Clinic Liver Cancer (BCLC) criteria guidelines by focusing on the need for robust preoperative assessment and innovative surgical strategies. Cirrhosis presents unique challenges and complicates liver resection due to the altered physiology of the liver, portal hypertension, and liver decompensation. The primary objective of this review is to discuss the current approaches in assessing the suitability of cirrhotic patients for liver resection and aims to identify which patients outside of the BCLC criteria can safely undergo liver resection by highlighting emerging strategies that can improve surgical safety and outcomes.

Splenomegaly is a marker of advanced chronic liver disease and portal hypertension in HIV infection.

OBJECTIVES: To evaluate the clinical significance of splenomegaly as a marker of underlying liver disease in people with HIV (PWH). METHODS: We included consecutive PWH from a prospective cohort from 2010 to 2020 with available liver stiffness measurement (LSM) and liver imaging to define splenomegaly (> 13 cm) within 1 year. Cut-offs of LSM > 10 kPa and > 21 kPa were used to identify advanced chronic liver disease (ACLD) and portal hypertension, respectively. Logistic regression multivariable analysis was employed to identify independent predictors of ACLD. RESULTS: In all, 331 PWH were included, 76% of them men, with a median (interquartile range) age of 51.3 (45-58) years, all receiving antiretroviral treatment, and 53% were HIV monoinfected. The PWH with splenomegaly exhibited a higher prevalence of ACLD compared with those with normal spleen size, as per LSM (26% vs. 9%; p = 0.009). Portal hypertension diagnosed by LSM was also more prevalent in PWH with splenomegaly than in those without (15% vs. 2%; p < 0.001). Independent predictors of ACLD were viral hepatitis coinfection [adjusted odds ratio (aOR) = 3.15, 95% confidence interval (CI): 1.65-6.0], lower platelets (aOR = 0.99, 95% CI: 0.99-0.99) and splenomegaly (aOR = 2.41, 95% CI: 1.17-4.99). In patients with available oesophagogastroduodenoscopy, splenomegaly was also associated with higher prevalence of oesophageal varices and other endoscopic findings of portal hypertension (38% vs. 17%; p = 0.027). CONCLUSIONS: Splenomegaly identified on routine imaging may have utility as a marker of ACLD and portal hypertension, prompting further investigations.

Autoimmune post-infantile giant cell hepatitis: a case report and review of the literature.

Giant cell hepatitis (GCH) is a rare entity in adults that is characterized by large multinucleated hepatocyte formation and parenchymal inflammation. We present a case of acute liver failure in a 33-year-old woman secondary to autoimmune hepatitis (AIH). A liver biopsy revealed submassive hepatocyte necrosis consistent with GCH. We conducted a literature review of 187 reported cases of post-infantile GCH in adults. AIH was the most commonly reported cause of GCH, but GCH was associated with a wide spectrum of etiologies, including infections, rheumatological diseases, hematological diseases, malignancies, and medications. The severity of disease can range from mild hepatitis to fulminant hepatic failure. The mortality rate among the cases in the literature was 18.82%. GCH is managed by treating the underlying cause, and ribavirin has been proposed as a treatment option for idiopathic GCH. A small number of patients progress to requiring orthotopic liver transplant, but recurrence is possible post-transplant.

Renal tubular injury in hyperbilirubinemia: Bile cast nephropathy.

The toxic renal accumulation of bile pigment sparked clinical intrigue almost a century ago. More recently, however, the identification of bile casts within renal tubules in patients with liver dysfunction has been largely overlooked. We have reviewed the literature, including natural history, pathophysiology, and potential treatment of bile cast nephropathy (BCN). We report two cases of acute kidney injury (AKI) associated with acute-on-chronic liver failure in which prolonged hyperbilirubinemia and bile cast identification on renal biopsy evoked the diagnosis of BCN.

Prevalence and predictors of nonalcoholic fatty liver disease in South Asian women with polycystic ovary syndrome.

BACKGROUND: Polycystic ovary disease (PCOS) may be a risk factor for nonalcoholic fatty liver disease (NAFLD) due to common pathogenetic pathways, including insulin resistance and obesity. Both PCOS and NAFLD are more severe in South Asian women. Data on NAFLD in South Asian women with PCOS are lacking. AIM: To investigate prevalence and predictors of NAFLD and liver fibrosis in PCOS patients from South Asia. METHODS: We conducted an observational routine screening program by means of transient elastography (TE) with associated controlled attenuation parameter (CAP). NAFLD was defined as CAP ≥ 288 decibels per meter. Significant liver fibrosis (stage 2 and higher out of 4) was defined as TE measurement ≥ 8.0 kilopascals. Elevated alanine aminotransferase (ALT) was defined as ALT > 24 IU/L, as per upper limit of normal reported in South Asian women. Biochemical hyperandrogenism was defined as free androgen index > 5. Predictors of NAFLD were determined by logistic regression analysis. RESULTS: 101 PCOS patients (mean age 36.3 years) with no significant alcohol intake or viral hepatitis were included. Prevalence of NAFLD and significant liver fibrosis was 39.6% and 6.9%, respectively. Elevated ALT was observed in 40% and 11.5% of patients with and without NAFLD, respectively. After adjusting for duration of PCOS and insulin resistance measured by homeostasis model for assessment of insulin resistance, independent predictors of NAFLD were higher body mass index [adjusted odds ratio (aOR) 1.30, 95% confidence interval (CI): 1.13-1.52], hyperandrogenism (aOR: 5.32, 95%CI: 1.56-18.17) and elevated ALT (aOR: 3.54, 95%CI: 1.10-11.47). Lifetime cardiovascular risk was higher in patients with NAFLD compared to those without NAFLD (0.31 ± 0.11 vs 0.26 ± 0.13). CONCLUSION: Despite their young age, NAFLD diagnosed by TE with CAP is a frequent comorbidity in South Asian women with PCOS and is strongly associated with higher body mass index and hyperandrogenism. Non-invasive screening strategies could help early diagnosis and initiation of interventions, including counselling on weight loss, cardiovascular risk stratification and linkage to hepatology care where appropriate.

Prevalence, Predictors, and Severity of Lean Nonalcoholic Fatty Liver Disease in Patients Living With Human Immunodeficiency Virus.

BACKGROUND: The burden of nonalcoholic fatty liver disease (NAFLD) is growing in people living with human immunodeficiency virus (HIV). NAFLD is associated with obesity; however, it can occur in normoweight (lean) patients. We aimed to investigate lean NAFLD in patients living with HIV. METHODS: We included patients living with HIV mono-infection from 3 prospective cohorts. NAFLD was diagnosed by transient elastography (TE) and defined as controlled attenuation parameter ≥248 dB/m, in absence of alcohol abuse. Lean NAFLD was defined when a body mass index was <25 kg/m2. Significant liver fibrosis was defined as TE ≥7.1 kPa. The presence of diabetes, hypertension, or hyperlipidemia defined metabolically abnormal patients. RESULTS: We included 1511 patients, of whom 57.4% were lean. The prevalence of lean NAFLD patients in the whole cohort was 13.9%. NAFLD affected 24.2% of lean patients. The proportions of lean NAFLD patients who were metabolically abnormal or had elevated alanine aminotransferase (ALT) were higher than among those who were lean patients without NAFLD (61.9% vs 48.9% and 36.7% vs 24.2%, respectively). Lean NAFLD patients had a higher prevalence of significant liver fibrosis than lean patients without NAFLD (15.7% vs 7.6%, respectively). After adjusting for sex, ethnicity, hypertension, CD4 cell count, nadir CD4 <200µ/L, and time since HIV diagnosis, predictors of NAFLD in lean patients were age (adjusted OR [aOR], 1.29; 95% confidence interval [CI], 1.04-1.59), high triglycerides (aOR, 1.34; 95% CI, 1.11-1.63), and high ALT (aOR, 1.15; 95% CI, 1.05-1.26), while a high level of high-density lipoprotein cholesterol was protective (aOR, 0.45; 95% CI, .26-.77). CONCLUSIONS: NAFLD affects 1 in 4 lean patients living with HIV mono-infection. Investigations for NAFLD should be proposed in older patients with dyslipidemia and elevated ALT, even if normoweight.

Optimizing patients with non-alcoholic fatty liver disease pre-transplant.

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Non-alcoholic steatohepatitis (NASH), which is the progressive counterpart of the disease, is becoming the leading indication for liver transplantation in North America. Owing to the lack of symptoms, NASH is often an incidental diagnosis, resulting in a significant proportion of patients being diagnosed when advanced liver disease has already developed. NAFLD has recently been characterized as the hepatic manifestation of metabolic syndrome. Consequently, it is a multisystem disease that often co-exists with several other conditions, such as obesity, diabetes, cardiovascular diseases, and extra-hepatic malignancy, which have an impact on selection of transplant recipients. The complexity of diagnostic approach, need for multidisciplinary clinical management, and lack of a specific treatment further complicate the picture of this extremely prevalent liver condition. NAFLD patients with advanced liver disease should be considered for early referral to liver transplant clinics for careful metabolic and cardiovascular risk stratification because they have worse survival rates after liver transplantation than other patients with chronic liver disease. Early referral will also facilitate optimization of metabolic comorbidities before proceeding with transplantation. This review provides an overview of strategies to identify patients with advanced NAFLD, with an emphasis on the management of associated comorbidities and optimal timing of pre-transplant evaluation. Other topics that have been shown to affect recipient optimization, such as the role of lifestyle changes and bariatric surgery in the management of obesity, as well as sarcopenia in decompensated NASH-related cirrhosis, are addressed.

Vitamin E is an effective treatment for nonalcoholic steatohepatitis in HIV mono-infected patients.

OBJECTIVE: HIV-infected patients are at increased risk of nonalcoholic steatohepatitis (NASH). Vitamin E is recommended for treatment of NASH in the general population. However, its safety and efficacy among HIV-infected patients remain unknown. DESIGN: Single-centre, phase IV, open-label, single arm clinical trial. METHODS: HIV mono-infected patients without significant alcohol intake or viral hepatitis coinfection were included. The diagnosis of NASH was based on the co-existence of fatty liver, diagnosed by controlled attenuation parameter (CAP) at least 248 dB/m and significant hepatocyte apoptosis, defined by the serum biomarker cytokeratin 18 (CK-18) greater than 130.5 U/L. Participants were treated with 800 IU daily of oral vitamin E (alpha-tocopherol) for 24 weeks, and followed for an additional 24 weeks postdiscontinuation. Generalized linear mixed effects models were used to evaluate changes in alanine aminotransferase (ALT), CAP and CK-18 at the completion of treatment and end of follow-up, controlling for pretreatment trends. RESULTS: A total of 27 patients were included. Four (15%) had a pretreatment liver biopsy, which confirmed the diagnosis of NASH in all cases. Compared with baseline, 24 weeks of vitamin E treatment improved ALT [-27 units/l; 95% confidence interval (CI) -37 to -17], CAP scores (-22 dB/m; 95% CI -42 to -1) and CK-18 (-123 units/l; 95% CI -201 to -46). Conversely, there was no change in BMI. No serious adverse event was reported and no patient was lost to follow-up. CONCLUSION: In this first clinical trial, we showed that vitamin E is an effective and well tolerated treatment for NASH in HIV-infected patients.

Liver-related Events in Human Immunodeficiency Virus-infected Persons With Occult Cirrhosis.

BACKGROUND: Human immunodeficiency virus (HIV)-infected patients are at increased risk of liver-related mortality. The effect of occult cirrhosis (OcC), defined as preclinical compensated cirrhosis without any clinical findings, on liver-related events is unknown. METHODS: HIV-infected patients from 2 Canadian cohorts underwent transient elastography (TE) examination and were classified as (1) OcC (TE ≥13 kPa with no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (2) overt cirrhosis (OvC) (TE ≥13 kPa with signs of cirrhosis); or (3) noncirrhotic patients (TE <13 kPa). Incidence and risk factors of liver-related events were investigated through Kaplan-Meier and Cox regression analyses, respectively. We estimated monitoring rates according to screening guidelines for hepatocellular carcinoma (HCC) by OcC and OvC status. RESULTS: A total of 1092 HIV-infected patients (51% coinfected with hepatitis C virus) were included. Prevalence of OcC and OvC at baseline was 2.7% and 10.7%, respectively. During a median follow-up of 1.8 (interquartile range, 1.5-2.8) years, the incidence of liver-related events in noncirrhosis, OcC, and OvC was 3.4 (95% confidence interval [CI], 1.2-7.3), 34.0 (95% CI, 6.0-104.0), and 37.0 (95% CI, 17.0-69.1) per 1000 person-years, respectively. Baseline OcC (adjusted hazard ratio [aHR], 7.1 [95% CI, 1.3-38.0]) and OvC (aHR, 8.5 [95% CI, 2.8-26.0]) were independently associated with liver-related events. Monitoring rates for HCC were lower in patients with OcC (24%) compared to those with OvC (40%). CONCLUSIONS: HIV-infected patients with OcC have a high incidence of liver-related events. Greater surveillance and earlier recognition with appropriate screening strategies are necessary for improved outcomes.

Screening for nonalcoholic steatohepatitis by using cytokeratin 18 and transient elastography in HIV mono-infection.

BACKGROUND AND AIM: HIV-infected individuals are at high risk of developing nonalcoholic steatohepatitis (NASH), a leading cause of end-stage liver disease in Western countries. Nonetheless, due to the invasiveness of liver biopsy, NASH remains poorly understood in HIV mono-infection. We aimed to characterize the prevalence and predictors of NASH in unselected HIV mono-infected patients by means of non-invasive diagnostic tools. METHODS: HIV-infected adults without significant alcohol intake or co-infection with hepatitis B or C underwent a routine screening program employing transient elastography (TE) with controlled attenuation parameter (CAP) and the serum biomarker cytokeratin-18 (CK-18). NASH was diagnosed non-invasively as the coexistence of fatty liver (CAP ≥248 dB/m) and CK-18 >246 U/L. Identified cases of NASH were offered a diagnostic liver biopsy. Predictors of NASH were determined by multivariate logistic regression analysis. RESULTS: 202 consecutive HIV mono-infected patients were included. NASH was non-invasively diagnosed in 23 cases (11.4%). Among them, 17 underwent a liver biopsy, and histology confirmed NASH in all cases. The prevalence of NASH was higher in patients with hypertriglyceridemia (17.1%), insulin resistance defined by homeostasis model for assessment of insulin resistance (HOMA-IR) (25%), those with detectable HIV viral load (42.9%) and those with elevated ALT (53.6%). After adjustment, higher HOMA-IR (adjusted odds ratio [aOR] = 1.20, 95% CI 1.01-1.43; p = 0.03) and ALT (aOR = 2.39, 95% CI 1.50-3.79; p<0.001) were independent predictors of NASH. CONCLUSIONS: NASH, diagnosed by a non-invasive diagnostic approach employing CK-18 and TE with CAP, is common in unselected HIV mono-infected individuals, particularly in the presence of insulin resistance and elevated ALT.

Hepatic steatosis progresses faster in HIV mono-infected than HIV/HCV co-infected patients and is associated with liver fibrosis.

BACKGROUND & AIMS: Hepatic steatosis (HS) seems common in patients infected with human immunodeficiency virus (HIV). However, the relative effect of HIV, as well as hepatitis C virus (HCV) in those co-infected, and the influence of HS on liver fibrosis progression are unclear. METHODS: The LIVEr disease in HIV (LIVEHIV) is a Canadian prospective cohort study using transient elastography and associated controlled attenuation parameter (CAP) to screen for HS and liver fibrosis, in unselected HIV-infected adults. HS progression was defined as development of any grade HS (CAP ⩾248dB/m), or transition to severe HS (CAP >292dB/m), for those with any grade HS at baseline. Fibrosis progression was defined as development of significant liver fibrosis (liver stiffness measurement [LSM] >7.1kPa), or transition to cirrhosis (LSM >12.5kPa) for those with significant liver fibrosis at baseline. Cox regression analysis was used to assess predictors of HS and fibrosis progression. RESULTS: A prospective cohort study was conducted, which included 726 HIV-infected patients (22.7% HCV co-infected). Prevalence of any grade HS did not differ between HIV mono-infected and HIV/HCV co-infected patients (36.1% vs. 38.6%, respectively). 313 patients were followed for a median of 15.4 (interquartile range 8.5-23.0) months. The rate of HS progression was 37.8 (95% confidence interval [CI] 29.2-49.0) and 21.9 (95% CI 15.6-30.7) per 100 person-years in HIV mono-infection and HIV/HCV co-infection, respectively. HCV co-infection was an independent negative predictor of HS progression (adjusted hazard ratio [aHR] 0.50, 95% CI 0.28-0.89). HS predicted liver fibrosis progression in HIV mono-infection (aHR 4.18, 95% CI 1.21-14.5), but not in HIV/HCV co-infection. CONCLUSION: HS progresses faster and is associated with liver fibrosis progression in HIV mono-infection but not in HIV/HCV co-infection. Lay summary: Fatty liver is the most frequent liver disease in Western countries. People living with HIV seem at high risk of fatty liver due to frequent metabolic disorders and the long-term effects of antiretroviral therapy. However, due to the invasiveness of liver biopsy, the traditional method of diagnosing fatty liver, there are few data regarding its frequency in people living with HIV. In this study, we used a non-invasive diagnostic tool to analyze the epidemiology of fatty liver in 726 HIV+ patients. We found that fatty liver affects over one-third of people living with HIV. When followed over time, we found that HIV+ patients without HCV co-infection develop fatty liver more frequently than those co-infected with HCV.

Decreased PCSK9 expression in human hepatocellular carcinoma.

BACKGROUND: The management of hepatocellular carcinoma (HCC) is limited by the lack of adequate screening biomarkers and chemotherapy. In response, there has been much interest in tumor metabolism as a therapeutic target. PCSK9 stimulates internalization of the LDL-receptor, decreases cholesterol uptake into hepatocytes and affects liver regeneration. Thus, we investigated whether PCSK9 expression is altered in HCC, influencing its ability to harness cholesterol metabolism. METHODS: Thirty-nine patients undergoing partial hepatectomy or liver transplantation for HCC were consented for use of HCC tissue to construct a tissue microarray (TMA). The TMA was immunostained for PCSK9. Imagescope software was used to objectively determine staining, and assess for pathological and clinical correlations. PCSK9 and LDL receptor mRNA levels in flash-frozen HCC and adjacent liver tissue were determined by quantitative RT-PCR. Serum PCSK9 levels were determined by ELISA. RESULTS: By immunohistochemistry, there was significantly lower expression of PCSK9 in HCC as compared to adjacent cirrhosis (p-value < 0.0001, wilcoxon signed-rank test). Significantly greater staining of PCSK9 was present in cirrhosis compared to HCC (p value <0.0001), and positivity (percentage of positive cells) was significantly greater in cirrhosis compared to HCC (p-value < 0.0001). Conversely, significantly higher expression of LDL-R was present in HCC as compared to the adjacent cirrhosis (p-value < 0.0001). There was no significant correlation of PCSK9 staining with grade of tumor, but there were significant correlations between PCSK9 staining and stage of fibrosis, according to spearman correlation test. PCSK9 mRNA levels were relatively less abundant within HCC compared to adjacent liver tissue (p-value =0.08) and normal control tissue (p-value =0.02). In contrast, serum PCSK9 levels were significantly increased among patients with HCC compared to those with chronic liver disease without HCC (p-value =0.029). LDL receptor mRNA was consistantly greater in HCC when compared to normal control tissue (p-value = 0.06) and, in general, was significantly greater in HCC when compared to adjacent liver (p-value = 0.04). CONCLUSIONS: The decreased expression of PCSK9 and conversely increased LDL-R expression in HCC suggests that HCC modulates its local microenvironment to enable a constant energy supply. Larger-scale studies should be conducted to determine whether PCSK9 could be a therapeutic target for HCC.

Prognostic Value of Non-Invasive Fibrosis and Steatosis Tools, Hepatic Venous Pressure Gradient (HVPG) and Histology in Nonalcoholic Steatohepatitis.

BACKGROUND & AIMS: Non-invasive diagnostic methods for liver fibrosis predict clinical outcomes in viral hepatitis and nonalcoholic fatty liver disease (NAFLD). We specifically evaluated prognostic value of non-invasive fibrosis methods in nonalcoholic steatohepatitis (NASH) against hepatic venous pressure gradient (HVPG) and liver histology. METHODS: This was a retrospective cohort study of 148 consecutive patients who met the following criteria: transjugular liver biopsy with HVPG measurement; biopsy-proven NASH; absence of decompensation; AST-to-Platelets Ratio Index (APRI), fibrosis-4 (FIB-4), NAFLD fibrosis score, ultrasound, hepatic steatosis index and Xenon-133 scan available within 6 months from biopsy; a minimum follow-up of 1 year. Outcomes were defined by death, liver transplantation, cirrhosis complications. Kaplan-Meier and Cox regression analyses were employed to estimate incidence and predictors of outcomes, respectively. Prognostic value was expressed as area under the curve (AUC). RESULTS: During a median follow-up of 5 years (interquartile range 3-8), 16.2% developed outcomes, including 7.4% who died or underwent liver transplantation. After adjustment for age, sex, diabetes, the following fibrosis tools predicted outcomes: HVPG >10mmHg (HR=9.60; 95% confidence interval [CI] 3.07-30.12), histologic fibrosis F3-F4 (HR=3.14; 1.41-6.95), APRI >1.5 (HR=5.02; 1.6-15.7), FIB-4 >3.25 (HR=6.33; 1.98-20.2), NAFLD fibrosis score >0.676 (HR=11.9; 3.79-37.4). Prognostic value was as follows: histologic fibrosis stage, AUC=0.85 (95% CI 0.76-0.93); HVPG, AUC=0.81 (0.70-0.91); APRI, AUC=0.89 (0.82-0.96); FIB-4, AUC=0.89 (0.83-0.95); NAFLD fibrosis score, AUC=0.79 (0.69-0.91). Neither histologic steatosis nor non-invasive steatosis methods predicted outcomes (AUC<0.50). CONCLUSIONS: Non-invasive methods for liver fibrosis predict outcomes of patients with NASH. They could be used for serial monitoring, risk stratification and targeted interventions.

Occult cirrhosis diagnosed by transient elastography is a frequent and under-monitored clinical entity.

BACKGROUND & AIMS: Diagnosis of preclinical compensated cirrhosis (occult cirrhosis, OC) is challenging due to lack of clinical findings. We evaluated prevalence and outcomes of OC by transient elastography (TE, Fibroscan(®)). METHODS: Eight hundred and seventy-one patients with compensated chronic liver disease (CLD) and TE examination were divided into: (i) OC (TE ≥ 13 kPa and no sign of cirrhosis, including absence of thrombocytopenia and signs of advanced liver disease on ultrasound or gastroscopy); (ii) clinically evident cirrhosis (TE ≥ 13 kPa with signs of cirrhosis); (iii) non-cirrhotic CLD (TE < 13 kPa). Outcomes included hepatocellular carcinoma (HCC), esophageal varices and ascites. Late diagnosis of outcomes was defined as HCC stage ≥intermediate by BCLC or variceal bleeding. RESULTS: Occult cirrhosis represented 12% of the cohort and 37% of cirrhotic patients. Independent predictors of OC were age [odds ratio (OR) 1.15; 95% confidence interval (CI), 1.04-1.26], HIV co-infection (OR 3.53; 95% CI, 1.85-6.76) and APRI (OR 2.63; 95 CI, 1.87-3.71). During a median follow-up of 24 (interquartile range 20-37) months, OC received less surveillance than clinically evident cirrhosis, with fewer ultrasounds (2.7 ± 1.5 vs 3.6 ± 2; P < 0.001) and gastroscopies (2 ± 0.8 vs 2.6 ± 1.4; P < 0.001). Incidence of outcomes was 3.5/100 per person-years (PY) (95% CI, 0.1-6.9) in OC, 0 in non-cirrhotic CLD and 9.8/100 PY (95% CI, 0.3-19.3) in clinically evident cirrhosis (P < 0.001). Late diagnosis occurred more in OC than clinically evident cirrhosis (60 vs 15%, P = 0.01). CONCLUSIONS: Occult cirrhosis is a frequent and under-monitored clinical entity associated with short-term risk of outcomes. TE may help early diagnosis, prompt initiation of surveillance and specific therapy for an otherwise unrecognized condition.

Care of the liver transplant patient.

OBJECTIVE: To provide an approach to the care of liver transplant (LT) patients, a growing patient population with unique needs. METHODS: A literature search of PubMed for guidelines and review articles using the keywords "liver transplantation", "long term complications" and "medical management" was conducted, resulting in 77 articles. RESULTS: As a result of being on immunosuppression, LT recipients are at increased risk of infections and must be screened regularly for metabolic complications and malignancies. DISCUSSION: Although immunosuppression is key to maintaining allograft health after transplantation, it comes with its own set of medical issues to follow. Physicians following LT recipients must be aware of the greater risk for hypertension, diabetes, dyslipidemia, renal failure, metabolic bone disease and malignancies in these patients, all of whom require regular monitoring and screening. Vaccination, quality of life, sexual function and pregnancy must be specifically addressed in transplant patients.

Physicians' practices for diagnosing liver fibrosis in chronic liver diseases: a nationwide, Canadian survey.

OBJECTIVE: To determine practices among physicians in Canada for the assessment of liver fibrosis in patients with chronic liver diseases. METHODS: Hepatologists, gastroenterologists, infectious diseases specialists, members of the Canadian Gastroenterology Association and/or the Canadian HIV Trials Network who manage patients with liver diseases were invited to participate in a web-based, national survey. RESULTS: Of the 237 physicians invited, 104 (43.9%) completed the survey. Routine assessment of liver fibrosis was requested by the surveyed physicians mostly for chronic hepatitis C (76.5%), followed by autoimmune/cholestatic liver disease (59.6%) and chronic hepatitis B (52.9%). Liver biopsy was the main diagnostic tool for 46.2% of the respondents, Fibroscan (Echosens, France) for 39.4% and Fibrotest (LabCorp, USA) for 7.7%. Etiology-specific differences were observed: noninvasive methods were mostly used for hepatitis C (63% versus 37% liver biopsy) and hepatitis B (62.9% versus 37.1% liver biopsy). For 42.7% of respondents, the use of noninvasive methods reduced the need for liver biopsy by >50%. Physicians' characteristics associated with higher use of noninvasive methods were older age and being based at a university hospital or in private practice versus community hospital. Physicians' main concerns regarding noninvasive fibrosis assessment methods were access/availability (42.3%), lack of guidelines for clinical use (26.9%) and cost/lack of reimbursement (14.4%). CONCLUSIONS: Physicians who manage patients with chronic liver diseases in Canada require routine assessment of liver fibrosis stage. Although biopsy remains the primary diagnostic tool for almost one-half of respondents, noninvasive methods, particularly Fibroscan, have significantly reduced the need for liver biopsy in Canada. Limitations in access to and availability of the noninvasive methods represent a significant barrier. Finally, there is a need for clinical guidelines and a better reimbursement policy to implement noninvasive tools to assess liver fibrosis.

Prevention and Management of Chronic Hepatitis B.

Chronic hepatitis B virus (HBV) infection affects an estimated 370 million people worldwide. HBV is endemic throughout the world, and insidiously causes liver damage over years and decades without any warning symptoms or signs. Up to 25-35% of infected individuals eventually die due to complications of liver cirrhosis and hepatocellular carcinoma (HCC) induced by HBV. Screening those individuals at risk of acquiring hepatitis B, and universal vaccination for prevention, would help in limiting the spread and public health repercussions of the virus. Although many new antiviral therapies have been developed for the management of hepatitis B, they still do not offer the possibility of cure. Most individuals who begin oral suppressive therapy will be indefinitely treated. Continuous suppression of HBV replication in individuals with advanced liver disease prolongs life, decreases the need for liver transplantation, and potentially reduces the risk for HCC. In this clinical review, we present a practical approach to prevention of HBV, its natural history and life cycle, as well as its management.

Chylous Ascites: Evaluation and Management.

Chylous ascites refers to the accumulation of lipid-rich lymph in the peritoneal cavity due to disruption of the lymphatic system secondary to traumatic injury or obstruction. Worldwide, abdominal malignancy, cirrhosis, and tuberculosis are the commonest causes of CA in adults, the latter being most prevalent in developing countries, whereas congenital abnormalities of the lymphatic system and trauma are commonest in children. The presence of a milky, creamy appearing ascitic fluid with triglyceride content above 200 mg/dL is diagnostic, and, in the majority of cases, unless there is a strong suspicion of malignancy, further investigations are not required in patients with cirrhosis. If an underlying cause is identified, targeted therapy is possible, but most cases will be treated conservatively, with dietary support including high-protein and low-fat diets supplemented with medium-chain triglycerides, therapeutic paracentesis, total parenteral nutrition, and somatostatins. Rarely, resistant cases have been treated by transjugular intrahepatic portosystemic shunt, surgical exploration, or peritoneovenous shunt.

Pretransplantation α-fetoprotein slope and milan criteria: strong predictors of hepatocellular carcinoma recurrence after transplantation.

BACKGROUND: Hepatocellular carcinoma (HCC) is a major cause of orthotropic liver transplantations (OLT). However, tumor recurrence remains a concern. Our group has shown that a rising natural α-fetoprotein (AFP) slope (NAS) correlates with tumor characteristics. We want to assess if a rising NAS predicts tumor recurrence. METHODS: We reviewed first OLT for HCC (n=144) at our center from 1992 to 2010. Patients with less than two AFP values before treatment were excluded (n=52). A rising NAS (>0.1 µg/L/day) was found in 28 patients whereas 64 presented a stable or dropping NAS. Demographics, pre-OLT therapy, and tumor characteristics were collected. Statistical analysis was performed using ANOVA, chi-square or Fisher's test, and logistic regression for recurrence after OLT. RESULTS: Demographics were similar among the recurrence (n=12) and nonrecurrence (n=80) groups. Patients who recurred received more treatment (P=0.017), had a higher number of lesions (P=0.025), a greater total tumor size (P=0.001), and a higher incidence of microvascular invasion (P=0.013). More patients exceeded the Milan criteria (75.0% vs. 31.3%, odds ratio [OR] 6.60, 95% confidence interval [CI] 1.45-4.05, P=0.008) and had a rising NAS (58.3% vs. 26.3%, OR 3.20, 95% CI 1.11-9.22, P=0.024) among the recurrence group. NAS was also a strong predictor of microvascular invasion (P=0.040). After correcting for age and sex, both a rising NAS (OR 3.98, 95% CI 1.01-15.81, P=0.039) and nonadherence to Milan criteria (OR 5.69, 95% CI 1.14-28.38, P=0.034) were strong predictors of recurrence after OLT. CONCLUSION: The NAS is a predictor of microvascular invasion, a finding exclusive to pathology and in itself a predictor of HCC recurrence after OLT. The NAS and Milan criteria are good predictors of recurrence. These results encourage a frequent monitoring of AFP variations before OLT.