分子吸附再循环系统对肝移植术早期成功率的影响

目的 探讨影响肝移植术早期成功率的危险因素,总结在肝移植术前应用分子吸附再循环系统(MARS)治疗对术后患者早期生存率的影响。 方法 回顾性分析50例肝移植患者术前80次MARS治疗的临床资料,对有关临床指标进行排序分析;术后生存30d的28例为生存组,死亡6例为死亡组,对部分术前危险因素进行回归分析。 结果 50例患者中免除移植出院8例,移植前死亡8例,34例过渡到移植,移植后死亡6例。单次6 h MARS治疗较大幅度降低患者血清总胆红素、肌酐、尿酸、血氨、肿瘤坏死因子α(TNF α)和白细胞介素-10(IL-10)水平,同时显著改善系列器官功能衰竭评分(SOFA)(P<0.05);移植术后早期死亡与术前SOFA、肌酐、国际标准化比率(INR)、TNF α和IL-10等存在明显相关性。 结论 术前SOFA、肌酐、INR、TNF α和IL-10水平是移植后早期死亡的主要术前危险因素,术前MARS支持可以显著改善这些危险因素,有效提高移植成功率,甚至避免移植手术。     

Preoperative risk factor analysis in orthotopic liver transplantation with pretransplant artificial liver support therapy

AIM: To assess the value of pre-transplant artificial liver support in reducing the pre-operative risk factors relating to early mortality after orthotopic liver transplantation (OLT). METHODS: Fifty adult patients with various stages and various etiologies undergoing OLT procedures were treated with molecular adsorbent recycling system (MARS) as preoperative liver support therapy. The study included two parts, the first one is to evaluate the medical effectiveness of single MARS treatment with some clinical and laboratory parameters, which were supposed to be the therapeutical pre-transplant risk factors, the second part is to study the patients undergoing OLT using the regression analysis on preoperative risk factors relating to early mortality (30 d) after OLT. RESULTS: In the 50 patients, the statistically significant improvement in the biochemical parameters was observed (pre-treatment and post-treatment). Eight patients avoided the scheduled Ltx due to significant relief of clinical condition or recovery of failing liver function, 8 patients died, 34 patients were successfully bridged to Ltx, the immediate outcome of this 34 patients within 30d observation was: 28 kept alive and 6 patients died. CONCLUSION: Pre-operative SOFA, level of creatinine, INR, TNF-α, IL-10 are the main preoperative risk factors that cause early death after operation, MARS treatment before transplantion can relieve these factors significantly.     

The molecular adsorbent recirculating system as a liver support system. Summary of Mexican experience

Aim. The aim of this study was to assess the effects of the molecular absorbent recirculating system (MARS) on patients with acute liver failure (ALF) and liver failure with cirrhosis (AoCLF) as well as in cholestatic patients with intractable pruritus in a Mexican population.Material and methods. From August 2003 to December 2011, MARS was used in 38 patients with ALF, 15 patients with AoCLF, and 17 cholestatic patients with intractable pruritus. The patients were examined using a standard liver function test and for vital signs, presence of ascites and encephalopathy before and after each treatment. The therapeutic response, patient status, follow-up status, and need for liver transplantation were determined.Results. Seventy-nine MARS procedures were performed. MARS was used for ALF in 54.3% of patients, AoCLF in 24.2%, and cholestatic disease in 21.5%. There were significant improvements in serum bilirubin (p = 0.000), aspartate aminotransferase (p = 0.000), alanine aminotransferase (p = 0.030), gamma-glytamyl transpeptidase (p = 0.044), alkaline phosphatase (p = 0.006), and encephalopathy grade (p = 0.000). Thirty-eight ALF patients were listed for emergency liver transplantation and treated with MARS; 20 of these patients died on a waiting list, 18 survived. only four underwent liver transplantation and 14 (37%) recovered without transplantation after the MARS procedure.Conclusion. MARS is a safe and effective procedure, especially for ALF patients. Our results suggest that MARS therapy can contribute to native liver recovery in ALF patients.     

Fulminant Hepatic Failure Bridged to Liver Transplantation with a Molecular Adsorbent Recirculating System: A Single-Center Experience

We herein describe the clinical course of a consecutive series of fulminant hepatic failure patients treated with a molecular adsorbent recirculating system (MARS), a cell-free albumin dialysis technique. From November 2000 to September 2002, seven adult patients ages 22–61 (median, 41), one male (14.2%) and six females (85.7%), affected by fulminant hepatic failure underwent seven courses (one to five sessions each, 6 hr in duration) of extracorporeal support using the MARS technique. Pre- and posttreatment blood glucose, liver function tests, ammonia, arterial lactate, electrolytes, hemodynamic parameters, arterial blood gases, liver histology, Glasgow Coma Scale, and coagulation studies were reviewed. No adverse side effects such as generalized bleeding on noncardiogenic pulmonary edema, often seen during MARS treatment, occurred in the patients included in this study. Six patients (85.7%) are currently alive and well, and one (14.2%) died. Four patients (57%) were successfully bridged (two patients in 1 day and two other patients in 4 days) to liver transplantation, while two (5%) recovered fully without transplantation. All the measured variables stabilized after commencement of the MARS. No differences were noted between the pre- and the post-MARS histology. We conclude that the MARS is a safe, temporary life support mechanism for patients awaiting liver transplantation or recovering from fulminant hepatic failure.     

Subtotal hepatectomy and whole graft auxiliary transplantation for acetaminophen-associated acute liver failure

Background:  An acetominophen overdose (AOD) is the leading cause of acute liver failure (ALF) in the UK and USA. For patients who meet the King''s College Hospital criteria, (mortality risk > 85%), an emergency orthotopic liver transplantation (OLT) is conventionally performed with subsequent life-long immunosuppression. A new technique was developed in 1998 for AOD-induced ALF where a subtotal hepatectomy (right hepatic trisectionectomy) and whole graft auxiliary liver transplant (WGALT) was performed with complete withdrawal of immunosupression during the first year post-operatively.Results:  During 1998–2010, 68 patients were listed for an emergency transplantation for AOD ALF at our institution: 28 died waiting, 16 underwent OLT and 24 a subtotal hepatectomy with WGALT. Eight OLT (50%) and 16 WGALT remain alive (67%); actuarial survival at 5 years OLT 50%, WGALT 63%, P = 0.37. All patients who had successful WGALT are off immunosuppression. Poor prognostic factors in the WGALT group included higher donor age (40.4 versus 53.9, P = 0.043), requirements for a blood transfusion (4.3 versus 7.6, P = 0.0043) and recipient weight (63.1 versus 54 kg, P = 0.036).Conclusion:  Although OLT remains standard practice for AOD-induced ALF, life-long immunosuppression is required. A favourable survival rate using a subtotal hepatectomy and WGALT has been demonstrated, and importantly, all successful patients have undergone complete immunosuppression withdrawal. This technique is advocated for patients who have acetominophen hepatotoxicity requiring liver transplantation.     

Cryptogenic cirrhosis is the leading cause for listing for liver transplantation in Sri Lanka

Hepatitis B and C are rare in Sri Lanka. Nonalcoholic fatty liver disease is increasing in the country. Eighty-one patients referred for liver transplantation (LT) over a period of 18 months were prospectively evaluated. Ninety-two percent (n = 74) were males. Cryptogenic cirrhosis was the leading indication for LT (58 %, n = 47) followed by alcohol in 27 % (n = 33). Hepatitis B and C were not seen in our cases. The liver biochemistry and clinical status of cirrhosis were similar in cryptogenic and alcoholic cirrhotics. Fourteen patients died while waiting for transplant, and nine transplants were performed. Cryptogenic cirrhosis is the leading cause for LT in Sri Lanka.     

Ten years of experience with liver transplantation for familial amyloid polyneuropathy in Japan: outcomes of living donor liver transplantations

OBJECTIVE: We summarize 10 years of experience with liver transplantation for FAP patients in Japan and review the current opinions regarding this treatment for FAP. METHODS AND PATIENTS: All basic report data on patients at the time of transplantation were registered with the Japanese Liver Transplantation Society (JLTS). Based on the JLST report data, more detailed information on FAP patients was requested from each center. RESULTS: Living donor liver transplantation (LDLT) for FAP patients was first performed in Japan in 1993. LDLT has since been performed in 41 FAP patients, including nine cases of temporary auxiliary partial orthotopic liver transplantation (APOLT). Orthotopic liver transplantation (OLT) from cadaveric donors for FAP patients began in 1999, but only one FAP patient has subsequently undergone this procedure. Of these total of 43 FAP patients, 36 are currently alive: the one-year survival rate of patients after transplantation was 93%, and the five-year survival rate of these cases was 77%. Preoperative clinical severity and the nutritional status of patients are correlated with their outcome after liver transplantation. Domino (sequential) liver transplantation has been carried out in 20 domino recipients with end-stage liver diseases. Of the 20 domino recipients, 12 are currently alive. CONCLUSION: For FAP patients, these outcomes after the operation were very similar to those of OLT from cadaveric donors reported in other countries. Therefore, we concluded that for the treatment of FAP, LDLT from a living donor is equally effective as OLT from a cadaveric donor.     

Liver Transplantation Avoided in Patients With Fulminant Hepatic Failure Who Received Albumin Dialysis With the Molecular Adsorbent Recirculating System While on the Waiting List: Impact of the Duration of Therapy

Eighteen patients with fulminant hepatic failure due to various medical causes were listed for emergency liver transplantation and treated with extracorporeal albumin dialysis sessions using the molecular adsorbent recirculating system (MARS) at our center over a 74‐month period. Due to improvement of liver function, transplantation could be avoided in 9 patients (50%, 95% confidence interval 29% to 71%) who fully recovered afterwards. This improvement rate was higher than the rate of improvement in the French cohort of fulminant hepatic failure patients with similar etiologies (19.3%, 95% confidence interval 14.9% to 24.6%, P = 0.002). In our 18 patients, there were no statistically significant differences in any baseline characteristics or in the time with liver failure meeting transplant criteria between the patients who improved while waiting and those who did not. However, the patients who improved received a greater number of sessions and a longer total duration of MARS therapy (all P < 0.001). In the whole study population, a MARS therapy duration ≥15 h was significantly associated with improvement of liver function without transplantation (adjusted adds ratio [OR] 65.76, 2.48–1743.11, P = 0.01). Tolerance of therapy was acceptable. These results suggest that MARS therapy could contribute to native liver recovery and is safe in patients on the waiting list for fulminant hepatic failure. A minimum duration of therapy (≥15 h) could be necessary to expect significant liver function improvement.     

肝移植后乙型肝炎复发的危险因素及预后分析

目的探讨乙型肝炎相关性肝移植患者术后在核苷(酸)类似物联合小剂量乙型肝炎免疫球蛋白的预防下乙型肝炎复发的危险因素及预后。方法 253例乙型肝炎相关性肝移植患者术前即开始给予核苷(酸)类似物预防,术中和术后均给予核苷(酸)类似物联合乙型肝炎免疫球蛋白处理。结果在253例肝移植患者中,死亡29例(11.5%);术前基础病为HBV相关性肝癌患者的病死率为21.2%,显著高于非肝癌患者的5.2%(P=0.000);乙型肝炎复发16例(6.3%);复发后均停用乙型肝炎免疫球蛋白,并调整核苷(酸)类似物,结果患者HBV DNA均<500IU/ml,肝功能稳定;Log-rank检验显示乙型肝炎复发后及时治疗对患者生存无明显影响;经Logistic多因素回归分析表明,术前HBeAg阳性、HBV DNA≥105IU/ml、HCC和HBV/YMDD变异是乙型肝炎复发的危险因素。结论肝移植能够有效治疗乙型肝炎相关性终末期肝病,在核苷(酸)类似物联合乙型肝炎免疫球蛋白预防后,仍有乙型肝炎复发,其对生存率的影响有待于观察。     

Clinical hepatocyte transplantation

A severe shortage of suitable allografts is a long-standing and worldwide problem for patients who are waiting for organ transplantation. Hepatocyte transplantation has been proposed as an alternative therapeutic approach for liver disease patients to address this urgent and unmet medical need. The cell replacement approach does not replace orthotopic liver transplantation (OLT), but rather it complements OLT especially for patients who do not require whole liver replacement, such as those with congenital metabolic disorders. This review article summarizes the current knowledge and limitations of clinical hepatocyte transplantation and aims to advance our understanding toward the goal of developing novel cell replacement therapies for patients who are on the OLT waiting list.     

Percutaneous radiofrequency ablation of hepatocellular carcinoma as a bridge to liver transplantation

Orthotopic liver transplantation (OLT) can be a definitive treatment for patients with hepatocellular carcinoma (HCC). Prolonged waiting times for cadaveric livers, however, may lead to dropout from the waiting list or worsened post-OLT prognosis as a result of interval tumor progression. Percutaneous radiofrequency ablation (RFA) is widely used for local control of small unresectable HCC, but its pretransplant role remains unclear. We studied the outcome of 52 consecutive patients accepted for OLT bearing 87 HCC nodules and treated with percutaneous RFA. On initial staging, the tumor burden exceeded the Milan criteria in 10 patients. Complete tumor coagulation was observed in 74 of 87 (85.1%) nodules based on postablation imaging. After a mean of 12.7 months (range: 0.3-43.5) on the waiting list, 3 of 52 patients (5.8%) had dropped out due to tumor progression. Forty-one patients had undergone transplantation, with 1- and 3-year post-OLT survival rates of 85% and 76%, respectively. No patient developed HCC recurrence. There were three major complications in 76 RFA procedures (hepatic arterial hemorrhage, small bowel perforation, and liver decompensation salvaged by OLT), without resultant death or dropout. In conclusion, percutaneous RFA is an effective bridge to OLT for patients with compensated liver function and safely accessible tumors. Tumor-related dropout rate and post-OLT outcome compared favorably with published controls of patients with early-stage disease. This can be attributed to the efficacy of RFA in producing local cure or curbing tumor progression during the waiting period.     

Is It Possible to Gain Extra Waiting Time to Liver Transplantation in Acute Liver Failure Patients Using Albumin Dialysis?

Hepatic encephalopathy (HE)‐associated brain edema is a common cause of death in acute liver failure (ALF). Molecular Adsorbent Recirculating System (MARS) albumin dialysis detoxifies endogenous and exogenous toxins from blood and improves HE. In this study we assessed the effect of MARS on increasing the length of time available while waiting for liver graft. Thirty‐seven patients with ALF who received a high‐urgent liver transplant (LTx) were divided into three groups according to the amount of histological necrosis in the explanted liver: group I = 100% necrosis; group II = 80–99% necrosis; group III = less than 80% necrosis. MARS was used continuously until LTx. Median time (range) on MARS treatment prior to LTx in groups I–III was 7 days (2–26), 6 days (1–17), and 5 days (1–15), and the median time on the waiting list was 5 days (1–11), 3 days (0–13), and 1 day (0–12), respectively. The HE grade prior to and after MARS was similar in all groups. In two patients the HE grade decreased during MARS treatment, even though the explanted liver showed a complete lack of viable cells. Overall 30‐day and one‐year survival were 97% and 92%, respectively, without differences between the three groups. In ALF patients the liver cell damage progressed to total or near total necrosis of the liver when the waiting time was prolonged. Yet, with MARS treatment some patients with total hepatic necrosis showed an absence of encephalopathy. With MARS treatment some patients might be able to wait longer for a LTx with good results.     

Liver transplantation for familial amyloidotic polyneuropathy in Australia

Familial amyloidotic polyneuropathy type 1 (FAP‐1) is a type of systemic amyloidosis caused by mutant transthyretin (mTTR) that is mainly produced in the liver. Most patients have progressive peripheral and autonomic neuropathy. Ten patients with FAP underwent orthotopic liver transplantation (OLT) at the Queensland Liver Transplant Service (Princess Alexandra Hospital, Brisbane, Australia). Nine patients are still alive, and one patient died of cardiac failure 10 days after OLT. Some symptoms of FAP were alleviated in some of the patients. OLT seems to be a worthwhile treatment for FAP, because it halts the progression of symptoms and achieves improvement in some patients.     

A 3‐year experience with Molecular Adsorbent Recirculating System (MARS): our results on 63 patients with hepatic failure and color Doppler US evaluation of cerebral perfusion

Abstract In our 3‐year experience, we treated 63 patients with Molecular Adsorbent Recirculating System (MARS). The patients were divided as follows: 10 primary non‐function (PNF) 16%, 10 delayed non‐function (DNF) 16%, 16 Fulminant hepatitis (FH) 24%, 23 acute decompensation of chronic liver disease (ACLF) 38%, and 4 hepatic resection 6%. All patients who underwent MARS treatment had bilirubin >15 mg/dL, Glasgow Coma Score between 9 and 11, ammonium >160 µg/dL and non‐coagulability. The determining factors taken into consideration for the continuation of MARS treatment were: an improvement in Glasgow Coma Score, and a decrease in ammonium and bilirubin. We also monitored hemodynamic parameters, acid–base equilibrium, and blood gas analysis before and after each treatment. In order to determine patients' neurological conditions, we not only took into account the Glasgow Coma Score, which does not give mathematically precise results but also took into account the fact that patients with hepatic coma had lower cerebral mean velocity in the cerebral arteries than patients without encephalopathy. For this reason, in the last 22 patients we monitored cerebral perfusion, determined by mean flow velocity (V_mean) in the middle cerebral artery. Our results were expressed as mean ± SD and we analyzed the differences between mean values for each variable, before and after treatment by means of Student's t‐test. At the end of treatment, we obtained significant P‐values for bilirubin, ammonium, Glasgow Coma Score and creatinine. In 16/20 patients, we could demonstrate a clear correlation between the improvement in clinical conditions (especially neurological status) and improvement in cerebral perfusion, measured by color Doppler US.     

Surgery for cholangiocarcinoma: the role of liver transplantation

Liver transplantation alone for unresectable hilar cholangiocarcinoma (CCA) is fraught with frequent recurrence and poor long-term survival. The Mayo Clinic developed a novel therapeutic protocol combining neoadjuvant chemoradiation and orthotopic liver transplantation (OLT) in 1993 to treat patients with unresectable hilar CCA or CCA arising in the setting of PSC. Aim. We recently reviewed our experience over the past 14 years with the specific aim to evaluate the long-term outcomes of CCA patients treated according to our study protocol. Methods. We analyzed data from all patients enrolled in the Mayo Clinic liver transplant protocol since 1993. Statistical data analysis of recurrence and survival rates was performed using the Kaplan-Meier method. Results. 148 patients were enrolled in the protocol. Of 90 patients who completed neoadjuvant therapy and subsequent OLT, 71 are alive and 19 have died – only 8 due to recurrent CCA. Nineteen patients are awaiting OLT and 39 were removed from the protocol owing to disease progression or death. Overall, 1-, 3-, and 5-year patient survival was 82%, 63%, and 55%, respectively; 1-, 3-, and 5-year survival after OLT was 90%, 80%, and 71%. Conclusions. Neoadjuvant chemoradiation and OLT achieves significantly lower recurrence and higher long-term survival rates than resection, OLT alone, or medical treatment in hilar CCA. Additional experience at independent transplant centers is necessary to confirm these encouraging results, address the role of neoadjuvant therapy and liver transplantation versus conventional resection, determine appropriate inclusion/exclusion criteria, and define the risk of disease progression while awaiting transplantation.     

Effect of hyponatraemia on outcomes following orthotopic liver transplantation

Background: Hyponatraemia increases risk of adverse outcomes following orthotopic liver transplantation (OLT), but it is unclear whether improvement of pretransplant hyponatraemia ameliorates post‐transplant complications. Aims: To assess impact of pretransplant hyponatraemia on post‐transplant outcomes. Methods: We performed a retrospective analysis of 213 patients with cirrhosis who underwent liver transplantation. Patients with serum sodium ≤130 mEq/L immediately before transplantation (‘hyponatraemia at OLT’; n=34) were compared with those who had experienced hyponatraemia but subsequently improved to a serum sodium >130 mEq/L at transplantation (‘resolved hyponatraemia’; n=56) and to those without history of hyponatraemia before transplantation (‘never hyponatraemic’; n=123). Primary endpoint was survival at 180 days post‐OLT. Secondary outcomes included time until discharge alive, complications during hospitalization, length of time ventilated and length of post‐transplant intensive care unit stay. Results: There was no survival difference at 180 days post‐OLT between groups. After transplantation, patients with either hyponatraemia at OLT or resolved hyponatraemia had longer time until discharge alive and had higher rates of delirium, acute renal failure, acute cellular rejection and infection than those who were never hyponatraemic. As compared with patients with hyponatraemia at OLT, those with resolved hyponatraemia were more likely to be discharged alive within 3 weeks, but other outcomes, including survival, did not differ significantly. Conclusions: We conclude that hyponatraemia at any time before liver transplantation is associated with adverse post‐transplant outcome, even when hyponatraemia has resolved.     

Cryoglobulinemia following liver transplantation for cirrhosis secondary to hepatitis C virus infection

Hepatitis C virus (HCV) infection has been linked with some extrahepatic immunologic abnormalities. Cryoglobulinemia is one of the most frequently reported. Nevertheless, there are only a few reports of cryoglobulinemia in the setting of liver transplantation. More studies are needed to clarify the frequency of post-OLT cryoglobulinemia in patients with HCV-related cirrhosis and its impact on OLT outcome. A case of a patient who underwent liver transplantation because of HCV end-stage liver disease and in whom cryoglobulinemia appeared 3 years after transplantation is reported. Treatment with cyclophosphamide and steroids was attempted but patient died of septicemia 3 years after liver transplantation.     

Acute hepatic failure: a Western perspective

Acute hepatic failure (AHF) is an uncommon, devastating syndrome, which results in death or the need for liver transplantation in more than 50% of cases. While AHF has numerous causes, most cases are due to viral hepatitis and drug toxicity or idiosyncratic reactions. A significant group with indeterminate causation remains, despite careful investigation. In many of these cases a viral aetiology is suspected, although yet not proven. Major differences exist in the aetiology of AHF between the West and Eastern countries. A wider range of aetiologies exists in the West. Common causes include acetaminophen toxicity and idiosyncratic drug reactions, while viral hepatitis is less frequent. Hepatitis E infection is rarely seen in Western countries in contrast to its high prevalence in the East. The mainstay of AHF management is supportive care in an intensive care unit. Liver transplantation is now the standard of care in many Western liver units for individuals who have a less than 20% probability of survival. Lack of availability of donor livers at short notice remains a significant problem. Methods of liver support used while waiting for a donor liver or for the native liver to regenerate include bioartificial livers, extracorporeal liver-assist devices, extracorporeal whole organ perfusion (human and transgenic pig) and hepatocyte transplantation. The effectiveness of these methods remains unproven and awaits controlled clinical trials. Both transplantation and liver-support methods require specialized units and expensive and complicated equipment. Further research is necessary to identify modalities of therapy that would be effective as well as widely accessible.     

Preconditioning by extracorporeal liver support (MARS) of patients with cirrhosis and severe liver failure evaluated for living donor liver transplantation -- a pilot study.

PURPOSE: The aim of this prospective study was to evaluate the effectiveness of preconditioning molecular adsorbent recirculating system (MARS) treatment on patients with acute-on-chronic liver failure (AoCLF), who were awaiting living donor liver transplantation (LDLT). PATIENTS AND METHODS: Between January and December 2001, 10 consecutive AoCLF patients (with progressive hyperbilirubinemia (>20 mg/dl) and hepatic encephalopathy grade > or =2) were studied. MARS was used in eight of these patients who were evaluated for LDLT during 2001. Three AoCLF patients who received LDLT before clinical use of MARS were used as historical controls. RESULTS: Because of a shortage of donors, only five out of 10 patients considered for LDLT could receive transplants. Three patients were treated with MARS for 8 h the day before receiving LDLT, and all three survived. The remaining two patients who received transplants, and who were not pretreated with MARS, died from sepsis and multi-organ failure within 2 weeks. Four of the patients who did not receive transplants because of donor shortage died despite 1 or 3 MARS treatments, however bilirubin levels and grade of encephalopathy were significantly reduced in these patients. CONCLUSIONS: Results of this small pilot study suggest that MARS, by reducing the severity of jaundice and encephalopathy, might be effective as a bridging option in AoCLF patients awaiting LDLT.     

Changing etiologies and outcomes of acute liver failure: A perspective from Japan

Acute liver failure in Japan usually consists of fulminant hepatitis (FH) due to viral infection, autoimmune hepatitis and drug-allergy-induced liver injury. The annual incidence of FH was estimated at 429 cases in 2004. FH is classified into acute or subacute type, and the prognosis of the latter is poor. Hepatitis B virus (HBV) is the most frequently identifiable agent that causes FH in Japan. Transient HBV infection is more prevalent in the acute than subacute type, whereas the frequency of HBV carriers is greater in the subacute type. FH due to HBV reactivation from resolved hepatitis B has been increasingly observed in patients with malignant lymphoma treated with rituximab and corticosteroid combination therapy. The prognosis is poor in HBV carriers with acute exacerbation, especially in patients with HBV reactivation from resolved hepatitis B. Despite careful investigation, the etiology is still unknown in 16% and 39% of the acute and subacute type of FH, respectively. Autoimmune hepatitis and drug-allergy-induced liver injury are found in 7% and 10%, respectively, and are more frequently observed in the subacute type of FH. Living donor liver transplantation is now the standard care for individuals with poor prognosis. Artificial liver support with plasmapheresis and hemodiafiltration plays a central role while waiting for a donor liver or for the native liver to regenerate. Further research is necessary to identify the causes of unknown origin. In addition, to improve the prognosis of FH, it is necessary to establish treatment modalities that are effective for liver regeneration.