Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.
Antiviral Agents ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Incidence ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Mortality ; Natural History ; Tenofovir

BACKGROUND: Liver disease is one of the top causes of death globally. Although liver transplantation is a very effective treatment strategy, the shortage of available donor organs, waiting list mortality, and high costs of surgery remain huge problems. Stem cells are undifferentiated cells that can differentiate into a variety of cell types. Scientists are exploring the possibilities of generating hepatocytes from stem cells as an alternative for the treatment of liver diseases. METHODS: In this review, we summarized the updated researches in the field of stem cell-based therapies for liver diseases as well as the current challenges and future expectations for a successful cell-based liver therapy. RESULTS: Several cell types have been investigated for liver regeneration, such as embryonic stem cells, induced pluripotent stem cells, liver stem cells, mesenchymal stem cells, and hematopoietic stem cells. In vitro and in vivo studies have demonstrated that stem cells are promising cell sources for the liver regeneration. CONCLUSION: Stem cell-based therapy could be a promising therapeutic method for patients with end-stage liver disease, which may alleviate the need for liver transplantation in the future.
Cause of Death ; Embryonic Stem Cells ; Hematopoietic Stem Cells ; Hepatocytes ; Humans ; In Vitro Techniques ; Induced Pluripotent Stem Cells ; Liver Diseases ; Liver Regeneration ; Liver Transplantation ; Liver ; Mesenchymal Stromal Cells ; Methods ; Mortality ; Stem Cells ; Tissue Donors ; Waiting Lists

PURPOSE: Hepatic hydrothorax is a complication of decompensated liver cirrhosis that is difficult and complex to manage. Data concerning the optimal treatment method, other than liver transplantation, are limited. This study aimed to compare the clinical features and outcomes of patients treated with various modalities, while focusing on surgical management and pigtail drainage. MATERIALS AND METHODS: Forty-one patients diagnosed with refractory hepatic hydrothorax between January 2013 and December 2017 were enrolled. RESULTS: The mean Child-Turcotte-Pugh and model for end stage liver disease scores of the enrolled patients were 10.1 and 19.7, respectively. The patients underwent four modalities: serial thoracentesis (n=11, 26.8%), pigtail drainage (n=16, 39.0%), surgery (n=10, 24.4%), and liver transplantation (n=4, 9.8%); 12-month mortality rate/median survival duration was 18.2%/868 days, 87.5%/79 days, 70%/179 days, and 0%/601.5 days, respectively. Regarding the management of refractory hepatic hydrothorax, surgery group required less frequent needle puncture (23.5 times in pigtail group vs. 9.3 times in surgery group), had a lower occurrence of hepatorenal syndrome (50% vs. 30%), and had a non-inferior cumulative overall survival (402.1 days vs. 221.7 days) compared to pigtail group. On multivariate analysis for poor survival, body mass index <19 kg/m², refractory hepatic hydrothorax not managed with liver transplantation, Child-Turcotte-Pugh score >10, and history of severe encephalopathy (grade >2) were associated with poor survival. CONCLUSION: Serial thoracentesis may be recommended for management of hepatic hydrothorax and surgical management can be a useful option in patients with refractory hepatic hydrothorax, alternative to pigtail drainage.
Body Mass Index ; Brain Diseases ; Drainage ; End Stage Liver Disease ; Fibrosis ; Hepatorenal Syndrome ; Humans ; Hydrothorax ; Liver Cirrhosis ; Liver Transplantation ; Methods ; Mortality ; Multivariate Analysis ; Needles ; Punctures ; Thoracentesis

PURPOSE: Donor safety is the most important problem of living donor liver transplantation (LDLT). Although laparoscopic liver resection has gained popularity with increased surgical experience and the development of laparoscopes and specialized instruments, a totally laparoscopic living donor right hepatectomy (LDRH) technique has not been investigated for efficacy and feasibility. We describe the experiences and outcomes associated with LDRH in adult-to-adult LDLT in order to assess the safety of the totally laparoscopic technique in donors. METHODS: Between May 2016 and July 2017, we performed hepatectomies in 22 living donors using a totally laparoscopic approach. Among them, 20 donors underwent LDRH. We retrospectively reviewed the medical records to ascertain donor safety and the reproducibility of LDRH; intra-operative and post-operative results including complications were demonstrated after performing LDRH. RESULTS: The median donor age was 29 years old and the median body mass index was 22.6 kg/m2. The actual graft weight was 710 g and graft weight/body weight (GRWR) was 1.125. No donors required blood transfusion, conversion to open surgery, or reoperation. The postoperative mortality was nil and postoperative complications were identified in two donors. One had fluid collection in the supra-pubic incision site for graft retrieval and the second had a minor bile leakage from the cutting edge of the right hepatic duct stump. All the liver function tests returned to normal ranges within one month. CONCLUSION: LDRH is a feasible operation owing to low blood loss and few complications. However, LDRH can be initially attempted after attaining sufficient experience in laparoscopic hepatectomy and LDLT techniques.
Bile ; Blood Transfusion ; Body Mass Index ; Conversion to Open Surgery ; Hepatectomy ; Hepatic Duct, Common ; Humans ; Laparoscopes ; Liver ; Liver Function Tests ; Liver Transplantation ; Living Donors ; Medical Records ; Mortality ; Postoperative Complications ; Reference Values ; Reoperation ; Retrospective Studies ; Tissue Donors ; Transplants

BACKGROUND: Bendamustine is an attractive option for the management of both de novo and relapsed lymphomas. It is being increasingly used in the conditioning regimen for autologous stem cell transplantation (SCT) and can be an alternative to the traditionally-used carmustine. In this study, we aimed to determine the safety and efficacy of bendamustine in the conditioning regimen for autologous SCT in refractory/relapsed lymphomas. METHODS: We designed a descriptive study to evaluate bendamustine in combination with etoposide, cytarabine, and melphalan (BeEAM) in the conditioning regimen for autologous SCT. RESULTS: Fourteen patients (median age, 28 yr) with Hodgkin's lymphoma (HL) (N=8), non-Hodgkin's lymphomas (NHL) (N=5), or peripheral T-cell lymphoma, not otherwise specified (PTCL NOS) (N=1) were included in the study. A median number of 5.95×10⁶ CD34+ cells/kg were transfused. Median times to absolute neutrophil count and platelet engraftment were 17 days and 24 days, respectively. The 100-day transplantation mortality rate was 28% (4 patients). Eight patients (57.14%) had GII-III acute kidney injury, four patients (28.5%) had GIII-IV hyperbilirubinemia, and twelve patients (85%) had GII-III diarrhea. After 3 months, 37% (5 patients) and 21.4% (3 patients) demonstrated complete response and partial response, respectively. The median follow-up was 5.5 months (15 days–19 mo). At the final follow-up, 7 patients (50%) were alive and in CR. CONCLUSION: Our study showed that bendamustine is a potentially toxic agent in the conditioning regimen for autologous SCT, resulting in significant liver, kidney, and gastrointestinal toxicity. Further studies are required to assess its safety and efficacy at reduced doses.
Acute Kidney Injury ; Bendamustine Hydrochloride ; Blood Platelets ; Carmustine ; Cytarabine ; Diarrhea ; Etoposide ; Follow-Up Studies ; Hodgkin Disease ; Humans ; Hyperbilirubinemia ; Kidney ; Liver ; Lymphoma ; Lymphoma, Non-Hodgkin ; Lymphoma, T-Cell, Peripheral ; Melphalan ; Mortality ; Neutrophils ; Stem Cell Transplantation ; Stem Cells

Nonalcoholic fatty liver disease (NAFLD), together with metabolic syndrome and obesity, has shown a rapid increase in prevalence worldwide and is emerging as a major cause of chronic liver disease and liver transplantation. Among the various phenotypes of NAFLD, nonalcoholic steatohepatitis (NASH) is highly likely to progress to development of end-stage liver disease and cardiometabolic disease, resulting in liver-related and non-liver–related mortality. Nonetheless, there is no standardized pharmacotherapy against NASH and many drugs are under development in ongoing clinical trials. To develop a successful anti-NASH drug, it is necessary to select an appropriate target population and treatment outcomes depending on whether the mode of action is anti-metabolic, anti-inflammatory or anti-fibrotic. Recently, innovative surrogate markers have been investigated to replace hard outcomes such as liver histology and mortality and reduce the clinical trial duration. Currently, several drugs with fast track designation are being tested in phase III clinical trials, and many other drugs have moved into phase II clinical trials. Both lean NAFLD and typical obese NAFLD have been extensively studied and genetic variants such as PNPLA3 and TM6SF2 have been identified as significant risk factors for lean NAFLD. In the near future, noninvasive biomarkers and effective targeted therapies for NASH and associated fibrosis are required to develop precision medicine and tailored therapy according to various phenotypes of NAFLD.
Biomarkers ; Drug Therapy ; Fibrosis ; Health Services Needs and Demand ; Liver ; Liver Diseases ; Liver Transplantation ; Mortality ; Non-alcoholic Fatty Liver Disease ; Obesity ; Phenotype ; Precision Medicine ; Prevalence ; Risk Factors

Cholangiopathies are rare diseases of the bile duct with high mortality rates. The current treatment for cholangiopathies is liver transplantation, but there are significant obstacles including a shortage of donors and a high risk of complications. Currently, there is only one available medicine on the market targeting cholangiopathies, and the results have been inadequate in clinical therapy. To overcome these obstacles, many researchers have used human induced pluripotent stem cells (hPSC) as a source for cholangiocyte-like cell generation and have incorporated advances in bioprinting to create artificial bile ducts for implantation and transplantation. This has allowed the field to move dramatically forward in studies of biliary regenerative medicine. In this review, the authors provide an overview of cholangiocytes, the organogenesis of the bile duct, cholangiopathies, and the current treatment and advances that have been made that are opening new doors to the study of cholangiopathies.
Bile Ducts ; Bile ; Bioprinting ; Humans ; Induced Pluripotent Stem Cells ; Liver Transplantation ; Mortality ; Organogenesis ; Rare Diseases ; Regenerative Medicine ; Tissue Donors

Disseminated neonatal herpes simplex virus (HSV) infection is a severe disease with a high mortality rate. Here, we report the patient presented with fulminant hepatic failure secondary to HSV infection followed by renal failure without any mucocutaneous symptoms. The patient recovered after treatment with acyclovir and peritoneal dialysis. This is the first known case of a patient in Korea who survived disseminated HSV infection with fulminant liver failure followed by renal failure without undergoing liver transplantation.
Acyclovir ; Hepatitis ; Herpes Simplex ; Humans ; Infant, Newborn ; Korea ; Liver Failure ; Liver Failure, Acute ; Liver Transplantation ; Mortality ; Peritoneal Dialysis ; Renal Insufficiency ; Simplexvirus

Multiple studies have shown that oral antiviral therapies reduced the incidence of hepatocellular carcinoma (HCC) and improved the survival of patients with chronic hepatitis B when compared with that of untreated patients. In particular, entecavir and tenofovir share the qualities of high efficacy in reducing the HBV DNA levels, and they have excellent tolerability and safety. These drugs modified the natural history of liver fibrosis, improve liver function, decrease the incidence of HCC, decrease the need for liver transplantation, and improve survival. Many studies have suggested that long-term antiviral therapy reduces the risk of HCC and liver cirrhosis in patients with chronic hepatitis. The mechanism of these drugs in reducing the risk of HCC is not clear. This article reviews the mechanisms of carcinogenic HBV by conducting a review of the literature on the efficacy of therapy for reducing the risk of HCC. A few recent articles have suggested that tenofovir offers advantages over entecavir in terms of HCC prevention, but these articles have the inherent limitations of observational data. No other head-to-head randomized trials exist. Further randomized studies would help provide stronger evidence of the association between the type of antiviral agent and the HCC outcomes. Only achieving complete viral eradication from the liver will truly decrease the mortality and incidence of HCC.
Antiviral Agents ; Carcinoma, Hepatocellular ; DNA ; Hepatitis B, Chronic ; Hepatitis, Chronic ; Humans ; Incidence ; Liver ; Liver Cirrhosis ; Liver Transplantation ; Mortality ; Natural History ; Tenofovir

Liver transplantation is a current definitive treatment for those with end-stage liver disease. Hepatic encephalopathy is a common complication of hepatic failure, which can be improved and aggravated by various causes. It is important to differentiate hepatic encephalopathy from other diseases causing brain dysfunction such as cerebral hemorrhage, which is also related to high mortality after liver transplant surgery. A 37-year-old patient was presented with acute liver failure and high ammonia levels and seizure-like symptoms. Computed tomography (CT) of his brain showed mild brain atrophy, regarded as a symptom of hepatic encephalopathy, and treated to decrease blood ammonia level. Deceased donor liver transplantation was performed and liver function and ammonia level normalized after surgery, but the patient showed symptoms of involuntary muscle contraction and showed loss of pupil reflex and fixation without recovery of consciousness. Brain CT showed brain edema and bilateral cerebral infarction, and the patient died after a few days. The purpose of this case report is to emphasize the importance of preoperative neurological evaluation, careful transplantation decision, and proper perioperative management of liver transplantation in patients with acute hepatic encephalopathy.
Adult ; Ammonia ; Atrophy ; Brain ; Brain Edema ; Cerebral Hemorrhage ; Cerebral Infarction ; Consciousness ; Hepatic Encephalopathy* ; Humans ; Liver Diseases ; Liver Failure ; Liver Failure, Acute* ; Liver Transplantation* ; Liver* ; Mortality ; Muscle, Smooth ; Pupil ; Reflex ; Seizures ; Tissue Donors