Management and outcome of hepatocellular adenoma with massive bleeding at presentation

AIM To evaluate outcome of acute management and risk of rebleeding in patients with massive hemorrhage due to hepatocellular adenoma(HCA). METHODS This retrospective cohort study included all consecutive patients who presented to our hospital with massive hemorrhage(grade Ⅱ or Ⅲ) due to ruptured HCA and were admitted for observation and/or intervention between 1999-2016. The diagnosis of HCA was based on radiological findings from contrastenhanced magnetic resonance imaging(MRI) or pathological findings from biopsy or resection of the HCA. Hemorrhage was diagnosed based on findings from computed tomography or MRI. Medical records were reviewed for demographic features, clinical presentation, tumor features, initial and subsequent management, short-and long-term complications and patient and lesion follow-up. RESULTS All patients were female(n = 23). Treatment in the acute phase consisted of embolization(n = 9, 39.1%), conservative therapy(n = 13, 56.5%), andother intervention(n = 1, 4.3%). Median hemoglobin level decreased significantly more on days 0-3 in the intervention group than in the patients initially treated conservatively(0.9 mmol/L vs 2.4 mmol/L respectively, P = 0.006). In total, 4 patients suffered severe shortterm complications, which included hypovolemic shock, acute liver failure and abscess formation. After a median follow-up of 36 mo, tumor regression in nonsurgically treated patients occurred with a median reduction of 76 mm down to 25 mm. Four patients underwent secondary(elective) treatment(i.e., tumor resection) to address HCA size of > 5 cm and/or desire for future pregnancy. One case of rebleeding was documented(4.3%). None of the patients experienced long-term complication(mean follow-up time: 36 mo). CONCLUSION With a 4.3% risk of rebleeding, secondary(elective) treatment of HCA after massive hemorrhage may only be considered in patients with persistent HCA > 5 cm.

Surveillance for hepatocellular carcinoma in chronic liver disease:Evidence and controversies

Primary liver cancer is the sixth most common cancer in the world and the third cause of cancer-related death.Hepatocellular carcinoma(HCC)represents more than90%of primary liver cancers and generally occurs in patients with underlying chronic liver disease such as viral hepatitis,hemochromatosis,primary biliary cirrhosis and non-alcoholic steatohepatitis.Especially cirrhotic patients are at risk of HCC and regular surveillance could enable early detection and therapy,with potentially improved outcome.We here summarize existing evidence for surveillance including ultrasound,other radiological modalities and various serum biomarkers,and current international guideline recommendations for surveillance.Ultrasound andα-fetoprotein(alone or in combination)are most frequently used for surveillance,but their sensitivities and specificities are still far from perfect,and evidence for surveillance remains weak and controversial.Various other potential surveillance tools have been tested,including serum markers as des-carboxyprothrombin,lectin-boundα-fetoprotein,and(most recently)circulating TIE2-expressing monocytes,and radiological investigations such as computed tomographyscan or magnetic resonance imaging-scan.Although early results appear promising,these tools have generally been tested in diagnostic rather than surveillance setting,and in most cases,no detailed information is available on their cost-effectiveness.For the near future,it remains important to define those patients with highest risk of HCC and most benefit from surveillance,and to restrict surveillance to these categories.

Covalently closed-circular hepatitis B virus DNA reduction with entecavir or lamivudine

AIM: To investigate the reduction in hepatitis B virus(HBV) covalently closed-circular DNA(ccc DNA) with entecavir(ETV) or lamivudine(LAM). METHODS: This analysis included patients who had participated in the randomized Phase Ⅲ study ETV-022 comparing ETV vs LAM in nucleos(t)ide-naive, HBe Agpositive patients. Patients received ETV(0.5 mg daily) or LAM(100 mg daily) for a minimum of 52 wk. Patients were eligible to participate in this sub-study if they had paired biopsies at baseline and week 48 with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA. The main objective was to compare changes in hepatic HBV ccc DNA and total hepatic HBV DNA at week 48 of ETV or LAM treatment, which was a secondary endpoint of study ETV-022. Additional post hoc analyses included linear regression analyses to assess associations of baseline levels and on-treatment changes of ccc DNA with other baseline factors [sex,age, serum HBV DNA, alanine aminotransferase(ALT), Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBV genotype], or ontreatment factors(changes from baseline at week 48 in serum HBV DNA, ALT, Knodell necroinflammatory score, Ishak fibrosis score, total hepatic HBV DNA, and HBe Ag loss at week 48).RESULTS: Overall, 305 patients(ETV = 159; LAM = 146) of ETV-022 had paired baseline and week 48 liver biopsies with evaluable measurements for hepatic HBV ccc DNA and total hepatic HBV DNA, and were included in this analysis. Baseline demographics and disease characteristics were comparable between the two arms. After 48 wk, ETV resulted in significantly greater reductions in hepatic HBV ccc DNA [-0.9 log10 copies/human genome equivalent(HGEq) vs-0.7 log10 copies/HGEq; P = 0.0033] and total hepatic DNA levels(-2.1 log10 copies/HGEq vs-1.6 log10 copies/HGEq; P < 0.0001) than LAM. Virologic, biochemical, and histologic response rates at week 48 were also greater with ETV than with LAM. Baseline HBV ccc DNA levels were positively associated with baseline levels of serum HBV DNA and total hepatic HBV DNA, and negatively associated with HBV genotype F. On-treatment changes in HBV ccc DNA levels were negatively associated with baseline levels of serum HBV DNA and baseline ALT, and were positively associated with on-treatment changes in the levels of serum HBV DNA, total hepatic HBV DNA levels, and ALT, change in Knodell necroinflammatory score, and HBe Ag loss.CONCLUSION: Forty-eight weeks of ETV resulted in greater reductions in ccc DNA and total hepatic HBV DNA than LAM, but long-term therapy may be needed for ccc DNA elimination.